WELCOME TO THE FIRST EVER
WORKSHOP ON MRI OF
NEUROMODULATION.
TARGET ENGAGEMENT,
NEUROMECHANISM AND BIOMARKER
DEVELOPMENT.
I'M FROM BERKELEY AND VERY PROUD
TO CO-CHAIR THIS WORKSHOP.
THIS WORKSHOP, I'M A SCIENTIST,
TO THE BEST OF MY KNOWLEDGE
FIRST OF ITS KIND IN HUMAN
HISTORY.
I THINK IT IS GREAT TO BE
SOMETHING, FIRST OFF, IN HUMAN
HISTORY, NO MATTER HOW SMALL OR
GREAT IT CAN BE.
AND I'M ALSO VERY HONORED.
THIS WORKSHOP WAS CO-SPONSORED
BY ISMRM AND ALSO NIH.
NIH IS VERY GENEROUS TO PROVIDE
THIS VENUE AND THE MANY SUPPORT.
YEAH, SO I WOULD SAY WE CAME A
LONG WAY FOR THIS WORKSHOP.
IT STARTS WITH GRASSROOTS
ACTIVITY.
SEVERAL OF US CALLED MEMBERS OF
THE ORGANIZING COMMUNITY, WE
ORGANIZED SOME MEMBER
INITIATIVES WORKSHOP A FEW YEARS
AGO FOLLOWED BY OHBM SYMPOSIUM.
WE FEEL THERE IS SOME ENERGY IN
THE COMMUNITY SO WE DISCUSSED
THIS IDEA.
THEN WE POST ON SOCIAL MEDIA ON
LINKEDIN.
WE GOT A LOT OF FANTASTIC ADVICE
AND FEEDBACK ESPECIALLY FROM
MANY OF YOU GUYS.
THAT LEADS TO THIS WORKSHOP AND
ORGANIZING COMMUNITIES.
MANY PEOPLE CONTRIBUTED, SO
THANK YOU.
ALSO WE GO THROUGH MANY
ITERATIONS WITH ISMRM.
SO I WANT TO THANK THE
ORGANIZERS, ISMRM ANN MARIE AND
RIHANNA.
SO WE ALSO SPONSORED BY
INDUSTRY.
WE HAVE AN R-13 GRANT AND IBIB.
AND WE HAVE THREE GENEROUS
INDUSTRY SPONSORS, ABBOTT, ROGUE
AND MAGVENTURE.
I DIDN'T SEE THE SETUP
EXHIBITION DESK YET.
GO CHECK OUT EVEN IF YOU CANNOT
AFFORD TO BUY THIS DEVICE.
SO I THINK EVERYBODY HERE ARE
PART OF THE COMMUNITY.
WE ARE STARTING WITH
NEUROMODULATION IMAGES.
I WANT TO SEE MORE AMBITIOUS
PEOPLE THAN A REGULAR
NEUROIMAGE.
WE ARE NOT SATISFIED WITH AS A
BYSTANDER TO BRAIN ACTIVITY.
WE WANT TO ALSO PARTICIPATION.
WE ALSO WANT TO DERIVE A CAUSAL
RELATIONSHIP.
SO THAT IS I THINK WHAT IS
TRENDING WITH A RANGE OF
NEUROMODULATION TACTICS FROM
ELECTRIC MAGNETISM, FROM
ULTRASOUND AND OPTICAL IMAGING.
SO I THINK THIS IS JUST A
CONVERGING FIELD.
AND IT ALSO NOT ONLY CROSSES
DIFFERENT MODALITIES, BUT
CROSSES DIFFERENT LEVELS FROM
BASIC SCIENCE TO IMAGING PHYSICS
TO NEUROSCIENCE AND EVENTUALLY
TO INDUSTRY, TRY TO TRANSLATE
COMMERCIALIZATION.
I THINK THAT IS WHAT WE ARE
STARTING ON, A MULTIDISCIPLINARY
CROSS-LEVELS, CROSS-SKILLS.
IF YOU LOOK AT THE PUBLICATION,
PUTTING PUBMED NEUROMODULATION,
IT IS CROSSING TO A THOUSAND
PEOPLE PER YEAR.
IN 30 YEARS, STARTING FROM THE
1990s AND I THINK THE DROP IS
BECAUSE OF COVID, BUT I THINK
THE FIELD IS GROWING.
I WOULD LIKE TO INVITE PROFESSOR
YEN-YU.
>>GOOD MORNING, EVERYONE, HERE.
AS WE HAVE 30% OF ATTENDEES
ONLINE, SO I WOULD JUST LIKE TO
SAY GOOD MORNING, GOOD
AFTERNOON, AND GOOD EVENING,
DEPENDING ON WHERE YOU ARE.
I'M YIHONG YANG.
AS THE CO-CHAIR OF THE WORKSHOP,
ALSO ON BEHALF OF THE NIH HOSTS,
I WANT TO WELCOME ALL OF YOU TO
THE WORKSHOP.
AS YOU KNOW IT IS VERY DIFFICULT
TO ORGANIZE SUCH A MEETING
DURING THE COVID.
WE STARTED LIKE TWO YEARS AGO,
GOING THROUGH PROCEDURES AND
APPROVALS.
FINALLY I WILL GET TO THE POINT
WE CAN ALL SIT DOWN AND HAVE
THIS WORKSHOP.
THE TOPIC OF THIS WORKSHOP IS
INTEGRATION OF IMAGING AND
NEUROMODULATION.
WE BRING THE EXPERTS IN THE
FIELD, FROM TECHNICAL
DEVELOPMENTS TO NEUROLOGICAL
PRESENTATIONS TO COME TOGETHER
AND HAVE A DISCUSSION.
I HOPE EVERYONE CAN LEARN
SOMETHING NEW AND MAKE SOME NEW
FRIENDS AND ENJOY THE WORKSHOP
IN THE NEXT COUPLE OF DAYS.
THANK YOU.
[ APPLAUSE ]
>>JUST A FEW LOGISTICS.
I THINK ONLINE, WE STILL DON'T
HAVE THE CHAT.
WE'RE STILL TRYING TO PUSH IT.
TODAY I THINK BEFORE LUNCH WE
WILL TAKE A GROUP PICTURE
TOGETHER.
>>ALSO ANOTHER QUICK
ANNOUNCEMENT.
THE KEYNOTE LECTURE WILL START
FROM 10:15.
SO IT WILL BE 15 MINUTES
EARLIER.
ALL RIGHT, SO WITHOUT FURTHER
ADO, WE CAN START THE FIRST
SECTION.
>>GOOD MORNING, EVERYONE.
I WOULD LIKE TO WELCOME YOU TO
THE FIRST SESSION OF THIS
WORKSHOP, MRI FOR
NEUROPHYSIOLOGICAL USING
NEUROMODULATION.
I WOULD LIKE TO INTRODUCE YEN-YU
SHIH.
WELCOME.
>>I DO HAVE A CONFLICT OF
INTEREST TO DECLARE.
I'M CONSULTING WITH -- SO WE
WANT TO LINK INFORMATION FROM
MOLECULAR AND CELLULAR ASPECTS
TO BEHAVIOR.
OFTENTIMES THE COMPLEX BEHAVIOR
IS NOT DIRECTLY REFLECTED BY
MOLECULAR ACTIVITY FROM A SINGLE
BRAIN REGION.
IN A FORM OF ORCHESTRATED
ACTIVITY FROM LARGER SCALES,
INCLUDING THE CIRCUIT AND
KNELTWORK OBSERVATIONS BY MRI.
THERE ARE INCREASING STUDIES TO
USE METRICS TO SEE IF THEY SERVE
AS A MEDIATOR FOR THIS
RELATIONSHIP AT THE BOTTOM.
KNOWING THIS IS IMPORTANT
BECAUSE WE WAND TO PREDICT
BEHAVIOR.
TO REACH THAT GOAL, THERE IS A
NEED TO BETTER UNDERSTAND HOW
FMRI SIGNAL IS FORMED.
WHAT NEURAL EVENT IS CONTRIBUTES
TO FMRI SIGNALS.
WE WOULD LIKE TO READ
INFORMATION FROM THE BRAIN THE
FMRI.
I WILL TOUCH ON
ELECTROPHYSIOLOGY, AN ELECTRICAL
CHEMICAL.
AND YOU CAN GENETICALLY EXPRESS
TO ALLOW THE CELLS TO SHINE
LIGHTS AND USE MORE OPTICAL
FIBER TO PICK UP THOSE SIGNALS.
WE ALSO WANT TO BETTER CONTROL
THE INFORMATION FLOW BY HAVING
THE ABILITY TO WRITE INFORMATION
INTO THE BRAIN THIS CAN BE DONE
ELECTRICALLY AND GENETICALLY
USING OPTICAL OR CHEMICAL
APPROACHES.
SO WE NEED TO BETTER UNDERSTAND
HOW AN F MRI SIGNAL IS FORMED.
SPECIFICALLY, THE ASPROECH WE
USE IS SPECTRAL PHOTOMETRY.
THESE ARE THE WAYS PEOPLE DO
FINSER PRINTING, THIS IS THE
OPTICAL VERSION OF IT.
EACH ONE HAS ITS UNIQUE PATTERN.
IF YOU CAN ACQUIRE DATA ACROSS A
WIDE RANGE OF SPECTRUM, YOU CAN
TRY TOLL ATTACH THE SPECIFIC
PROFILE OF THE FINSER PRINT TO
EXTRACT THE CO-EFFICIENT OF THE
SENSOR ACTIVITIES.
THERE ARE A LARGE NUMBER OF
SENSORS BEING DEVELOPED.
GCAMP, CALCIUM ACTIVITY IN
GREEN, JRGECO CALCIUM ACTIVITY
IN RED.
GLUTAMATE, GABA AND THE VIDEO ON
THE RIGHT SHOWS THE SET UP WE
HAVE.
THE GLUTAMATNERGIC SPECTRUM.
IT IS A SINGLE FIBER WE CAN GET
INPUT AND OUTPUT ACTIVITY
SIMULTANEOUSLY.
YOU DON'T HAVE TO USE TWO
FLUORESCENT SENSORS.
YOU CAN USE THIS TO LOOK AT
CUPELING.
FOR THIS SETUP WE EXPRESSED
GCAMP IN THE CORTEX OF THE RAT
AND INJECTED A RED FLUORESCENT
DYE.
THIS IS A FLUORESCENT DYE THAT
WILL CIRCULATE IN YOUR BLOOD
STREAM.
THOSE FAMILIAR WITH MEASURING
BLOOD VOLUME USING MRI, THIS IS
CONCEPTUALLY SIMILAR.
WE CAN DO AN EXPERIMENT AND GET
THIS GCAMP ACTIVITIES, THE
PHOTOMERRY AT THE RIGHT VOLUME.
SO THIS TYPE OF STUDY OR
INFORMATION DOESN'T NECESSARILY
HAVE TO COME FROM A STIMULUS
EVOKED EVENT.
I'M SHOWING YOU EXAMPLES THAT WE
CAN ACTUALLY PULL THE
INFORMATION OR THE RELATIONSHIP
NEURONAL.
THIS IS THE RECORDED GCAMP
ACTIVITY FROM THE CELLS AND
USING THE CBV MEASURE.
WE CAN EM PEERICALLY DERIVE A
RESPONSE FUNCTION.
THIS IS TO CONVOLUTE THIS TO
PREDICT THE UNDERLYING CBV
CHANGES AND THE MEASURE OF CBV
IS SHOWN IN RED.
THEY HAVE HIGH CORRELATIONS.
THIS APPROACH IS PRETTY ROBUST.
THIS VIDEO I'M SHOWING YOU WAS
FROM A SINGLE ANIMAL.
THE FIBER PLUGGING INTO THE
BRAIN AND ACQUIRING THE NEURONAL
AND VASCULAR SIGNAL
SIMULTANEOUSLY, BUT FEEDING THIS
INFORMATION TO THE DECONVOLUTION
PIPELINE.
BEYOND ONE MINUTE WE CAN GET A
STABILIZE HRF PATTERN THAT
DESCRIBES THE RELATIONSHIP
BETWEEN NEURONAL AND VASCULAR
ACTIVITY HERE.
WE SCALED THIS UP AND BUILT FOUR
CHANNEL SYSTEMS THAT ALLOWS FOUR
INDIVIDUAL FIBERS INTO DIFFERENT
BRAIN AREAS AND MEASURE THE
SIGNAL SIMULTANEOUSLY.
IN THIS PARTICULAR EXPERIMENT WE
PUT IN THESE CORTICAL REGIONS.
YOU CAN SEE THE CONSISTENT
PATTERN HERE, WHICH IS GOOD,
RIGHT, BECAUSE THAT MEANS FMRI
THE WAY WE INTERPRET FMRI DATA
HAS A REASONABLY SOLID
FOUNDATION.
THERE MIGHT ALSO BE SOME
EXCEPTIONS WHERE NEUROVASCULAR
COUPLING RULES MAY NOT APPLY.
WE RAN INTO THIS THROUGH A
DEVELOPMENT WITH OUR
COLLABORATORS A FEW YEARS AGO TO
MAKE FOR STIMULATION RECORDINGS.
TO WALK YOU THROUGH THE
DEVELOPMENT.
WE HAD FLEXIBLE ELECTRODES AND
CONTACT LEADS MADE BY GOLD AND
COVERED WITH ORIDIUM OXIDES.
THIS IS A MINIMUM INTENSITY
PROJECTION FROM A 3D SPINNING
DATA.
THIS WE CAN PASS A QUITE HIGH
LEVEL OF THE CURRENTS FOR
MULTIPLE TIMES.
AND ALSO IN VIVO, WE CAN PUT IT
IN ANIMAL BRAINS AND LOOK OVER
THE COURSE OF 50 DAYS.
THIS PICTURE SHOWS WE ARE USING
A FORCEP TO PUT IT ON THE TABLE.
IT COMES WITH A BENEFIT TO
REDUCE SCARS ONCE YOU IMPLANT
THIS INTO THE SUBJECT'S BRAINS.
IN A FORM OF MRI COMES WITH AN
ADDED EXTRA BENEFIT YOU CAN BEND
ELECTRODE AND USE ANY COIL
HOUSING TO DO YOUR EXPERIMENT.
WE TRIED TO PASS CURRENTS TO
DIFFERENT LOCATIONS, DIFFERENT
ELECTRODES THAT HAVE BEEN
IMPLANTED.
THESE CAN CAPTURE BETTER.
WHEN WE ARE STIMULATING
DIFFERENT PORTION OF THE
ELECTRODES WE ARE GOING TO DRIVE
DIFFERENT CORTICAL ACTIVATION
BECAUSE WE ARE RECRUITING
DIFFERENT FIBER GOING TO THE
CORTEX.
THIS PROVIDES US THE ABILITY TO
DO STIMULUS EVOKED FUNCTIONAL
ACTIVITIES WITH A REASONABLY
HIGH THROUGHPUT COMPARED TO A
SINGLE ELECTRODE.
THE PROBE CAN BE USED FOR
RECORDING.
I'M SHOWING YOU A PROFILE
FOLLOWING DIFFERENT LAYERS AND
INSIDE A MRI TO CAPTURE SINGLE
UNIT ACTIVITY.
WITH THIS PROBE OUR LAB WAS
INTERESTING NO KNOWING WHAT IS
THE SPATIAL TEMPORAL PATTERN IN
THE BRAIN REGIONS CLINICIANS ARE
PICKING TO TREAT PARKINSON'S
DISEASE FOR EXAMPLE.
WE DID THIS EXPERIMENT AND PUT
ELECTRODES IN THE RODENT BRAIN.
STM IS A THIN STRUCTURE.
THE AREAS ABOVE AND BELOW HAD
VERY DIFFERENT FIRING PATTERN.
WE CAN USE THIS SAME ELECTRODE
TO PICK UP THE LOCATION OF THE
STN AND COVER THE SURGERY UP AND
COME BACK TO THIS SAME LOCATION
AND AS YOU CAN SEE FROM THE
PICTURES ON THE RIGHT DERIVE A
PATTERN.
WE ARE SEEING SOME RESPONSES
FROM THE RAPHE, CEREBELLUM AND
WE SAW THIS NEGATIVE EVOKED FMRI
SPOBSS IN THE STRIDUM AREA.
AT THE TIME WE DID NOT HAVE A
GOOD WAY TO EXPLAIN THOSE
RESULTS.
IN A SEPARATE STUDY, INCLUDING
SUBSTANTIAL SNR IN THE EXTERNAL
GPE.
SO KNOWING THAT ELECTRICALLY
STIMULATING THOSE REGIONS WILL
RECRUIT -- TO FIRE NEURONS WE
ARE INTERESTED IN KNOWING WHY
DRIVING THIS ACTIVITY WOULD LEAD
TO A NEGATIVE FMRI RESPONSES.
SO WE WENT ON TO ASK ANOTHER
QUESTION?
CAN WE PROBE IN THE SOURCE OF
THIS NEGATIVE FMRI SIGNAL WITH A
CELL TYPE OR PATHWAY SPECIFIC
STIMULATION AND IN RODENT MODEL,
WE HAVE ACCESS TO A VERY
POWERFUL TOOL TO GENETICALLY
EXPRESS THIS ON CHANNELS AND
SOMETIMES IN THE FORM OF
RECEPTORS AND WHEN YOU SHINE THE
LIGHT WITH APPROPRIATE
WAVELENGTHS, YOU CAN DRAW
ACTIVITIES FOR SPECIFIC CELLULAR
POPULATION.
INSIDE MRI THE SET UP IS
STRAIGHT FORWARD.
BUILD A COIL.
SO WE WENT ON TO INTERROGATE A
FEW CIRCUITRIES THAT ARE
RELEVANT TO THE STRIATUM, WERE
RECRUITING AS YOU CAN SEE FROM
THIS RESULT, WE ARE LEARNING
THAT FIRING EXCITERY INPUT
DOESN'T NECESSARILY ALWAYS LEAD
TO A POSITIVE FMRI RESPONSE.
IN THIS CASE UNDER OUR
EXPERIMENTAL CONDITIONS IT CAN
LEAD TO NEGATIVE FMRI SIGNAL.
MOVING ON WE ALSO DID THE SAME
TO DIRECTLY STIMULATE THE
STRIATUM NEURONS.
WE STIMULATED THE GCE CELL BODY.
BY DOING THIS EXPERIMENT WE
REALIZED THAT ACTIVATION OF
LOCAL STRIATUM NEURON CANS CAUSE
THIS NEGATIVE FMRI RESPONSE.
THERE IS ANOTHER INTERESTING
FINDING WHEN WE TRY TO TARGET
DOPAMINENERGIC NEURONS THAT SENT
A LOT TO THE STRIATUM REGION AND
SEEING POSITIVE INSTEAD OF
NEGATIVE RESPONSES.
WE REPORTED THIS BY A PAPER IN
2016, BUT WE ARE NOT THE ONLY
GROUP THAT SAW THIS.
THERE ARE OTHER PAPERS LISTED
HERE SEEING THE SAME THING.
WE ARE TRYING TO FIND THE
UNDERLYING ACTIVITY.
WE ARE TRYING TO MEASURE
POTENTIAL AND THE MULTIUNIT
ACTIVITY UNDER THE SAME
EXPERIMENTAL CONDITIONS WE
CREATED A NEGATIVE RESPONSE.
INDEED WE ARE SEEING THE
INCREASES IN POWER AT A BAND WE
MODULATED AND INCREASING IN
SPIKING ACTIVITY.
WE KNOW THIS VALIDATION IS NOT
ENOUGH.
WE WANT TO DO MORE THOROUGH
INVESTIGATIONS OF THIS.
THAT IS THE POINT WE BROUGHT
THIS FIBER PHOTOMETRY APPROACH.
BY THE TIME WE WERE READY TO
LAUNCH THIS EXPERIMENT, THIS IS
SHOWING YOU THE CONTROL
EXPERIMENTS WHERE WE EXPRESS IN
THE PROTEIN INTO THE CORTICAL
ACTIVITIES.
THIS PROTEIN'S INTENSITY OF
LIGHT HAS NOTHING DO WITH THE
ACTIVITY.
WE ARE STILL SEEING CHANGES, A
DECREASE IN THE SIGNAL THAT WE
MEASURE BY THIS OPTICAL FIBER.
SO WHY?
WE WENT ON QUITE A BIT OF A
JOURNEY TO FIGURE OUT THE
UNDERLYING REASON AND WE FIGURED
OUT THIS IS ACTUALLY BECAUSE THE
HEMOGLOBIN CHANGES, OR THE
CONCENTRATION OR AMOUNT OF
HEMOGLOBIN CHANGES.
HEMOGLOBIN IS VERY GOOD AT
STOPPING THE LIGHT.
AS WE ARE OPERATING UNDER THE
RULE OF DRIVING ACTIVITIES,
FUNCTIONAL HYPER -- THE INCREASE
IN HEMOGLOBIN WERE A SIGNATURE
CAL THAT CAN HAPPEN IN TWO
PHASES.
THE LIGHT COMING OUT FROM THE
OPTICAL FIBER BEFORE IT REACHES
THE TARGETED CELLS AND THE
EMISSION LIGHT FROM THE CELLS
BEFORE IT GOES BACK TO THE
OPTICAL FIBER.
WE KNOW THAT WE NEED TO SOLVE
THESE ISSUES.
AND WE FIGURE OUT A WAY TO
ACTUALLY CORRECT THIS TYPE OF
CONTAMINATION.
I'M NOT GOING TO GO INTO THE
DETAIL HERE.
THE INFORMATION WAS IN THIS
PAPER PUBLISHED BY ZHANG, CELL
REPORTS METHODS THIS YEAR.
OXY AND DEOXY HEMOGLOBIN OVER
TIME USING THE SPECTRAL
INFORMATION TO COLLECT THE
HEMOGLOBIN AND RESTORE THE
NEURAL ACTIVITY TO MAKE A STEP
CLOSER TO THE REAL UNDERLYING
EVENT.
WE NEED TO GET THE ACCURATE
NEURONAL ACTIVITY AND TIME SCALE
TO MODEL THE RELATIONSHIP.
SO MOVING ON, WE DID AN
EXPERIMENT BY PUTTING AN
ELECTRODE TO STIMULATE THE
MULTICORTEX.
MULTICORTICAL REGIONS PROVIDE
EXCITERY.
LATERALLY TO THE STRIATUM.
SO THOSE ARE THE TWO LOCATIONS
WHERE WE DID THIS FIBER
EXPERIMENT, WE PUT IN FIBER TO
MEASURE THEIR SIGNALS.
BY STIMULATING THE UPSTREAM
MOTOR CORTEX WE CAN DETECT THE
DOWNSTREAM ACTIVITY SHOWN IN THE
PANEL C AND D.
YOU CAN SEE FROM THESE TWO
REGIONS WE ARE GETTING A SIMILAR
PATTERN OF THE CELLULAR CALCIUM
EVENTS.
THE ACCOMPANYING HEMODIE MA'AMIC
RESPONSE IS VERY DIFFERENT.
THE NEUROVASCULAR COUPLING SEEMS
QUITE SIMILAR ACROSS CORTICAL
REASONS, BUT THERE MAY BE
DIFFERENCE BETWEEN THE CORTEX
AND THE STRIATUM.
THAT EXPERIMENT WAS DONE ANIMALS
WHO WERE UNDER ANESTHESIA.
WE USED THE SAME APPROACH WITH
FOOTSHOCK, WHICH WOULD DRIVE THE
ACTIVITY AND SAMPLING THE
SPONTANEOUS SPIKES FROM THIS
STRIATUM NEURONS.
WHILE WE HAVE INCREASE IN
CALCIUM ACTIVITIES, THERE IS AN
ASSOCIATED TIME LOCKED CVV
CHANGES MEASURED BY THE FIBER.
SO WHAT IS THE MECHANISM?
COULD IT BE SOME NEURAL CHEMICAL
INFLUENCES TO THESE SIGNALS?
TO ADDRESS THIS WE COUPLED FMRI
WITH ADDITIONAL NEUROMODULATION
APPROACH WITH PHARMACOLOGY THAT
ALLOWS US TO INTERROGATE SOME OF
THE MECHANISM RESPONSIBLE FOR
THIS NEGATIVE RESPONSE.
THE SPECIFIC EXPERIMENT WE ARE
DOING HERE IS EXPRESSING VIRAL
VECTORS AND INJECTING INTO THE
DORSAL STRIATUM.
INSTEAD OF STIMULATING THE
STRIDAL CELL BODIES, WE ARE
PUTTING THEM DOWNSTREAM TO ALLOW
US TO REKREUTZ AND GO BACK AND
FIRE THE STRIADAL CELL BODIES.
BY DOING THE EXPERIMENT WE ARE
NOT ADJUST AVOIDING THE HEATING
ART FACT THAT CAUSED BY THE
LIGHT REPORTED BY MANY
COLLEAGUES IN THE FIELD WE ARE
CREATING EXTRA SPACE TO PUT IN
INTRACRANIAL FUSION INTO THE
DORSAL STRIATUM.
THESE ARE QUITE COMPLICATED
EXPERIMENTS.
WE STRUGGLE QUITE A BIT TO GET
THIS TYPE OF STUDY LAUNCHED.
EACH ANIMAL IS SCANNED FOR ABOUT
TWO HOURS.
DURING THAT PERIOD WE HAVE
REPEATED OPTICAL STIMULATION TO
SNR TO TRY THE STRIADAL
ACTIVITY.
THE BLUE IS THE ACTIVITY.
THE RESPONSE IS TIME LOCKED TO
THAT.
THE PINKISH HORIZONTAL BAR AT
THE BOTTOM OF EACH GRAPH
INDICATES THE FLUIDS OR
COMPOUNDS WE ARE INFUSING.
YOU CAN SEE FROM PANEL B,
INFUSION OF SALINE DOESN'T
AFFECT IT.
THE STRIADAL RESPONSE, BUT
INFUSING LIDOCAINE, WHICH CAN
SUPPRESS THE ACTIVITY LOCALLY,
WE CAN USE THAT TO KNOCK OFF THE
NEGATIVE SIGNALS.
WE ALSO USED ACETYLCHOLINING A
NIS TO TARGET THE GI COUPLE
RECEPTOR HENCE SUPPRESSING THE
STRIADAL ACTIVITY.
THIS NEGATIVE RESPONSE IS
RELATED TO THE LOCAL STRIATUM
NEURONS.
WE TRIED TO LOOK INTO DIFFERENT
TYPE OF NEUROCHEMICAL SIGNAL
REPORTED TO BE RELATED TO THE
STRIDAL MICROCIRCUITRIES,
ACETYLCHOLINE, BRBB, 3226 AND
SHARING 22390 AND THESE ARE
DOPAMINE D5 AND D1D2ING A NIS
COCKTAILS, NONE OF WHICH
SUPPRESSED THE NEGATIVE RESPONSE
SIGNIFICANTLY.
HOWEVER, WHEN WE INFUSE NOR-BNI.
WHEN WE CHECKED FOR THE OUTPUT
EXPRESSION, WE CAN SEE THE
EXPRESSION LOCATED CLOSE BY THE
STRIADAL MICROVESSELS.
WE TOOK A STEP BACK AND BROUGHT
THINGS TO EXVIVO AND LOOKING AT
USING A TECHNIQUE MICOSCOPY TO
LOOK FOR THE CHANGES DIRECTLY.
HERE WE HAD THE STRIDAL BRAIN
SLIDES, INFUSE WITH TXA2 AND
CSF.
TO SEE WHICH BLOOD VESSELS ARE
RESPONSIVE.
WHEN WE PROFUSE DADLE, A
CAFFEINE OPIOID RECEPTORING A
NIS, WE CAN FURTHER CONSTRICT
VESSELS IN THIS CASE.
WHEN WE STOP THIS PER FUSION,
THE VESSEL DOESN'T RELAX AS YOU
CAN SEE FROM THE PICTURES ON THE
RIGHT.
THIS INDICATES OPIODNURGIC MAY
HAVING SOMETHING TO DO WITH THE
VASO CONSTRICTION IN THE AREA.
THE POSITIVE RESPONSES.
HERE THE PICTURES ON THE LEFT
SHOWS A SET UP WE TRIED TO MAKE,
ELECTROCHEMICAL MEASURES OF --
USING A FULL SELL SETTING AND
FOLLOWED BY IN VIVO EXPERIMENT.
THIS CAN BE DONE WITH FMRI, A
SIMPLE IDEA WHERE WE INTERWEAVE
THE RECORDING TO MAKE IT AWAY
FROM THE PULSES OR EPI GRADIENT
SWITCHING.
WITH THIS APPROACH WE CAME BACK
TO OUR QUESTION WHICH IS WHAT IS
THE UNDERLYING EVENTS THAT IS
HAPPENING WHEN WE DRIVE
DOPAENERGIC.
YOU CAN SEE IN PANEL C ON THE
RIGHT, WE ARE INVOKING THE
POSITIVE FMRI RESPONSES THROUGH
THIS MANIPULATION AND WHEN WE
UNCOUPLE THIS WITH SPECK -- WE
ARE SEEING INCREASING IN
DOPAMINE.
IN THE CASES WE SAW THE NEGATIVE
RESPONSES, STIM LATING THE
THALAMUS, WE ARE NOT SEEING
DOPAMINE CHANGES.
THIS HIGHLIGHTS THE POTENTIAL
INVOLVEMENT OF THIS
NEUROCHEMICAL SIGNALS IN
DICTATING THE VASCULAR RESPONSE
OUTCOMES.
AFTER HAVING THESE FINDINGS WE
ARE INTERESTED IN KNOWING IF
THERE ARE OTHER NEUROCHEMICALS
THAT DISASSOCIATE NEURONAL AND
VASCULAR RESPONSES.
WE USED A TECHNIQUE HERE
SIMILAR, BUT WE CAN EXPRESS THE
RECEPTOR OF DESINDER DRUGS,
DREADD.
THIS RECEPTOR RESPONDS TO A
SPECIFIC DREAADD ACTIVATOR.
YOU CAN INJECT THE DRUGS AND
MODULATE THE CELL ACTIVITY IN
THE MORE CHRONIC FASHION.
SO WE HAVE ACCESS TO THESE
ANIMALS, TRANSGENETIC MOUSE
LINES THAT HAS THE DREADD
RECEPTORS EXPRESSED IN THE
NEURONS RESPONSIBLE FOR THE
MAJORITY OF NOREPINEPHRINE IN
THE BRAIN.
WE KNOW IT IS A NEUROMODULATOR
AND A GOOD VASO CONSTRICTOR.
WE EXPANDED THIS INTO THREE
BANDS.
SO IN THE GREEN ZONE WE ARE
MEASURING THE NOREPINEPHRINE
RELEASE, IN THE RED LOCAL
NEURONAL ACTIVITIES, THE GRAY
ZONE WE ARE USING A RED DYE TO
MEASURE THE VASCULAR ACTIVITY AT
THE SAME TIME.
THIS EXPERIMENT YOU CAN SEE THE
RED VERTICAL BAR IS WHEN WE
INJECTED DREADD.
SEE INCREASES IN CELL SPIKING
ACTIVITIES, CALCIUM ACTIVITIES
AND DECREASE IN BLOOD VOLUME.
THIS IS A DISASSOCIATION BETWEEN
THE NEURONAL ACTIVITY, COMPARED
TO THE EXPECTED NEURONAL AND
VASCULAR RELATIONSHIPS.
SO AGAIN THESE FINDINGS WERE
CORROBORATED BY THE FMRI
OUTCOMES.
I'M NOT GOING TO GO INTO THE
DETAIL HERE, BUT THE DREADD
MODLATOR CAN SUPPRESS THE CVV
CHANGES IN THE BRAIN AND
DOWNSTREAM NETWORK MODULATIONS.
TO SUM UP, FMRI COUPLED WITH
NEURAL STIMULATION AND RECORDING
TOOLS IN ANIMALS CAN GIVE US THE
OPPORTUNITY TO DO MECHANICISTIC
STUDIES DIFFICULT TO IMPLEMENT
IN HUMAN SUBJECTS.
THE HEMODYNAMIC FUNCTIONS ARE
CONSISTENT ACROSS SEVERAL
CORTICAL REGIONS, HOWEVER THIS
RELATIONSHIP MIGHT NOT HOLD IN
SOME BRAIN REGIONS, FOR EXAMPLE
THE STRIATUM.
WITH THE NEURAL ACTIVITIES IN
THE STRIATUM AND DOWNSTREAM
OPIODERGIC SIGNALLING RELATED TO
NEGATIVE FMRI RESPONSES.
NOREPINEPHRINE IS A STRONG
MODULATOR AND VASO CONSTRICTOR.
DECREASE IN HEMO DYNAMIC FMRI
MEASURES DOES NOT NECESSARILY
TRANSLATE TO A SUPPRESSION OF
NURNL AL -- NEURONAL ACTIVITY.
A BETTER UNDERSTANDING OF THE
FMRI SIGNAL HAVING THIS READ AND
WRITE ABILITY WILL HELP BRIDGE
INFORMATION ACROSS TEMPORAL
SCALES AND SOMETIMES ACROSS
MODALITIES.
PEOPLE WHOSE NAMES ARE
HIGHLIGHTED DID THE HARD WORK.
WE THANK YOU NIH AND WE THANK
YOU FOR YOUR ATTENTION.
>>ANY QUESTIONS?
I GUESS I WILL START.
I THINK THAT IS QUITE
INTERESTING YOUR RESPONSES IN
THE STRIATUM FOR NEUROVASCULAR
COUPLING IS DIFFERENT FOR THE
CORTEX.
DO YOU HAVE ANY IDEA BECAUSE OF
THE NEUROTRANSMITTER INVOLVEMENT
OR NEUROVASCULAR ANATOMICAL
REASON?
>>YEAH.
SO THE AREA HAVE VERY DIFFERENT
ANATOMICAL DISTRIBUTION OF THE
CELL TYPES AN DENSITY IN THE
CEREBRAL CORTEX.
VASCULAR IS A LOT DIFFERENT.
THERE IS A LOT OF WORK THAT
NEEDS TO BE DONE TO FURTHER
DISSECT THE INFORMATION WE HAVE
DONE.
AGAIN, THIS IS GOING TO BE A
LONG JOURNEY TO FIGURE OUT, WE
HAVE TO HAVE THE ABILITY TO
CONTROL EACH FACTOR.
AND PROBABLY TO ASK WHICH IS
NECESSITY FOR EACH TO GENERATE A
SIGNAL AND THAT IS WHAT WE ARE
STILL ACTIVELY PURSUING.
>>THAT IS GREAT WORK.
OBVIOUSLY, TO LOOK AT THE
RELATIONSHIP BETWEEN THE FMRI
SIGNAL AND NEUROTRANSMISSION,
THAT IS -- FOR UNDERSTANDING OF
THE SIGNAL.
NOW MOST OF THE WORK IS ON THE
SUBJECTS.
WHAT IS FOR THE POPULATION,
DISEASE POPULATION, WHAT
HAPPENED?
>>YEAH.
WE HAVEN'T HONESTLY GOTTEN INTO
THE DISEASE MODEL JUST YET.
THERE ARE ALREADY A WHOLE LOT OF
THINGS THAT NEED TO BE BROUGHT
BACK TO THE FIRST QUESTION,
THERE ARE SO MANY THINGS WE NEED
TO STUDY IN THE HEALTHY
CONDITION.
I THINK WE NEED TO TAKE STEP BY
STEP AND OBVIOUSLY, THERE ARE
MANY DISORDERS WHERE THE
OPIOIDERGIC AND DOPAMINEERGIC
HAS BEEN AFFECTED.
IN SOME OF THE EXPERIMENTS, THE
PILOT EXPERIMENT WE DID IN SORT
OF PARKINSON'S MIMICRY OF A
MOUSE MODEL, WE COULD SEE R
VERY, VERY BIG DIFFERENCES IN
THE DOPAMINE IN TERMS OF THE
RESPONSES.
IT IS AN INTERESTING LINE TO
PURSUE FURTHER.
[ INAUDIBLE ]
>>SORRY.
I CAN'T HEAR YOU.
>>PROBABLY YOU WANT TO USE THE
MICROPHONE.
>>ARE THESE RESULTS RECORDING
RESTING STATE?
>>SOME OF THE EXPERIMENTS I
SHARE WITH YOU WERE DONE IN THE
RESTING STATE SETTING.
SOME WERE STIMULUS INVOKED
RESPONSES.
THIS COULD BE DONE BOTH WAYS.
>>AND ALSO FOR THE NEGATIVE
RESPONSE, I SAW FOR THE SPATIAL
PATTERNS THERE IS SOME POSITIVE
RESPONSE VERY CLOSE TO IT.
ARE THESE TWO MIGHT BE RELATED?
LIKE EXAMINE THE RELATIONSHIP?
>>RIGHT.
THERE ARE SOME EXPERIMENTS THAT
WE, INDEED, SAW THE POSITIVE
RESPONSES.
OBVIOUSLY, FOR EXAMPLE, WHEN WE
TRIED THE DOPAMENERGIC
RESPONSES.
WE ARE SEEING A POCKET OF
RESPONSE IN THIS AREA THAT COMES
WITH SURROUNDING NEGATIVE
SIGNALS.
THAT IS AN INTERESTING PATTERN
WE NEED TO STUDY.
TO SOME EXTENT WE ARE WORRIED
ABOUT POTENTIAL HEAT RELATED
COMPOUNDS.
WHEN WE DELIVER LIGHT INTO THE
LOCAL AREA, MRI IS QUITE
SENSITIVE TO THOSE TEMPERATURE
RELATED SIGNAL CHANGES THAT
COULD CREATE A SIGNALLING
PATTERN.
WE DON'T KNOW IF THAT IS
VASCULAR RELATED.
THAT IS WHY WE WENT ON FOR
PHOTOMETRY TO CIRCUMVENT
PROBLEMS.
>>OKAY.
THANK YOU.
>>ANY OTHER QUESTIONS?
OKAY.
THANK YOU VERY MUCH.
>>YEAH.
[ APPLAUSE ]
>>ALL RIGHT.
THE SECOND SPEAKER OF THE
SESSION IS DR. HANBING LU FROM
NATIONAL INSTITUTE ON DRUG
ABUSE.
HE IS TALKING ABOUT FOCAL TMS ON
RODENT MODELS.
>>GOOD MORNING.
GOOD AFTERNOON.
SO I GUESS I WOULD LIKE TO START
BY THANKING THE ORGANIZERS FOR
ORGANIZING THIS WORKSHOP AND FOR
THE OPPORTUNITY TO PRESENT OUR
WORK.
SO MY TALK IS AS FOLLOWS.
I WILL GIVE BRIEF BACKGROUND ON
TMS AND AN IMPORTANT QUESTION
WHICH I THOUGHT WAS IMPORTANT.
WHY IS THE EFFICACY OF TMS AND
BACK TRANSLATION OF STUDIES.
WE WILL TOUCH ON TRANSLATIONAL
WORK FOR MECHANICISM AND
EFFICACY OF TMS IS THE PURPOSE.
THE "NEW YORK TIMES" RAN THIS
ARTICLE IN 2018, THE TITLE OF
THIS ARTICLE WAS ONE SON, FOUR
OVERDOSES, SIX HOURS.
THE IMPACT OF ADDICTION TO THE
INDIVIDUALS.
AND TO FAMILIES.
SO CONVENTIONAL ADDICTION
TREATMENT IS BASED ON PHARMACO
THERAPY.
THE NEUROIMAGING FAILED MANY
PEOPLE.
BRAIN CIRCUITS INDICATED DRUG
ADDICTION IN THIS CASE
IMPLICATING COCAINE DEPENDENCY
THROUGHOUT MODELS.
SO WE ARE ASKING WHAT IT CAN DO
WITH THIS.
USING TMS HAS BEEN APPROVED BY
FDA FOR DEPRESSION TREATMENT AND
IT IS
[INDISCERNIBLE] TMS WORKS BY
APPLYING VARIOUS 2,000 VOLTS
WHICH WILL GENERATE HIGH
MAGNETIC FIELD, 1.5 TESLA OR
HIGHER.
STIMULATES THE BRAIN.
WE ARE HOPING TO -- AND IT
FAILED TO APPLY TO ADDICTION
TREATMENT.
MOST WIDELY USED IS REPETITIVE
TMS.
IN THIS PROTOCOL FOUR SECOND OR
20 SECOND.
DURING THE FOUR SECOND PERIOD
TMS IS APPLIED AT 10 HERTZ.
THE OTHER ONE IS A TWO SECOND
ARM PERIOD.
BURSTS OF A PULSE ARE REPEATED.
IN THIS CASE EACH BURST CONSISTS
OF THREE PULSES, SEPARATED BY
50HERTZ.
THE INTERVAL IS 200 MILLISECOND
OR 5 HERTZ.
THIS IS A FREQUENCY RANGE.
# FOR CONVENTIONAL TREATMENT
37.5 MINUTE PR SESSION.
[INDISCERNIBLE] SO THIS IS
REALLY REMARKABLE TO ME.
HOW GOOD ARE EFFICACY?
IT IS RELATIVELY MODEST.
SUGGESTING THE EMISSION RATE 15%
HIGH.
AND THE RESPONSE RATE ABOUT 18%
HIGHER.
ACTIVE V. SHAM RTMS
[INDISCERNIBLE] HOW TMS WORKS.
WE DON'T KNOW WHY SOME PATIENT
RESPOND WELL, SOME PATIENT NOT.
THERE COULD BE MANY REASONS.
SO I WAS THINKING ABOUT MAYBE WE
SHOULD DO SOME ANIMAL WORK TO
BACK TRANSLATE USING THE ANIMAL
MODEL TO MIMIC TMS CONDITIONS.
IN THIS CASE I THOUGHT IT WOULD
BE IMPORTANT.
THE SECOND WOULD BE
[INDISCERNIBLE] THINK ABOUT THE
TMS MULTICORTICAL EACH PASS
EVOKING A SIGNAL.
THE SIZE OF THE COIL TO PRODUCE
SINGLE TWITCHES.
WAY MUCH DOWN FROM HERE, FROM
MONKEY TO RAT BRAIN THERE IS
TREMENDOUS DIFFERENCE.
SO WE
[INDISCERNIBLE] SO ONE QUESTION
IS THE RAT BRAIN, A LARGER ONE,
REGARD TO BRAIN SIZE.
SO THE ANSWER IS NO.
1991 PUBLISHED THIS PAPER.
IN THIS PAPER SIMULATE A 5
CENTIMETER COIL AND REDUCED BY
25 TIMES.
[INDISCERNIBLE] A TREMENDOUS
CHALLENGE IN ELECTROMAGNETIC
STRESS.
THIS IS STATE OF THE ART.
BUT LOOKING HERE, IT IS VERY
DIFFICULT TO IMAGINE
[INDISCERNIBLE] SO WE WORK ON
THIS PROBLEM ON AND OFF FOR
QUITE A FEW YEARS AND TRY
DIFFERENT METHODS.
EVENTUALLY RELATIVELY THE SAME
PER METHOD.
IN THIS CASE INSTEAD OF MAKING
THE COIL PRETTY THIN, WE MADE
THE COIL THICK AND THEN WE PUT
IT IN MAGNETIC CORE IN THE
MIDDLE.
THE MAGNETIC CORE CAN ENHANCE,
GUIDE, AND FOCUS TO THE BOTTOM
REGION HERE.
SO THAT IS WAS KIND OF A
CONCEPTIONAL IDEA.
THIS IS A COIL WE BUILT.
THIS IS CORE SIZE DISABILITY
MAYBE I CAN SAY.
THIS IS FIRST PROTOTYPE COIL WE
BUILT.
AND WE HAVE BUILT QUITE A FEW
AFTERWARDS.
SO I WILL SHOW YOU ONE NICE
HERE.
IN THIS MOUSE, YOU WILL NOTICE
THAT TMS -- SO IN THIS CASE TMS
CONNECT
[INDISCERNIBLE]
ANYWAY, IT IS A PROBLEM AND
UNFORTUNATELILY I WAITED TOO
MUCH TIME HERE.
YEAH.
ANYWAY, WHAT I CAN SAY IS WHEN
TMS IS GIVEN, THIS BODY PART,
THIS IDEA.
ANYWAY.
SO IT IS MORE EXCITING -- THE
COIL AND THE POSITION IS
CHALLENGING HERE.
IN THIS CASE WE COME UP WITH ONE
IDEA TO USE HEADPOST ON THE
SCALP.
THE COIL GUIDE DESIGNED SO WE
CAN PUT THE COIL TOWARDS THE
TARGETED REGION IN RATS HERE.
SO THE COIL GUIDE IS DETACHABLE.
AND HERE IS THE COIL HERE.
AS YOU CAN IMAGINE, WE CAN THE
COIL GUIDE IS THICKER TO WE CAN
TARGET THE RIGHT REGIONS.
AGAIN, THE TMS CONDITIONS.
SO TYPICALLY MULTIVERSION IN
[INDISCERNIBLE] YOU INPUT THE
ELECTRODES INTO SPECIFIC MUSCLE
AND THE RECORDING IS HERE.
THIS IS ONE PIECE OF DATA.
FROM ONE RAT.
[INDISCERNIBLE] WE CAN SAY THE
MOTOR EVOKED POTENTIAL IS ONE
MILLIMETER IS REDUCED
DRAMATICALLY.
AND BASED ON THE EVIDENCE WE
THINK IS HERE.
I WILL GIVE YOU AN EXAMPLE HERE.
[INDISCERNIBLE] UNFORTUNATELY,
THE SONG IS NOT -- ANYWAY.
OKAY.
SEW THEN WE ASK THE QUESTION HOW
IS IT ACTIVATED BY TMS COIL.
IN THIS PART WE KIND OF USE
GLUCOSE AS INDICATOR OF WHICH
CORTICAL REJOON ACTIVATED BY
TMS.
WE USED A FLUORESCENT INDICATOR.
IN THE IMAGING FIELD, THE 2NBDG
WORKS.
IN THIS CASE IT IS GLUCOSE
REPLACED WITH THE FLUORESCENT
HERE.
OTHERWISE IT IS METABOLISM.
THIS IS FLUORESCENT ASSUMPTION.
THIS HAS BEEN APPLIED TO THE MAP
[INDISCERNIBLE] INCREASING
UPTAKE WHICH YOU HAVE TO BE
CAREFUL TO EMPHASIZE HERE.
WE USE A PRODUCT CODE DEVELOPED
FROM THIS GROUP AND WE DID A
HEAD IMPLANTATION, HABITUATION.
[INDISCERNIBLE] FOR ABOUT 20
MINUTES.
TMS FOR 45 MINUTES AND
[INDISCERNIBLE] I CHOSE THIS TO
LOOK AT THIS REGION, THE
DIFFERENT REGIONS I WILL SHOW
YOU LATER.
YOU SEE THE ENHANCED REGION IN
THIS REGION AND SOME WERE HERE.
AND
[INDISCERNIBLE] THE SAME MODULE
ON TOP.
SO THE SAME DATA
[INDISCERNIBLE] THIS IS A
PRIMARY MOTOR REGION.
THIS IS A PRIMARY -- SO IT
COVERS THIS MUCH WE CAN CHECK
OUT IN THE MAP.
WE DID 106% AND 110%.
ONE MILLIMETER APART.
IT IS SIGNIFICANT HERE, BUT
OTHERWISE THERE WAS A
MILLIMETERISH ACTIVATION HERE.
SO WITH THIS, ONE VERY NICE
SIMULATION
[INDISCERNIBLE] AND WHAT IN THIS
STUDY IS UNIQUE KIND OF
CONSTRUCT A MODEL BASED ON
NEURONAL ACTIVITIES IN THE
CORTEX REGIONS.
A NICE DATABASE WITH THIS MODEL.
THE CELLS AND CONNECTIONS AND
CELL TYPES AND SO ON.
WE DID TMS SIMULATION.
TMS ACTIVATED WITH LOWEST
INTENSITY LAYER 5 PYRAMIDAL
CELLS.
OUR DATA IS PRETTY MUCH
SUPPORTED THE SIMULATIONS.
HOWEVER, IN THIS CASE
FLUORESCENT DYE AND
MICROINJECTION AND
[INDISCERNIBLE] TRANSPORTED.
IT IS AN IMITATION THE CELL
TAKES ON ABOUT 200MICRON BELOW
SURFACE.
[INDISCERNIBLE] YOU CAN LOOK
DEEP ON THE SURFACE.
TMS HAS VERY NICE FLUORESCENT
RESPONSE, BUT HERE SEEMS NOT.
ANYWAY, SOME TECHNICAL
QUESTIONS.
[INDISCERNIBLE] IN ANY CASE,
THERE IS A LONG WAY TO GO TO
UNDERSTAND WHAT TMS IS DOING.
SO IN CONCLUSION, I HOPE I HAVE
GIVEN YOU SOME EVIDENCE TMS COIL
WITH RATS
[INDISCERNIBLE].
ONE EVIDENCE MEP RECORDING AND
GLUCOSE UPTAKE.
AND WE FOUND CELLS ACTIVATED BY
TMS.
[INDISCERNIBLE]
>>TREMENDOUS WORK IS NEEDED FOR
TMS.
OUR RODENT TMS MODEL OFFERS
CERTAIN DEGREE OF FACE VALIDITY.
I WILL SWITCH TO TALK ABOUT SOME
TRANSLATIONAL WORK.
IN THIS CASE, WE'LL ASK THE
QUESTION, CAN WE ENHANCE THE
EFFICACY WHILE MAINTAINED
IDENTICAL TIME EFFICIENCY OF
TBS?
SO EFFICACY IS MODEST.
SO THE QUESTION WE ARE TRYING TO
ASK, CAN WE ENHANCE THE EFFICACY
OF TIME EFFICIENCY TBS.
TO ANSWER THIS QUESTION, LET'S
TAKE ONE STEP BACK.
WE ARE NOW
[INDISCERNIBLE] AND 50 HERTZ.
SO WE ARE THINKING ABOUT ONE
STEP BACK.
SO
[INDISCERNIBLE] PATTERNED
STIMULATION AT THE THETA
FREQUENCY IS OPTIMAL FOR
INDUCTION OF HIPPOCAMPAL
LONG-TERM POTENIATION.
THIS GROUP APPLIED FOUR TO FIVE
ELECTRICAL PULSES AT 100 HERTZ.
SO THESE PULSE PATTERNS.
100 HERTZ FOUR TO FIVE
PULSE/BURST OF ELECTRICAL
STIMULATION.
TMS GIVEN 50 HERTZ.
SO WE -- TO PUT IT THIS WAY, I
DO NOT SAY ANY SCIENTIFIC
JUSTIFICATION THAT THREE PULSE
AT 50 HERTZ IS BEST.
YOU CAN INDUCE PLASTICITY.
WHAT ABOUT FOUR PLULS, FIVE
PULSE, SIX PULSE BURST.
WHAT IS GOING TO HAPPEN?
WE DEVELOPED A MACHINE THAT CAN
DELIVER UP TO SIX PULSE PER
PERSON.
YOU CAN REACH 4,3500 AMPS AND
2,000 VOLTS.
SIX PULSES.
WE ARE FIXING AT SIX.
WE USE THE SAME
[INDISCERNIBLE] IN THIS CASE.
WE MEASURE THE POTENTIAL AND
CONDITION SO THREE OR FIVE OR
FIVE OR SIX PULSE.
THE AFTER EFFECTS AT DIFFERENT
TIME POINTS.
WE WILL COMPARE TO THE RESPONSE
UNDER THESE CONDITIONS.
AND THE RESULT IS HERE.
SO THIS TEST AND COMPARISONS SO
WE ARE COMFORTABLE WITH THE
FINDINGS HERE.
WE FOUND SIX PULSE IS
SIGNIFICANT HIGHER PONCE THAN
FOUR OR THREE AND FIVE IS
SIGNIFICANTLY HIGHER THAN THREE.
HOW MUCH?
50%.
SO WE ARE VERY EXCITED ABOUT
THIS FUNDING.
WE ARE HOPING WE CAN APPLY THIS
TO HUMANS.
AND WITH THAT, I HOPE I CAN
CONVINCE -- DELIVER THIS MESSAGE
TO YOU.
WE DEVELOP A NEW PARADIGM CALLED
A HIGH DENSITY TEST, WHICH HAS
ENHANCED EFFICACY OF 50%.
SO FURTHER STUDY IS NEEDED TO
POTENTIAL FOR THIS PARADIGM AND
ACTIVELY PURSUE THIS LINE.
THESE ARE THE PEOPLE WITH WHICH
I COLLABORATED.
THIS PROJECT INVOLVED A LOT OF
PEOPLE AND I WOULD LIKE TO
MENTION THEM.
THIS WAS SUPPORTED BY NIDA, IRP.
MANY GOOD PROJECTS HAVE A
HYPOTHESIS TO START WITH AND NO
PRELIMINARY DATA TO START WITH.
IT IS VERY DIFFICULT TO GET
FUNDED.
I REALLY APPRECIATE IT.
[INDISCERNIBLE] I HAVE HAD
TREMENDOUS SUPPORT.
THANK YOU FOR YOUR ATTENTION.
[ APPLAUSE ]
>>ALL RIGHT.
OPEN FOR QUESTIONS.
YOU CAN USE THE MICROPHONE OVER
THERE.
>>I'LL ASK A QUESTION.
VERY IMPRESSIVE LATERAL
RESOLUTION.
DO YOU HAVE ANY IDEA WHAT THE
AXIAL RESOLUTION OF YOUR COIL
IS?
HOW DEEP DOES THE FIELD GO?
>>THAT IS A GOOD QUESTION.
THAT IS MORE DEPENDING ON HOW
MUCH POWER YOU ARE GIVEN.
THAT IS VERY TRICKY TO -- IT IS
KIND OF VERY HARD QUESTION TO
ANSWER.
AND WE HAVE SORT OF DATA --
LARGE TECHNIQUE TO METHODS
SIMILAR TO MAPPING.
[INDISCERNIBLE] YOU COULD GIVE
140% OF POWER YOU COULD REACH
[INDISCERNIBLE].
>>OKAY.
[INDISCERNIBLE]
>>YES.
>>WITH THE SIX PULSES, DO YOU
THINK THERE COULD BE LIMITATION
IN HEATING THE COIL IN HUMAN?
>>THAT IS A GOOD QUESTION.
[INDISCERNIBLE]
PRETTY GOOD.
IN OUR ANIMAL STUDIES WE
BASICALLY GAVE DRY ICE ON TOP
AND -- THE COIL.
WHEN THAT IS THE CASE, WE GAVE
ONE SESSION -- FOR 200 SECONDS,
THERE IS NO PROBLEM.
HUMAN TMS, WE WOULD HAVE TO TEST
IT.
I THINK IT SHOULD WORK.
YEAH.
THANK YOU.
>>THANK YOU FOR YOUR
INTERESTING TALK.
I HAVE TWO QUESTIONS.
ONE IS DOES THE USE OF THIS CORE
CHANGE THE DEPTH FOCALITY TRAIT
OR THE SAME AS YOU WOULD
OTHERWISE SEE FOR A ROUND COIL,
JUST THAT IT IS VERY FOCAL?
SO WHEN YOU PLOT DEPTH VERSUS
FOCALITY, WOULD YOU SEE THE SAME
TRAIT WHEN YOU SCALE YOUR IRON
CORE?
IS IT BETTER OR A VERY FOCAL
VERSION OF BOTH?
AND THE SECOND QUESTION IS IRON
CORES TEND TO SEPARATE FOR VERY
HIGH FIELD STRENGTH.
DO YOU SEE CHANGES OF THE PULSE
SHAPE WHEN YOU GO TO HIGHER
INTENSITIES?
OF THE ELECTRICAL FIELD OF PULSE
SHAPE.
>>THIS IS REALLY GOOD, VERY
DEEP ENGINEERING AND PHYSICS
QUESTIONS.
THANK YOU.
[INDISCERNIBLE]
A CERTAIN RANGE YOU CAN GO.
SO, YES, IN OUR CASE,
[INDISCERNIBLE] YOU FEEL THE
PULSE SHAPE.
WHEN WE GIVE VERY HIGH
[INDISCERNIBLE] JO THE PULSE
PATTERN IS DIFFERENT FROM THE
REGULAR ONES.
IT IS A MAJOR ISSUE WITH RESULT
OF COIL SO THICK.
THE TOP -- I DID NOT MENTION
THAT.
THE COIL --
[INDISCERNIBLE]
>>WE CAN DISCUSS MORE.
>>THANK YOU.
[ APPLAUSE ]
>>ALL RIGHT.
THANKS, HANBING.
OUR NEXT SPEAKER IS JAN KUBANEK
FROM THE UNIVERSITY OF UTAH
TALKING ABOUT THE MECHANISMS OF
TRANSCRANIAL FOCUSED ULTRASOUND.
WELCOME.
>>I MUCH APPRECIATE THE
INVITATION.
ABOUT ONE IN THREE PEOPLE WITH
MENTAL AND NEUROLOGICAL
DISORDERS ARE RESISTANT TO
TREATMENTS.
AND THAT HAS BEEN A MAJOR ISSUE.
WHAT CAN WE DO ABOUT THAT?
ONE OF THE KEY CHALLENGES WITH
TREATING DISORDERS THAT DON'T
RESPOND TO CURRENT TREATMENTS IS
THE FACT THAT THESE DISORDERS
TYPICALLY INFLUENCE OR AFFECT
DEEP BRAIN CIRCUITS.
STRUCTURES IN THE LIMBIC AND
BASAL GANGLION.
IT HAS BEEN DIFFICULT TO
MODULATE THESE CIRCUITS WITH THE
GOAL TO RETURN THEM BACK TO
NORMAL STATE.
SO YOU MAY MENTION ONE APPROACH
WOULD BE TO IMPLANT STIMULATION
ELECTRODES INTO THE STRUCTURES
OF BRAIN STIMULATION.
THIS HAS BEEN PERFORMED FOR
NEUROLOGICAL DISORDERS IN
PARTICULAR MOVEMENT DISORDERS
QUITE EFFECTIVELY.
THE SURGICAL RISKS, THOUGH, ARE
QUITE LIMITING IN TERMS OF
PERFORMING THESE PROCEDURES FOR
TREATMENTS OF MENTAL DISORDERS.
THERE IS ONE EXCEPTION FOR
OBSESSIVE COMPULSIVE DISORDER.
TO COVER COME THESE SURGICAL
LIMITATIONS, WE WOULD LIKE TO BE
ABLE TO MODULATE THE BRAIN
TARGETS, BUT IN A NONINVASIVE
WAY WITHOUT THE RISK OF
SURGERIES.
WE HAVE RECENTLY ACHIEVED
NONINVASIVE MODULATION OF THE
BRAIN STRUCTURES USING
ULTRASONIC WAVES.
HERE ULTRA SOUND WAS FOCUSED
INTO A DEEP BRAIN OF A
PARLIAMENT WITH MAJOR
DEPRESSION.
THE DELIVERY WAS NONINVASIVE,
THE CUPELING TRANSDUCER ARRAY.
WE TARGETED THIS BECAUSE THERE
IS EVIDENCE FROM DEEP BRAIN
STIMULATION FROM CLINICAL TRIALS
THAT MAY BE A KEY TARGET IN THE
LIMBIC NETWORK THAT IS INVOLVED
IN MAJOR DEPRESSION.
WE WERE ABLE TO OBSERVE CHANGES
IN THE ACTIVITY IN RESPONSE TO
BRIEF LOW PULSES OF THE
STIMULATION.
SO THIS IS VERY EXCITING.
THE BRIEF PULSES CAUSED
INHIBITION OF THE NEURAL
ACTIVITY.
HERE IS MORE DETAILED.
THESE ARE FLUCTUATION OF THE
ACTIVITY, NICELY TIME LOCKED TO
THE STIM LACE ONSETS AND
OFFSETS.
THERE WAS A DECREASE IN ACTIVITY
IN RESPONSE TO THE BRIEF PULSES
OF THE ULTRASOUND.
OF COURSE THIS IS ONE OF THE
FIRST APPLICATIONS OF THIS MODEL
IN HUMANS.
SO WE PERFORM A -- STIMULATION,
INSTEAD OF FOCUSING THE
ULTRASOUND INTO THE TARGET, WE
EMITTED IT AS A BRAIN WAVE.
IT WAS THE SAME ENERGY GOING
INTO THE BRAIN, INTO THE
SUBJECT.
NOW IT WAS NOT FOCUSED, IT WAS
DILUTED.
IT IS A NICE CONDITION BECAUSE
WE DELIVER THE SAME ENERGY INTO
THE SUBJECT, COUPLING AND OTHER
CONDITIONS ARE THE SAME, BUT NOW
WE DON'T FOCUS THE ULTRA SOUND.
IN THAT CASE WE DID NOT OBSERVE
CHANGES IN THE ACTIVITY.
TO NAVIGATE YOU THROUGH, THE
BLUE IS THE TARGET WE END UP IN
OUR TARGETING SYSTEM AND THE RED
IS THE ACTUAL ACTIVATION OF THE
SIGNATURE CAL.
WE HAD A NICE SPATIAL OVERLAP
THERE AND THERE WAS A VERY
STRONG EFFECT GIVEN THE
RELATIVELY WEAK PULSES WE
DELIVERED.
BECAUSE THE PATIENT HAD A MAJOR
DEPRESSION, OUR MAIN TARGET WAS
REALLY CLINICAL AND THAT WAS TO
IMPROVE THESE SIGNS.
IN FACT, WHEN WE DELIVERED
ULTRASOUND OF SUBSTANTIAL
DURATION, LONGER THAN ABOUT 20
SECONDS, THE PATIENT DID NOTICE
CHANGES IN MOOD.
THE PATIENT REPORTED
IMPROVEMENTS IN THE LEVELS OF
DEPRESSION SCALE FROM MINUS 3 TO
3.
AND ALSO ANXIETY.
ANXIETY IS OFTEN CO-MORBID WITH
DEPRESSION.
WE PROBED THE GENERAL VALENCE.
DOES THE SUBJECT FEEL BETTER.
IT WAS THE CASE WHEN WE
STIMULATED THE -- BUT NOT WITH
THE SHAM STIMULATION, WHICH WAS
NOT FOCUSED.
THESE EFFECTS WERE SPECIFIC TO
THE SUB GENERAL AND
INTERESTINGLY BRIEF DURATION DID
NOT INDUCE CHANGES IN MOOD.
IT HAD TO BE A SUSTAINED
STIMULATION LONGER THAN 20
SECONDS TO SHOW AN EFFECT IN A
PATIENT.
THESE WERE COLLECTED BY BRIAN
MICKEY.
FOR DEPRESSION THERE ARE
INCUMBENTS IMPLICATED IN THIS
DISORDER.
WE HAVE A TOOL TO NONINVASIVELY
MODULATE THESE BRAIN STRUCTURES.
THAT IS OUR GOAL IN ONGOING
CLINICAL TRIAL.
AND, OF COURSE, MANY OTHER
DISORDERS ARE ASSOCIATED WITH
MULTIFUNCTIONAL BRAIN CIRCUITS,
ANXIETY, CENTRALIZED PAIN AND
ADDICTION AS WE HEARD IN THE
TALK BEFORE.
BECAUSE WE HAVE THE ABILITY TO
MODULATE DEEP BRAIN STRUCTURES,
WE WILL ALSO PURSUE THESE
INDICATIONS IN THE FUTURE.
SO THIS METHOD AS A TREMENDOUS
POTENTIAL.
IN THIS TALK, I WILL TALK ABOUT
THE KEY FEATURES, THE KEY
STRENGTHS OF FOCUSED ULTRASOUND
FOR BRAIN DISORDERS, ADDRESS THE
MECHANISMS AND DISCUSS THE
LIMITING BARRIERS THAT HAVE BEEN
HOLDING US BACK AND NEEDED TO BE
OVERCOME.
SO LET'S START WITH THE KEY
STRENGTHS OF ULTRASOUND.
IT IS POSSIBLE TO STIMULATE THE
BRAIN WITH ELECTRONIC OR
MAGNETIC FIELDS.
THERE IS HIGH INTENSITY AT THE
SOURCE SUCH AS THE ELECTRODES OR
THE MAGNETIC COIL.
AND THE FIELDS DROP FAIRLY WITH
DISTANCE SO WE GET -- LOW WITH
DEPTH.
ULTRASOUND CAN NOW FOCUS THE
ENERGY INTO DEEP BRAIN STRUCTURE
OF INTEREST.
WE NOW HAVE THE OPPOSITE
SITUATION, THE INTENSITY IS LOW
AND INTENSITY OF TARGET IS HIGH.
THAT IS WHAT WE WOULD LIKE TO
HAVE.
WHERE DOES THIS DIFFERENCE COME
FROM IN TERMS OF PHYSICS.
THESE ENERGIES CONSTITUTE FIELDS
WHEREAS FOCUS ULTRASOUND IS A
SET OF WAVES THAT CAN PROPAGATE
THROUGH SPACE AND YOU CAN PLAY
SPATIAL TRICKS LIKE THIS TO
MAXIMIZE THE ENERGY DELIVERED
INTO THE TARGET WHILE MINIMIZING
THE ENERGY ELSEWHERE.
SO FOCUS ULTRASOUND COMBINES
BENEFICIAL TRIAD OF PROPERTIES.
IT MAY EMERGE AS AN ALTERNATIVE
THAT COMBINES THE STRENGTH OF
THE EXISTING MODALITIES.
ONE THING THAT IS WORTH NOTING
IS THE FLEXIBILITY OF DELIVERY.
IT CAN PROPAGATE WITHIN THE
TISSUE FAST WITHIN MICK RO
SECONDS AND IT IS POSSIBLE TO
DEFINE THE TARGET OF THE
MODULATION.
JUST BY SETTING THE EMISSION
PATTERN WITH THE RIGHT TIMING,
YOU CAN FOCUS THE ULTRASOUND
INTO SPECIFIC TARGETS AS SHOWN
IN THE SIMULATION.
AND BY CHANGING THE SETTINGS,
AGAIN, YOU CAN REACH YET A
DISTINCT TARGET.
THIS IS A NICE FLEXIBLE WAY TO
MODULATE WITH HIGH TEMPORAL
PRECISION WHERE THE MRI IS BEING
DELIVERED.
IT MAY BE HELPFUL TO ELICIT
SPECIFIC PATTERNS OF SPATIAL
TEMPORAL ACTIVATION FOR
DISORDERS THAT ARE CHARACTERIZED
BY NONFUNCTIONING TIMING, NOT
JUST SPACE.
IT HAS BEEN KNOWN FOR QUITE SOME
TIME MRI CAN MODULATE EXCITABLE
CELLS.
IN THE PAST DECADE SEVERAL
GROUPS HAVE SHOWN THAT
ULTRASOUND IN THE CORTEX OF
RODENTS HAVE RESPONDED.
THIS HAS BEEN TAKEN INTO THE
HUMAN BRAIN AND THERE ARE
STUDIES, MAYBE A DOZEN OR MORE,
TO BEGIN TO APPLY ULTRASOUND TO
THE HUMAN BRAIN.
SO LET'S TALK BRIEFLY ABOUT THE
MECHANISMS THAT ARE INVOLVED IN
THE NEUROMODULATION HERE.
WE AND OTHERS HAVE FOUND THAT
THE MECHANICAL PRESSURE WAVE
ASSOCIATED WITH ULTRASOUND IS
ASSOCIATED WITH RADIATION FORCE
THAT PUSHES ON MEMBRANES AND
TARGET STRUCTURES.
IMAGINE A PIECE OF MEMBRANE THAT
EXPRESSES ION CHANNEL SUCH AS
SODIUM SELECTIVE ION CHANNEL AND
THE PIECE OF MEMBRANE IS
INFLUENCED OR IMPACTED BY THE
MECHANICAL RADIATION FORCE.
SO WHAT WE HAVE FOUND IS THE
MEMBRANE IS AFFECTED BY THE
ONSET AND ALSO THE OFFSET OF
THAT PRESSURE PULSE.
THE ION CHANNEL OPENS IN
RESPONSE TO THESE EVENTS AND
CURRENTS FLOW THROUGH.
SO THAT HAS BEEN FOUND TO BE THE
CASE IN NEURONS BY SEVERAL
GROUPS.
AND ALSO IN GLIAL CELLS.
I WILL TALK ABOUT IT IN JUST A
BIT.
YOU MIGHT NOW ASK WHAT KINDS OF
ION CHANNELS ARE SENSITIVE TO
THE ULTRASOUND?
HERE IS AN INTRIGUING STUDY THAT
SHOWED THERE IS GOING TO BE AN
ENTIRE CASCADE OF EVENTS GOING
ON.
THE ULTRASOUND CAN BE DELIVERED
ON TO A CELL MEMBRANE EXPRESSING
ION CHANNELS, MAKING ION
MECHANICANOSENSITIVE CHANNELS
THAT CAN INCREASE IN
INTRACELLULAR CALCIUM.
WHICH CAN IN TURN AMPLIFY THE
RESPONSES OF MANY OTHER ION
CHANNELS.
SO THERE CAN BE A NUMBER OF
EVENTS INVOLVED IN
NEUROMODULATION.
ONE PARTICULAR EXCITING FINDING
IS ULTRASOUND CAN MODULATE GLIAL
CELLS.
WHICH HAS A MAIN POTENTIAL IN
USING NEUROPLASTIC EVENTS, IN
PARTICULAR BECAUSE IT HAS BEEN
FOUND THAT ULTRASOUND CAN
ACTIVATE A CASCADE OF EVENTS
LEADING TO AN ACTIVATION OF MDA
RECEPTORS.
AS YOU ARE AWARE, THAT COULD
LEAD TO LONG-TERM POTENTIATION
AND DEPRESSION.
ONE ION CHANNEL IS A MECHANIC NO
SENSITIVE ION CHANNELS THAT
RESULTS IN -- RECEPTORS.
WHEN WE THINK ABOUT THE
EXCITABLE TISSUE AS IN THE MODEL
HERE SIMPLIFISIMPLIFIED, ULTRAS
ACTIVATE THE CHANNELS IN THAT
MODEL.
YOU MAY NATURALLY ASK IN THE
FOLLOWING WAYS.
THE ULTRASOUND PRESSURE WAVE AT
SPECIFIC FREQUENCY CAN MODULATE
THE DISTANCE OF THE AND THAT
CHANGES CAPACITANCE WITH THE
SAME FREQUENCY OF MODULATION.
IF YOU COMPUTE CURRENT, A
DERIVATIVE OF THAT, YOU SEE THAT
CHANGES OF CAPACITANCE OVER TIME
DO RESULT IN CURRENT FLOWING
INTO THE MEMBRANE.
THE CHANGE IN CAPACITANCE DUE TO
ULTRASOUND LEAD TO MEMBRANE
CURRENTS WHICH INCREASE SPIKING
ACTIVITY AND FIRING.
THAT HAS BEEN MODELLED AS A VERY
DETAIL LEVEL.
THERE ARE SEVERAL NICE PAPERS
AND THERE IS SOME EVIDENCE, SOME
EXPERIMENTAL EVIDENCE THAT THIS,
INDEED, MAY BE THE CASE.
SO TOGETHER ULTRASOUND CAN
CHANGE CAPACITANCE OF MEMBRANES.
WE SHOULD ASK NOT WHAT IS A
MECHANISM UNDERLYING
NEUROMODULATION, BUT WHAT
MECHANISMS ARE INVOLVED.
THERE WILL BE MANY.
THE RADIATION FORCES ASSOCIATED
WITH THE ULTRASOUND, THE CYCLE
BY CYCLE PRESSURES INDUCED BY
ULTRASOUND AND HIGH ENOUGH
PRESSURES BY HEATING.
SO MANY MECHANISMS.
SO LET ME BRIEFLY NOW TALK ABOUT
THE BARRIERS THAT HAVE BEEN
HOLDING US BACK IN DEVELOPING IN
LARGE SCALE AND APPLYING TO
HUMANS.
THE KEY BARRIER HAS BEEN THE
SKULL AS WE HAVE ACOUSTICALLY
ISOLATED ENVIRONMENT, SO
[INDISCERNIBLE] ESPECIALLY AT
HIGH FREQUENCIES.
WE HAVE MEASURED IN THREE EX
VIVO SKULLS.
YOU SEE THAT ON AVERAGE ITS
MAJOR, FACTOR OF 18 OF
ATTENUATION, THAT IS HUGE, AND
FOR US THE VARIABILITY IS
ENORMOUS WITHIN AND ACROSS
INDIVIDUALS.
IT IS HARD TO PREDICT BECAUSE OF
THAT VARIABILITY HOW MUCH
ULTRASOUND IS DELIVERED INTO THE
TARGET.
SO WE HAVE DONE ANALYSIS IN
HUMANS WHERE THOSE MEASUREMENTS
AND CONVERTED THE GIVEN
INTENSITIES WITH FREE FIELD IN
THE SKULL INTO THE INTENSITY
DELIVERED TO THE TARGET THROUGH
THE SEGMENTS OF THE SKULL AND WE
HAVE FOUND THAT THOSE DELIVERED
THROUGH THE SKULL WERE QUITE LOW
WITH RESPECT TO THE THRESHOLDS
WITH NEUROMODULATION SHOWN IN
RODENTS.
THAT TELLS US THAT
NEUROMODULATION SO FAR HAS BEEN
QUITE LOW IN HUMANS.
YOU MIGHT ACTUALLY ASK, WHY
DON'T WE JUST SCALE THE
INTENSITIES UP?
WE CANNOT QUITE DO THAT.
WHEN YOU LOOK AT THE HISTOGRAM,
THE LESS ATTENUATION HAPPENS
MOST FREQUENTLY.
IF WE WERE TO SCALE BY 18, IN
MANY CASES WE OVERSHOOT THE
ESTIMATED INTENSITY EFFECT AND
IT WOULD HURT OR HARM THE
SUBJECT.
A SIMPLE SCALING IS NOT A
SOLUTION.
I SHOULD TELL YOU THAT THERE ARE
TWO KINDS OF VIBRATIONS BY THE
SKULL.
THE SKULL SPEEDS UP PROPAGATION
OF THE ISSUE TO MAXIMIZE THE
INTENSITY THAT ARRIVES AT THE
TARGET AT THE SAME TIME.
IN FACT, IT HAS BEEN SOLVED MORE
OR LESS THIS ISSUE.
[INDISCERNIBLE] BASED ON CT
SCANS TO ALLOW RESEARCHERS TO
FOCUS CONSTRUCTIVELY FOR THE
DEPHASING.
A MORE IMPORTANT ISSUE
ESPECIALLY FOR THESE REVERSIBLE,
NONSURGICAL TREATMENTS IS THE
ATTENUATION OF ULTRASOUND BY THE
SKULL.
WE NEED TO DELIVER DETERMINISTIC
DOSE INTO SPECIFIC TARGETS
BECAUSE WE WOULD LIKE TO INDUCE
EFFECTS THAT EXCEED CERTAIN
THRESHOLD WHILE THAT STIMULATION
BEING SAVED.
SO THERE IS A FAIRLY NARROW
WINDOW OF INTENSITIES WE WOULD
LIKE TO DELIVER.
THAT SO FAR HAS NOT BEEN SOLVED.
THIS IS A VERY DIFFICULT ISSUE
AND IT IS SOMETHING WE HAVE BEEN
FOCUSING ON.
SO WE HAVE BEEN WORKING ON THIS
FOR ALMOST THREE YEARS NOW AND
WE HAVE FINALLY BEEN ABLE TO
SOLVE THIS ISSUE.
WE HAVE DEVELOPED A NEW APPROACH
THAT DIRECTLY MEASURES THE
ATTENUATION OF ULTRASOUND
THROUGH THE HUMAN SKULL AND
COMPENSATES FOR IT.
THIS IS NO IN REVISION, SO
HOPEFULLY YOU WILL BE ABLE TO
LEARN THE DETAILS ABOUT THAT
METHOD SOON.
HERE IS THE RESULT.
IN BLACK WE SHOW WHAT WE WOULD
LIKE TO DELIVER IN BRAIN
TARGETS.
EFFECTIVE INTENSITIES.
THE SKULL IN FRONT OF THE
ULTRASOUND, YOU SEE HOW SEVERITY
OF ATTENUATION IS AFFECTED.
WE HAVE FOUND JUST LEAVING IT
THERE LEAVES TO POOR EFF
EFFECTIVE
EFFECTIVENESS, NO
NEUROMODULATION IN MOST CASES.
YET WHEN APPLY THE CORRECTION,
WE CAN RESTORE QUITE ACCURATELY
IN ALL CASES.
THIS WAS KEY TO OBTAIN A RESULT
LIKE THIS.
THE MODULATION OF THE TARGET IN
THIS PATIENT WAS POSSIBLE ONLY
WHEN WE APPLIED THE CORRECTION.
WITHOUT THAT CORRECTION, WE
DON'T SEE STIMULATION EFFECTS.
SO THIS IS REALLY KEY
MANIPULATION THAT IS NECESSARY.
ONE THING I SHOULD ALSO NOTE
HERE IS THAT THE SUBJECT, THIS
IS OUR FIRST SUBJECT, VERY
RECENT, HAD LONG HAIR.
AND ACTUALLY, IN PATIENTS WITH
MENTAL DISORDERS WE WOULD LIKE
NOT TO SHAVE THE HEAD.
THAT WOULD BE A MAJOR BARRIER.
THAT ALLOWS US TO COMPENSATION
FOR HAIR, POTENTIAL BUBBLES IN
THE COUPLING AND OTHER BARRIERS.
THIS IS EXCITING BECAUSE IT
MAKES THAT APPROACH PRACTICAL.
TALK ABOUT THE SECOND BARRIER,
THAT HAS BEEN THE NEED FOR
SUSTAINED EFFECTS OF THE
NEUROMODULATION.
THE PREVIOUS LITERATURE HAS
MOSTLY FOCUSED ON TRANSIENT
EFFECTS, A BRIEF PULSE OF
ULTRASOUND GOING INTO CORTEX,
IMMEDIATE TWITCH AND THE EFFECTS
GO AWAY.
YET TO TREAT PEOPLE WE NEED TO
REWIRE THOSE BRAIN TARGETS.
SO HOW DO WE GO ABOUT THAT WITH
ULTRASOUND INDUCING CHANGES IN
HUMANS IS NOT POSSIBLE IN
TEMPERAMENTS OF SAFETY.
WE DEVELOPED A NON-HUMAN PRIMATE
MODEL.
THE' TRANSDUCER IS 256 THE
ANIMAL IS AWAKE AND WE CAN
ENGAGE THEM IN STANDARD TASKS
SUCH AS STANDARD DISCRIMINATION
TASKS.
WE CAN DELIVER THE ULTRASOUND
AND REPEAT IT DAY BY DAY.
THE ANIMALS CAN COME BACK NEXT
DAY, BE MOUNTED INTO THE SAME
LOCATION AND WE CAN DELIVER THE
ULTRASOUND.
SO WE HAVE DELIVERED THE
ULTRASOUND INTO THE LEFT AND
RIGHT BECAUSE THOSE ARE THE
RELAY NUKELY THAT PASS VISUAL
INFORMATION INTO THE BRAIN.
SO IN VISUAL TASKS YOU MAY
MENTION THIS IS AN IDEAL BRAIN
TARGET.
WE START WITH 30-SECOND
STIMULATION, LOW TO MIDDLE
STIMULATION.
WE ARE FINDING EFFECTS OF
STIMULATION, ALL OUR DATA PUT
TOGETHER, 52 SESSIONS, OR 53,
DEPENDING IF WE DELIVERED INTO
THE LEFT OR THE RIGHT.
IT IS QUITE REMARKABLE FOLLOWING
THE 30-SECOND SONICATION, THE
EFFECTS ARE SUSTAINED UP TO 20
SECONDS AND THEY DEPEND ON
WHETHER WE STIMULATED THE LEFT
OR THE RIGHT LGN.
WE HAVE ALSO FOUND THAT THERE
WERE CHANGES IN NEURAL ACTIVITY
WHEN WE RECORDED FROM THE
IMPLANTED PINS.
THERE WAS AN INCREASE IN HIGH
GAMMA ACTIVITY THAT HAD GOOD
AGREEMENT IN TERMS OF TIME
COURSE WITH THOSE BEHAVIORAL
EFFECTS.
SO THESE SUSTAINED EFFECTS ARE
VERY INTERESTING AND HAVE A HIGH
POTENTIAL.
JUST 30 SECONDS LEADS TO
SUSTAINED EFFECTS.
IT APPEARS THE ULTRASOUND IS
SCULPTING THE SIR CATS AND
ACTIVATING THE GLIAL CELLS AND
LEADING TO CHANGES.
WHAT IS ALSO IMPORTANT IS THE
ULTRASOUND, THERE WAS NO MORE
SIM LUS.
THESE EFFECTS CANNOT BE DUE TO
SOME OTHER EFFECTS ASSOCIATED
WITH ULTRASOUND.
WE ALSO TESTED BRIEFER STIMULI
AND WE DIDN'T SEE NOTABLE
EFFECTS WHEN THE STIMULI WERE
BRIEF.
IT WAS NECESSARY TO USE LONGER
DURATI
DURATIONS.
IN OUR RECENT PATIENT, 20
SECONDS OR LESS THERE WERE NO
EFFECTS ON MOOD.
THEY STARTED TO SHOW ONCE
STIMULATION EXCEEDED THAT TIME
FRAME, SO LONGER THAN 30
SECONDS, LET'S SAY.
AND THERE IS ONE MORE APPROACH
THAT CAN BE USED TO HAVE THESE
EFFECTS.
IT IS AN APPROACH THAT HAVE BEEN
WORKED ON.
WE WILL HEAR A TALK DEDICATED TO
THIS APPROACH.
IN THIS APPROACH DRUGS CAN BE
ENCAPSULATED I IN CARRIERS THAT
ARE BIOCOMPATIBLE.
THEY HAVE A RECORDED RESPONSE TO
THE ULTRASOUND.
IT CAN BE CARBON OR SOME OTHER
CHEMICALS.
THAT RESPONDS IN RESPONSE TO THE
MECHANIC PRESSURE WAVE, THE
VIBRATION THAT VIBRATE THE NANO
PARTICLES AND YOU GET RELEASE OF
THE DRUG ENCAPSULATED.
THIS IS AND ATTRACTIVE APPROACH
BECAUSE IT ALLOWS TO RELEASE TO
SPECIFIC LIMBIC CIRCUITS
LOCALLY.
IF YOU THINK OF SOMETHING THAT
CAUSES NEUROEFFECTS, SYLLISIBEN
AND KETAMINE CAN OPEN A NEW
AVENUE OF TREATMENT.
WE HAVE IMPLANTED PORTS INTO OUR
MONKEYS TO TEST THE
EFFECTIVENESS AND SAFETY.
AS A STARTING POINT, WE
ENCAPSULATED INTO -- BECAUSE IT
WILL SHOW WHAT SHOULD HAPPEN
WHEN PROPOFOL IS RELEASED.
WE DELIVERED THE ULTRASOUND INTO
THE LEFT AND RIGHT LGN.
WE USED RELATIVELY MEDIUM
ULTRASOUND, NOT A HIGH PRESSURE,
TO RELEASE THE PROPOFOL.
AND WE FOUND IT WORKS.
THE PROPOFOL WAS ABLE TO
MODULATE THE NON-HUMAN PRIMATE
BEHAVIOR IN A POLARITY SPECIFIC
MANNER.
IT DEPENDED IF THE PROPOFOL WAS
RELEASED IN THE RIGHT OR LEFT
LGN.
IT FLIPPED POLARITY IN THAT
CASE.
AS WE WOULD EXPECT, THE MONKEY
SHOWED A BIAS IN HIS BEHAVIOR,
CONSISTENT WITH THE LGN CIRCUIT.
I SHOULD STRESS THIS IS EXACTLY
THE OPPOSITE RESULT THAN WE SAW
WHERE THE ULTRASOUND STIMULATION
ALONE.
THOSE WERE EXCITERY EFFECTS AND
THESE ARE INHIBITORY WHICH YOU
WOULD EXPECT IF PROPOFOL IS
RELEASED.
THE TIME IS CONSISTENT WITH THE
GENERAL DURATION OF THE
INHIBITORY EFFECTS OF ULTRASOUND
OF A DOZEN MINUTES OR SO.
SO IT IS QUITE EXCITING THAT
NONHUMAN PRI MATES ALLOW US TO
ASSESS SAFETY.
WE DID SEVERAL BLOOD DRAWS IN
TWO MONKEYS SO FAR AND WE DIDN'T
FIND ANY NOTABLE ISSUES
REGARDING THESE CLINICAL TESTS.
THERE WAS AN ELEVATED WHITE
BLOOD CELL COUNT.
FAIRLY CONSISTENTLY ELEVATED
FOLLOWING AN INJECTION, BUT IT
WAS STILL WITHIN NORMAL VALUES.
AND IN A SECOND ANIMAL, THAT WAS
LESS PRONOUNCED ELEVATED WHITE
BLOOD CELL INCREASE.
SO THE MONKEYS ARE ABLE TO
PERFORM THE TASK AND THE NEXT
DAY WE DON'T DETECT ANY
BEHAVIORAL DEFICITS EITHER.
IT APPEARS THIS APPROACH WILL BE
APPLICABLE TO HUMANS BECAUSE IT
APPEARS TO BE SAFE ON NONHUMAN
PRIMATES.
SO LET ME SUMMARIZE.
LOW INTENSITY ULTRASOUND IS
IMPORTANT TO MODULATE DEEP BRAIN
STRUCTURES NONINVASIVELY.
BY VIRTUE OF IT BEING A
MECHANICAL WAVE, IT CAN VIBRATE
MEMBRANES AND ION CHANNELS AND
THIS WAY MEDIATE NEURAL
EXCITABILITY.
IT MAY MODULATE NOT ONLY
NEURONS, BUT GLIAL CELLS.
WHICH IS IMPORTANT IF WE START
THINKING OF NEUROPLASTIC
EFFECTS.
THE KEY BARRIER IN TERMS OF
APPLYING IN HUMANS IS THE HUMAN
SKULL.
NOEFL APPROACHES CAN OVERCOME
THIS BARRIER.
WE CAN THINK OF THIS ISSUE AS
BEING SOFT.
THE SECOND BARRIER IS TO INDUCE
EFFECTS SO SUBJECTS DON'T HAVE
TO COME FOR TREATMENT TOO OFTEN.
ONE OF THE APPROACHES WE HAVE
FOUND IN MONKEY AND HUMANS IS TO
DELIVER SUSTAINED MODULATION.
NOT MILICMILICLISEMILLISECONDS.
BUT UP TO 30 MINUTES OR SO.
AN INTRIGUING ADDITIONAL
APPROACH WITH SPECIFIC DRUGS
THAT CAN INDUCE DURABLE EFFECTS
IN THE CIRCUITS.
IN THIS MANNER THE DRUG WILL BE
DELIVERED ONCE WITH THE HOPES
THAT THE EFFECTS WILL OUTLAST
THE RELEASE FOR DAYS AND WEEKS
AND POTENTIALLY EVEN MONTHS.
SO THIS WORK HAS BEEN POSSIBLE
DUE TO MANY OUTSTANDING STUDENTS
IN MY LABS AND POST DOCS.
AND ALSO WITH THE HELP OF
COLLABORATING PSYCHIATRIST AND
NEUROLOGISTS AND THE SUPPORT OF
NIH AND THE FOCUSED ULTRASOUND
FOUNDATION.
I THANK YOU VERY MUCH FOR YOUR
ATTENTION.
>>QUESTIONS.
>>YEAH.
HI.
SO STUDIES WITH LOW INTENSITY
FOCUS ULTRASOUND TO OPEN UP THE
BLOOD/BRAIN BARRIER HAVE SHOWN
MICROHEMORRHAGE OR HEATING.
IF YOU ARE GOING FOR 30 SECONDS,
DO YOU KNOW IF THINGS ARE
GETTING HOT?
DO YOU KNOW WHETHER THERE IS
LONG-TERM DAMAGE?
>>THE ULTRASOUND
NEUROMODULATION DOES NOT INJEBLT
BUBBLES SO IT IS NOT OPENING THE
BLOOD/BRAIN BARRIER.
YOU CAN DO IT IF YOU WOULD LIKE
TO DELIVER LARGE AGENTS, STEM
CELLS, GENES, IT IS POSSIBLE TO
INJECT MICROBUBBLES INTO THE
BLOOD STREAM AND VIBRATIONS OF
MICROBUBBLES CAN OPEN THE
BLOOD/BRAIN BARRIER.
IT IS AN INTRIGUING NEW
APPLICATION WHICH I HAVEN'T
TALKED ABOUT TODAY.
YOU MIGHT BE TALKING -- MAYBE
YOU THOUGHT THE NANO PARTICLES.
>>I ASKED ABOUT THE
TEMPERATURE, THE HEATING.
>>THESE ARE LOW INTENSITY
LEVELS.
WHEN WE MEASURED THE HEATING IT
IS BELOW .1 DEGREE CELSIUS, SO
IT IS SUB THERMAL.
THOSE ARE NOT SURGICAL HIGH
INTENSITY TO ABLATE TISSUES.
THEY ARE KNOWN FOR REVERSAL
SAFE.
>>AWESOME WORK.
I WANT TO KNOW IF THERE WAS ANY
ASSOCIATION IN YOUR MEASURING OF
IMAGES YOU FOUND IN VARIOUS
BEHAVIORAL SYMPTOMS THAT YOU SAW
CHANGES IN?
>>MM-HMM.
SO YOU MIGHT BE REFERRING TO
CHANGES IN FUNCTIONAL
CONNECTIVITY.
WE ARE LOOKING AT THAT.
WE HAVE COLLECTED THESE DATA
ABOUT TWO WEEKS AGO, SO WE ARE
NOT ANALYZING THEM.
SO FAR WE HAVE ONLY LOOKED AT
THE IMMEDIATE CHANGES IN THE --
ACTIVITY.
WE DO HAVE THE DATA SO WE WILL
BE ANALYZING THEM
>>ARE ANY OF THE CHANGES IN THE
IMMEDIATE BOLD ACTIVITY
ASSOCIATED WITH THE CHANGES --
>>GOOD QUESTION.
THE BOLD CHANGES ARE FAIRLY
IMMEDIATE.
THE BEHAVIORAL CHANGES THAT
REQUIRED AT LEAST 30 SECONDS OR
LONGER STIMULATION.
IT APPEARS THE LONGER THE
STIMULATION, THE MORE THE
SUBJECT FELT POSITIVELY.
>>SO YOU SEE THAT AS A TARGET
ENGAGEMENT AND THERE IS NO
ASSOCIATION WITH CHANGE IN
BEHAVIORAL BUT LOOKING INTO THE
LONGER BOLD CHANGES?
>>SO LIKELY THERE ARE ACUTE
EFFECTS OF THE NEUROMODULATION
AND SUSTAIN THE STIMULATION
BECAUSE SUBJECTS DID MENTION AND
THIS IS SUBJECTIVE EVIDENCE THAT
SHE FELT BETTER OVER THE WEEKEND
WHEN WE STIMULATED ON FRIDAY.
THERE MAY BE SOME EFFECTS, WE
HAVE TO INVESTIGATE THAT.
IN THE MONKEYS WE CAN DO IT AT
THE MECHANICISTIC LEVEL TO
QUANTIFY AS STIMULATION OF DOSE,
DURATION AND ENERGY.
IN HUMANS WE CAN AT LEAST
COLLECT SO FAR THIS VERBAL
EVIDENCE.
>>AWESOME.
THANK YOU.
>>THANK YOU FOR A VERY
INTERESTING TALK.
>>SPEAK UP, PLEASE.
>>I HAVE TWO QUESTIONS.
FIRST ONE IS DOSE CORRECTION
METHOD.
>>AND SPEAK UP EVEN MORE.
>>THE FIRST ONE IS ABOUT THE
DOSE TRANSMISSION, THE DOSE
CORRECTION SCAN OR METHOD BASED
ON TRANSMISSION MEASUREMENTS.
SO MY FIRST QUESTION WOULD BE IS
IT SUITABLE FOR ALL BRAIN
REGIONS YOU WANT TO STIMULATE OR
ONLY DEEP AREAS WHERE YOU CAN DO
THAT?
THE SECOND QUESTION IS
ESPECIALLY FOR THOSE PATIENTS OR
SUBJECTS YOU HAD TO UPSCALE THE
INTENSITY A LOT TO REACH
EFFECTIVE LEVELS IN THE TARGET.
DID YOU THEN HAVE HEATING
PROBLEMS IN THE SKULL?
>>MM-HMM.
TO ANSWER THE FIRST QUESTION,
THE DEVICE HAS ABOUT 30
MILLIMETER RADIUS OF TREATMENT.
SO IF IT IS POSITIONED IN A
CERTAIN LOCATION, ELECTR
ELECTRONICALLY, THE TARGET CAN
BE STEERED IN THAT RADIUS.
IT COULD GO BEYOND BUT YOU WOULD
INDUCE SIDE LOBES AND
UNDESIRABLE ISSUES, BUT IT IS
POSSIBLE TO MOVE THE DEVICE.
IF MORE FRONTAL APPLICATIONS ARE
DESIRED, YOU CAN SIT MORE IN THE
FRONT OR IN THE BACK.
SO THAT HOPEFULLY ANSWERS THE
FIRST QUESTION.
AND THE SECOND QUESTION IS IF WE
ARE CORRECTING FOR THE SKULL,
THE SKULL CAN BE THICK IN SOME
PATIENTS OR ACOUSTICALLY
SUBSTANTIAL WHETHER WE WOULD
INDUCE HEATING OF THE SKULL?
SO THOSE ARE EXPOSURE LEVELS
BELOW THE FDA 5-10K
RECOMMENDATIONS AND LOW AND
CONSERVATIVE.
WHEN WE DID CALCULATIONS WHETHER
THE INCREASE IN SKULL HEATING WE
WERE STILL BELOW SAFE LEVELS
BELOW 1 DEGREE CELSIUS.
WE HAVE NOT BEEN CONCERNED ABOUT
THAT, BUT WE SHOULD MEASURE THAT
CAREFULLY.
>>THANK YOU.
>>I HAVE ONE QUESTION, IF THERE
IS TIME.
CAN YOU TELL US A LITTLE BIT
ABOUT HOW YOU TARGET WITH THAT
DEVICE IN THE SCANNER FOR THE
HUMANS?
>>YES.
SO THIS DEVICE IS DESIGNED TO
REQUIRE MRI ONCE AND THAT IS
REALLY FOR PRACTICAL REASONS,
RIGHT?
LONG-TERM TRAIN OF STIMULATION
WOULD LIMIT THE SUBJECT TO GO
INTO MRI EVERY SINGLE TIME.
WE HAVE DESIGNED A MASK USED FOR
RADIOOLOGICAL TREATMENTS TO FIX
THE SUBJECT'S HEAD IN THE SAME
LOCATION WITH THE LOCATION OF
THE ARRAYS.
WE CAN TAKE MRI ONLY ONCE, GET
THE BRAIN ANATOMY, GET THE
LOCATION OF THE ARRAYS, THEN WE
STIMULATE, WE VALIDATE THE
TARGET ENGAGEMENT USING BOLD AS
WE HAVE SEEN IT AND THE SET UP
CAN BE TAKEN OUTSIDE OF MRI.
THE SUBJECT IS POSITIONED, THE
HEAD IS POSITIONED IN THE SAME
LOCATION.
WE KNOW WHERE THE MRI SITS.
SO IT IS POSSIBLE TO STIMULATE
OUTSIDE OF MRI.
IN FACT, DURING THE
QUANTIFICATION OF THE BEHAVIORAL
SIGN AND SYMPTOMS THAT IS
EXACTLY WHAT WE DID.
THAT WAS DONE OUTSIDE OF MRI.
>>ANY OTHER QUESTIONS?
MAYBE LAST ONE.
>>I JUST HAVE ONE LAST
QUESTION.
TO SEE THIS AS A DURABLE LONG
LASTING THERAPY, DO YOU THINK IT
WOULD REQUIRE MULTIPLE SESSIONS
OF FOE CUBED ULTRASOUND.
IF THAT IS THE CASE, DO YOU
THINK IT INCREASES THE BRAIN
TISSUE OF INFARCTION SO SAFETY
CONCERN THERE?
>>IT IS A GOOD QUESTION.
REGARDING DURABLE SUSTAINED
EFFECTS HOW OFTEN DO THEY NEED
TO BE REPEATED?
WE THINK OF IT AS TMS, A SINGLE
SESSION OF TMS MAY HAVE EFFECTS,
BUT NEEDS TO BE REPEATED FOR
SEVERAL WEEKS.
THAT IS MY EXPECTATION THAT WILL
BE THE CASE.
WE MAY BE ABLE TO SHORTEN THE
TIME.
MAYBE IT WILL BE A MATTER OF
DAYS INSTEAD OF WEEKS, BUT THI
NEEDS TO BE TESTED IN THIS
CLINICAL TRIAL.
REGARDING SAFETY N THE MONKEYS
WE HAVE BEEN REPEATING THESE
STIMULATION PROTOCOLS DAILY.
AND THEY ARE MEDIUM INTENSITY
ULTRASOUNDS.
NOW WE ARE EXCEEDING THE FDA
RECOMMENDATIONS, OUR PROTOCOL
ALLOWS US TO DO THAT AND WE
DON'T SEE ANY SAFETY CONCERNS.
THE MONKEYS COME BACK THE NEXT
DAY AND THE PERFORMANCE GOES UP
IN TIME.
IF WE ARE DAMAGING THE LGS, IF
WE ARE CAUSING DAMAGE,
PERFORMANCE WOULD GO DOWN.
IF ANYTHING, IT GOES UP OVER
TIME AFTER MONTHS AND MONTHS OF
STIMULATION.
I'M NOT TOO CONCERNED BASED ON
THOSE DATA, OBVIOUSLY, WE NEED
TO TEST IT AT HUMANS.
>>THANK YOU VERY MUCH.
WE'LL LEAVE IT THERE.
>>THANK YOU.
[ APPLAUSE ]
>>SO I THINK THAT ENDS THIS
FIRST SECTION.
TAKE A BREAK AND STRETCH OUT AND
COME BACK 10:15.
>>I GUESS LET'S GET
STARTED FOR A VERY EXCITING
KEYNOTE LECTURE.
I'M SO DELIGHTED TO INTRODUCE
THE KEYNOTE SPEAKER TODAY FOR
OUR WORKSHOP.
DR. SARAH LISANBY FROM THE
NATIONAL INSTITUTE OF MENTAL
HEALTH AND FOR MANY OF YOU, I
THINK I DON'T REALLY NEED AN
INTRODUCTION BECAUSE YOU KNOW
HER.
SHE IS WELL KNOWN.
AND DR. LISANBY IS
INTERNATIONALLY RENOWNED
INNOVATOR OF NEUROMODULATION
TECHNOLOGIES AND IS CURRENTLY
SERVING AS DIRECTOR OF THE
DIVISION OF TRANSLATIONAL
RESEARCH AT THE NIMH.
SHE ALSO RUNS THE NONINVASIVE
NEUROMODULATION UNIT, KIND OF
RESEARCH UNIT AT NIMH,
INTRAMURAL RESEARCH PROGRAM.
BEFORE COMING TO NIH PROBABLY
LIKE FIVE YEARS AGO, SHE WAS THE
CHAIR OF THE DUKE UNIVERSITY
DEPARTMENTAL PSYCHIATRY, SHE
BUILT SPECIALIZING PROGRAMS OF
CONVERGENCE OF PSYCHIATRY,
NEUROSCIENCE AND ENGINEERING.
SHE HAS 280 PAPERS AND HAS
RECEIVED NATIONAL AND
INTERNATIONAL RECOGNITION
EVIDENCED BY NUMEROUS AWARDS.
>>THANK YOU FOR THAT VERY KIND
INTRODUCTION AND FOR THE
OPPORTUNITY TO SPEAK AT THIS
REALLY GREAT MOTING ON MRI OF
NEUROMODULATION.
I WAS ASKED TO GIVE A KIND OF
BIG PICK KWHUR -- PICTURE
OVERVIEW SO THAT IS WHAT I
BROUGHT TODAY.
I TOLD YIHONG IF I WASN'T
INVITED TO SPEAK, I WOULD WANT
TO BE IN THE AUDIENCE BECAUSE IT
IS VERY GOOD TALKS.
I'M GOING TO START WITH THE
BOTTOM LINEUP FRONT.
NEUROMODULATION ADDS A LOT TO
THE FIELD OF MRI.
IN FACT, YOU SAW THAT IN ONE OF
THE FIRST TALKS ABOUT HOW
READING AND WRITING INTO THE
BRAIN CAN HELP UNDERSTAND THE
MECHANISMS OF, FOR EXAMPLE, THE
BOLD RESPONSE.
SO NEUROMODULATION CAN GIVE TO
MRI THE ABILITY TO MOVE FROM
CORRELATION TO CAUSATION AND
ALSO TO TEST THE FUNCTIONAL
SIGNIFICANCE OF MRI-DERIVED
MEASURES.
I WILL GIVE SOME EXAMPLES OF
MRI-DERIVED MEASURES OF
FUNCTIONAL AND STRUCTURAL
CONNECTIVITY.
THE FLIP SIDE OF THE COIN IS MRI
HAS A LOT TO ADD TO
NEUROMODULATION.
IT HAS HELPED US IN THE FIELD OF
NEUROMODULATION TO UP OUR GAME
IN MANY WAYS.
FOR EXAMPLE, HAVE TOOLS TO
QUANTIFY THE DOSE OF STIMULATION
THAT HELPS TO PLAIN VARIABILITY
AND RESPONSE ACROSS MODALITIES
OF NEUROMODULATION AS WELL AS
WITHIN MODALITY ACROSS
INDIVIDUALS TO BETTER UNDERSTAND
INDIVIDUAL VARIATION AND
RESPONSE.
MRI HAS TO NEUROMODULATION TO
ENHANCE THE SPATIAL PRECISION OF
NEXT GENERATION TOOLING TO MAKE
THEM MORE FOCAL AND HAVE A
BETTER TARGET TO NONTARGET RATIO
AND IMPROVE SPES FIS TIS.
I IT HELPS UH US MOVE FROM
PATIENTS OF SYMPTOM CLUSTERS OF
SELF-REPORT TOWARDS GROUPING AT
A BRAIN LEVEL USING DATA-DRIVEN
MEASURES THAT REFLECT BRAIN
ACTIVITY.
THIS IS AN APPROACH CALLED
BIOTYPING.
IT HELPS US TO DEFINE TARGETS,
TO DEMONSTRATE WE CAN REACH THE
TARGET AND HELPS US VERIFY
TARGET ENGAGEMENT, WHETHER THESE
ARE SUPERFICIAL TARGETS, DEEP
TARGETS OR DISTRIBUTED NETWORKS.
IT HELPS US TO ACHIEVE PRECISION
TARGETING AT AN INDIVIDUAL LEVEL
WHICH IS THE HOLY GRAIL FOR US,
IT HAS BEEN FUNDAMENTAL TO TRY
TO ACHIEVE THE PRECISION OF
NEUROMODULATION FOR BRAIN
HEALTH.
SO TO SAY THAT ANOTHER WAY, I
REALLY THINK OF MRI AND
NEUROMODULATION AS TWO SIDES OF
THE SAME COIN.
ALTHOUGH MY EXAMPLES IN MY TALK
WILL BE LARGELY DERIVED FROM TMS
AND ECT.
OTHER MODALITIES ARE WELL
REPRESENTED IN THIS WORKSHOP
INCLUDING FOCUS ULTRASOUND AND
OTHER TECHNIQUES.
ON CAL GENETICS AND OTHER
TECHNIQUES.
ON THE MRI SIDE THIS IS HELPFUL
TO BUILD UPON AND TEST
HYPOTHESES BY PROBING THE
NETWORK AND CHANGING ACUTELY OR
CHRONICALLY IN THE TARGETED
NETWORK.
IN TERMS OF MOVING FROM
CAUSALITY, MRI CAN BE VERY
USEFUL FOR INFERRING CAUSALITY
IN COMPUTATIONAL APPROACHES TO
CAUSAL INFERENCE.
WE CAN NAIL DOWN AND VALIDATE
THOSE CAUSAL RELATIONSHIPS BY
CHANGING ACTIVITY IN THE CIRCUIT
WITH STIMULATION.
TARGETS CAN BE IDENTIFIED USING
IMAGING, BUT WE REALLY WANT TO
USE THAT TO DEVELOP TARGETED
INTERVENTIONS TO IMPROVE BRAIN
HEALTH.
AND THEN I MENTIONED
INDIVIDUALIZED BIOTYPING WHICH
CAN HELP TRANSLATE THOSE MORE
BRAIN-BASED CLUSTERING OF
PATIENTS INTO PERSONALIZED
TREATMENTS SO THAT IS THE
CONCEPTUAL LEVEL, SO LET'S NOW
DIVE IN.
THESE ARE MY TWO CENTS OR YOU
CAN THINK OF IT AS TWO SLIDES OF
THE SAME COIN.
WHAT DOES NEUROMODULATION ADD TO
MRI?
HOW CAN WE MOVE FROM CORRELATION
TO CAUSIZATION?
I'M GOING TO GIVE YOU SOME
EXAMPLES.
THIS IS FROM A METTA ANALYSIS OF
MRI STUDIES THAT HAVE IDENTIFIED
A FRONTAL PARI ETAL NETWORK
CAUSE L IN CERTAIN ASPECT OF
COGNITIVE PROCESSING WHICH
INVOLVES DECEPTION.
DECEPTIVE PROCESSING TASKS.
WE WOULD LIKE TO KNOW THIS IS
RESPONSIBLE FOR THE COGNITIVE
DECEPTION WHICH HAS MANY COMPLEX
COMPONENTS.
WE APPLIED TMS TO RIGHT AND LEFT
PREFRONTAL CORTEX AND WE FOUND
WE COULD CHANGE THE PROCESSING
TIME IN DECEPTION TASK
STIMULATING PRIOR CORTEX NOT
FRONTAL CORTEX.
IT HAPPENED AT A SFESK LATENCY,
240 MILLISECONDS AFTER THE
STIMULUS ONSET.
THIS IS WHEN WE WOULD HAVE
PREDICTED BASED ON EVENT RELATED
STUDIES THAT REGION OF THE BRAIN
WOULD BE INVOLVED IN THE
PROCESSING THAT THE PROCESS TIME
WAS INDICATING.
BASICALLY THE TAKE HOME IS, YES,
STIMULATING THE PARIATEL NODE
WAS CAUSAL, BUT ADDS TO THAT
SOME TEMPORAL INFORMATION TO BE
HARD TO OBTAIN FROM TYPICAL FMRI
SEQUENCES.
LE ME DRILL DOWN ON
SPECIFICITIES.
THIS IS WORK LED BY BRUCE LUBER
AT COLUMBIA.
BASED ON PAUL'S WORK USING EEG
GATED FMRI, THERE WAS A MODEL OF
THREE SPATIALLY DISTRIBUTED
NETWORKS THAT ARE ACTIVATED IN A
TEMPORAL SEQUENCE WHILE SUBJECTS
PERFORM A SPECIFIC VISUAL
DISCRIMINATION DECISION-MAKING
TASK.
SO WE WANTED TO STUDY, IS THIS
FUNCTIONAL?
CAN WE STIMULATE NODES WITHIN
THIS NETWORK AND SEE IF WE
DISRUPT VISUAL DECISION MAKING
IN THE MANNER THIS MODEL WOULD
PREDICT?
THAT IS WHAT WE DID.
WE DELIVERED PRECISELY TIMED TMS
TO A PARTICULAR NODE IN THIS
NETWORK, LATERAL OCCIPITAL
CORTEX HERE, AT A RANGE OF TIMES
RELATIVE TO THE STIMULUS ONSET,
WHICH IS SHOWN ON THE X AXIS
HERE AND WE FOUND WE GOT A
PREDICTED SLOWING DOWN OF THE
REACTION TIME ON THE VISUAL
DECISION MAKING WHEN THE TMS WAS
GIVEN AT 400 MILLISECONDS, BUT
NOT LATER OR EARLIER, WHICH
WOULD HAVE BEEN PREDICTED BY THE
MODEL BECAUSE THIS -- OOPS, I'M
SORRY, LET ME GO BACK.
THE LATE RAL OCCIPITAL NETWORK
HAPPENED AT LATER STAGES OF THE
PROCESSING.
THE TAKE HOME IS WE CAN
BASICALLY PROVIDE SOME CAUSAL
VERIFICATION OF WHERE AND WHEN
PROCESSING HAS OCCURRED AND IS
OCCURRING BASED ON FMRI-BASED
MODELS.
NOW, CAN WE USE NEUROMODULATION
TO TEST THE SIGNIFICANCE OF
OTHER MRI DERIVED MEASURES AT
THE ANATOMICAL LEVEL?
I WILL GIVE YOU EXAMPLES OF
TESTING FROM DTI OF STRUCTURAL
CONNECTIVITY.
AND SO THIS IS WORK LED BY BRUCE
LUBER AND -- WHO YOU WILD HEAR
FROM LATER IN THE WORKSHOP.
WE WANTED TO PROVIDE
TRANSSYNAPTIC ACCESS SUCH AS THE
SUB GENUAL CORTEX SHOWN IN THE
RED.
USING DTI, WE IDENTIFIED A WHITE
MATTER TRACK WITH STRONG
CONNECTIVITY FROM THE FRONTAL
POLE TO THE SGACC.
AND WE WOULD LIKE TO KNOW THAT
IS A STRONG, ANATOMICAL
CONNECTION, IS IT FUNCTIONAL?
IF WE STIMULATE THE FRONTAL POLE
CAN WE CHANGE THE SUB GENUAL
SINGULATE?
THAT IS WHAT WE DID.
YOU CAN SEE IN THE IDEAL LOW
DOTS THAT IS WHERE THE SCALP
LOCATIONS WHERE AND WE PUT THE
TMS COIL IN THE FMRI SCANNER TO
CONDUCT A CONCURRENT TMS FMRI A
TECHNOLOGY YOU WILL HEAR MORE
ABOUT IN THIS WORKSHOP.
WE WERE ABLE TO DEMONSTRATE
THROUGH THIS TMS PULSES WITH THE
EK OPLANAR PULSES WE COULD FIND
A DOSE DEPENDENT INCREASE ON THE
BOLD RESPONSE IN THE SUBG NEXT
UAL AN TIERIER SINGULATE.
TMS CAN BE USEFUL IN VERIFYING
THE FUNCTIONAL SIGNIFICANCE OF
STRUCTURAL CONNECTIVITY DERIVED
FROM DTI AND ALSO, BY THE WAY,
THIS COULD BE A NOVEL APPROACH
FOR TARGETING DEEP BRAIN
STRUCTURES THROUGH TRANSSYNAPTIC
TARGETING.
ANOTHER MEASURE NEUROMODULATION
CAN BE HELPFUL IN UNPACKING IN
HUMANS IS MEASURES OF NETWORK
CONTROLLABILITY.
AGAIN, STICKING IN THE
ANATOMICAL REALM BASED ON DTI.
YOU CAN SEE THE MODAL
CONTROLLABILITY THAT HAS BEEN
BASED ON A GROUP OF SUBJECTS
USING DTI.
THE CONCEPT IS DIFFERENT
ANATOMICAL TARGETS HAVE
DIFFERENT DEGREES OF CENTRALITY
IN TERMS OF CONNECTION WITH THE
REST OF THE THE NETWORK.
A PREDICTION IS A BRAIN AREA
WITH HIGH DEGREE OF MODAL
CONTROLLABILITY SHOULD BE MORE
EFFECTIVE TO SHIFT THE BRAIN TO
DIFFICULT TO ACHIEVE BRAIN
STATES.
WE WANTED TO TEST IS THAT THE
CASE?
LET'S TRY TO SHIFT BRAIN STATE
BY STIMULATING DIFFERENT AREAS
OF THE BRAIN THAT HAVE DIFFERENT
DEGREES OF MODAL
CONTROLLABILITY.
WE USED A TASK WE KNEW WE COULD
MANIPULATE WITH TASK, THIS WAS
WORK LED BY BRUCE LUBER AND
DANNHAUER AND BEYNEL AND MEMBERS
OF OUR TASK FORCE.
YOU CAN SEE THE EFFECT WAS SEEN
AT THE HARDER VERSION OF THE
TASK AND WE ASKED WHETHER THE
DEGREE OF BEHAVIORAL CHANGES IN
WORKING MEMORY WAS RELATED TO
THE MODAL CONTROLLABILITY OF THE
TARGET WE STIMULATED?
SO HERE YOU SEE WE HAVE
STIMULATED THE MODAL
CONTROLLABILITY OF WHERE EACH
SUBJECT GOT THEIR TMS.
AND WE FOUND THAT THE DEGREE OF
MODAL CONTROLLABILITY ON THE X
AX SITUATION PREDICTED THE
BEHAVIORAL EFFECT OF TMS ON THE
Y AXIS.
SO THE TAKE HOME IS
NEUROMODULATION COULD BE USEFUL
IN UNDERSTANDING THE FUNCTIONAL
SIGNIFICANCE OF DTI-BASED
MEASURES OF NETWORK
CONTROLLABILITY AND ALSO LED TO
LIZZIE ANN HAVING A BRIGHT IDEA
WHICH THIS COULD REPRESENT A
NOVEL APPROACH TO
CONTROLLABILITY BASED TARGETING
FOR NONINVASIVE BRAIN
STIMULATION.
I'M GOING TO LOOK AT THE OTHER
SIDE OF THE COIN HERE AND TALK
ABOUT WHAT MRI ADDS TO THE FIELD
OF NEUROMODULATION.
I'M GOING TO CONSTRAIN THIS TO
MY ALLOTTED 45 MINUTES.
SO DOSE QUANTIFICATION IS REALLY
KEY.
I'M GOING TO START BY DEFINING
WHAT DOSE IS FOR NEUROMODULATION
AND GIVE YOU SOME EXAMPLES OF
HOW THIS CAN BE USEFUL IN
NEUROMODULATION.
SO TYPICALLY WE THINK OF THE
DOSE OF NEUROMODULATION TO BE
THE DOSE OF LITERALLY WHAT WE
DIAL ON TO THE BOX OF THE
STIMLATOR, THE FREQUENCY PULSE
DURATION, INTENSITY.
AND/OR THE ELECTRODE POSITION,
THEIR SHAPE.
THE COIL SHAPE AND ORIENTATION
RELATIVE TO THE TARGET BRAIN
STRUCTURE.
ALL OF THAT CAN BE DESCRIBED AND
USUALLY IS DESCRIBED IN METHODS
SECTIONS OF PAPERS AND IT
CERTAINLY INFLUENCES THE IMPACT
OF THE STIMULATION.
IT IS ONLY HALF OF THE STORY OR
YOU COULD ARGUE LESS THAN HALF.
THE REST OF THE STORY IS WHAT
HAPPENS AFTER YOU INJECT THAT
ENERGY INTO THE HEAD AND IT
REACHES THE BRAIN, WHERE IT
INDUCES ELECTRICAL FIELDS OR
ACOUSTIC WAVES AS YOU HEARD
ABOUT WHICH OPEN ION CHANNELS OR
YOU ARE DELIVERING A MAGNETIC
FIELD INDUCING A FIELD WITH TMS.
THAT CHANGES BRAIN ACTIVITY IN
SOME WAY.
SO THOSE PARTS OF THE RECEIVED
DOSE ARE RALLY INFLUENCED
DRAMATICALLY BY ANATOMICAL
DIFFERENCES, DIFFERENCES IN
ANATOMY, THE STRUCTURE OF THE
HEAD AND THE BRAIN.
PHYSIOLOGICAL DIFFERENCES,
NEUROPHYSIOLOGICAL DIFFERENCES
AND BRAIN STATE.
THESE PARTS ARE NOT USUALLY
REPORTED IN METHODS SECTIONS,
BUT INCREASINGLY WE ARE SEEING
SOME OF THESE BEING MORE
STANDARDLY REPORTED, ESPECIALLY
THE ELECTRIC FIELD.
IF WE FOCUS OUR ATTENTION ON
THIS ASPECT OF THE RECEIVED
DOSE, YOU CAN SEE HOW MRI IS KEY
IN UNDERSTANDING THIS.
WHAT DO I MEAN BY THAT?
SO WE WANT TO QUANTIFY THE
ELECTRIC FIELD.
WE CAN USE STRUCTURAL MRI TO
SIMULATE THE BRAIN.
IT CAN ALLOW US TO DEMONSTRATE
WHETHER OUR STIMULATION PARADIGM
IS ABLE TO REACH THE TARGET
BRAIN AREA AT A DOSE THAT IS
ABOVE THRESHOLD FOR INDUCING
NEURONAL DEPOT LARIZATION OR
CHANGING NEURONAL ACTIVITY.
AND ALLOWS TO IDENTIFY THE
DEGREE OF THE TARGET VERSUS
NONTARGET STIMULATION.
SO CROWE MIGHT BY ABLE TO REACH
A DEEP BRAIN TARGET WITH A
REALLY BIG TMS COIL, BUT YOU ARE
NOT DOING THAT SELECTIVELY.
PHYSICS EXPLAINS THAT.
AS YOU SEE HERE, THE DEPTH
FOCALITY TRADEOFF, WE HAVE
MODELLED MANY DIFFERENT TMS
COILS IN THE NUMBERED CIRCLES
AND ON THE X AXIS IS THE DEPTH
AND Y IS DEGREE OF SPREAD.
THE DEEPER YOU GO, THE LESS
FOCAL YOU ARE.
THAT IS IMPORTANT TO KNOW WHEN
YOU ARE TRYING TO REPORT THE
RESULTS OF YOUR EXPERIMENTS TO
KNOW THAT, YEAH, MAYBE YOU WERE
ABLE TO REACH THE INSULA, BUT
YOU WEREN'T ONLY STIMULATING THE
INSULA, AT LEAST IN THE CASE OF
TMS.
WHAT ABOUT NEURONAL ACTIVITY?
MRI CAN HELP US THERE AS WELL,
FMRI OR OTHER MEASURES, ARTERIAL
SPIN LABELING, MRSPECTROSCOPY,
THIS CAN HELP QUANTIFY THE STATE
OF BRAIN AT THE TIME OF
STIMULATION WHICH INFLUENCES
RESPONSE TO STIMULATION.
WHEN WE PUT THE TMS COIL IN THE
SCANNER AND DO CONCURRENT TMS
MRI, WE CAN MUSH R MEASURE ACUTE
RESPONSE TO THE STIMULATION.
I SHOWED YOU AN EXAMPLE,
STIMULATED THE FRONTAL POLE AND
GETTING A RESPONSE.
AND WITH PRE-POST PARADIGMS, SUB
ACUTE AND COURSES OF STIMULATION
TO UNDERSTAND HOW THEY WORK AT A
BRAIN LEFT.
SO MRI IS REALLY BIG AND CENTRAL
TO ALL OF THESE ASPECTS OF
QUANTIFYING DOSE AND
UNDERSTANDING DOSE.
SO LET'S TALK ABOUT HOW WE CAN
USE THESE TOOLS OF DOSE
QUANTIFICATION TO BETTER
UNDERSTAND AND DEVELOP NEXT
GENERATION NEUROMODULATION
TECHNOLOGIES.
SO THESE TOOLS CAN HELP US
UNDERSTAND VARIATION IN RESPONSE
TO STIMULATION ACROSS DIFFERENT
MODALITIES.
I'M GOING TO GIVE YOU AN EXAMPLE
FROM ECT, RIGHT UNILATERAL
PLACEMENT WHERE THE RIGHT
HEMISPHERE OR BILATERAL ECT
WHERE YOU HAVE ONE ELECTRODE ON
EACH SIDE OFD THE HEM FEAR.
THESE DIFFER DRAMATICALLY IN
COGNITIVE SIDE EFFECTS.
SIGNIFICANT AMNESIA WITH
BILATERAL COME BARED TO THE YUP
LATERAL.
WHY IS THAT?
WHY IS THIS SUCH A DRAMATIC
DIFFERENCE.
YOU CAN SEE RIGHT OFF THE BAT,
THERE ARE TREMENDOUS DIFFERENCES
IN THE DISTRIBUTION OF ELECTRIC
FIELD AND THIS MIGHT GIVE US
CLUES AS TO WHY THESE MODALITIES
DIFFER SO SIGNIFICANTLY IN TERMS
OF SIDE EFFECTS.
NOW, IF WE STICK WITHIN ONE
MODALITY, WE HAVE THE PROBLEM
WITH INDIVIDUAL VARIATION
BETWEEN PEOPLE.
EFIELD MODELING CAN HELP US
THERE.
YOU WILL HEAR MORE FROM E ZHENG.
THIS IS THE SAME DOSE GIVEN TO
PATIENTS WITH DEPRESSION.
THE E FIELD STRENGTH ACROSS
INDIVIDUALS.
XI SHOWED ON THE X AXIS IS THE
HIPPOCAMPUS AND THE Y AXIS
COGNITIVE CORRELATION, MORE
COGNITIVE IMPAIRMENT.
REALLY IMPORTANT IF WE SEEK TO
UNDERSTAND WHY SOME PATIENTS ARE
MORE SUSCEPTIBLE TO THIS
COGNITIVE SIDE EFFECT THAN
OTHERS AND MAY GIVE US CLUES TO
DEVELOP NEXT GENERATION
TECHNOLOGIES TO BE SAFER FOR
PATIENTS.
SO -- ON THAT POINT, HOW CAN WE
USE THIS TO INFORM THE
DEVELOPMENT OF NEW THERAPIES
THAT WOULD BE SAFER?
HERE I'M SHOWING YOU THE
ELECTRIC FIELD STIMULATION OF
THE THREE CONVENTIONAL
ELECTROPLACEMENTS, BILATERAL, BF
AND RUL.
THE AQUA COLOR IS AT THRESHOLD
FOR NEURONAL DEPOT LARIZATION.
ALL THE ENTIRE BRAIN WITH ALL
THREE OF THESE ELECTRODE
PLACEMENTS IS AT THRESHOLD OR
HIGHER.
THE RED AREAS ARE THREEFOLD
ABOVE THRESHOLD OR HIGHER.
IT IS WHOLE BRAIN STIMULATION.
SO WE CAN USE THESE INSIGHTS TO
DEVELOP NOVEL ELECTROPLACEMENTS
TO TRY TO MINIMIZE THIS.
I'M SHOWING YOU THREE
EXPERIMENTAL FORMS OF SEIZURE
THERAPY.
YOU CAN SEE THESE THREE
EXPERIMENTAL PLACEMENTS ARE ABLE
TO REDUCE THE VOLUME OF TOTAL
BRAIN STIMULATED ABOVE THRESHOLD
AND IN THE CASE OF THE MAGNETIC
SEIZURE THERAPY ON THE FAR RIGHT
IT IS MINIMIZED AND LIMITED TO
SUPERFICIAL CORTEX.
WE HAVE SHOWN YOU CAN DRAW
REGIONS OF INTEREST AROUND THE
HIPPOCAMPUS AND YOU CAN SEE HERE
THAT THE EXPERIMENTAL ECT
ELECTRODE PLACEMENTS REDUCE THE
E-FIELD IN THE HIPPOCAMPUS
COMPARED TO CONVENTIONAL
ELECTRODE PLACEMENT, BUT STILL
AT THRESHOLD.
THE BLUE BAR IS MAGNETIC SEIZURE
THERAPY.
NOW WE CAN INDUCE SEIZURES
WITHOUT GETTING HIPPOCAMPUS FROM
E-FIELD EXPOSURE.
THIS IS IMPORTANT FOR SAFETY.
FROM HUMAN DATA THE SPEED OF
REORIENTATION CORRELATED WITH
RETROGADE AMNESIA AND ECT AND
THE RED BARS MST IN THE BLUE
BARS.
MINIMIZING E-FIELD EXPOSURE, WE
ARE ABLE TO INDUCE SEIZIERS WITH
MINIMAL COGNITIVE SIDE EFFECTS.
ANOTHER THING THAT MRI CAN ADD
TO NEUROMODULATION IS A NEW WAY
OF UNDERSTANDING
HETEROGENERALITY IN PATIENT
GROUPS CALL BIOTYPING.
IF WE CLUSTER PATIENTS USING
PSYCHIATRIC DIAGNOSIS, BASED ON
SYMPTOM SELF-REPORT, AN APPROACH
THROUGH THE DSM, CLASSICAL
CLASSIFICATION.
A GROUP OF PATIENTS WITH
DEPRESSION, A GROUP WITH ANXIETY
AND A GROUP WITH SKITS FRE --
SCHIZOPHRENIA.
THE CONCEPT HERE IS WE COULD USE
OBJECTIVE MEASURES OF BRAIN
FUNCTION LIKE MRI MAYBE COUPLE
THAT WITH OTHER MEASURES OF
NEUROPHYSIOLOGY AND ON THE BRAIN
BASIS, RESORT THOSE PATIENTS
INTO DATA-DRIVEN BIOTYPES.
GROUPS OF PATIENTS MORE SIMILAR
TO EACH OTHER AT THE LEVEL OF
OBJECTIVELY MEASURED BRAIN
STRUCTURE, FUNCTION OR ACTIVITY.
THIS BIOTYPING APPROACH CAN BE
USEFUL IN TERMS OF SELECTING
TREATMENTS THAT ARE RIGHT FOR
EACH PATIENT.
THIS WAS SHOWN BY DRYSDALE AND
LISTON AND COLLEAGUES THAT TOOK
A GROUP OF PATIENTS WITH
DEPRESSION AND USED RESTING
STATE FUNCTION CONNECTIVITY MRI
TO DERIVE FOUR BIOTYPES, THOSE
SIGNIFICANTLY PREDICTED THE
LIKELIHOOD OF PATIENTS
RESPONDING TO TMS FOR
DEPRESSION.
THE BLUE ARE PATIENTS MORE
LIKELY TO RESPOND TO TMS.
THIS APPROACH CAN BE USEFUL
UNDERSTANDING HETEROGENERALITY
AS WELL AS FOR SELECTING
PATIENTS WHO MAY OR MAY NOT
RESPOND TO A STANDARD THERAPY.
WHAT WE WOULD LIKE TO DO IS HAVE
A THERAPY FOR EACH PATIENT.
WE WANT TO BE ABLE TO USE THIS
BRAIN INFORMATION TO
INDIVIDUALIZE THE TREATMENT SO
THAT THE PATIENT IN FRONT OF YOU
COULD RESPOND.
AND PART OF THAT IS ABOUT
FINDING THE RIGHT TARGET FOR
EACH PATIENT.
MRI REALLY CAN HELP US WITH
TARGETING, WHETHER STRUCTURAL OR
FUNCTIONAL, MRI OR CONNECTIVITY.
OSCILLATIONS, THESE ARE
DIFFERENT LEVELS OF ANALYSIS TO
SEARCH FOR TARGETS AND THEY ARE
NOT MUTUALLY EXCLUSIVE BECAUSE
THEY ARE ALL GOING ON IN YOUR
BRAIN AT THE SAME TIME.
WHEN WE THINK ABOUT STRUCTURAL
OR FUNCTIONAL TAR AL TARGETING
LOOKING FOR THE PLACE TO PUT THE
COIL.
WE ARE THINKING ABOUT HOW TO
CONTROL THIS NETWORK, THIS
DISTRIBUTED NETWORK AS YOUR
TARGET AND IN TERMS OF
NEUROOSCILLATIONS, NEURODYNAMICS
SO TARGETING IN THE TEMPORAL
DOMAIN.
WHEN YOU ARE TRYING TO FIND
SIGH
SITES, YOU ARE TRYING TO TARGET
CIRCUITS ARE TRANSSYNAPTIC
TARGETING.
I SHOWED YOU THAT.
WHEN WE ARE TARGETING
NEURODYNAMICS WE ARE TRYING TO
TARGET THE TEMPORAL DOMAIN SO I
CALL THAT TEMPORAL TUNING.
THESE APPROACHES CAN BE COMBINED
TO TRY TO FIND WHERE AND WHEN
AND HOW TO STIMULATE FOR EACH
PATIENT.
NOW, I GAVE YOU ONE EXAMPLE
ALREADY OF TRYING TO ACCESS A
DEEP TARGET.
USING STRUCTURAL CONNECTIVITY.
I'M GOING TO GIVE YOU A
DIFFERENT EXAMPLE THAT COMES
FROM WORK FROM LIZZIE ANN
BEYNAL.
SHE WANTED TO TARGET THE
AMYGDALA.
SHE WANTED TO HAVE PRECORTEX
STRONG FUNCTION CONNECTIVITY
WITH THE AMYGDALA.
SHE IDENTIFIED OF REGIONS OF THE
BRAIN THAT HAS CONNECTION WITH
THE AMYGDALA.
SHE TOOK THAT INFORMATION INTO
THE LAB, USED NEURONAVIGATION,
STRUCTURAL AND FUNCTIONAL MRI TO
NAVIGATE THE COIL TO THIS TARGET
IN EACH SUBJECT AND STIMULATE
WITH TMS.
WHAT SHE FOUND WAS A SIGNIFICANT
INCREASE IN THE CHANGE IN THE
AMYGDALA ACTIVATION OF THE
TASK-BASED FMRI WITH ACTIVE TMS
IN THE BLUE COMPARED TO SHAM IN
THE RED.
THIS IS AN EXAMPLE OF USING
FUNCTIONAL CONNECTIVITY TO REACH
A DEEP BRAIN TARGET.
I MENTIONED STRUCTURAL AND
FUNCTIONAL CONNECTIVE TARGETING,
WHICH IS BETTER OR MAYBE WE
SHOULD BE USING BOTH.
HERE IS AN EXAMPLE FROM THE
FIRST STUDY FROM BRUCE LUBER
WHERE WE USED STRUCTURAL
CONNECTIVITY TO TARGET.
SO THE STRUCTURAL CONNECTIVITY,
HERE WERE SCALP LOCATIONS FOR
THE FRONTAL POLE.
IN THE SAME PATIENTS WE HAD
RESTING STATE FUNCTIONAL MRI.
WE COMPUTED WHERE THE FUNCTIONAL
TARGET WOULD HAVE BEEN.
THAT IS ON THE RIGHT.
THOSE ARE THOSE BLUE DOTS.
WHAT WE FOUND IS THE EFFECT OF
OUR STRUCTURALLY TARGETED TMS
HAD -- WAS IN THE ACC WAS
NEGATIVELY CORRELATED WITH THE
DISTANCE OF OUR COIL LOCATION
FROM THE FUNCTIONAL TARGET.
SO WE DON'T KNOW IF PUTTING THE
COIL ON THE FUNCTIONAL TARGET
WOULD HAVE BEEN BETTER, BUT IT
DOES SUGGEST TARGETING COULD BE
IMPROVED BY INCORPORATING
INFORMATION FROM STRUCTURAL AND
FUNCTIONAL CONNECTIVITY.
ONCE YOU HAVE IDENTIFIED YOUR
TARGET AND SHOWN YOU CAN REACH
IT WITH YOUR INTERVENTION, YOU
WANT TO KNOW IF YOU CAN ENGAGE
IT.
HAVE YOU CHANGED ACTIVITY IN
THAT SITE OR NETWORK THAT
CONTINUES AFTER YOU STOP
STIMULATING?
HERE I'M USING AN EXAMPLE AGAIN
FROM BRUCE LUBER.
WE USED A TMS NEURONAVIGATED TO
INDIVIDUAL SITES THAT WERE
ACTIVATED USING A PRIMING TASK.
THIS IS PATIENTS WITH DEPRESSION
WHO WERE RECEIVING SIMULTANEOUS
COGNITIVE BEHAVIORAL THERAPY AND
TMS FOR DEPRESSION.
WE DID FMRI BEFORE AND AFTER THE
COURSE OF TREATMENT.
FOLLOWING TREATMENT, THE PATIENT
SHOWED SIGNIFICANT REDUCTION IN
DEPRESSION SCORES SHOWN ON THIS
HAMILTON RATING SCALE.
THE IMPORTANT PART IS THE
PRE/POST MRI SHOWS PRE-TMS IN
THE DARK BLUE TO POST-TMS IN THE
LIGHT BLUE AN INCREASE IN THE
TARGET.
THIS DEMONSTRATED WE WERE ABLE
TO ENGAGE THIS LIMBIC CIRCUIT
FOLLOWING A COURSE OF CHRONIC
TMS.
WE ARE DOING THE RANDOMIZED
CONTROL TRIAL CURRENTLY WHERE
OUR OUTCOME MEASURE IS NOT
DEPRESSION SCORES BUT CHANGE IN
CIRCUIT EXPRESSION.
WE ARE TRYING TO DETERMINE
WHETHER WE ARE ABLE TO ENGAGE
THE TARGET AND IF WHEN WE DO
ENGAGE THE TARGET DOES THE
PATIENT'S DEPRESSION GET BETTER?
THIS BLINDED TRIAL IS BEING LED
BY LIZZIE ANN BEYNEL.
IT IS AN EXAMPLE OF INDIVIDUAL
TARGETING BECAUSE WE ARE PUTTING
ALL PATIENTS THROUGH THE
SCANNER.
SO THAT LEADS ME TO THE PART ON
PRECISION TARGETING.
WE WOULD LIKE TO DEVELOP TOOLS
AND PRACTICAL PIPELINES TO
DISSEMINATE THE ABILITY TO DO
THIS TARGETING ACROSS LABS AND
ACROSS CLINICS, ULTIMATELY.
PERSON SELK TARGETING OF
NEUROMODULATION.
USE IMAGING TO IDENTIFY THE
PERSON'S SPECIFIC COIL PLACEMENT
AND ORIENTATION AND ACHIEVE THE
DESIRED E-FIELD IN THE TARGET OR
TARGETED NETWORK.
HERE IS ONE EXAMPLE OF ONE SUCH
PIPELINE LIZZIE ANN USED IN HER
WORK.
THIS INCORPORATES STRUCTURAL AND
FUNCTIONAL IMAGING, E-FIELD
MODELS AND DIFFERENT LOCATIONS
TO OPTIMIZE THE COIL PLACEMENT
AND/OR ORIENTATION.
THIS IS WORK FROM STANHAUR, TAP.
WHAT CROWE ARE SEEING HERE IS
THE HIGH-LEVEL WORK.
IT INCORPORATES STRUCTURAL AND
FUNCTIONAL IMAGING,
INTEROPERABILITY WITH SIM LIBS.
IT IS ENHANCING COIL PLACEMENT
FOR EXPERIMENTS.
AS THESE PIPELINES BECOME
DISSEMINATED IT ALLOWS TO
INCREASE RIGOR AND TO SEE IF WE
CAN REPLICATE THE SAME
EXPERIMENT AND GET THE SAME
RESULTS RATHER THAN HAVING
EVERYONE REINVENT THEIR OWN
WHEEL.
COULD THIS BE USEFUL?
THE STANFORD NEUROMODULATION
THEORY FOR TREATMENT OF
DEPRESSION USED RESTING STATE
MRI TO TARGET TMS IN PATIENTS
WITH DEPRESSION.
THEY WERE TARGETED PREFRONTAL
CORTEX -- IT IS SO IMPORTANT FOR
DEPRESSION.
THEY GIVE PATIENTS 10 TREATMENTS
A DAY FOR FIVE DAYS WITH THETA
BURST.
YOU HEARD ABOUT THAT IN AN
EARLIER TALK.
ENSIVE STIMULATION IN A SHORT
PERIOD OF TIME.
THEY REPORTED IN THE RANDOMIZED
SHAM CONTROLLED TRIAL IS THIS
POTENT ANTI-DEPRESSION RESPONSE
WITH THE ACTIVE SAINT COMPARED
TO SHAM ON THE OPEN CIRCLES ON
THE MADRAS, WHICH IS A MEASURE
OF DEPRESSION.
SCORES 52% WITH ACTIVE AND 11%
WITH SHAM.
IT IS A BIG EFFECT SIZE AND
RAPID.
CONVENTIONAL TMS PROTOCOLS
REQUIRE FOUR TO SIX WEEKS TO
SHOW THERAPEUTIC BENEFIT.
WE NEED STUDIES TO UNPACK WAS IT
THE INDIVIDUALIZED TARGETING,
THE INTENSE OF TREATMENT
SCHEDULE OR BOTH THAT LED TO
THIS IMPRESSIVE THERAPEUTIC
OUTCOME?
YOU ARE PROBABLY THINKING WHEN
IS MRI GOING TO GET APPROVED FOR
TMS AND DEPRESSION?
I'M GLAD YOU ASKED BECAUSE IT IS
ALREADY IS.
I'M GETTING CHOKED UP, BUT I'M
ACTUALLY COUGHING.
IT IS ALREADY ON LABEL.
IT HAPPENED LAST MONTH.
THE SAME APPROACH RECEIVED
FIVE-10K APPROVAL IN THE U.S.
FOR SUBSTANTIAL EQUIVALENCY TO
OVER TMS DEVICES FOR TREATMENT
OF DEPRESSION.
MRI INFORMED TARGETING FOR TMS
DEPRESSION IS A PRESENT DAY
REALITY, ACCORDING TO THE FDA.
AS EXCITING AS THAT IS, THAT IS
JUST THE BEGINNING.
WE NEED MORE RESEARCH TO
UNDERSTAND THE TEST RELIABILITY
NOW THAT MRI-BASED TARGETING IS
FDA APPROVED, WE NEED TO KNOW WE
CAN DO THIS RELIABLY AND
UNDERSTAND HOW TO IMPLEMENT
THIS.
WE NEED TO UNDERSTAND THIS
SCALEABILITY OF THIS APPROACH
ACROSS LABS, ACROSS CLINICS.
CLINICIANS ARE GOING TO WANT TO
USE TOOLS THAT ARE MORE
EFFECTIVE THAN EXISTING TOOLS.
WE WANT TO UNDERSTAND WHAT
EVIDENCE IS REQUIRED FOR PAIRS
TO COMPENSATE FOR THE MRI PART
OF THIS TARGETING SO IT CAN GET
PAID FOR.
OF COURSE, INSURANCE APPROVAL IS
IMPORTANT FOR CLINICAL ADOPTION.
AND WE NEED THOSE UNPACKING
STUDIES TO UNDERSTAND WHETHER IT
IS THE MRI INFORMED TARGETING OR
TENSIVE TBS THAT WERE IMPRESSIVE
IN THE RESULTS.
I TALKED ABOUT ADULT
APPLICATIONS.
MRI CAN HELP US UNDERSTAND HOW
TO TAILOR NEUROMODULATION TOOLS
FOR THE DEVELOPING BRAIN SO THAT
WE CAN ADVANCE IN TERMS OF CHILD
AND ADOLESCENT BRAIN HEALTH AND
ALSO TO HELP US UNDERSTAND
CONDITIONS THAT HAVE A HIGH
DEGREE OF INDIVIDUAL VARIATION
AT THE BRAIN LEVEL SUCH AS
AUTISM SPECTRUM DISORDERS FOR
EXAMPLE.
YOU MIGHT BE WONDERING, THOSE
ARE GREAT RESEARCH GOALS.
WHERE ARE WE GOING TO GET FUNDED
DO DO THAT RESEARCH?
I'M GLAD YOU ASKED.
WE HAVE A SUITE OF OPPORTUNITIES
AT THE NIH THAT SUPPORT ALL
PHASES OF THE DEVICE DEVELOPMENT
LIFE CYCLE.
FOR EXAMPLE, AT THE LEVEL OF
NIMH AS WELL AS BRAIN INITIATIVE
AND COMMON FUND FUNDING
OPPORTUNITIES THAT FUND STAGES
OF DEVICE DEVELOPMENT TO FUND
STUDIES THAT EXAMINE MECHANISMS
AND TARGET DISCOVERY.
ALSO THE LEVEL OF CLINICAL
TRIALS OF NOVEL DEVICES.
I ONLY HAVE TIME TO HIGHLIGHT
ONE OF THESE.
THE BLUEPRINT MED TECH FUNDING
OPPORTUNITY.
BLUEPRINT MEDTECH SUPPORTS THE
DEVELOPMENT OF HUMAN GRAY
PROTOTYPES BY GIVING RESEARCHERS
ACCESS TO TRANSLATIONAL
RESOURCES AND EXPERTISE.
I'M SHOWING YOU THE TYPING OF
RESOURCES NIH IS PROVIDING TO
INVESTIGATORS.
RESOURCES FOR DEVICE PROTOTYPE
AND BENCH TESTING, BUSINESS
DEVELOPMENT, INDUSTRY EXPERTS,
REGULATORY COMPLIANTS, BY
COMPATIBILITY, ANIMAL STUDIES,
FIRST IN HUMAN AND CLINICAL
TESTING.
A WHOLE SUITE OF SUPPORT THAT
MOST DEVELOPERS OR INNOVATORS AT
UNIVERSITIES MAY NOT HAVE ACCESS
TO.
WE WANT TO PROVIDE WRAP AROUND
SERVICES TO ENABLE YOUR GREAT
NEW IDEAS TO GO THROUGH THESE
DIFFERENT TRANSLATIONAL STAGES.
WE HAVE DR. LIZZIE AN CODAVICH.
SHE DIRECTS THIS PROGRAM ON
NEUROMODULATION.
THE GOAL IS TO DEVELOP AND
REFINE MULTIMODAL COMBINATION
MODULATION WITH AN ETCH SIS ON
SYNERGI
SYNERGISTIC.
REACH OUT TO LIZZIE TO LEARN
MORE ABOUT THAT PROGRAM.
WE ARE HIRING IF YOU WOULD LIKE
TO LEAD CUTTING-EDGE FUNDING
PROGRAMS.
I'M HIRING FOR TWO PROGRAM
OFFICERS AND ANY PSYCHIATRY
RESIDENTS GETS EXPERIENCE WITH
THESE THERAPIES COME SEE ME
BECAUSE WE ARE RECRUITING FOR A
CLINICAL FELLOW.
HERE ARE CONTACTS FOR LIZZIE AND
OTHERS WHO LEAD OUR PROGRAMS
WITH DEVICE DEVELOPMENT AND
NEUROMODULATION.
AND TO CONCLUDE WHERE I STARTED.
NEUROMODULATION ADDS TO MRI THE
ABILITY TO MOVE BEYOND
CORRELATION TOWARDS CAUSATION
AND TEST FUNCTIONAL SIGNIFICANCE
OF MRI-DERIVED AMERICAN YOURS
AND I SHOWED YOU SOME EXAMPLES.
MRI ADDS TO NEUROMODULATION THE
ABILITY TO QUANTIFY THE DOSE AND
EXPLAIN ACROSS MODALITIES AND
ACROSS INDIVIDUALS.
IT HELPS US TO UNDERSTAND THE
SPATIAL PERFORMANCE OF
NEUROMODULATION TOOLS TO MOVE
BEYOND SIMPLE GROUPINGS IN
PSYCHIATRY TO HELP US BETTER
SELECT THE RIGHT PATIENT FOR THE
RIGHT TREATMENT AS WELL AS TO
CONSTRAIN HEAT ROGENE IFRKS TY.
IT HELPS DEFINE AND REACH
TARGETS AND ACHIEVE THIS VISION
OF NEUROMODULATION AND TARGETING
AT THIS LEVEL.
AND IT IS ON LABEL TODAY FOR
DEPRESSION.
I WANT TO RECOGNIZE THE MEMBERS
OF THE NIMH NEUROMODULATION UNIT
MANY OF WHOM ARE HERE IN
ATTENDANCE TODAY AND I'M HAPPY
TO TAKE YOUR QUESTIONS.
THANK YOU.
>>THANKS SO MUCH.
VERY NICE, ALL OF YOU AND VERY
USEFUL INFORMATION FOR THE
GRANTS.
QUESTIONS?
PLEASE GO TO THE MICROPHONE.
>>HI.
SO THANK YOU.
YOU ARE VERY INSPIRATIONAL.
SO YOU LOOKED AT THE LONG-TERM
EFFECTS OF TMS USING FUNCTIONAL
MRI AND THROUGH ACT VASE.
HAVE YOU LOOKED AT IT IN TERMS
OF CONNECTIVITY?
DOES IT LOOK LIKE THE DIFFUSION
TENSOR WEIGHTED DIFFERENT AFTER
AND BEFORE TMS?
>>YEAH.
I DID NOT SHOW YOU DTI POST TMS.
THERE ARE STUDIES THAT DO LOOK
AT WHETHER TMS OR OTHER FORMS OF
INTERVENTION LIKE ECT CAN CHANGE
DTI MEASURES.
I DON'T PERSONALLY HAVE DATA ON
THAT.
I KNOW SOME STUDIES HAVE LOOKED
AT THAT.
I THINK MUCH OF THE FOCUS HAS
BEEN ON THE FUNCTIONAL MEASURES
AND A PARTICULAR CHANGE IN THE
RESTING STATE CONNECTIVITY AND
SEEING IF THOSE TRACK WITH
CLINICAL RESPONSE.
WHAT I SHOWED YOU WAS A
TASK-BASED FMRI NOT RESTING
STATE CONNECTIVITY.
I THINK YOU ARE HEARING MORE,
PERHAPS IN THE SESSION THAT
FOLLOWED.
>>THANK YOU VERY MUCH.
SUCH A NICE PRESENTATION AND SIN
INSPIRING AS ALWAYS.
I WAS WONDERING THE RECENT FDA
APPROVAL.
IN MY UNDERSTANDING THIS IS THE
FIRST TIME WE HAVE SORT OF A
PROTOCOL, A FAMOUS PROTOCOL THAT
RECEIVES APPROVAL FOR
PSYCHIATRIC DISORDER IN
COMBINATION WITH FMRI.
WHAT ARE THE POTENTIAL
CHALLENGES HAVING THE PROTOCALS
BY UNIVERSITIES?
THE FUTURE ASPECTS OF MRI AND
NEUROMODULATION IN THAT
DIRECTION?
>>SO, THERE IS A TENSION HERE,
ISN'T THERE?
TO BE A GOING CONCERN TO BRING
TOOLS TO THE CLINIC, YOU NEED A
COMPANY THAT MAKES THE TOOL THAT
BRINGS THE TOOL TO THE CLINIC.
INTELLECTUAL PROPERTY IS A KEY
ELEMENT THAT ENABLES COMPANIES
TO FUND RAISE AND TO DEVELOP
TECHNOLOGIES TO GET THEM TO THE
CLINIC.
AND SO PATENTS ARE A MAJOR PART
OF HOW ALL OF THE TOOLS WE USE
TODAY IN IMAGES AND
NEUROMODULATION GOT THERE.
THE PART OF THAT TENSION IS ALSO
THE DESIRE TO HAVE OPEN SOURCE
ACCESS SO THAT WE CAN VERIFY AND
REPLICATE.
AND SO THERE'S -- I THINK YOU
ARE REFERRING TO THE ALGORITHM
THAT IS USED FOR TARGETING.
WE WOULD REALLY LIKE TO BE ABLE
TO HAVE OPEN-SOURCE ALGORITHMS
SO THE ACADEMIC COMMUNITY CAN
REPLICATE AND UNDERSTAND AND
IMPROVE UPON.
SO I THINK THAT IS A FUTURE
CHALLENGE FOR THE FIELD TO
GRAPPLE WITH.
HOW BEST TO DO THAT IN A WAY
THAT ALLOWS THE TECH SPACE TO
ADVANCE.
SO THAT WE WILL HAVE INDUSTRY
PARTNERS TO HAVE THE THINGS WE
NEED TO DO RESEARCH AND HAVE
CLINICAL WORK.
I WILL PUT A PLUG FOR ACADEMIC
PUBLICATIONS.
IT IS REALLY USEFUL TO SCIENCE
TO REPORT AS MUCH AS ONE CAN
ABOUT WHAT YOU ACTUALLY DID,
INCLUDING THE ALGORITHM.
YOU KNOW, OPEN SOURCE, NOT JUST
HERE IS YOUR DATA THAT IS
AVAILABLE, BUT HERE IS YOUR
PIPELINE OF HOW YOU ANALYZED
WHAT WAS YOUR ALGORITHM FOR
TARGETS?
HERE IS YOUR GETHUB LINK.
HERE IS WHERE WE CAN FIND OPEN
SOURCE AND TAKE YOUR DATA AND
REPRODUCE YOUR ALGORITHM AND GET
THE SAME RESULT AS WELL AS TAKE
THE ALGORITHM WITH OUR DATA AND
SEE IF WE GET THE SAME RESULT.
THAT IS SORT OF OPEN SOURCE
ENVIRONMENT CAN ACCELERATE
DISCOVERY.
SO DOES THAT -- I WOULD LOVE TO
HEAR YOUR ANSWER TO THAT
QUESTION?
>>THAT IS THE CHALLENGE WE HAVE
IN OUR TEAM RIGHT NOW, IN TERMS
OF HOW MUCH TRANSPARENCY YOU
HAVE FOR THE ALGORITHMS WE ARE
DEVELOPING AND HOW MUCH WE NEED
TO GO TOWARDS THAT DIRECTION OF
MAKING PATENTS.
THAT IS ALWAYS A TENSION BETWEEN
ACADEMIC MIND AND INDUSTRIAL
SORT OF ASPECTS OF THAT.
THANK YOU FOR YOUR INPUT.
I THINK THAT WILL BE AN
INTERESTING DISCUSSION WITHIN
THE COMMUNITY THAT WE HAVE.
PROBABLY SEEING WHETHER WE HAVE
THE BEST WAY TO PROMOTE SCIENCE
IN THAT DIRECTION.
THANK YOU.
>>ALL RIGHT.
THANKS AGAIN.
>>YEAH.
THANK YOU.
>>DUE TO THE TIME, WE HAVE TO
MOVE TO THE NEXT SECTION.
>>ALL RIGHT.
THE NEXT SESSION MRI IN TMS.
THIS IS A TOPIC VERY NEAR AND
DEAR TO MY HEART.
I WANT TO SAY IT IS WONDERFUL TO
BE DOING THIS RESEARCH IN AN ERA
WHERE HOLLY LISANBY IS AT NIH,
ALL OF US IN THE U.S. ARE
BENEFITING FROM HER LEADERSHIP.
THANKS FOR THAT.
OLIVIER, I WILL LET YOU GO.
>>I DON'T HAVE ANY FINANCIAL
INTERESTS TO DISCLOSE.
SO I'M NOT FROM THE U.S.
I'M FROM EUROPE.
AND I WOULD LIKE TO POINT OUT WE
ARE ALSO GOING IN THE SAME
DIRECTION, TRYING TO PROMOTE
OPEN SCIENCE, REPRODUCEABLE
RESEARCH.
AND I WOULD LIKE TO SHOW THE
EXAMPLE OF THAT PARTICULAR
PLATFORM, THE HUMAN NEUROSCIENCE
PLATFORM.
WE ARE NOT ACADEMICS, BUT WE ARE
STAFF WHO SUPPORTS ACADEMICS OR
ANYONE, COULD BE INDUSTRY, TO DO
HUMAN NEUROSCIENCE.
WE HAVE ALL THESE DIFFERENT
PLATFORMS AT OUR DISPOSAL OPEN
TO EVERYONE.
WE HAVE THE EXPERTISE AN
EQUIPMENT THEY CAN USE.
IT HAS BEEN VERY BENEFICIAL, IN
PARTICULAR, FOR EVERYTHING THAT
IS MULTIMODEL BECAUSE WE ARE ON
THE SAME.
AND PEOPLE ARE COMBINING ALL OF
THESE TOGETHER.
WE DID VIRTUAL REALITY WHILE
DOING TMS, TEMPORAL INFERENCE
INSIDE THE MRI, CONCURRENT MRI
WHICH THIS TALK IS GOING TO
FOCUS ON.
OUTLINE OF THE PRESENTATION.
THE DIFFERENT CHALLENGES OF
CONCURRENT MRI.
YOU HAVE SEEN THE BIG PICTURE.
NOW WE WILL DEVIL HOW OWE DO
CONCURRENT TMS-MRI.
AND WHAT IS LEFT TO SOLVE.
OKAY.
SO THERE ARE DIFFERENT WAYS TO
COMBINE MRI AND TMS, BUT YOU CAN
CATEGORIZE THEM INTO THE OFFLINE
APPROACH WHERE YOU WOULD FIRST
DO AN MRI SCAN TO DERIVE SOME
PARTICULAR TYPE OF METRICS AND
DO TMS AND THEN AFTER THAT YOU
WOULD DO ANOTHER MRI SCAN.
AND IN THAT CASE, YOU DO
CONVENTIONAL TMS AND MRI.
THERE IS NO INTERACTION.
THIS IS, I WOULD NOT SAY EASY,
BECAUSE YOU KNOW IF YOU WORK IN
THE FIELD YOU KNOW THE TRICKS.
IF YOU WANT TO DO ONLINE TMS,
WHILE THE SUBJECT IS INSIDE MRI
THIS IS WHERE THINGS GET TRICKY
OR INTERESTING.
THAT IS A TYPICAL TMS EXPERIMENT
SET UP.
TMS, TMS HOLDER, CHAIR FOR THE
SUBJECT, NAVIGATION CRITICAL TO
TARGET PROPER AREA AND SOME KIND
OF TMS CONTROLLED DEVICE.
YOU MIGHT WANT TO RECORD SOME
MUSCULAR RESPONSE.
THAT IS THE TYPICAL SET UP.
YOU HAVE A VERY STRONG MAGNETIC
FIELD AND ALSO YOU HAVE A VERY
TIGHT SPACE.
VERY RESTRICTED SPACE INSIDE THE
MRI.
AND THESE ARE THE MAJOR
CONSTRAINTS.
BASED ON THIS, THE DIFFERENT
CHALLENGES ARE THE FOLLOWING.
WE ARE GOING TO GO THROUGH THE
LIST TOGETHER.
BASICALLY NAVIGATION IN THE MRI.
ARE WE TARGETING THE PROPER
AREA.
DOES THE QUESTION OF THE MRI
COIL AND WHETHER IT IS
COMPATIBLE WITH TMS.
THE QUESTION OF THE TMS COIL,
WHICH IS AS IMPORTANT.
HOW DO YOU PERFORM SHAM OR
CONTROL EXPERIENCE INSIDE THE
MRI?
WHAT IS THE DIFFERENCE BETWEEN
SIMULTANEOUS AND CONCURRENT USE
OF TMS AND MRI AND HOW YOU DO
IT.
HOW DO YOU CONTROL TMS CONTROL
SYNCHRONIZATION AND PROPER
QUALITY OR CO-REGISTRATION OF
DATA?
SO WE'VE SEEN THAT WITH NEW
NAVIGATION, YOU CAN ACTUALLY TRY
TO DEFINE YOUR TARGET, EITHER
BASED ON STRUCTURAL DATA, T1,
122, TRACTOGRAPHY OR FUNCTIONAL.
YOU GET THE SOFTWARE AND
ACTIVATION LAB TO YOUR FAVORITE
NEURONAVIGATION SOFTWARE.
YOU DEFINE YOUR TARGET.
NOW, TO DO IT INSIDE THE MRI IS
TRICKY.
THERE ARE BASICALLY TWO WAYS TO
DO IT.
YOU CAN DO IT RETROSPECTIVELY,
WHICH MEANS YOU WILL FIND OUT
AFTERWARDS IF YOU WERE ACTUALLY
TARGETING THE PROPER AREA, WHICH
COULD EXPLAIN WHETHER YOUR DATA
MADE SENSE OR NOT.
WHAT YOU NEED TO DO IS PUT
MARKERS ON YOUR TMS COILS SO YOU
CAN SEE IN THE MRI IMAGES WHERE
IT IS LOCATED.
THERE IS VARIOUS WAYS TO GO
ABOUT IT.
THE TYPE OF MARKERS YOU CAN USE.
SOME PEOPLE HAVE BEEN USING
MUSTARD AS WELL AS THE
COMMERCIAL MARKERS AND YOU CAN
SEE IN THESE EXAMPLES ON T2
WEIGHTED IMAGE HOW YOU CAN LATER
FIND OUT WHERE YOUR COIL WAS.
THIS IS CHEAP AND EASY TO
IMPLEMENT.
YOU NEED THOSE LABELS.
YOU MIGHT WANT TO 3-D PRINT
SOMETHING, BUT YOU ARE SENSITIVE
TO ANY MOTION THE SUBJECT MIGHT
MOVE.
SO IT REQUIRES A LOT OF SKILLS
TO PUT IT RIGHT AT THE BEGINNING
OF THE SESSIONS AND IN CASE THE
SUBJECT MOVES, IT TAKES TIME TO
READJUST.
THE OTHER SOLUTION IS CONTINUOUS
MONITORING.
IN THAT CASE IT IS AN ACTUAL
CONTINUOUS REAL TIME
NEURONAVIGATION SO YOU NEED
MOTION TRACKERS ON THE TMS AND
THE SUBJECT, JUST LIKE YOU WOULD
DO ON THE REGULAR TMS
EXPERIMENT.
THAT IS TRICKY BECAUSE OF THIS
PACE.
YOU CAN SEE HERE A COUPLE OF
EXAMPLES WHERE YOU HAVE THE
CAMERA WHICH IS LOCATED ON THE
FAR SIDE OF THE MRI BED AND THEN
HERE THE DIFFERENT TRACKERS, ONE
ON THE FOREHEAD, ONE OF THE TMS
COIL AND YOU TRY TO HAVE THIS
LINE OF SIGHT BETWEEN THE TWO.
THIS IS ANOTHER EXAMPLE HERE.
SO THE PROS.
THIS CONTINUES.
IT IS A FEEDBACK THAT IS
POSSIBLE IF THE SUBJECT IS
MOVING.
YOU CAN FEED HIM SOME KIND OF
TARGET THE SAME WAY WHEN WE DO
NAVIGATION.
SUBJECT IS ACTIVELY INVOLVED IN
THE POSITION.
THIS IS NOT EASY.
YOU NEED CAMERA ROD AND SEDUP
AND KEEP THE LINE OF SIGHT
ALWAYS AVAILABLE IS TRICKY AS
SOON AS YOU WANT TO DO A VISUAL
STIMULUS, THE SUBJECT IS LOOKING
AT SOMETHING IT BECOMES REALLY
COME POLITIC -- COMPLICATED.
THERE IS AT THE MOMENT NO REAL,
I WOULD SAY, APPROPRIATE
SOLUTION.
EVEN THE COMMERCIAL ONE ARE NOT
OPTIMAL.
YOU NEED TO TRAIN YOUR PATIENTS
THAT IS VERY WELL BEHAVE.
IT WOULD BE INTERESTING,
ACTUALLY, TO MAYBE CONSIDER
DIFFERENT WAYS OF DEVELOPING
THIS TECHNOLOGY.
MAYBE HAVING SOME KIND OF
MULTICOIL CAPABILITY SO EVEN IF
THE SUBJECT IS MOVING YOU CAN
TRY TO DEFINE THE TARGET WHEN
THE SUGGEST IS STILL INSIDE THE
MRI.
HERE I THINK THE COMMUNITY
REALLY NEEDS TO MAKE AN EFFORT
INTO FINDING A PROPER SOLUTION
BECAUSE THIS IS A BIG PROBLEM
WITH CONCURRENT TMS-MRI.
THE TMS COILS ARE LARGE.
SO IF YOU WANT TO USE A
CONVENTIONAL MRI COIL BASICALLY
YOU ARE LEFT WITH THE ONLY
OPTION WHICH IS BIRD CAGE COIL.
IT MEANS THAT POTENTIALLY YOU
HAVE POOR MRI SIGNAL AND NO
MULTIBAND CAPABILITY.
AND THAT IS A PROBLEM WHEN YOU
WANT TO DO FMRI.
ALSO YOU MIGHT HAVE LESS
FLEXIBILITY IN COIL POSITIONS
BECAUSE THE BIRD CAGE IS STILL
RESTRICTED ON THE SIDE, THE
SPACE THAT YOU HAVE.
SO FOR THAT REASON SOME
DEDICATED MRI SURFACE COILS HAVE
BEEN DEVELOPED AND THEY LOOK
LIKE THIS.
SO IN WHITE IS YOUR TMS COIL SO
YOU CAN STIMULATE INSIDE THE MRI
IN BLUE IS THE MRI COIL.
ONE OF THEM IS DIRECTLY CLIPPED
INSIDE THE TMS COIL SO YOU HAVE
A GOOD SIGNAL AT THE AREA YOU
ARE PRIMARILY TARGETING.
YOU CAN SEE IN THIS DPLAMPL IS A
SECOND BLUE ONE THERE BASICALLY
TO MAKE SURE YOU HAVE MRI SIGNAL
ON THE OTHER SIDE OF THE BRAIN.
I DON'T WANT TO SAY BIRD CAGE
COILS.
I USE THAT WITH WHOLE BRAIN
IMAGING.
IF YOU ARE INTERESTED IN DOING
INDIRECT STIMULATION, STIMULATE
ON CORTEX BUT INTERESTED IN
SOMETHING DEEP IN THE BRAIN AND
YOU WANT INFORMATION THERE, KEEP
IN MIND SPACE IS VERY LIMITED SO
YOUR TYPICAL TARGETS FOR TMS
WOULD BE M1 OR SMA.
ON THE OTHER HAND, FOR THE
SURFACE COILS IT IS ADVANTAGEOUS
TO DETECT TMS ACTIVITY NEAR THE
COILS TO SOW HAVE SIMILAR TO
BIRD CAGE AND MORE VERSATILE IN
TERMS OF GEOMETRY AND TARGETS.
IF YOU WANT MULTIBAND
CONNECTIVES, YOU NEED TO COMBINE
COILS TOGETHER AND IN THAT CASE
YOU HAVE A MUCH BETTER SMA IN
HALF OF THE BRAIN.
THIS IS THE SOLUTION THAT WE ARE
CONSIDERING IN OUR LAB AND THIS
IS WHAT A TYPICAL SET UP IS
LIKE.
YOU CAN SEE HERE, THIS IS THE
TMS COIL, ONE MRI COIL CLIPPED
TO IT AND THERE IS ANOTHER ONE
HERE.
HERE WE WOULD BE STIMULATING,
FOR EXAMPLE, VRKSZ 5 IN THAT
PARTICULAR EXAMPLE.
FOR THE TMS COIL, OF COURSE, IT
MUST CONTAIN NO -- MATERIAL.
THE STRONG STATIC BE ZERO AND
THE DYNAMIC MAGNETIC FIELD DUE
TO RAPID SWITCHING OF THE GRADE
YENS WHEN FUNCTIONAL MRI.
IT IS IMPORTANT TO USE A COIL
WHICH IS MORE COMPATIBLE BECAUSE
THE OTHER ONES CAN MOVE OR
BREAK/EXPLODE.
SO YOU REALLY DO WANT THAT.
IN TERMS OF PULSES -- PULSES
HAVE A LOWER TMS CODE.
THIS IS ACTUALLY BENEFICIAL.
IN TERMS OF VERY CONCRETE
ASPECTS YOU ALWAYS NEED A WAVE
GUIDE AND LOW-PASS FILTER TO
REMOVE WITH THE EQUIPMENT.
SOMETHING THAT NEEDS TO BE TAKEN
INTO ACCOUNT IS TO WORK ON THESE
DIFFERENT FILTERS.
A LOT OF TMS COILS HAVE
COUNTERS.
IT IS EASY TO DEPLETE THESE TMS
COILS RUNNING AN MRI EXPERIMENT.
WE LEARN ON THAT AND WORKED WITH
MANUFACTURERS SO THIS PROBLEM
DOESN'T ARISE ANYMORE.
IN PRACTICE, THOSE COILS EXIST.
THEY ARE COMMERCIALLY AVAILABLE
WITH FDA APPROVAL, BUT THEY ARE
AVAILABLE, IT DOESN'T MEAN THEY
ARE PERFECT.
WHEN YOU DISCHARGE THE TMS COIL
INSIDE THE MRI YOU INDUCE A BIG
FORCE.
SOME OF THE LORENTZ FORCE
COMPENSATE, NEVERTHELESS, THERE
IS A LOT OF STRESS ON THE COILS
WHICH IS WHY YOU NEED TO SEND
THEM BACK TO BE REFURBISHED
AFTER A FEW THOUSAND PULSES.
WHICH MEANS YOU NEED TO DESIGN
YOUR EXPERIMENTS PROPERLY SO
THAT IN PRACTICE YOU CAN DO IT
WITH A SINGLE COIL OR AT LEAST
TAKE INTO ACCOUNT WHEN YOU ARE
RECRUITING A SUBJECT YOU MIGHT
HAVE SOME DOWN TIME.
TMS COILS MUST BE COOLED DOWN SO
YOU MUST HAVE ACCESS TO COMPRESS
SOR OR COOLER.
SOMETHING THAT IS EXTREMELY
IMPORTANT IS TMS COILS INSIDE
THE MRI ARE LESS STRONG THAN
OUTSIDE.
SO TYPICALLY YOU CANNOT REACH
THIS 140% OF MOTOR THRESHOLD
LIKE YOU WOULD BE ABLE TO IN THE
REST OF THE EXPERIMENT.
YOU NEED TO PAY ATTENTION TO THE
EXPERIMENTAL DESIGN.
THERE ARE DIFFERENT REASONS FOR
THAT.
BASICALLY THERE IS, IF YOU ARE
USING THESE DEDICATED MRI COILS,
YOU INTRODUCE AN EXTRA DISTANCE
BETWEEN THE TMS COIL AND THE
BRAIN.
SO YOU LOSE POWER THERE.
YOU WOULD HAVE A LONGER CABLE
BETWEEN THE TMS COIL AND THE
STIMLATOR.
THE TMS STIMLATOR LOCATED
OUTSIDE OF THE MRI ROOM.
THIS EXTRA DISTANCE DECREASES
THE POWER.
AND JUST THE FACT OF BEING IN A
STRONG MAGNETIC FIELD DECREASES.
I WOULD ENCOURAGE THOSE ASKING
FOR THE MORE POWERFUL VERSION OF
THE STIMLATOR WHEN YOU ARE
PARTICIPA
PARTICIPATING.
COIL HOLDER IS NECESSARY BECAUSE
THEY ARE HEAVY.
NOT FOR V1 OR V5 BECAUSE YOU ARE
LYING ON IT.
THIS IS WHAT A TYPICAL COIL
HOLDER WOULD LOOK LIKE HERE.
THE WAY THEY ARE DESIGNED TO
HAVE ALL ACCESS OF FREEDOM SO IN
THEORY YOU CAN HOLD THE TMS IN
WHATEVER POSITION YOU LIKE.
IN PRACTICE IT IS DIFFICULT TO
USE.
THE SUBJECT MOVES ONLY A LITTLE,
YOU NEED TO ROTATE THREE OR FOUR
OF THE DIFFERENT KNOBS TO GO
BACK TO A PROPER POSITION.
WE HAVE SOME WORK TO DO THERE.
AND IN THE MEANTIME, IT REQUIRES
A LOT OF SKILL TO BE ABLE TO DO
IT PROPERLY.
WHICH IS ALSO SOMETIMES GOOD
THAT WE HAVE A PLATFORM SO THAT
WE MAKE SURE IT STAYS WITH US
AND DOESN'T LEAVE WITH THE PH.D.
STUDENTS OR POST DOC.
IN TERMS OF SHAM CONTROL, WELL,
THIS IS A POPULAR PROBLEM FOR
TMS.
TMS STIMULATES A LOT OF NOISE.
THESE ARE ALL AMPLIFIED INSIDE
THE MRI.
SHAM COILS CANNOT BE USED SO
THERE ARE DIFFERENT SOLUTIONS.
BASICALLY EACH GROUP HAS ITS
PREFERRED TECHNIQUE.
SO SOME LIKE AN ACTIVE CONTROL
SITE, FOR EXAMPLE, THE VERTEX.
SOME DO THE SAME TMS PROTOCOL
UNDER A DIFFERENT MRI TASK.
COMPARING HIGH AND LOW INTENSITY
TMS TO HOPE LOW INTENSITY
PROFINDS THE SAME CONFOUNDS.
IF YOU RETATE YOU NEED TO TAKE
THE SUBJECT OUT AND DO
MANIPULATION OR INTRODUCE
PLASTIC AS AN EXTRA DISTANCE.
TO HAVE SOME OF THE COMPOUNDS AT
LEAST SIMILAR.
SO ALL OF THESE HAVE BEEN
CONSIDERED.
THERE'S NOT A CLEAR WINNER, TO
MY KNOWLEDGE HERE.
AND IN MY DEFENSE, ON THE
PARTICULAR APPLICATIONS THAT YOU
ARE DOING.
NOW, I WANT TO MENTION ABOUT
SIMULTANEOUS TMS FOR MRI.
IF YOU ARE REALLY SIMULTANEOUS,
BASICALLY, YOU WON'T GET ANY MRI
SIGNAL.
THE PMS TMS REDUCES YOUR MRI
SIGNAL TO 0, DEPENDING ON WHEN
YOU ARE PULSING IN THE SPACE.
WE INTRODUCED A SMALL GAP
BETWEEN THE TMS AND THE NEXT
VOLUMES.
IT HAS BEEN DONE AND VERIFIED BY
A FEW GROUPS.
75 TO 100 GAP.
YOU RECOVER MAGNETICIZATION AND
WHAT WE DO IN PRACTICE IS WE DO
EVERYTHING WE CAN WITH YOUR
USUAL 64, 32 CHANNEL MRI COIL
AND YOU ONLY CHANGE THE SETUP
FOR THE FMRI PART.
AND MAYBE SOME ADDITIONAL SCANS
TO DO COIL DEMONSTRATION.
FOR THE SEQUENCE YOU MIGHT
DEPEND ON THE PROTOCOL YOU WANT
TO DO.
YOU NEED TO INTRODUCE GAP
BETWEEN MRI VOLUMES.
DEPENDING ON THE FREQUENCY, YOU
CAN DO DIFFERENT THINGS.
WE HAVE SEEN SOME NICE EXAMPLES
IN THE PREVIOUS PRESENTATION.
A NICE BOLD ACTIVATION TO SEE
THE RESPONSE WHEN WE DO TMS.
IN TERMS OF METHODS, IT IS NICE
MOST PRODUCT SEQUENCE FROM THE
MANUFACTURERS ARE CAPABLE OF
INTERLEAVING.
LEAVING A GAP BETWEEN VOLUMES OR
SEGMENTS OF SLIDES SO IT IS
POSSIBLE FOR US WITH A GOOD SIN
K
SYNCHRONIZIZATION.
THERE IS NO MEASURE FOR WHERE
THE TMS IS TARGETING WHICH IS
WHY WE NEED TO USE
NEURONAVIGATION.
BECAUSE THE TMS KILLS ALL THE
SIGNAL THAT IS EVERYWHERE, THAT
IS DIFFICULT TO DO.
IT WOULD BE GREAT IF SOMEONE
CAME UP WITH A GENIUS IDEA TO GO
AROUND THIS PARTICULAR PROBLEM.
THERE IS ONE FOR TDCS AND I
THINK WE HAVE A TALK LATER ON
THIS PARTICULAR TOPIC.
SYNCHRONIZIZATION IS NOT A
PROBLEM.
THERE ARE TOOL BOXES AND OPEN
ACCESS.
MANY OF THEM SO WE CAN EASILY
CONTROL THE TMS AND HAVE A VERY
GOOD SYNCHRO NISZ --
SYNCHRONIZATION.
YOU WANT TO TRIGGER FAST, YOU
GET VERY GOOD SYNCHRONIZATION.
THE DIFFERENT SETUPS.
ON THE LEFT TMS ON M1, THE
SUBJECT IS FULLY INSTALLED.
THERE IS AN ADDITIONAL MRI COIL
TO RECOVER THE SIGNIFICANT AT
THE SPINE LEVEL.
THIS IS TMS PERFORMED ON V5.
HERE THE OTHER COIL WAS PUT ON
THE VERTEX.
THE MRI RECEIVED COIL IS
DIFFERENT, TWO BIG LOOPS, ONE OF
THE LEFT, ONE OF THE RIGHT AND
PUT YOUR FIGURE 8 COIL ON THE
TOP.
THIS IS GOOD FOR SOME
APPLICATIONS, LIKE I SAID, BUT
MAYBE NOT ALL OF THEM.
ANOTHER FEW SLIDES BEFORE THE
SUBJECT ARRIVES, IT LOOKS LIKE A
MESS.
WHEN THE SUBJECT IS INSTALLED,
NO NAVIGATION, NO MARKERS.
WHEN THE SUBJECT IS FULLY IN
PLACE THIS IS HOW IT WOULD LOOK.
IF YOU LOOK AT THE CONSULT ROOM
YOU SEE BECAUSE WE TRY TO REDUCE
CABLE LEJTS, THE MRI IS IN THE
ROOM JUST BEHIND.
WE HAVE THE STIMLATOR KIND OF IN
FRONT OF THE -- SORRY, OF THE
CONSOLE, OF THE MRI CONSOLE AND
THE CONNECTION IS SIMPLY A FEW
CABLES THERE.
NOW, IN TERMS OF QUALITY,
BASICALLY FOR EVERYTHING WHICH
IS STRUCTURAL YOU HAVE THE SAME
MRI QUALITY YOU ARE USED TO
BECAUSE YOUD ARE USING THE SAME
MRI COIL YOU ARE USED TO AND YOU
ONLY USE YOUR DEDICATED SETUP
FOR FMRI AND A BIT FOR
DEMONSTRATION.
THIS IS HOW IT LOOKS FOR A
SINGLE VOLUME WHEN YOU ARE USING
THIS DID KATED TMS COILS.
YOU CAN SEE WE HAVE THE MARKERS
TO CHECK THE POSITION
RESPECTIVELY AND THE ACTIVATION
WORKS PRETTY WELL.
WE DO ALTERNATING PHASE TO
ACCOUNT FOR THE DISTORTIONS.
LIKE ANY MRI PROTOCOL, REALLY.
WE HAVE A STUDY THAT SHOWS IT
WORKS REALLY WELL.
IT IS SIDE DEPENDENT AND POWER
DEPEND AND WE GET GOOD RESULTS
WITH OUR USUAL METHODS.
I JUST WANT TO MENTION THIS
POINT.
IT WAS A PROBLEM, BUT IT IS ONE
THAT IT IS EASY TO GO AND SOLVE
FOR.
IT IS TYPICALLY DIFFICULT TO TMS
MRI DATA ACQUIRED WITH A
DIFFERENT COIL BECAUSE YOU HAVE
A DIFFERENT CONTRAST AND A
DIFFERENT B1 COVERAGE.
YOU OMITTED ONE STEP WITH
DIFFERENT CONTRACT WITH THE SAME
B1 COVERAGE.
IN THAT CASE THIS IS YOUR FMRI
IMAGE.
YOU WOULD REQUIRE A STRUCTURAL
SCAN.
SO VERY SMI EFFICIENT WITH THE
SAME COIL SO THEY ARE
CO-REGISTERED TOGETHER.
THE SUBJECT IS WITH THE SAME
MRI COIL AND YOU CHANGE THE
SOFTWARE AND USE THE BODY COIL
INTEGRATED WITH THE SCANNER
GIVING YOU DIFFERENT B1.
AND YOU CAN EASILY CO-REJ TER
TOGETHER AND USE THIS ONE AS AN
INTERMITTENT STEP.
SO I THINK THIS IS A VERY
EXCITING TIME TO DO RESEARCH IN
THIS FIELD.
THERE HAVE BEEN RECENT ADVANCES
IN TERMS OF NEW TECHNOLOGY
AVAILABLE AND SOMETHING WE HAVE
NOT MENTIONED, ALL THESE
DIFFERENT LEARNING ALGORITHM
IMPACTING THE FIELD OF MRI AND
IT IS UNCLEAR HOW WE CAN BENEFIT
FROM THEM IN THIS FIELD.
ALL OF THIS TECHNOLOGY IS NOW
AVAILABLE WITH CLINICAL GRADE
AND THE TYPE THAT PLATFORMS ALSO
EXISTING PERMIT TO MAKE THEM
AVAILABLE TO POTENTIALLY A
LARGER COMMUNITY, WHICH DO NOT
HAVE NECESSARILY ACCESS TO
AFFORD THIS EXPENSIVE MACHINE,
BUT YOU CAN DO YOUR OWN
EXPERIMENTS LIKE THIS.
SO THERE ARE STILL AREAS OF
IMPROVEMENT AND OPEN QUESTION I
MENTIONED IN PRACTICAL ABILITY
AND HOW DO DO A GOOD SHAM
DESIGN.
WE HAVE SEEN THIS IN THE
PREVIOUS TALK.
THERE IS A LOTS OF WORK GOING ON
RIGHT NOW AND THIS IS GREAT AND
WE NEED TO TWO FURTHER AND REACH
CONSENSUS.
SAME THING FOR THE STIMULATION
OF DEEP BRAIN STRUCTURE.
WHAT IS MORE APPROPRIATE?
STRUCTURAL, FUNCTIONAL, MAYBE A
COMBINATION OF BOTH.
ALSO MAYBE -- IT IS INTERESTING
TO GO TO HIGHER FIELD STRENGTH
IF YOU ARE LOOKING AT TMS AND
SEE HOW WE CAN HAVE AN
INDIVIDUAL BRAIN ACTIVITY, WHICH
IT GIVES US IN TERMS OF FMRI.
IT IS VISIBLE ON A SINGLE
SUBJECT.
IN THAT CASE, THE TMS TECHNOLOGY
IS DIFFICULT TO DIVIDE UP SO
THESE ARE ALL INTERESTING
TOPICS.
I'M ALSO GLAD TO SEE THAT THERE
IS THIS WORKSHOP.
THERE IS ANOTHER ONE THAT HAS
BEEN CREATED ON CONCURRENT
TMS-FMRI WHICH IS GOING TO BE
RENEWED EVERY YEAR.
THIS COMMUNITY CAN EXCHANGE
SEVERAL TIMES A YEAR AND TRY TO
PROGRESS AS FAST AS POSSIBLE.
SO THANK YOU FOR YOUR ATTENTION.
[ APPLAUSE ]
>>THERE IS ALSO A SLACK
WORKSPACE FOR THAT GROUP THAT
PEOPLE ARE WELCOME TO JOIN.
SO ANYBODY WHO IS ACTUALLY DOING
TMS-MRI AND WANTS TO BE ON THE
SLACK, I WILL BE HAPPY TO INVITE
YOU IF ANYBODY WANTS TO JOIN.
ANY QUESTIONS?
>>I'M A NEUROLOGIST IN MED
OFFICE FOR FDA.
JUST CO-MODERATING.
I HAVE A QUICK QUESTION ABOUT
THE SURFACE COIL.
DOES IT HAVE ANY ADVANTAGE OF
PREVENTING THE SPREAD OF CURRENT
STIMULATION?
AND THE OTHER IS CAN IT BE USED
FOR ALL THE TMS, LIKE ITBS.
>>WHICH COIL, SORRY?
>>THE SURFACE COIL.
>>YEAH.
>>I DON'T THINK THEY ARE VERY
EFFICIENT, THIS TYPE OF COIL.
SO IN THEORY, IT GIVES YOU
FLEXIBILITY IN TERMS OF WHAT YOU
CAN DO BECAUSE THEY ARE VERY
VERSATILE.
BUT I WOULD GO FOR THIS
DEDICATED MRI COILS, I THINK, IF
I WANT TO HAVE -- I MEAN, IF WE
ARE TRYING TO DEVELOP THIS
TECHNOLOGY, I THINK WE WANT TO
HAVE THE BEST TOOL AT EACH PLACE
AND THESE WERE NOT DEVELOPED
ESPECIALLY FOR THIS, YOU ARE
LACKING A BIT OF SIGNAL COMPARED
TO THESE OTHER NEW TOOLS SO WE
SHOULD REALLY GO FOR THAT.
>>THANK YOU.
>>I WOULD SAY, IT DOESN'T HAVE
TO DO WITH THE SURFACE COIL, BUT
THE TMS DEVICE ITSELF IS CAPABLE
OF RTMS.
THERE IS AN AIR COOLED VERSION
OF THE TMS COIL SO YOU CAN RUN
RTMS SESSIONS WITH IT.
IT IS UNRELATED TO THE MRI
SURFACE COIL.
>>THANKS.
>>NO QUESTIONS.
OKAY.
THANKS VERY MUCH.
>>THANK YOU.
[ APPLAUSE ]
>>BARAN IS COMING UP AND
GETTING SET UP, WE ARE A
CLOSE-KNIT COMMUNITY.
THE GROUP IN CYPRUS, A BUNCH OF
PEOPLE WERE ABLE TO ATTEND.
I HIGHLY ENCOURAGE YOU TO ATTEND
IF YOU CAN, A BEACH RESORT, A
BEAUTIFUL PLACE, IF YOU ARE UP
FOR THAT, WE WOULD LOVE TO SEE
YOU.
BARAN AYDOGAN.
>>THANK YOU.
I'M HAPPY TO BE HERE IN PERSON.
I'M DOING RESEARCH FELLOW AT THE
A.I.VIRTANEN INSTITUTE FOR
MOLECULAR SCIENCES AT THE
UNIVERSITY OF EASTERN FINLAND.
WE ORIGINALLY THIS SLOT TO BE
PRESENTED BY HIM AND HE GLADLY
ACCEPTED.
HE WANTED TO BE WITH US IN HERE
TODAY, BUT UNFORTUNATELY, HE HAD
TO CANCEL.
BECAUSE HE WAS ASKED TO SPEAK IN
A GRANT PANEL IN BRUSSELS.
WE AGREED THAT I WILL TRY TO
MAKE A PRESENTATION WHERE THE
WORK HE HAS BEEN LEADING AT
AALTO OVER THE YEARS AND OUR
JOINT WORK IN THE MOST RECENT
YEARS.
SO THE FIRST HALF OF THE
PRESENTATION WILL BE MAINLY
ABOUT HIS CONTRIBUTION AND THE
TEAM AT AALTO.
I DON'T HAVE ANYTHING TO
DECLARE.
SO THIS TALK A GENERAL ASPECT.
I NEED TO THANK THE KEYNOTE
SPEAKER.
MAYBE FROM THE POINT OF THE
RESEARCH DONE IN FINLAND.
I DIVIDED IT INTO THREE WHERE I
WILL MENTION ANALYSIS
PERSPECTIVE, MRI IS UTILITY AND
TARGETING PERSPECTIVE AND JOINT
PERSPEC
PERSPECTIVE.
SO LET'S GET STARTED.
ANALYSIS.
AS WE HEARD ALREADY IN THE
MORNING, TMS AFFECTS THE BRAIN
IN COMPLICATED WAYS.
EXACT IS MULTIDIMENSIONAL, LET'S
SAY.
IF YOU ARE CURIOUS ABOUT WHAT IS
BEING STIMULATED, I HIGHLY
RECOMMEND THIS PAPER RECENTLY
PUBLISHED ON THIS.
ONE IMPORTANT THING TO HIGHLIGHT
IS THAT TMS CAUSED STIMULATION,
AUDITORY AND SENSORY.
NEVERTHELESS, WE HAVE A GENERAL
UNDERSTANDING OF WHAT IS
HAPPENING.
WE BASICALLY RUN A LARGE AMOUNT
OF CURRENT IN A COIL.
THIS IS, OF COURSE, TRACE A
MAGNETIC FIELD THAT LEADS TO E
FIELD, ELECTRIC CURRENT IN THE
TISSUE, CHANNELS TO OPEN AND
ACTION POTENTIALS.
THESE PROPAGATE THROUGHOUT THE
BRAIN AND THROUGH SYNAPTIC
ACTIVATIONS.
THROUGHOUT THE PROCESS WE HAVE
POST SYNAPTIC -- BECAUSE WE CAN
DETECT.
SO THE MEASUREMENT OF EEG WITH
CONCURRENT TMS HAS BEEN LEAD IN
THE 1990s ACTUALLY.
THIS IS WHAT A TMS-EEG SETUP
LOOKS LIKE.
THE VALUE IS WE WILL HAVE HIGH
TEMPORAL DYNAMICS MEASURED BY
EEG.
OF COURSE, EEG DOESN'T LIKE TMS
MUCH.
WE HAVE ARTIFACTS.
THERE ARE GOOD ALGORITHMS TO
CLEAR UP THESE ARTIFACTS.
ALREADY IN THOSE TIMES, THE
UTILITY OF MRI WAS CLEAR IN
1990s BASED ON THE DATA
COLLECTED IN THIS STUDY.
THE SOURCES ACTIVATED IN THE
BRAIN WERE MEASURED USING
NEUROESTIMATE.
SO THIS SLIDE WILL BE VERY
CROWDED AND I WILL STEP OUT OF
WHAT IS BEING DONE OUTSIDE
BECAUSE THESE ARE QUITE EXCITING
DEVELOPMENTS IN OUR FIELD
NOWADAYS.
WHAT EXCITED ME ARE BIOPHYSICAL
BASED SIMULATIONS WHICH WE HEARD
IN THE MORNING.
THESE WANT TO GO TO CELLULAR
LEVEL MECHANISMS OF HOW TMS
AFFECTS THE BRAIN AND THEY HAVE
POTENTIAL TO INFORM US MORE
PRECISELY ABOUT WHAT IS GOING ON
AND DEVELOP NEW TREATMENT
OPPORTUNITIES.
AS SOMEONE WHO IS HEAVILY
INVOLVED IN THE MRI RESEARCH,
I'M VERY INTERESTED TO FOLLOW
WHERE THIS RESEARCH WILL GO
BECAUSE THERE ARE A LOT OF
PARALLEL DEVELOPMENTS WHICH
COULD HELP THIS TYPE OF
RESEARCH.
IN THE DIFFUSION MRI COMMUNITY
WE HAVE BIOPHYSICALLY
MICROSTRUCTURE MODELS COMING.
IN THIS PAPER, THE MODEL IS ABLE
TO INFORM US ABOUT THE CORTICAL
SITE OF ARCHITECTURE TELLING US
ABOUT THE SOMA AND NEURIT
DENSITY.
THIS COULD BE TIED TO CELLULAR
PROFILING AND HEAVILY USED IN
BIOPHYSICAL AS WELL.
WE HAVE AN INCREASING STRENGTH
IN OUR SCANNERS.
THE DEVELOPMENT LEADING TO
HIGHER B VALUES IN DIFFUSION
SCANNERS.
THESE ARE ABLE TO PROVIDE FINER
AND FINER MICROSTRUCTURE
INFORMATION.
THE AXON DIAMETER G RATIOS COULD
BE IN THE FUTURE POSSIBLE TO BE
MEASURED BECAUSE THEY ARE CLOSED
TYPE CONDUCTION.
ON A HIGHER LEVEL WE ARE SEEING
TOOLS FOR CIRCUIT AND MASS
MODELING.
FOR EXAMPLE THIS TOOL, STEPHANIE
JONES IS DEVELOPING OR REALLY
LOOKING AT THIS CIRCUIT LEVEL
ACTIVITIES, WHICH ALSO TIES TO
SYSTEM LEVEL OPERATION OF THE
BRAIN, WHICH WE CAN LEVERAGE MRI
INFORMATION, FOR EXAMPLE.
THESE STRUCTURE CIRCUITS, A
DIVISION OF MRI TRACT.
WE WILL HERE MORE DOWN TO
MOLECULAR.
WE WILL HAVE IMAGING WHICH ARE
EXCITING TO FOLLOW.
I WOULD LIKE TO TALK ABOUT THE
TARGETING PERSPECTIVE, NAVIGATED
TMS APPROACH.
FOR EXAMPLE, MANY THIS CASE WE
HAVE STRUCTURAL MRI AND THE TMS
AND THE PATIENT'S HEAD.
AND WE CAN ACTUALLY SEE WHERE
THE TMS COIL IS LOCATED WITH
RESPECT TO THE SUBJECT'S BRAIN.
THIS IS USED FOR PRESURGICAL
LOCALIZATION FOR PREFRONTAL
CORTEX.
THIS IS FDA APPROVED.
AND HERE ARE SOME RESULTS FROM
CORTICAL MAPPING.
WE CAN SEE HERE ON THE LEFT
NAVIGATED TMS MAPPING, WHICH IS
NONINVASIVE, SOME MUSCLES AND WE
CAN SEE ON THE RIGHT THE
CRANIOTOMY, THERE IS A GOOD
MATCH BETWEEN THE TWO.
WE MAYBE CAN DO BETTER.
NOW WE ARE DEVELOPING ALGORITHMS
IN OUR HARDWARES, WE CAN DO
MODELING USING REALISTIC HEAD
MODELS.
THIS COULD BE VERY USEFUL TO
HAVE IN YOUR NEURAL NAVIGATION
SYSTEMS FOR BETTER TARGETING.
I WITHOUT LIKE TO SPEND A FEW
WORDS ABOUT WHAT WE CAN DO
BEFORE THIS.
BECAUSE THESE E-FIELD MODELING
ARE BASED ON CORE GEOMETRY,
WHICH MAY NOT BE ENOUGH AS THE
PREVIOUS SPEAKER MENTIONED, PUT
TMS COILS INSIDE MRI AND THE
VIBRATIONS.
SO IT MIGHT BE VALUABLE TO HAVE
EXPERIMENTAL WAYS OF MEASURING
THE E-FIELD.
AND IN THIS STUDY, AN APPARATUS
TO MEASURE THE E-FIELD BY TMS
COIL IS SUGGESTED.
THESE TOOLS ARE ALSO USEFUL, FOR
EXAMPLE, TO MAKE THIS MULTILOCAL
TRANSCRIPTION STIMULATION
SYSTEMS.
IN THIS CASE WE ARE LOOKING AT A
FIVE-COIL ARRANGEMENT.
EACH OF THESE COILS ARE ACTUALLY
ABLE TO CREATE THEIR OWN E-FIELD
PROFILES.
WHEN YOU STACK ALL OF THESE ON
TOP OF EACH OTHER AND RUN
DIFFERENT CURRENT COMBINATIONS,
IT IS POSSIBLE TO MOVE THE
EFIELDS ELECTRICALLY.
WHEN AFFIXED ON A CERTAIN PART
OF THE HEAD, WE ARE ABLE TO MOVE
THIS E-FIELD MAXIMUM BY RUNNING
DIFFERENT CURRENTS THROUGH THIS
COIL.
HERE THEY ARE.
AGAIN, PREVIOUSLY MENTIONED,
THESE SET UPS CAN BE QUITE HEAVY
TO HANDLE, EVEN OUTSIDE THE TMS.
SO THERE'S EFFORTS TOWARDS A
ROBOTIC SYSTEM TO HOLD THESE
COILS TOGETHER.
AS YOU CAN SEE HERE, WE ALSO
HAVE BEEN PUTTING SOME EFFORT ON
THE ROBOTIC PART.
WE CAN SEE REAL TIME COMPUTED
FIBER TRACKS.
I WOULD LIKE TO SPEND A FEW
MINUTES TO TALK ABOUT THAT.
I HAVE A BETTER VIDEO FOR IT.
SO HERE WE SEE THE OPERATOR
HOLDING THE TMS COIL AND THE
SUBJECT'S HEAD IS REGISTERED
WITH THE MRI AS WELL.
SO CONVENTIONAL NAVIGATION
SYSTEMS ARE CAPABLE OF SHOWS
THIS.
BUT THE DTI INFORMATION IS
COMING RATHER NEW.
WE ARE ABLE TO COMPUTE THE
TRACKS REAL TIME WHILE THE
NAVIGATION INTERFACE IS RUNNING.
BECAUSE THIS IS NOT THAT WELL
KNOWN AND NOT STUDIED BY MANY
GROUPS AND I HAVE BEEN THE MAIN
PERSON RESPONSIBLE FOR DOING
THIS, I WOULD LIKE TO SPEND A
FEW MINUTES TO DESCRIBE HOW WE
ARE DOING IT.
WE ARE USING OUR OWN FIBER
TRACKING ALGORITHM.
AND FOR THAT, WE HAVE DEVELOPED
A SOFTWARE CALLED TRACKER.
THIS IS A GENERAL PURPOSE
DIFFUSION MRI-BASED TRACK TOOL.
IT IS WRITTEN IN CC LGBTQIA+.
IT HAS A PYTHON AND IS INTENTED
SO PEOPLE CAN DEVELOP THEIR OWN
DEVICE.
TREKKER HAS NO DEPENDENCIES.
IT RUNS ON COMPUTER CLUSTERS TO
RUN ON BIG DATA.
THERE IS A WEBSITE FOR IT.
THE REASON WE MADE OUR OWN
TRACKING ALGORITHM, WAS NOT TO
MAKE IT FAST, BUT THE REASON WAS
TO MAKE IT GOOD SO WE CAN HAVE
BETTER AND MORE ACCURATE
REPRESENTATION OF THE BRAIN.
TREKKER HAS BEEN IN ALL COMP
TIGS SINCE 2017.
IN LAST YEAR THE TOP THREE TEAMS
ALL USED TREKKER AND WE WERE
ONLY LUCKY TO WIN IT.
WE HAD SAUL NUANCES IN OUR
ROBOT.
BUT THE -- I HAVE BEEN WORKING
ON TREKKER SINCE 2015.
THIS MAKES IN OUR CASE THE REAL
TIME.
IT IS LARGELY A SOFTWARE
PROJECT.
SO I MENTIONED THAT WE MADE THIS
SO PEOPLE CAN DO THEIR OWN
TRACTOGRAPHY.
I WOULD LIKE A QUICK
DEMONSTRATION.
YOU JUST IMPORT A TRACKER
PACKAGE, UPLOAD FOD, INPUT AND
JUST RUN.
SIX LINES OF CODE.
[INDISCERNIBLE] IN THE
NAVIGATION SITE, WE JUST GET
THESE DIE NAM CLICK FROM THE
NAVIGATION SYSTEM AND VISUALIZE.
OF COURSE, IT IS EASY FOR ME TO
SAY BECAUSE WE HAVE A NAVIGATION
SOFTWARE EFFORT GOING ON AT
AALTO.
SOME OF THE FEATURES OF THIS
REAL TIME TRACTOGRAPHY IS
NAVIGATION.
SO WE ARE ABLE TO CREATE
THOUSANDS OF STREAMLINES IN A
FEW SECONDS.
THIS IS IN THE C PLUS PLUS
VERSION IN PYTHON.
IT IS A LITTLE SLOWER, TO BE
HONEST, BUT MOST IMPORTANTLY,
YOU MAY WONDER IF THE QUALITY IS
LOWER BECAUSE WE ARE DOING IT IN
REAL TIME.
ACTUALLY, QUALITY IS NOT LOW
WHEN YOU COMPARE TO THE STATE OF
OFFLINE PIPELINES BECAUSE WE USE
EXACTLY THE SAME PROTOCOL.
NOTHING IS DIFFERENT.
IT IS THE SAME QUALITY.
WE ACTUALLY LEVERAGE ANATOMICAL
CONSTRAINTS SO THERE IS REALLY
NO LOSS.
OFFLINE, OF COURSE, CAN PROVIDE
SOME COMPLEMENTARY INFORMATION
FOR CONNECTIVITY OF OTHERS, FOR
EXAMPLE, BUT WE HAVEN'T TESTED
THAT.
IN DIFFERENT WAYS IT IS BETTER
THAN STATE OF THE ART OFFLINE.
BECAUSE WE CAN CHANGE THE
PARAMETERS IN REAL TIME.
THIS MIGHT BE USEFUL IN CERTAIN
APPLICATIONS, FOR THOSE WHO ARE
FAMILIAR WITH TRACTOGRAPHY MAY
UNDERSTAND THIS.
THIS IS AN INTERESTING FEATURE.
THE OTHER FEATURE IS MORE
INTERESTING BECAUSE OF THE WAY
WE ARE VISUALIZING DYNAMICALLY
THIS ACTUALLY COMES WITH CERTAIN
DIFFERENT OPPORTUNITIES FOR
EXAMPLE WE DO VISUALIZATION
TO -- STREAMLINES ARE MORE
LIKELY TO BE POSITIVE --.
IN THE FINAL PART I WOULD LIKE
TO TALK ABOUT ANALYSIS AND
TARGETING.
THESE ARE GENERALING ILY ABOUT
FUTURE PLANS, ACTUALLY.
IN THE PREVIOUS PART I TALKED
ABOUT THE STRUCTURAL IMAGES AND
E-FIELD.
THERE IS A DOWN SIDE IN THEIR
STUDY AND THEY ARE REQUIRED
BEFORE THE EXPERIMENT.
SO, OF COURSE, THERE IS TO BE
VALUABLE IF WE CAN SEE
ACTIVATION WHERE WE ARE HITTING
OR WHICH CIRCUITS ARE WE
TARGETING DURING THE EXPERIMENT.
SO THE MEASUREMENTS WITH FMRI
COULD BE HIGHLY USEFUL
CONCURRENTLY.
WE WOULD ACTUALLY LIKE TO
INCLUDE FEEDBACK FROM FMRI.
WHICH THE ESPECIALLY YOU MIGHT
APPRECIATE IT IS A QUITE
CHALLENGING SET UP TO PUT
EVERYTHING IN THE SCANNER, BUT
THIS APPROACH COULD ENABLE THIS
IN THE FUTURE.
SO THE IDEA HERE IS TO USE FMRI
FEEDBACK AND LOOK AT THE
ACTIVATION AND CHANGE THE TARGET
LOCATION.
SO THIS IS MAYBE TO SET TARGET.
BUT, OERNN THE OTHER HAND, AS T
KEYNOTE SPEAKER MENTIONED, WE
HAVE TIME.
THERE IS ANOTHER ROLE WITH THE
TARGETING.
ALTHOUGH WE MAY BE AFFECTING IN
THE E-FIELD A SIMILAR NEURONAL
POPULATION, BUT MIGHT BE
ACTIVATING DIFFERENT CIRCUITS OR
DIFFERENT CELLS OR DIFFERENT
WAY.
SO THIS STUDY SHOWS THERE IS
THIS KIND OF DEPENDENCY, TIME
DEPENDENCY BASED ON TMS TRIGGER.
SO WE WOULD LIKE TO CLOSE THE
LOOP ON THIS SIDE.
THIS BRINGS US TO TWO LOOPS.
WE NAMED THIS DUAL CLOSED LOOP
APPROACH.
I GUESS THERE MIGHT BE OTHER
PEOPLE WHO AIM FOR THIS PURPOSE.
THIS IS WHAT WE CALL IT.
IN THE GUIDANCE TMS PROJECT
WHICH JUST RECENTLY STARTED,
THIS WILL BE TRIED IN THE NEXT
FIVE YEARS.
AND WE ARE TRYING TO MAKE THIS
SETUP DUAL APPROACH TO HELP
TREAT DEPRESSION.
BECAUSE THAT IS AN IMPORTANT
DISEASE AND THERE ARE REALLY
STRONG HYPOTHESIS OF THE
STIMULATION OF SINGLE PORTALS
THAT COULD BE MAYBE HELPFUL.
IN THE GUY-IN TMS PROJECT IS
INDIVIDUALIZED.
YES.
AND, OF COURSE, WHAT WE STARTED
WITH WAS THE HARD PROBLEM HERE,
WHICH IS THE CLOSE-LOOP EEG.
BECAUSE THE OTHER PART, THE
CLOSED LOOP FMRI IS A HARDER
PROBLEM.
WHAT WE DID WAS START WITH A CAR
BIN WIRE LOOP WITH SIMULTANEOUS
EEG RECORDING THIS WAS MOSTLY
DONE BY -- HE IS A BACHELOR'S
DEGREE WITH THIS WORK.
WE CAN SEE EEG RECORDING
SIMULTANEOUS WITH MRI.
WHICH ARE
[INDISCERNIBLE] AND HERE WE SEE
THE GRADING ART FACT IN BLUE AND
BLACK IS THE REFERENCE SIGNAL.
THEN WE CAN SEE THE ALPHA PEAK
POWER QUITE CLEARLY.
HE MEASURED THE EEG PHASE AND IN
THE COMING CONFERENCE IN
PORTUGAL HE IS GOING TO PRESENT
HIS RESULTS.
SUFFICE TO SAY IT IS POSSIBLE TO
DO FACE, EEG FACE TRIGGERS.
WE HAD THE TRIGGERS COMING FROM
THE CLOSED UP DEVICE.
SO WITH THAT, I WOULD LIKE TO
END AND I THANKS MY GRANT
AGENCIES AND CLABTORS AND
ESPECIALLY DOCTOR ILMONIEMI FOR
LEADING THIS WORK AND THE TEAM
AT ACTION ALTO AS WELL.
WE HAVE BEEN DOING A LOT OF WORK
WITH THE EXPERIMENTS.
AND WE WORK WITH MANY CENTERS
FOR CLOSED LOOP EEG SITE AND THE
FMRI SITE AND THESE PEOPLE HAVE
BEEN INSTRUMENTAL FOR RUNNING
OUR EXPERIMENTS AND THANK YOU
FOR YOUR ATTENTION.
[ APPLAUSE ]
>>SO WITH THE TREKKER SOFTWARE,
IF THERE IS SOME WAY OF
BALANCING FOR EXAMPLE THE
QUALITY OF THE IMAGING DATA THE
USER UPLOADS WITH HOW ROBUST THE
TRACKS ARE IN NORMATIVE SPACE.
IF IT IS A BIG, WELL KNOWN
TRACK.
IF THE IMAGING DATA ARE BETTER
YOU WOULD HAVE MORE CONFIDENCES.
IS THERE SOME WAY OF BALANCING
THOSE?
>>THAT IS A VERY GOOD QUESTION
AND, OF COURSE, TREKKER HAS A
LOT OF PROBLEMS.
I THINK I ALWAYS TRY TO CONVINCE
PEOPLE THEY REALLY NEED TO HAVE
SOMEONE WHO KNOWS THE
LIMITATIONS OF TRACKTOGRAPHY.
IF YOU ARE NOT SURE WHAT YOU ARE
LOOKING AT, IT IS EASY TO BE
CONVINCED THEY ARE RIGHT.
THIS IS NOT A PROBLEM FOR
NEUROSURGEONS BECAUSE THEY
KNOW -- WHEN THEY LOOK AT
TRACTOGRAPHS, THEY AUTOMATICALLY
KNOW WHICH ONES TO BE WRONG.
YOUR QUESTION IS VERY RELEVANT
BECAUSE IT IS NOT KNOWN TO MANY
PEOPLE.
SO I SUGGEST A TRAINING OR
COLLABORATING WITH PEOPLE WHO
ARE TRAINED.
>>THANKS.
ANOTHER QUESTION?
>>YES.
I MIGHT HAVE A QUESTION.
DOES YOUR TRACTOGRAPHY, YOUR
REAL TIME NAVIGATION TAKE INTO
ACCOUNT COIL ORIENTATION?
>>I'M SORRY.
COIL ORIENTATION, IS THAT TAKEN
INTO ACCOUNT?
>>WE ARE EDITING E-FIELD, THE
RESULTS I SHOW DON'T TAKE INTO
ACCOUNT THAT.
>>ALL RIGHT.
WONDERFUL.
THANKS VERY MUCH.
>>THANK YOU.
>>
[ APPLAUSE ]
.
>>WE ARE TELLING YOU ABOUT ALL
KINDS OF IMAGING.
>>THANK YOU FOR THE NICE
INTRODUCTION.
THESE ARE MY AREAS OF INTEREST.
I HAVE A LICENSED AGREEMENT WITH
DSMI.
THIS IS THE OUTLINE OF MY
PRESENTATION, BUT BEFORE I GO
INTO MY PRESENTATION, THE FIRST
THING I WANT TO DISCUSS IS WHY
WE WANT TO COMBINE TMS MRI AND
EEG AND WHY IT IS IMPORTANT FOR
BASIC NEUROSCIENCE.
I WILL TALK ABOUT THE FUTURE
IMPROVEMENTS OF TMS/FMRI
EXPERIMENT.
THIS IS THE WORK I HAVE BEEN
DOING.
THESE ARE TWO PROJECTS,
MULTICHALLENGE -- TOWARDS THE
END OF THE PRESENTATION I WILL
SWITCH GEARS AND TALK ABOUT
INTERACTIONS BETWEEN THE SYSTEMS
AND HOW THEY AFFECT THE IMAGE
QUALITY AND THE SAFETY.
SO COMBINING TMS WITH FMRI HAS
THE POTENTIAL TO INCREASE OUR
UNDERSTANDING OF THE
RELATIONSHIPS BETWEEN BRAIN
NODES AND WHY IS THIS?
WE KNOW FMRI IS A PERFECT TOOL
TO KEEP TRACK OF BRAIN ACTIVITY.
IT HAS A HIGH SPECIAL RESOLUTION
TO KNOW WHERE THE ACTIVATION
COMES FROM.
EEG IS GREAT TO KEEP TRACK OF
THE BRAIN ACTIVATION BASED ON
THE NEURAL RESPONSE, IT IS
CAPABLE TO KEEP TRACK OF THE
TIMING.
IT HAS A GREAT HIGH TEMPORAL
RESOLUTION.
IT IS DIFFERENT TO KNOW WHERE
THE ACTIVATION COMES FROM.
THE LOCALIZATION IS VERY
DIFFICULT.
LUCKILY WE HAVE TMS.
BEFORE THIS, I WANT TO SAY THESE
TWO, THE EEG AND FMRI ARE VERY
COMPLEMENTARY.
AND IMAGING METHODS.
WE HAVE TMS THAT CAN ACTIVATE IN
A NONINVASIVE WAYS IN VERY WELL
DEFINED TIME POINTS.
IT CAN ADD A FACTOR TO THE EEG
AND FMRI.
I THINK ADDING IT CAN BRING
EVERYTHING TOGETHER TO FINALLY A
BLAINING TOOL.
-- A BRAIN MAPPING TOOL.
THIS IS GREAT FOR NEUROSCIENCE.
CLINICAL REV LANCE FOR THE
CLINICAL APPLICATION OF TMS.
WE KNOW 20% OF AMERICANS SUFFER
FROM MENTAL HEALTH DISORDERS.
ANXIETY DISORDERS ARE MOST
COMMON.
MAJOR DEPRESSION AFFECTS MORE
THAN 17 MILLION OF PEOPLE IN
AMERICA AND IN THE REST OF THE
WORLD, OF COURSE.
WE HAVE HEARD THE TREATMENTS ARE
USUALLY MEDICATIONS AND THEY CAN
HAVE SEVERE EFFECTS ON THE
PATIENT'S LIFE.
THERE ARE MANY PATIENTS THAT
DON'T FIND ANY RESPONSE TO THESE
MEDICATIONS.
SO LUCKILY, THE FDA HAS APPROVED
THE BRAIN STIMULATION
TREAT THESE MENTAL HEALTH
PROBLEMS.
THERE IS A LOT OF EVIDENCE THAT
SAYS THE EFFICACY OF THESE
TREATMENTS DEPEND WHERE WE HAVE
STIMULATED.
AND WHEN WE ARE STIMULATION.
WHEN WE ARE APPLYING THE
STIMULATION, THE BRAIN STATE
WHEN APPLYING THE STIMULATION.
TO ENHANCE THE EFFICACY OF THE
TREATMENTS WE HAVE TO COMBINE
THE SPECIAL NFLGS WITH THE
APPLICATION OF THE TMS.
AS I SAID BEFORE, I THINK THE
BIGGEST CHALLENGE COMBINING TMS
AND FMRI IS THE LACK OF
DEDICATED INSTRUMENTATION.
IF YOU SEE AVAILABLE SETUPS THAT
WERE AVAILABLE BEFORE 2015, YOU
HAVE 32 CHANNEL CORD.
AND UNFORTUNATELY THESE 32
CHANNEL COILS, WHICH MOVE FMRI
TO A NEW LEVEL OF SIGNIFICANCE,
THEY CANNOT BE USED WITH THE TMS
BECAUSE THERE IS A LACK OF SPACE
FOR THE TMS.
WE KNOW THEY ARE GREAT FOR FULL
HEAD COVERAGE.
THEY OFFER THE IMAGES THAT
REALLY HAVE IMPROVED THE TIME
RESOLUTION OF THE FMRI.
SO THE COILS WE WERE ABLE TO USE
THE SIX CHANNEL COIL AND BIRD
CAGE COIL.
IT IS VERY TRICKY BECAUSE YOU
HAVE TO KNOW WHERE YOU ARE
STIMULATING DURING THESE
EXPERIMENTS.
FRMPL, THE BIRD CAGE COIL DID
NOT ALLOW ANY PARALLEL IMAGING
CAPABILITIES.
FOR MY PH.D. I DEVELOPED A COIL
PLACED UNDER THE TMS AND ON TOP
OF THE SUBJECT.
WE SOLVED MOST OF THE PROBLEMS.
WE ENABLED FOR THE FIRST TIME
THIS TYPE OF IMAGES.
OUR WORK WAS PRESENTED IN OUR
PUBLICATION IN 2015 AND WE WERE
ABLE TO SHOW WE ACHIEVED FIVE
TIMES MORE SNR THREE CENTIMETERS
TO THE COIL COMPARED TO THE BIRD
CAGE COIL.
WE WERE ABLE TO SHOW 42% OF THE
BRAIN IS IMAGED WITH THE SAME
SNR AS THE BIRD CAGE COIL.
WE DID AN ASSESSMENT OF THE --
WHEN WE ACCELERATE IMAGES WE
LOSE SNR.
THE QUARTER ROOT OF R, WE CANNOT
GET RID OF THAT.
THERE IS THE GEOMETRICAL FACTOR
THAT IS AN INDICATOR FOR THE
FEASIBILITY OF REDUCING
ACQUISITION TIME BY R.
WE STUDIED G FACTOR OF OUR COIL.
WE PLACED THE COIL HERE AND
CALCULATED THE G FACTOR AND WE
SAW THE ACCELERATION FACTOR 2.
WE DID NOT HAVE AN INCREASE IN
THE G FACTOR AND WE DID NOT SEE
ANY REDUCED SNR IN THE IMAGES
ANY OF THE 3, 4, OR 5
CENTIMETERS AWAY FROM THE COIL.
HOWEVER, FOR THE ACTIVATION
FACTOR THREE, WE SAW -- AT
4CENTIMETERS.
THESE HERE YOU CAN SEE ARE
ACTIVATION MAPS OF OUR RESULTS.
I THINK THE MOST IMPORTANT
PERMANENT RESULT THAT WE GOT WAS
THE FULL RESPONSE WAS CORRELATED
TO THE TMS INTENSITY.
SORRY, I FORGOT TO SAY WE USE
FOUR INTENSITIES IN THIS STUDY.
TWO WERE OTHER THRESHOLD, ONE AT
THRESHOLD AND ONE UNDER TLOESH
HOLD.
-- THRESHOLD.
NOW WE CAN SAY THERE IS A NEW
STATE OF THE ART.
YOU CAN USE TWO COILS TO HAVE
ONE WITH STIMULATION AND ONE ON
THE OTHER PART.
SO IT IS THEE AXIS TMS COIL
BECAUSE IT CONSISTS OF THREE
COIL, X, THE Y AND THE Z.
# HERE YOU SEE THE AIR COOLING
TUBES, EVERYTHING IS EMBED AND
ATTACHED TO A TUBE THAT IS GOING
BE USED FOR FIXATION.
THEN WE WE USE A SAFETY NET.
THIS COIL HAS BEEN DESIGNED AND
DEVELOPED BY US AND TRISTAN
TECHNOLOGIES AND THE OVERVIEW OF
THE SYSTEM IS PRESENTED HERE.
THE ARROWS FOR THE MULTICHANNEL
TMS SYSTEM AND THE WITHHOLD
HEAD.
SO IN THE LEFT PART OF THE
IMAGE, YOU SEE ALL THREE OF WHAT
THE RF COIL LOOKS LIKE.
THE DESIGN WAS TO HAVE HOLES SO
WE COULD REPLACE THE TMS COILS
DIRECTLY ON THE HEAD.
SO WE NEEDED TO HAVE A VERY
COMPACT MODEL.
SLIGHT INCLINATION OF THE HEAD
TO PLACE ELEMENTS ON THE POST
STIMULATION OF THE HEAD.
FOR THE COIL, WE ARE REPLACING
ALL ELECTRONICS SO DWOENT HAVE
ANY CABLES AROUND TO MESS UP
WITH THE MULTICHANNEL DMS.
THEN WE PLACE THE PREAMPLIFIERS
ON THE SIDE OF THE COIL AND THE
REAR PART.
SO WE HAVE DONE A PERFORMANCE.
WE DID -- WE HAVE CALCULATED THE
SNR PERFORMANCE AND COMPARED
THEM WITH A 32-CHANNEL WITH TWO
COMMERCIAL COILS, 32-CHANNEL
COIL AND 20-CHANNEL COIL AND WE
CAN SEE HERE, I'M SHOWING YOU
THE VALUES FOR THESE SLIDES.
WE ARE CLOSER TO THE PERFORMANCE
OF THE 20-CHANNEL COIL AND
32-CHANNEL COIL BECAUSE WE HAVE
SEEN SOME CASE IN THE SNR WHERE
WE HAVE THE TMS COILS.
I JUST WANT TO POINT OUT WE HAVE
DONE ALL THESE MEASUREMENTS WITH
THE TMS UNITS HERE WHICH ARE
ONLY C COILS.
HERE YOU HAVE THE PILOT IMAGING
CAPABILITIES COMPARED TO THE 32
CHANNEL AND 20 CHANNEL.
WE HAVE SHOWN WE CAN SEE THAT IT
IS VERY SIMILAR TO THE 32
CHANNEL.
MUCH BETTER THAN THE 20 CHANNEL
COIL.
WE CAN USE TWO, THREE, AND FOUR
WITH TWO BY TWO AND THREE BY
THREE WITHOUT THE SNR SIGNAL.
TO SUM UP THIS MULTICHANNEL TMS
PROJECT, WE SAID IT IS VERY
DIFFICULT TO ENSURE THE SAME
TARGET.
IT IS GREAT WORK WITH
MULTICHANNEL TMS IN THE SCANNER.
FOR THAT, WE HAVE BUILT THE TMS
MR COIL.
IT WILL ACHIEVE THE FULL BRAIN
COVERAGE THAT WE NEED AND
PERFORMS CLOSE TO 20-CHAN
RECEIVE ARRAY IT WILL HAVE THE
CAPACITY TO USE HIGH
ACCELERATION FACTORS TO HAVE A
MULTICHANNEL TMS TO USE WITHOUT
MOVEMENT.
SO NOW I'M GOING TALK ABOUT THE
SECOND PROJECT.
SO NOW THERE IS A LOT OF
DEVELOPMENT IN FLEXIBLE COILS,
THE IDEA IS TO HAVE JUST A CAP
TO ALLOW TO USE THE TMS
TOGETHER.
IT IS A CAP.
IT BECOMES EASY TO ADD THE EEG.
THAT IS WHAT WE THOUGHT AND WE
PROPOSED THAT AND IT HAS BEEN
THE RF EEG CAP IS SHOWN IN BLUE.
IT WILL BE ATTACHED TO A EEG
CAP.
WE WILL HAVE 24 CHANNELS.
THINK KNOW KNOW.
>>HOWEVER, YOU'VE SEEN THE
STANDARD FMRI MESSAGE, WE WERE
ABLE TO PERSIST OR TO GET RID OF
THIS ARTIFACTS AND I WANT TO
TELL YOU HOW CLOSE TO THE
TELOMERE THEY WERE CAPTURED AND
ALSO IN THE SIGNAL METHODS THAT
WE USE, SO IN CONCLUSION WE DID
NOT SEE A DEGRADATION OF THE EEG
DATA CAUSED BY [INDISCERNIBLE].
WE ALSO DID AN ASSESSMENT OF THE
QUIEWLT OF THE IMAGE, AND THIS
IS THE CHANNEL, THAT'S WHY YOU
DON'T HAVE FULL BRAIN COVERAGE
YET AND THEN WE PLACE THE
ELECTRODES COMPARED TO HOW WE
DHAINCH TO THE ORIGINAL SNR MAP
AND WE DIDN'T SEE A DIFFERENCE
WHEN WE PLACED THEM HERE.
WE HAVE REPORTED IN 2020 THE P1
EFFECT THAT I WILL TALK ABOUT
THE AT END OF THE PRESENTATION
BUT WE DID NOT SEE ANY NEW
EFFECTS FROM THE--WE DIDN'T SEE
ANY EFFECT SAYS OF THE QUALITY
OF IMAGE.
SO TO SUM UP WHAT WE WANTED TO,A
CHIEF, WE THOUGHT THE RPG
CAPITAL THAT WE WANT TO,A CHIEF
IS HAVE A FULL HEAD COVERAGE,
HIGH VALUE IMAGE FACTORS WITH
LOW DEFECTORS, WE WANT TO HAVE
MORE FLEXIBILITY FOR THIS FMRI
AND EXPERIENCE.
AND WE WANTED TO HAVE THIS
INTERNATIONAL
CLASSIFICATIONICATION WITH EEG.
SO OUR RESULTS HAVE SHOWN THAT
WE DID NOT SEE ANY DETERIORATING
EFFECTS AND WE PLACED THEM ON
THE RF ELEMENTS.
WE DID NOT SEE ANY EFFECTS ON
THE EGFR SIGNAL AND WE DIDN'T
SEE NEW EFFECTS ON THE MR
IMAGING SO WE DO BELIEVE THAT
THE RFEG CAP IS THE SOLUTION TO
OPTIMIZE COMPARING TMS FMRI AND
ELECTROPHYSIOLOGICAL DAT A. SO
NOW LET ME CHANGE A BIT OF THE
TOPICS AND I WANT TO DISCUSS A
BIT INTERACTIONS BETWEEN THE
SYSTEM SYSTEM.
SO I'M JUST GOING TO TALK ABOUT
TMSRA AND WE HAVE 2 VERY STRONG
FACTORS THAT IS THE TMS AND THE
MR, WE ARE PUTTING THEM TOGETHER
IS THEY HAVE TO BE PART OF THE
SAME GROUP.
SO AS YOU KNOW TMS PRODUCES HIGH
FER ENSEL IN SHORT TIMES AND IT
PRODUCES FIELDS UP TO TESLA
RANGES AND THESE ARE GOING TO
LIVE INSIDE OF THE 3 TESLA FIELD
OF THE MR SYSTEM.
THIS IS GOING TO HAVE AFFECT ON
THE OTHER SYSTEMS BECAUSE THEY
ARE BOTH VERY SENSITIVE TO ANY
MAGNETIC FIELD.
SO THIS IS A SUMMARY OF THESE
INTERACTIONS, I HAVE DIVIDED
THEM WITH RESPECT TO WHICH PART
OF THE SYSTEM OF THE MR SYSTEM
IS INTERACTING AND WHICH IS THE
CONSEQUENCE OF THIS INTERACTION
OF THE IMAGE EFFECT OR
SPECIFICITY CONCERN.
SO I'M GOING TO GO INTO DETAILS,
ALL OF THIS.
SO BASICALLY THE EFFECTS, THE
EEIVETS THAT HAVE AN
IMPLICATIONS IN THE IMAGING
QUALITY.
SO AS I SAID BEFORE, WE HAVE
MODULATING SO WE WILL HAVE BIG
GEOMETRICAL DISTORTIONS, WE KNOW
THIS CAN BE CORRECTED BUT UP TO
A CERTAIN DEGREE AND THIS IS
ALWAYS A BIT OF THE QUALITY OF
THE SYNAPSE, HOWEVER IF THESE
DISTORTIONS ARE SO HUGE AND WE
HAVE SIGNATURES NILE VIRUS DROP
OFFS THERE'S NO WAY TO RECOVER
THEM.
SO THE ONLY THANS WE HAVE IS
AUXILIARY IMAGING, WE HAVE TO
USE THE SPACING SO THAT THE
DISTANCE OR THE FACING OF THIS
IS MINIMIZED FOR BOXES FOR
NEIGHBORING BOXES IN THE
DIRECTION.
THE ONLY PROBLEM IS THE FASTER
PRECISION METHODS OF COURSE
REQUIRES VERY HIGH SNR.
SO WE HAVE WHAT WE NEED TO
SPECIALIZE OUR--TO BE ABLE TO
ACQUIRE THE SIGNAL FASTER.
DID EMPLOY NOW, I WANT TO TALK A
LITTLE BIT ABOUT THE TORQUES
THAT WE APPLIED IN THE SCANNER,
THE TMS WILL TRY TO ALIGN TO THE
BUZZIER FIELD AND THIS IS DUE TO
STRONG LARGE FORCES.
WE HAVE A HUGE TORQUE SO WE NEED
TO FIXATE IT OTHERWISE IT'S
GOING TO VIBRATE OR IT CAN BE A
SAFETY ISSUE.
RESPIRATORY SO WE HAVE SOLUTIONS
OUT THERE BY VENDORS AND 1 OF
THE CONSEQUENCES OF THIS
VIBRATION IS THIS HUGE SOUND
THAT IT PRODUCES.
SO BECAUSE THE SOUND IS ALSO
PRODUCED INSIDE THE BOARD, THE
BIEWRD ACTS LIKE A SPEAKER SO
THE PRACTICAL RECOMMENDATION IS
SOME NOISE ABSORBING MATERIAL
LINING FOR THE TORQUE.
AND WE HAVE THE MOTOR
INTERACTION AND THIS WILL HAVE
OF COURSE AN EFFECT ON IMAGING,
RIGHT?
SO THERE IS THIS PAPER, THIS
SEMINOLE PAPER, WE CAN TALK
ABOUT IT FROM 2003 BUT I REALLY
RECOMMEND YOU TO KNOW WHEN YOU
ARE PLACING YOUR PULSES, SO WE
DID THIS WORK WITH THE ISOMERS
AND WE PLACED THE PROCESS IN
DIFFERENT MOMENTS IN THE
SEQUENCE, SO HERE, WE PLACE IT
AT 0, JUST AFTER THE TRIGGER, 20
AND DWNCHT POINTS AND THE MOMENT
I WANT TO CLOSE TO THE RF
POLICIES OF THE IMAGING
GRADIENTS, THEN WE HAVE MADE
SIGNAL DROPS, THIS IS A
MULTIBAND ACQUISITION SO WE YOU
HAVE EFFECTS ON BOTH THE SLICES
THAT ARE APPLIED BUT AS I SAY
THAT RECOMMENDATION, YOU HAVE TO
KNOW WHEN YOU ARE PLACING YOUR
TMS PULSES, YOU HAVE TO KNOW
WHAT IS HAPPENING IN YOUR
SEQUENCE.
THEN I WENT TO REPORT THIS
EFFECT ON THE B1 PLAOF THE AS
DISCUSSED BEFORE, SO BECAUSE WE
ARE THIS HUGE VOLTAGE PULSES RF
PULSES, THIS IS GOING TO INDUCE
A RECURRENCE ON OVER TMS.
AND SO EVEN THOUGH WE MIGHT BE
VERY NICE FOR THE VOLUME CORD,
THESE ARE GOING TO PRODUCE
ANOTHER FIELD WHICH WILL BE
SUPER IMPOSED TO THE B1 PLAZ
MIDS MID.
SO WE'RE GOING TO HAVE
ENHANCEMENTS IN THE CASE OF THE
FIELD, WHICH MEANS WE WILL HAVE
LESS SIGNAL OR LESS ON THESE
REGIONS, THE GOOD NEWS IS THIS
EFFECT IS PRETTY CHAL O, IN IS
VERY FAST WITH RESISTANCE, BUT
IT'S IMPORTANT TO KEEP IT IN
MIND OF COURSE WE ARE THINKING
THIS, WE THINK OF THE EQUAL
CHANGES.
THE GOOD NEWS IS THIS IS THE
INFORMATION THAT WE REPORTED
THIS IN 2020, THE GOOD NEWS IS
THIS IS NOT THE CASE, WE ARE NOT
CHANGING THE DISTRIBUTION
SIGNIFICANTLY, WE SHOWED THAT
ONLY--LESS THAN 1
[INDISCERNIBLE] WAS CHANGED WHEN
THE PLACED THE TMS IN THE
VOLUME.
AND FINALLY--SO THE REFERENCE
ROLE IS JUST A LOOP, IT IS
ALWAYS THE SAME DISTANCE WHICH
CHANGES THE TMS LOOP FROM 1 TO
EACH OTHER.
WE ALSO DID SOME MEASUREMENTS OF
THE NORMALIZED CCNR, WE TOOK OUT
THE BAY 1 SPECIFIC SO THERE'S
OTHER SEARCH SIMULATIONS ARE
HEAR FOR MEASUREMENTS SO WE SAW
A SIGNIFICANT DROP HERE IN THE
MIDDLE OF THE COIL, THIS IS LIKE
[INDISCERNIBLE] FROM THE MSR
CORONAL SLICES SO WE HAVE
IMPORTANT DROPS HERE AND 10 WE
SAW THEM THE SAME MEASUREMENTS.
SO WHAT WE SEE IS THAT THE
EFFECTS OF THIS HAS DEGREES,
INCREASES WHEN THE TMS IS
FARTHER FROM THE
[INDISCERNIBLE].
SO OVERALL EXPLANATION FOR THESE
EFFECTS IS THAT IT SAYS THE
MRSENIOR PRODUCES THE CURRENTOT
DMS AND THESE ARE SUPER IMPOSING
THOSE FOR THE WORK AND WHY WE
SEE THESE EFFECTS.
SO WE WANT TO SHOW YOU WHAT WE
FIND, WE HAD SIMILAR EFFECTS
FROM THE MEASUREMENTS AND THE
SIMULATIONS AND WE CAN SEE THAT
BEFORE THE MEASUREMENTS, 1
CENTIMETER AWAY FROM THE TMS
GROUP.
WE HAVE CHANGES OF ABOUT
15--LESS THAN 15% HOWEVER THE
SIMULATIONS GAVE US HIGH SNR
DROPS SO WE HAVE TO CLASSIFY
WHERE THESE COME FRU BUT IT IS
STILL INTERESTING.
SO I TALK ABOUT THE
SPECIALIZATION HOW WE SAID THEM,
HOW WE ENABLE THE IMAGING, AND
WITH THE ACTIVATION FACTOR 2 I
HAVE FOUND THE WORK THAT WE ARE
DOING HERE AT THE CENTER, WE ARE
TRYING TO ACHIEVE FULL COVERAGE
AND WE WANT TO,A LOW FINALLY THE
TRACKING OF THE HOT SPOTS IN
CASE THE MOVE SAYS AND SO THIS
IS A MULTIINTEGRATED SYSTEM AND
THEN I HAVE PREPERRED THE RFEG
CAP WHICH WILL DO TD FULL
COVERAGE AND ENHANCE THE
FLEXIBILITY OF THE EXPERIMENTS
AND INTEGRATE EEG AND OF COURSE
IF IT'S MULTITALENTED EMS
FOR--FOR EQUAL USE THAT ARE
FOCUSING OF THE HOT SPOT IN CASE
OF A PATIENT MOVEMENT AND THEN I
DISCUSSED THE INTERACTIONS, I
WANT YOU TO TAKE THEM INTO
CONSIDERATION, THERE IS WORK TO
BE DONE AND BE ANALYZED IT WILL
BE GREAT IF WE KEEP WORKING IN
THIS FIELD.
AND WITH SLIDE I WANT TO THANK
MY COLLABORATORS, OUR TEAMERS,
OUR INDUSTRIAL COLLABORATORS AND
I'M THANK YOU FOR YOUR ATTENTION
AND I AM HAPPY TO ANSWER YOUR
QUESTIONS.
[ APPLAUSE ]
>>I MIGHT HAVE A QUICK SILLY
QUESTION, BUT THANK YOU IT WAS
INFORNLAATIVE FOR ME, SO THE
PURPOSE OF THE INTEGRATION OF
EEG IS IT FOR THE NEUROFEEDBACK
PURPOSE OR TO DETECT OR TO
DETECT--
>>IT'S NOT LIKE THE CLOSED LOOP
DIRECTION, LIKE WHAT WE WERE
TALKING ABOUT THE CLOSED LOOP,
DUAL CLOSED LOOP DIRECTION SO
WHAT WE WANT TO DO IS WITH THE
EEG, KNOW WHEN WE HAVE APPLY THE
TMS AND EVERYTHING WE WANT TO DO
EVERYTHING WITH THE SCANNER, SO
WE WANT TO KNOW WHERE WE ARE
APPLYING THE TMS, AND WITH THE
FMRI AND WITH THE EEG ACCIDENT
WE WANT TO FIGURE WHEN THE TMS
PULSES AND WE WENT ON TO SEE IF
THERE'S A DIFFERENCE, BASED ON
FMRI ACCURACYS THAT WE OBTAIN.
>>IS IT CONVENTIONAL EEG?
>>WELL IT'S CONVENTIONAL,
COMPATIBLE EEG, BUT YES, THE
WHYED IS TO DO THIS FOR ALL
THESE ARTIFACTS AND REMOVE
EVERYTHING ONLINE, AND GIVE IT
THE FACE WITH--WHATEVER FEATURE
WE WANT TO DEFINE, IT'S GOING TO
BE USED TO TRACK OR TO TRIGGER
THE TMS AND THEN SEE IF WE CAN
SEE DIFFERENCES.
>>THANK YOU.
>>YES.
NYES, SO I HAVE--DO YOU PLAN ON
FOR THE RFEEG HEAD CAP HAVING
SHIMMING CAPABILITIES TO TRY TO
HELP SOME OF THE [INDISCERNIBLE]
IN HOMOGENERATED AITY ISSUES?
FOR EXAMPLE, THOSE COIL VS A
UNINTERRUPTED PATH FOR DC
CURRENTS SO I WONDERING IF YOU
HAVE--
>>NO, WE HAVE NOT PLANNED THEM
WITH THIS, WE HAVE NOT PLANNED
THEM WITH THIS, THANK YOU.
>>VERY IMPRESSIVE.
CAN YOU ELABORATE A LITTLE BIT
ABOUT [INDISCERNIBLE], CHANNEL,
IT LOOKS LIKE MAYBE HOW MANY?
NWE WILL HAVE 60 ELEMENTS AND
EACH OF THESE COILS ARE 3 COILS
WHICH ARE THESE 3 ACCESSING TO
THE COILS, I WENT FAST THROUGH
EVERYTHING, IT'S A LOT OF
INFORMATION AT ONCE BUT EVERY
STIMULATION UNIT, I WANT TO CALL
IT LIKE THAT BECAUSE OTHERWISE
WE HAVE TOO MANY COILS AND THEY
ARE 16 OF THEM ALL OVER THE
HEAD, I CAN SHOW YOU THE
FIGURES.
>>CAN YOU STEER THEM?
LIKE STEER THE STIMULATION--
>>WHAT WE WANT TO STEER IS THE
INDUCING FEED, WE DON'T WANT TO
MOVE THEM IN THE SCANNER.
YEAH, WHAT WE ARE GOING TO
CHANGE IS THE CURRENTS THAT WE
ARE PASSING THROUGH THE
ELEMENTS.
THAT'S WHAT WE ARE GOING TO
STEER BUT WE DON'T WANT TO MOVE
THEM.
>>HERE THAT'S THE BEST SHOT.
THESE ARE THE STIMULATION UNITS.
HERE WE ARE JUST PLACING SOME
PLACE HOLDERS, THESE ARE ALL
SEQUENCED TO DO THE PERFORMANCE.
WE REALIZE THAT PLACING THE
ACCESS COILS DELIVERS THE SAME
INFORMATION FOR THE SNR
PERFORMANCE.
THAT'S WAWE DID BUT THE FINAL
SYSTEM IS GOING TO LOOK LIKE
THIS.
HERE IT IS.
THERE ARE 16 OF THEM, THAT'S WHY
THERE ARE 16 HOLES AND YES, THE
ELEMENTS GO THROUGH IT.
THROUGH THE RF HOLES ARE REALLY
SURROUNDING THEM.
DO YOU NEED AN INDIVIDUAL TMS
CAPACITIOR FOR EACH CHANNEL,
EACH 1 HAS A STIMULATOR, IT'S A
48 SIMULATOR RUN, THAT'S TRUE.
WE SIT EVERY SINGLE 1, IT'S A
HUGE SYSTEM, YEAH.
>>THANKS.
>>I KNOW WE'RE RUNNING A BIT
LATE SO WE CAN APPROACH THE
SPEAKER AFTERWARDS BUT I DON'T
KNOW THE FORMAT OF THE PROFFERED
PAPERS BUT WE'RE OVER TIME
LUCIA, THANK YOU VERY MUCH.
[ APPLAUSE ]
ALL RIGHT AS JULIAN GETS SET UP
HERE ON THE TALK TWISTED PAIR
RECEIVER COILS FOR A COMBINED
TMS/EEG/FMRI SYSTEM.
>>THANK YOU FOR THE
INTRODUCTION.
TODAY I WILL TALK ABOUT THE WORK
I'VE DONE WITH THE RECEIVER
COILS THAT CAN HOPEFULLY BE USED
FOR SUCH A COMBINED SYSTEM.
SO HERE ARE MY DECLARATIONS.
SO AS MULTIMODAL IMAGING
TECHNIQUES BECOME MORE COMMON AS
WE'VE SEEN IN MANY OF THE
PREVIOUS TALKS, THE GET FILLED
WITH LESS AND LESS SPACE FOR
LARGE SCALE RECEIVER RATES BUT
THERE'S A CLEAR NEED TO HAVE
THIN AND FLEXIBLE CLEAR ELEMENTS
AS YOU BUILD THOSE LARGE
RECEIVER COILS IN THESE VERY
TIGHT FITTING AREAS.
SO FOR EXAMPLE WHEN YOU WANT TO
COMBINE EMS WITH EEG/FMRI,
BECAUSE AS WE'VE SEEN WE'VE USED
THIS PICTURE, IT'S LIMITING WHEN
YOU HAVE THIS BIG BULKY
COMMERCIAL COIL AND WITH
SOMETHING LIKE A CONFIRMAL HEAD
KOIM, YOU CAN UNLOCK THE FULL
POTENTIAL OF RANGE OF MOTION OR
THAT TMS COIL.
AND 1 OF THE ADDED BENEFIT
SYSTEM THAT BECAUSE WE TRY TO
MAXIMIZE FOR THE PROXIMITY OF
THE MAXIMIZE THE PLACEMENT OF
THE TMS COIL, WE ALSO GET SNR
BENEFITS BECAUSE AS RECEIVER
COILS GET CLOSER TO THE BODY,
YOU DO GAIN SNR AND THAT MIGHT
BE BENEFICIAL IN THE SENSE THAT
YOU GAIN BETTER DIAGNOSTIC
QUALITY IMAGES BY JUST
INCREASING--ESSENTIALLY GETTING
CLOSER TO THE IMAGING AREA YOU
WANT TO IMAGE.
AND I WANT TO SHINE SOME LIGHT
ON SOME OF THE PREVIOUS WORK
THAT'S BEEN DONE IN COILS SO
HERE YOU SEE SOME SCREEN PRINTED
RECEIVER COILS THAT HAVE A LOT
OF BENEFIT AND A LOT OF
IMPROVEMENTS FOR PEDIATRIC
IMAGING.
THERE'S ALSO BEEN A LOT OF GREAT
WORK IN ESSENTIALLY USING IT ON
ELASTIC TUBES TO BUILD THESE
VERY THIN STRETCHABLE AND
ELASTIC RECEIVER COILS OR
LASTING BENEFIT OR ANYTHING OF
JOINTS.
AS WE'VE SEEN IN THE PREVIOUS
TALK, THERE'S ALSO BEEN A LOT OF
WORK ON THESE COAXIAL COILS THAT
USE THIS COAXIAL TRANSMISSION
LINE THAT'S FLEXIBILITY TO
ESSENTIALLY ACHIEVE A VERY FIN
AND FLICKSIBLE RECEIVER COIL AND
THEY'VE BEEN SHOWN FOR HANDLING
THE GLOVER AWAY AND RF/EEG CAP
EVEN WITH ALL THE INTERFACE
ELECTRONICS.
AND THERE'S ALSO THE EEG AIR
COILS THAT USE THESE INTEGRATED
CAPACITIVE WIRES AND
[INDISCERNIBLE] AMPLIFIERS TO
ACHIEVE A VERY THIN AND
FLEXIBILITY RECEIVER COIL THAT
ALSO HAS VERY ADEQUATE FINE
TUNING PERFORMANCE.
SO KIND OF TAKING INSPIRATION
FROM THE COAXIAL COILS AND THE
AIR COIL, I ESSENTIALLY DESIGNED
A TWISTED PAIR RECEIVER COIL
THAT IS VERY THIN AND
FLEXIBILITY CAN AND HAS THE
IMAGING TO BE USED IN THIS
SYSTEM.
SO IN WORK I AIM TO COMPARE THE
TWISTED PAIR COIL TO A COAXIAL
AND STANDARD COIL IN TERMS OF
IMAGING PERFORMANCE AND ALSO IN
TERMS OF SAFETY TO INSURE THAT
WE CAN ACTUALLY PLACE THIS COIL
IN YOUR PATIENT AND AFTER A
VERIFYING ITS PERFORMANCE AND
SAFETY, PROCEEDED TO BUILD A 15
CHANNEL HEAD ARRAY THAT HAS FULL
COVERAGE OF THE BRAIN AND CAN
EVENTUALLY BE MODIFIED TO THE
ELECTRODES AND BE COMBINED IN A
SYSTEM, BUT TO GET TO A SPECIFIC
COIL, YOU NEED TO START WITH
PTFD TWISTED WIRE.
SO IF YOU KNOW A LITTLE BIT
ABOUT ELECTRICAL ENGINEERING IF
YOU HAVE TBO PLATES AND PUT A
DIALETTIC BETWEEN THEM, YOU GET
A CAPACITY, IF YOU DID IT WITH A
WIRE, YOU GET A FLEXIBLE
CAPACITIOR AND THEN YOU CAN FORM
IT INTO A LOOP AND TURN IT INTO
A CANNED WHAT AND YOU MAKE 1 CUT
WHERE YOU INTERACT THE COIL WITH
THE SCANNER AND ADD THE
INTERFACE ELECTRONICS AND
ANOTHER GAP AND OPPOSING WIRE
AND THIS ALLOWS IT TO BECOME
RESIDENT AND SENSITIVE TO THE
MOTOR INDUCED SIGNALS CAUSED BY
THE SPINS.
WITH ALL THESE ELEMENTS,
POTENTIALLY ONLY TAKE UP 1 PBT
28-MILLIMETERS OF SPACE, WE
STILL HAVE WORK TO DO TO GET THE
ELECTRONICS TO GET A LITTLE BIT
THINNER.
SO HOW ABOUT SNR PERFORMANCE, DO
THESE COILS PRODUCE WELL, 1
METRIC WIEWSED TO USE TO SEE IF
IT WORKED WELL, WAS THE RATIO
QUALITY FACTOR WHEN THE COIL IS
LOADED AND UNLOADED AND WE WANT
THIS RATIO TO BE I GREATER THAN
2 AS THAT KIND OF SHOWS THAT THE
SIGNAL THAT WE RECEIVE IS BODY
NOISE DOMINANT.
SO THE RATIO IS LOTS GREATER
THAN 2, THAT MEANS MOST OF THEM
IN THE SIGNAL IS COMING FROM THE
BODY, AS YOU SEE HERE THE
TWISTED PAIR RECEIVER COIL
BECAUSE OF IT'S LOW DIALECT
RICK, RECEIVES A LOADED TO KEY
LOADED RATIO THAT'S GREATER THAN
THAT OF A COAXIAL COIL DUE TO
HAVING INS TRINSIC LOSS.
SO HERE WE TAKE A SINGLE COIL
IMAGE AND WE TACK A PROFILE AND
LOOK AT THE SNR AND WE SEE THAT
THE TWEOF THED COIL CAN FORM
VERY WELL COMPARED TO CONTROL
COIL AND WE SEE A LITTLE BIT OF
REDUCTION IS NSNR PERFORMANCE
DUE TO ADDED LOSSES AND WHAT
ABOUT THE FULL SAFETY, DOES IT
COIL--CAN YOU PUT THIS NEAR A
PATIENT WELL, YOU CAN, SO HERE
WE SO THAT THE TUNING
PERFORMANCE HAD IS DONE BY
ACTIVELY TUNING, FROM THE 2
STAINS WE SEE AT LEAST 30 DB
ISOLATION AND THIS COULD BE
BETTER BUT WHEN WE LOOK AT D1
MAPS WE SEE THAT A COIL ON A
PHANTOM WE DO SEE ANY VERYIATION
IN THE CLIPPING.
AND WHAT ABOUT HEELTING SO THESE
GET HOT, WELL WE PUT 15 OF THEM
IN AN ARRAY AND THEN WE RAN A
HEAT SEQUENCE UNDER THE SCANNER
AND WE DID NOT SEE ANY
SIGNIFICANCE OR HEAT SPOTS EVEN
AFTER THIS VERY INTENSE OF HEAT
SEQUENCE.
SO WITH ALL THAT IN COMBINATION,
WE DECIDED TO PUT SOME OF THESE
TWISTED PAIR ELEMENTS ON A NOMEX
SKITTOMA CAP TO FORM THIS 15
CHANNEL HEAD ARK RAY.
AND IF YOU CAN SEE HERE ON A
PERSON IT FITS COMFORTABLE, VERY
THIN BUT YOU SLEEP APNEA AND
OBESITYY A POTENTIAL PROBLEM
HERE, THERE'S ALL THIS WIRING
HERE SO WITH THIS CURRENT
INTEGRATION, WE CAN'T PASS A
COIL OVER IT BUT IF YOU WRAP THE
COILS MORE LIKE BRAIDS INSTEAD
OF A PONY TAIL, CAN YOU GET THE
FULL RANGE OF MOTION FOR THE TMS
COIL.
HERE WE LOOK AT SNR DATA SO THE
15 CHANNEL ARRAY, CAN YOU SEE
HAS A 2 TIMES SNR GAIN AT THE
PERIPHERIES AND WE SEE IT HAS A
NOISE CORRELATION THAT'S BETTER
THAN THE E, G HEAD COIL AND WE
WERE ABLE TO ACHIEVE THIS REALLY
GOOD NOISE CORRELATION WITHOUT
HAVING TO PUT THE AMPLIFIER SO
CLOSE TO THE ACTUAL COIL.
AND HERE ARE SOME 3D T1 IMAGES
WE TOOK ON THE SCANNER WITH WITH
2 BY 2 ACCELERATIONING LEADING
TO 2 MINUTES AND 40 SECONDS.
SO TO CONCLUDE FUTURE WORK, JUST
15 CHANNEL ARRAY IN SNR AND SNR
AND ALSO TAKEN--THEY TAKE THE
MAPS THAT THE COIL WILL MAINTAIN
SNR EVEN UNDER ACCELERATED
CONDITIONS.
WE ALSO HOPE TO INTERFERON-GAMMA
T-CELLUALLY IMPLEMENT THE
ELECTRODES OF THIS,A RAY AND DO
FEASIBILITY AND SAFETY TESTING
WITH EMS AND EEG TO INSURE
PROPER SAFETY.
SO I WOULD LIKE TO ACKNOWLEDGE
MY ADVISORS, MY MENTORS AND MY
UNDERGRADUATE STUDENTS WHO HAVE
BEEN EXTREMELY VITAL IN THIS
WORK.
THANK YOU.
[ APPLAUSE ]
>>ALL RIGHT, LET'S LIMIT IT TO
1 QUESTION PERSPEAKER SINCE
WE'RE WAY OVER TIME PLEASE?
>>ONE QUESTION, ACTUALLY DID
YOU HAVE A TO INVESTIGATE OR
CONFIRM THE PRANCE OF THIS COIL
IN EMERGING ITS OF MUTUAL OR
DECOUPLING.
JUST BY USING MORE NOISE
AMPLIFIERS OR MECHANICAL ARRAY
OR DID YOU HAVE A CHANCE TO
COMPARE YOUR COIL WITH THE
COAXIAL COILS.
>>THAT'S A GOOD QUESTION, AND I
HAVE A ABSTRACT FROM THE
[INDISCERNIBLE] AND WHAT I
SHOWED IS AT LEAST IF YOU USE
THE SAME WORK AND THE SAME
AMPLIFIER I DID NOT SEE A
DIFFERENCE IN THE DECOUPLING
PERFORMANCE BETWEEN THE TWISTED
PAIR AND THE COAXIAL.
>>THANK YOU.
NEXT SPEAKER READY?
[ APPLAUSE ]
>>ALL RIGHT, THANKS EVERYONE.
I HAVE NOTHING TO DECLARE, SO
STROKE IS THE LEADING CAUSE OF
ADULT DISABILITY AND THE
RECOVERY OF MOTOR FUNCTION IS
IMPORTANT FOR GETTING BACK TO
ACTIVITIES OF DAILY LIVING BUT
PREDICTING MOTOR STROKE RECOVERY
IS ACTUALLY REALLY, REALLY
DIFFICULT FOR AN INDIVIDUALIZED
PARTICIPANT AND ACCURATE
ROGINOSEIS WOULD ENABLE FOR THE
REALISTIC GOAL SETTING AS WELL
AS MORE EFFICIENT ALLOCATION OF
CLINICAL RESOURCES.
SO IN ORDER TO SORT OF ADDRESS
THIS, CATHY AND WINSTON IN 2012
CAME UP WITH THE PREP ALGORITHM
WHICH PREDICTS THE POTENTIAL FOR
UPPER EMILY MOTOR RECOVERY SO
THEY FIRST TOOKA A BEHAVIORIAL
SCORE AND IF THAT PARTICIPANT
GOT ABOVE A CERTAIN THRESHOLD
THEY PREDICTED A COMPLETE
POTENTIAL FOR UPPER LIMB
RECOVERY.
IF THEY WERE BELOW A CERTAIN
BEHAVIORIAL THRESHOLD THEY WENT
TO TRANSCRANIAL MAGNETIC
STIMULATION TO SEE IF THEY COULD
ELICIT A MOTOR EVOKED POTENTIAL.
AND IF THEY WERE ABLE TO, THEY
PREDICTED THERE WOULD BE A
NOTABLE UPPER LIMB RECOVERY AND
IF THE MEP WAS ABSENT, THEY WENT
TO MRI AND PREDICTED EITHER
LIMITED OR NO RECOVERY.
BUT WHAT IF, THE APPARENT
ABSENCE OF AN MEP DOES NOT MEAN
THEREYA A LACK OF REHABILITATION
PROTENTIA AND COUPLED WITH THAT
BECAUSE WE'RE TALKING ABOUT
CHRONIC STROKE AND LESIONS, WHAT
IF THE CHRONIC STROKE LESION IS
NOT HOMOGEANIOUS AND THERE IS IN
FACT TISSUE THERE THAT WE CAN
STIMULATE?
SO I WILL SHOW YOU A CASE REPORT
STUDY WHERE WE DEMONSTRATE THAT
NEURAL SUBSTRATES OF
REHABILITATION DO EXIST IN THE
MEP AND IN THE ABSENCE OF A
SIGNAL AND 1 WEIGHTED T-IMAGE.
SO HERE'S MY CASE REPORT ON 55
YEAR-OLD MALE POST STROKE AND
PRESENTED WITH AFACIA AND UPPER
AND LOWER MOTOR EXTREMITY PIM
PAIRMENT.
HERE YOU CAN SEE THE LESION ON
THE T21 AND THE T28 IMAGES BUT
BEFORE I GO INTO THE CASE STUDY
REPORT, I WOULD LIKE TO TELL YOU
ABOUT TIGER MRI, IT'S A NEW WAY
TO LOOK AT CHRONIC STROKE
LESIONS CROSS LINKING IF YOU
LOOK AT THE T1 WAVE IMAGE, THE
LESION IS MAINLY DARK AND IN THE
IMAGE FOR YOU BUT IF YOU IF YOU
CONTRAST BETWEEN THESE IMAGES
YOU GET THIS TIGER SCORE AND I
WILL ORIENT YOU AND I WILL CALL
KAFITATION SO THESE ARE CSF
FILLED SPACES THOSE ARE BOTH
DAMAGED TISSUES SO THERE'S NO
REAL ISSUE THERE.
SO I WANT TO ORIENT YOU TO THESE
BLUE AND GREEN REGIONS THAT I
WILL CALL KAFITATIONAL AND I
WILL DEFINE THOSE AS DAMAGE
TISSUE WITHIN THE LESION BUT
THEY MAY STILL CONTAIN LIVING
CELL BODIES AND THOSE ARE THE
AREAS THAT I THINK WE CAN TRY TO
STIMULATE WITH TMS AND OTHER
NEUROMODLATTORY TECHNIQUES, EVEN
IN THE CHRONIC STROKE LESION TO
TRY AND ILLICIT A RESPONSE AND
LET'S SEE WHAT UPONS.
SO IF WE COME BACK TO THE CASE
REPORT STUDY YOU CAN SEE IN THE
T1 WEIGHTED IMAGE IT'S VERY DARK
AND INSIDE THERE IS QUITE A BIT
OF KAFITATION IN THIS
PARTICIPANT BUT THERE ARE
ISLANDS OF POTENTIAL TISSUE
RIGHT SO IF WE ZOOM IN ON THE
SAGITTAL AND I WILL BASICALLY DO
TMS ASSESSMENTS SO I WILL TARGET
THE M1 AREA.
AND YOU CAN SEE HERE THAT M1
AREA WOULD BE KIND OF IN HERE,
THERE'S NOT MUCH OF ANY SIGNAL
THERE ON THAT T1.
IF YOU LOOK AT THE TARGET
IMAGES, YOU CAN SEE THIS LITTLE
HOOK.
THAT'S WE WILL TRY TO TARGET DP
IF WE LOOK AT PROFUSION IMAGING
THAT IS INDEED PROFUSED.
SO WE ARE GOING TO COLLECT TMS
DATA BOTH SINGLE AND PAIR
PULSEMENT AND WE WILL CONTRACT
THAT DURING LIPSE AND
[INDISCERNIBLE].
SO WE WILL DO THAT DURING THE
ENGAGEMENT OF THE HAND SO EVEN
THOUGH THEY HAD A CHRONIC STROKE
LESION WITHIN M1, THEY WERE ABLE
TO GRAB THE HAND, IT WAS
DIFFICULT, WE HAD TO TAKE
SEVERAL BREAKS BUT WE DID IT
FROM THE LESS AFFECTED AND
AFFECTED HANDS.
SO LET'S FIRST LOOK AT THE
NONLESIONED HEMISPHERE.
SO IF WE STIMULATE ON THE
NONLESION HEMISPHERE WITH THE
SINGLE PULSE, WE WILL SEE A NICE
BIG MEP AND THAT'S WHAT WE GET
AND I WILL MARK THE AMPLITUDE
BASED WITH THESE RED BARS.
SO IF WE THEN CONDITION THAT MEP
FROM A PULSE FROM THE LESIONED
HEMISPHERE, WE DO STILL GET THE
REDUCTION OF MEP AMPLITUDE AND
IF WE DO WITH A LEAKY
EXPERIENCE, EVEN GREATER
REDUCTION, AND IF WE KIND OF
DISPLAY THAT GRAPHICALLY, HERE'S
SINGLE PULSE, AND WE OBSERVE
THAT THE LESIONED HEMISPHERE ON
TO THE NONLESIONED HEMISPHERE
DOES REDUCE THE HEMISPHERE AND
WE WILL INTERPRET THAT IS FROM
THE LESIONED HEMISPHERE TO THE
NONLESIONED HEMISPHERE.
SO SOMETHING STILL EXISTS.
NOW IN YOUR MIND SWAP THAT TMS
CONFIGURURATION, NOW WE WILL TRY
TO STIMULATEOT LESIONED
HEMISPHERE, WE WILL TRY TO
CONDITION FROM THE NONLESIONED
HEMISPHERE, ALL RIGHT, SO, IF
WE--IF THERE WERE AN INTACT
BRAIN, WE WOULD EXPECT A NICE
BIG MEP RESPONSE RIGHT HERE, WE
DON'T SEE IT, RIGHT?
BUT I WOULD ARGUE THAT WE
ACTUALLY DO NOT SEE A COHERENT
MEP AND IN FACT IF WE PULL THIS
APART, TRIAL BY TRIAL YOU CAN
SEE THAT THERE'S POTENTIALLY A
VOLLEY OF MEPs THAT ARE NOT
LINING UP IN TIME, LIKE WE WOULD
EXPECT IN A NORMAL HEALTHY
PARTICIPANT.
SO COULD THAT VOLLEY OF MEPs
REALLY INDICATE THAT THEREY A
DNCH CONTRIBUTION FROM DIFFERENT
MOTOR UNITS THAT HAVE DIFFERENT
ARK MOUNTS OF DAMAGE.
POTENTIALLY.
SO IF WE THENNADAD IN A
CONDITIONING PULSE FROM THE
NONLESIONED HEMISPHERE INTO THE
MIX, CAN YOU SEE ACTUALLY NOW
THOSE MEPS ARE STARTING TO LINE
UP SO CAN YOU START TO SEE SOME
SORT OF AVERAGE MEP RESOLVE, AS
WELL AS A SILENT PERIOD.
AND IF WE DO THAT SO IF WE PULL
THAT APART, YOU CAN SEE THAT
THOSE MEPs, THAT VOLLEY OF
MEPs THAT WERE ALL OVER THE
PLACE IN TIME, NOW KIND OF START
TO LINE UP AND THEY'RE FOLLOWED
BY A SILENT PERIOD BUT WE STILL
KIND OF HAVE THAT VOLUME OF
MEPs AS WE GO THROUGH TIME AND
THE SAME THING HAPPENS WITH
LIHI, AGAIN WE GET THE AVERAGE
MEP AND POTENTIALLY A LONGER
SILENT PERIOD.
AND IF WE PULL THAT APART, SAME
STORY, WE HAVE THE MEPs NOW
LYNNING UP BUT STILL A VOLLEY OF
MEPs AS WE GO THROUGH TIME.
SO OUR OBSERVATION IS THAT THAT
CONDITIONING PULSE FROM THE
NONLESIONED HEMISPHERE CAUSES AN
MEP AND THE SILENT PERIOD TO BE
DETECTED FROM THE LESION
HEMISPHERE, AND WE'RE GOING TO
INTERPRET THAT AS THERE'S INHIB
THORS THORY PROJECTIONS FROM THE
CONTRACT TO THE HEMISPHERE,
THERE'S INHIBITORY PROJECTIONS
FROM BOTH HEMISPHERES EVEN IN
THE PRESCRIBING ENCYCLOPEDIAS OF
THAT LESION, SO WE WENT TO
RESTING STATE TO REALLY SEE, CAN
WE LOOK AT THIS SYSTEM, EVEN
THOUGH IT'S BROKEN.
AND ON THE BOTTOM HERE IS
THE--WE SEE IT FROM THE SAME
REGIONS THAT WE DID THE TMS
STIMULATION AND ON THE BOTTOM
HERE IS THAT IS A COHORT OF 17
HEALTHY OLDER ADULTS AND YOU CAN
SEE IF YOU SEE FROM IPSE, YOU
GET A NICE HOMOLOG FROM THE
OTHER HEMISPHERE, SAME WITH
CONTRA.
WE DO NOT SEE THAT IN THE CASE
STUDY REPORT.
RIGHT?
SO THAT EXPECTED M1 TO M1
CONNECTIVITY IS NOT THERE EVEN
THOUGH WE'RE GETTING THAT TMS
INHIBITORY RESPONSE WITH THE
PARAPULSE EXPERIMENT.
HOWEVER, WE ALSO SEE THAT EACH
SEED IS CONNECTED TO--WE THEN
GET BACK A SIGNIFICANT TOPIC
ACTIVITY SO THE WAY WE WILL
INRETINAL LOCATION THIS IS THAT
THE M1 SMA M1 FUNCTIONAL
CONNECTIT IS PROBABLY AS
ALTERNATE ROUTE FOR THAT
INHIBITORY PROJECTION THAT WE'RE
SEEING IN THE TMS EXPERIMENTS.
SO IN SUMMARY I HOPE I CONVINCED
YOU IT IS FEASIBLE TO APPLY TMS
OVER THE CHRONIC STROKE LESION,
THAT MRI CAN GUIDE THE LOCUST OF
STIMULATION USING TARGET AND
BLOOD FLOW MAPS.
IN THIS CASE STUDY REPORT WE
SHOWED BI-DIRECTIONAL INHIBITORY
PROJECTIONS BETWEEN NONLESION M1
AND EVEN THOUGH THE PARTICIPANTS
DO NOT HAVE A DETECTABLE
COHERENT MEP IN THE PRESENCE A
CONDITIONING STIMULUS,A A
COHERENT PERIOD FOLLOWED BY
ANOTHER COULD BE DETECTED AND
FINALLY RESTING STATE FMRI
DETERMINED THAT THE M1-M1
FUNCTIONAL CONNECTIVITY IS
LIKELY ROUTED THROUGH SMA AND
THANK YOU FOR YOUR ATTENTION AND
I'M HAPPY TO TAKE ANYY REQUESTS.
[ APPLAUSE ]
>>VERY INTERESTING TALK CAN YOU
TALK MORE ABOUT HOW THE TIGR WAS
CALCULATED?
>>YEAH, SURE IT IS, I CAN SHOW
YOU IN THE BREAK, WE HAVE AN
ENTIRE PAPER ON THAT BUT IT'S
LITERALLY A DIVISION OF TQ
DIVIDED BY T1.
SO INSTEAD OF THE MILEIN MAPS
THAT THEY'VE BEEN DOING WHICH IS
T1 DIVIDED BY T2, WE'RE DOING T2
OVER T1 AND JUST LOOKING AT TD
LESION AREA AND YEAH, HAPPY TO
DISCUSS MORE.
>>AWESOME THANK YOU, WE CAN
ONLY DO 1 QUESTION, WE'RE WAY
OVER TIME.
SORRY, PLEASE APPROACH THE
SPEAKERS AFTER.
NEXT WE HAVE DR. FEI DU FROM
HARVARD MED ON MOLECULAR
MECHANISMS UNDERLYING DISRUPTED
BRAIN CIRCUITS, MULTIMODAL
NEUROIMAGING AND BRAIN
STIMULATION APPROACHES.
>>HELLO EVERYBODY, I NO
FINANCIAL ISSUES TO REPORT SO
HERE IS MY TITLE: MOLECULAR
MECHANISMS UNDERLYING DISRUPTED
BRAIN CIRCUITS MULTIMODAL
NEUROIMAGING AND BRAIN
STIMULATION APPROACHES.
EACH PART HAS ITS OWN FUNCTION
IT'S ALSO DEEP LINE OF WORK, WE
WORKED TOGETHER WE COULD START
BY STRUCTURAL MG OR
[INDISCERNIBLE] FOR COLLECTIVE
DNS.
REALLY THIS BRAIN SECLUDED
PROGRAM HAS BEEN A LOT OF
NEUROBRAIN DISORDERS BUT
[INDISCERNIBLE], HOW CAN WE
TREAT THIS?
THIS IS MY IMPORTANT
PRESENTATION TO DATE.
SO HERE I GIVE AN EXAMPLE, 2
NETWORK, 1 IS DESIGN NETWORK AND
1 IS [INDISCERNIBLE] NETWORK WE
JUST PROCEED FOR THE WHOLE BRAIN
MAPPING YOU CAN SEE 1 COLOR THAT
WENT FROM [INDISCERNIBLE] AND
THE OTHER COLOR IS THE WORK.
SO THIS IS [INDISCERNIBLE] AND
WE CALL THIS THE
ANTICORRELATION, BUT THIS IS A
LOT OF NEURAL DISORDERS,
ANTICORRELATION IS CLEAR AND BY
DISORDER REALLY YOU CAN FIND THE
ADR RESEARCH, TOO, THIS IS WHAT
WE CALL CANNED WHAT, ANOTHER IS
THE TEST FOR [INDISCERNIBLE]
HERE, WE CO ACTIVATION AND
DEACTIVATION, CANNED WHAT FOR
WORK IN MEMORY BECAUSE WE ARE
VERY INTERESTED IN A
[INDISCERNIBLE] BRAIN DISORDERS.
YOU CAN SEE THERE HAS BEEN FOR
MY SUMMARY [INDISCERNIBLE] COLOR
THAT'S WHY THE--ACTUALLY THAT'S
FROM THE [INDISCERNIBLE], AND
SOME REGION EXCITED, ACTUALLY
[INDISCERNIBLE] LIKE HERE, LIKE
REALLY, WE TALK ABOUT THIS AND
DIVISION, DEACTIVATION WHEN WE
[INDISCERNIBLE] STARTING, USE
HERE OR PEOPLE JUST USE
[INDISCERNIBLE].
THAT'S [INDISCERNIBLE], PEOPLE,
PEOPLE WILL GET THIS ACTIVITY
AND [INDISCERNIBLE], SO HERE WE
HAVE THESE MDR RECEPTOR
ANTAGONIST SO THIS
NEUROTRANSMITTER [INDISCERNIBLE]
SOMETHING IN THIS CASE, SO THIS
IS THE PICTURE HERE IS BASED ON
MOLECULAR [INDISCERNIBLE] RESK
OF PATIENT.
SO IT'S REALLY COMPLICATED STORY
BUT PEOPLE DON'T KNOW EXACTLY
THE MECHANISM BUT BASE CAN BE
DISFUNCTIONING AND MDR HYPER
FUNCTION [INDISCERNIBLE] AND
RESEARCH NEEDED TO
[INDISCERNIBLE] SYNAPSE HERE.
SO HERE JUST RUNS THE
SPECTROSCOPY, WE CAN SEE
[INDISCERNIBLE] BUT USUALLY THIS
DOSE METER KD--SALLY IS
DIFFICULT TO MEASURE BECAUSE OF
THE SENSITIVITY ISSUE, SO HERE I
SHOW YOU JUST CHOOSE 2, 1 IS
[INDISCERNIBLE], MPFC AND
ANOTHER EXAMPLE IS DLPFC, AS
SHOWN HERE.
SO HERE YOU SEE AN INTERESTING
ANOMALY, [INDISCERNIBLE] THAT'S
IN THE SAME REGION, YOU KNOW
SAME REGION, THIS IS THE
CITATION, SO THEY CAN SAY IT HAS
A HIGHER FUNCTION HERE, BUT THE
VERY INTERESTING HERE, WITH THE
ASSOCIATE INVITED FOR LONG
DISTANCE BETWEEN [INDISCERNIBLE]
BECAUSE THIS LOCAL THEN PROJECT
TO ANOTHER [INDISCERNIBLE] HERE.
BUT INTERESTINGLY, CAN YOU SAY
THIS PATIENT, THIS RELATIONSHIP
CORRELATION BY THE MPFC, AND
DLPFC, THIS [INDISCERNIBLE]
HERE.
SO NOW, YOU KNOW PEOPLE KNOW
BRAIN [INDISCERNIBLE] BROKEN, WE
WANT TO RECOMPUTE THIS
COLLECTION, BUT REALLY WE
MEASURE ABOUT WHICH TARGET FOR 1
STABILIZE AND WHAT'S IT IT'S
WORK IS IT CITATION, WHATEVER,
SO QUICKLY I MENTION, FOR THIS
PEOPLE WE JUST THOUGHT ABOUT IT,
IT'S PURE, IT'S THE RIGHT COLOR
BUT FULL UP, YOU WILL SEE THIS
IS APPROACHING AND AM CAN BACK,
THIS IS VERY INTERESTED IN THE
[INDISCERNIBLE] BASE LINE, GABBA
IS THE LAST COMPARED TO
[INDISCERNIBLE], CAN IT COMES
BACK, TOO, THIS IS 1 DOSE METER
AND ANOTHER WITH MOW
STIMULATION, YOU SAY, OH IT'S
CITATION DURING--MAYBE SOME
REGION IS SLEEPY, HE'S QUITE
DEPRESSED WE CALCULATE, WE THINK
IT WOULD HELP AN ENERGY SYSTEM
BECAUSE WE OTHER
[INDISCERNIBLE].
THIS PAPER PUBLISHED MANY YEARS
AGO, YOU KNOW WE HAVE VALIDATED
[INDISCERNIBLE] STRONG WITH
NEUROACTIVITY AND ADDED A VERY,
VERY DEEP CORRELATION, IT ALMOST
REDUCED 50%, THAT MEANS 50% IN
THE SUPPORT SYSTEM LIKE THAT,
RIGHT?
SO THEN, I WILL TALK QUICKLY, WE
REALLY HAVE SOME
[INDISCERNIBLE], TRANSFER, WE
CAN [INDISCERNIBLE], AND ALL
THIS ACTIVITY WITH THE SLIDE,
YEAH, I WILL NOT HAVE TOO MUCH
TIME FOR THIS DETAIL, BUT REALLY
WE COME IN AND WE MEASURE THE
COUNTER FUNCTION
[INDISCERNIBLE].
HERE, PATIENT WE SOON FOUND THAT
THE [INDISCERNIBLE] ACTIVITY IS
[INDISCERNIBLE].
SO NOW WE WANT TO LOOK AT HOW
ENERGY WITH FUNCTION SO HERE ON
TOP OF ENERGY MEASUREMENTS IS MP
REGION BUT WE FIRST LOOK AT
CONNECTIVITY IN THE SAME WAY AS
MP DID, AND WITH SOME OTHER
WORK, DEFENDING OUR WORK, CAN
YOU SEE, [INDISCERNIBLE] HAS A
VERY VERY CERTAIN CIRCUITRY WITH
[INDISCERNIBLE] WITH SLIDE BUT
IN PATIENT, CAN YOU SAY THIS
PATIENT IS COMPROMISED OR
BIPOLAR DISORDER.
YES, WE HOPE THIS SORT OF
[INDISCERNIBLE] WORK BUT VERY
INTERESTING, [INDISCERNIBLE]
WORK, THIS IS STILL THERE BUT
IT'S COMPLEMENTING THIS PATIENT.
BASED ON THIS RESEARCH WE
BELIEVE ENERGY DEMAND AND LARGE
SCALE BRAIN WORK, THERE YOU CAN
SIMPLY PLACE TOGETHER AND MAKE
BREAK FUNCTION WORK COGNITIVE
FUNCTION IN A VERY EXACT
FUNCTION.
SO NOW, OF COURSE, WE CAN HAVE
FIBERS AND DO ORIENTATION, LIKE
[INDISCERNIBLE] SO NOW I TAKE
[INDISCERNIBLE] AS WELL.
AND WE QUALIFY [INDISCERNIBLE]
AND WITH PATIENT PSYCHEOSEIS,
THEN WE FOUND THE MEASURE HAS A
VERY GOOD MEASURE FOR EACH OTHER
AND WITH THE PATIENT WHICH
INDICATES THE LOWER ENERGY
GENERATION RATES WITH DECREASED
NEUROTRANSMISSION MIGHT DISRUPT
THE LONG DISTANCE AND LARGE
SCALE NEURONAL COMMUNICATIONS.
AND THEN OUR STUDY REVEALED THE
GENERAL PRINCIPLE OF BRAIN
ENERGY ACTIVITY, ORGANIZATION
AND SUGGESTS THAT THE
METABOLISM, THAT'S IT AND THANK
YOU SO MUCH FOR YOUR ATTENTION.
[ APPLAUSE ]
THAT WAS AMAZING AMOUNT OF
INFORMATION CONDENSED INTO A
VERY SHORT PERIOD, IF THERE ARE
ANY--ANYBODY WHO'S NOT SO
STUNNED AND STILL PROCESSING IF
THEY HAVE A QUESTION?
THAT WAS REALLY FANTASTIC.
OKAY, IF THERE ARE NO QUESTIONS,
I THINK THE NEXT TECHNOLOGY
TRANSFER ON THE DOCKET IS A
LUNCH AND A GROUP PICTURE, IF
YOU DIDN'T BRING HALLOWEEN
COSTUME, YOU WILL BE FITTED WITH
1 AND THAT'S ALL THE NEWS I HAVE
>>WELCOME BACK
FROM LUNCH.
I'M WYNN LEGON
FROM VIRGINIA TECH,
TALK ABOUT THE LOW INTENSITY
EFFECTS OF ULTRASOUND AND USE
WITH MRI IMAGING.
THIS IS WORK DONE AT HARVARD
WELL THEY BUILT A DECRANE
UTILIZED RABBIT MODEL AND THEY
SHOWED THEY COULD INDUCE A MOTOR
RESPONSE IN THE MOTE OR CORTEX
WHERE THEY WERE DIRECTING THE
FOCUS BEAM AND YOU CAN SEE HERE
FROM THE HUMAN DYNAMIC RESPONSE
FUNCTION, YOU GOT A NICE SET OF
RESPONSE FUNCTION, THIS IS
INDEPENDENT OF INTENSITY, SO
DOUBLING THE INTENSITY DID NOT
DOUBLE THE EFFECT SIZE.
WORK FROM LEMAN CHEN'S GROUP AND
I THINK SHE'S HERE AND ALSO
CHARLES CASKY'S GROUP AT
VANDERBILT ABOUT WORK IN THE
NONHUMAN PRIMATE, IN THIS CASE
THEY WERE TARGETING SOMAT O
SENSORY AREAS AND PULLING AREAS.
EVEN THE DIAGRAMOT TOP WAS
SHOWING AREAS THAT WOULD RESPOND
TO THE FINGER TOUCH, ON THE
BOTTOM IS WHEN THEY DELIVERED
ULTRASOUND TO THE SAME AREA AND
SHOWED A SIMILAR BOLD PATTERN
AND YOU CAN SEE DOWN THERE IN
IMAGE D, WE HAVE A NICE
HEMODYNAMIC RESPONSE FUNCTION TO
THE ON OFF OF THE ULTRA SOWBD IN
THE PINK LINES, VERSUS THE GREEN
LINES.
SO MY LAB HAS DONE A BIT OF WORK
EXAMINING THE EFFECT OF LIFU AND
FMRI BOLD HUMANS, WE DELIVERED
THE ULTRASOUND TO THE FINGER TO
SEE IF WOULD GET A PULSE
RESPONSE.
WE DELIVERED 2 DIFFERENT WAVE
FORMS, SO PUNS IN THIS CASE
MEANS PERIPHERAL ULTRASOUND AND
M WAS INDUCE THE MECHANICAL
STIMULATION AND T WAS A
TECHNICAL GENERATION AND PEEZ
WERE ABLE TO GENERATE THESE
RESPONSES IN THESE HIERARCHICAL
AREAS TO DIFFERENT PERIPHERAL
SENSATIONS.
SO THIS IS THE EARLY WORK TO SEE
IF CAN THE EFFECT OF BOLD
ACTIVITY DIRECT ACTIVITY THROUGH
TRANSCRANEIO APPLICATION
ULTRASOUND.
AND SO WE DID A LOT OF WORK IN
THE EARLY DAYS WITH COMMERCIAL
TRANSDUCERS TRYING TO PAIR THIS
TO 3 T MRI AND WE CAN SEE WE'RE
HAVING DIFFICULTIES, SO, OUR
INITIAL TRANSDUCERS THAT DO HAVE
3 T CONTRAST AND IT DID PRODUCE
QUITE A BIT OF ARTIFACT AND SO,
THERE IS 1 KIND OF STORY HERE OR
MESSAGE THAT IN THE EARLY DAYS
WHEN YOU COULD BUY A COMMERCIAL
TRANSDUCERS THAT THEY WERE NR
SAFE BUT WHAT THEY WEREN'T WAS
MR COMPATIBLE SO WE HAD RAY LOT
OF ARTIFACT ISSUES.
SO THESE WERE SOME OF OUR
EARLY--SHOWS 3 SUBJECTS HERE
WHERE WE DID HAVE HINTS OF
BOLDER RESPONSES BUT I DID HAVE
SUBJECTS WHERE WE WERE NOT ABLE
TO GET A ROBUST RELIABLE BOLD
SIGNAL.
BUT WE'VE BEEN WORKING ON THIS
AND 1 OF THE ISSUES TO REMOVE
THE ARTIFACT FROM A TRANSDUCER
IN THE HEAD COIL, YOU CAN SEE
FROM THE PHOTOGRAPHS ON THE LEFT
THAT WHAT WE ENDED UP DOING IS
WE ENDED UP SEEING WHAT
COMPONENTS OF THE TRANSDUCERS
LED TO THE ARTIFACTS SO HOW DID
WE ELIMINATE SOME OF THIS, SO
CAN YOU SEE THE TRANSDUCER IN
THE HEAD IN THE BOTTOM AND HOW
WE CAN FIT IT IN THE HEAD ON THE
PHOTO ON THE TOP LEFT.
WE DID A LOT OF EXPERIMENTS AND
WE WE CAN GET CERAMICS AND GET
IT FROM THE PET, AND DIFFERENT
LENGTHS THEN IT'S NOT JUST THE
PZT ELEMENT THAT HAS ARTIFACTUAL
ISSUES AND SOMETIMES THE EPOXYS
AND THE PLASTICS HAVE THIS THESE
ISSUES.
SO YOU DO HAVE SOME SUCCESS, YOU
CAN SHOW HAD SOME OF THESE
ARTIFACTS BUT FROM ALL OF THESE
STUDIES, WE WERE HAPPY TO SAY WE
WERE ABLE TO PRODUCE OUR OWN
TRANSDUCERS THAT DID HAVE VERY
LITTLE ARTIFACT AND WE'RE
SHOWING DATA FROM A 70S GROUP.
YOU CAN SEE THE SEQUENCES ARE
QUITE NICE NOW SO THESE ARE
IMAGING TAKEN WITH OUR CUSTOM
HOM MADE TRANSDUCE THEY'RE IS 3
TN17 COMPATIBLE.
IN THIS CASE, THE STUDY WE'RE
NOT INTERESTED IN INDUCING A
BOLDER RESPONSE, WE WERE
INTERESTED IN SEEING WHAT AN
ULTRASOUND DID TO A PREVIOUS
ULTRASOUND RESPONSE, SO IF YOU
DID IT WITH A FINGER YOU COULD
GET A NICE BOLDER RESPONSE.
SO IN THIS STUDY WE HAD
PARTICIPANTS MOVE MIDDLE FINGER,
INDEX FINGER, RING FINGER AND IF
WE AFFECTED THOSE COULD WE GET
NEUROMODDULATION, SO I'M SOING
THE DISPLACEMENT FROM THE FINGER
REPRESENTATIONS AND THE SPOINT
THAT LOW INTENSITY FOCUSED URLT
RASOUND OF 500 K HERTZ DOES
CONFIRM THE SPATIAL RESOLUTIONS,
IN THIS CASE, THE DATA ON THE
RIGHT IS FROM 5 SUBJECTS AND WE
DID NOT SEE AN INCREASE OR
DECREASE IN THE HEMODYNAMIC
AGNITUDE BUT WE DID SEE A CHANGE
IN THE VOLUME OF THAT EFFECT AND
THAL CASE, THIS IS THE DATA FROM
THE INDEX FINGER AND THEN THAT
DATA, THAT AFFECT DID NOT
TRANSLATE TO THE INDEX, TO THE
MIDDLE FINGER OR TO THE RING
FINGER.
AND SO THIS IS A BIT OF A
BACKGROUND, IT'S LED TO OUR
STUDIES NOW WHERE WE'RE REALLY
INTERESTED IN,A PLYING SOWBD FOR
PAIN INDICATION SO INSTEAD OF
LOOKINGA THE PRIMARY MOTOR
CORTEX, WE WERE INTERESTED IN
LOOK BEING AT THE ANCILLARY
CORTEX, SO HERE'S THE CORTEX AS
PICTURED HERE, IT'S DEEP THROUGH
THE CORTICALE SURFACE IT'S
COVERED BY THE PERIPHERAL LOBE,
SO IT'S QUITE DIFFICULT TO
ACCESS NONINVASIVELY, I THINK
WE'VE SEEN A LOT OF WORK HERE
TODAY ABOUT THE LIMITATIONS OF
TMS FOR DEATH PENETRATION AND SO
1 OF THE VALUE PROPOSITIONS,
BENEFIT OF ULTRASOUND IS THAT IT
DOES HAVE DEPTH PENETRATION AND
YOU CAN MODIFY THE RESOLUTION OF
IT TO TARGET AN AREA LIKE THE
INSIEWLA, SO THERE'S SEVERAL
DATA POINT SUGGESTING IT IS THE
PAIN PROCESSING HERE, CAN YOU
SEE ON THE LEFT THAT THE
MAJORITY OF THE DISCIPLINARY
SYNAPTIC PROJECTIONS FROM THE
LATERAL SPINE INFLAMMATORY TRACT
DO TERMINATE THE ENSUE LA SO
THIS IS A TARGET AREA.
SO THESE--THE COLOR--SORRY I'M
LEARNING HOW TO USE THIS THING.
IT CAN BE DIVIDED BROADLY INTO
AN ANTER ANTERIOR AND POSTERIO.
SO WE WANTED TO TRY BOTH TO SEE
IF WE WOULD GET DIFFERENT
EFFECTS WITH ULTRASOUND.
AND SO JUST TO CONFIRM THAT YOU
CANNOT TARGET THE INSULIN VERY
WELL WITH TMS OR TDCS, THIS IS
WORK I'M DOING IN COLLABORATION
WITH ALEX AT THE UNIVERSITY OF
MINNESOTA.
THE TOP ROW IS AN EFIELD FOR A
TYPICAL 8 COIL TARGETING THE
INSIEWLA SO ALEX HAS A NICE
PIPELINE TO ITERATE THROUGH
SEVERAL DIFFERENT LOCATIONS OF
THE TMS COIL OR THE ELECTRODES
TO TRY TO OPTIMIZE A TARGET
LOCATION AND YOU CAN SEE FROM
BOTH THE TMS AND THE TDCS DATAOT
BOTTOM, THESE WERE THE BEST
CONFIGURURATIONS FOR THESE 2
METHODOLOGIES TO TARGET THE
INSULA, AND YOU SEE THAT THE
FIELD DID SNOT REACH THE INSU LA
AT ALL.
THIS IS DIFFICULT TO DO WITH
MAGNETIC STIMULATION AND WE
THINK WE HAVE A NICE OPPORTUNITY
TO SEE IF THE ULTRASOUND WILL
AVENGHT THE PAIN PROCESSING.
SO HERE'S SOME ACOUSTIC MODELS
THAT WE DO IN OUR LAB, SHOWING
SPATIAL SPECIFICITY OF
ULTRASOUND, I APOLOGIZE IF THE
IMAGES ON THE LEFT, IT'S HARD TO
SEE THE BEAM SO CAN YOU NOTICE
THAT IF YOU LOOK AT THE
CALIFORNIAOR BAR AND THE IMAGES
ON THE LEFT, WE'RE DELIVERING
WHAT 70-PASCAL OUTSIDE THE HEAD
AND THEN IF YOU LOOK AT THE
IMAGE ON THE RIGHT, THE MODEL'S
PREDICT PROBABLY ABOUT A 4 FOLD
LOSS OF ENERGY GETTING INTO THE
HEAD.
SO THIS IMAGE ON THE RIGHT HERE
IS THE IMAGE FROM THIS CUT
THROUGH THIS LINE HERE ON THIS
TRANSVERSE IMAGE OR CORONA IMAGE
AND THIS IS THE IMRKS Y IMAGE
AND YOU CAN SEE LIFE DOES
CONFER, THE SPATIAL
SELECTATIVITY TO INDIVIDUALLY
TARGET GIRI WITHIN THE INSULA.
SO HERE WE'RE TARGETING THE
INFERIOR INSULA, AND THE
POSTERIOR INSIEWLA LANGUAGE
PATHOLOGISTS THIS YEAR, AGAIN
THIS IS THE IMAGE TAKEN HERE IN
THIS TRANSVERSE SLICE AND
CORONAL SLICE AND YOU CAN SEE
HERE WE'RE TARGETING THE JOINT
GYRUS AND THE INSULA, AND I WILL
TALK MORE ABOUT THIS, THERE IS B
MEMBER IDENTIFICATION IN THIS
CASE, SO YEN IN HIS EARLIER
TALK, THIS IS A MAJOR ISSUE
FIDUCIARY ULTRASOUND
TRANSCRANIALLY, SO IT DOES
ATTENUATE THE BEAM AND I WILL
TALK A BIT ABOUT HOW WE CAN
MITIGATE THESE THINGS.
YES, OKAY, SO THIS IS THE
PROBLEM WITH THE SKULL.
SO THIS IS WORK DONE WE'RE
LEGALLY INTERESTED IN SEEING IF
WE COULD USE ULTRASOUND TO
TARGET THE CEREBELLUM.
AND SO HERE WE HAVE A MODEL WITH
SAGITTAL SLICE SHOWING THAT YES,
WE HIT THIS PRETTY DEFINED
THEME, TARGET THE CEREBELLUM,
EVERYTHING LOOKS NICE AND FINE
AND DANDY BUT WHEN YOU LOOK AT
THE TRANSVERSE SLICE, CAN YOU
SEE HOW THE MORPHOLOGY CAN
REALLY MISDIRECT THE BEAM, SO IN
THE LIFE OR WORLD WE HAVE TO
COMPENSATE FOR NOT ONLY THE
ATTENUATION OF THE SKULL, BUT
ALSO THE MORPHOLOGY OF THE SKULL
TO MISDIRECT THE BEAM.
SO BACK TO THE PAIN STUDIES, SO
THIS WAS A GENERAL METHODOLOGY.
THIS IS KIND OF A 2 PART STUDY.
WE HAD RESTING STATE CONDITION
IN THE YELLOW AND MY STUDENT
ANDREW WILL TALK MORE ABOUT THE
RESTING STATE DATA LATER AND I
WILL TALK ABOUT THE EVENT
RELATED DATA RIGHT NOW, AND SO
THIS IS A HEAT RELATED STUDY SO
THIS IS A DEVICEOT LEFT TO
DELIVER A PAINFUL STIMULUS TO
THE DORSAL OF THE HAND WHERE THE
SUBJECT HAD TO RATE IT ON A
BUTTON BOX.
SO THEY WOULD DO THIS BEFORE
ULTRASOUND AND THEN WE WILL
DELIVER ULTRASOUND AND SO THIS
IS A BIT DIFFERENT THAN THE
CONCURRENT LIFE THAT I SHOWED
EARLIER, WE'RE NOT DELIVERING
ULTRASOUND DURING POLED
ACQUISITION, THIS IS MORE--THIS
IS A PREPOST DESIGN.
AND SO IN THIS CASE, WE
DELIVERED A HUNDRED STIMULATIONS
OF LIVE FLOW AT AN INTERVAL OF
5-SECONDS AND THEN WE DID THE
PAIN TESTING AGAIN AFTERWARDS
AND WE HAD 3 CONDITIONS, WE HAD
AN ACT OF [INDISCERNIBLE]
CONDITION WHERE WE DELIVER IT TO
THE VORTEX, AND IN THIS CASE WE
DELIVER IT AT THE DORSAL AND WE
DELIVERED IT AT 2 DIFFERENT
INTENSITIES.
AND OF COURSE, WE USE MRI GUIDED
STEREO TAXIC NAVIGATION SO THIS
IS THE EXACT SYSTEM YOU WOULD
USE FOR A TMS STUDY AND IT'S
EASILY RETROFITTED TO AN
ULTRASOUND TRANSDUCER.
THE ONLY THING YOU HAVE TO DO IS
CHANGE THE Z-OFFSET IN THESE
SYSTEMS AND SO IT'S--IT PAIRS
REALLY EASILY HERE'S AN EXAMPLE
OF A CORTICALE TRANSDUCER AND
YOU CAN SEE HOW WE'RE USING A
TRADITIONAL TMS STEREOTYPE IN
THE NAVIGATION SYSTEM, TO DO
ONLINE TESTING AND SEE EACH
UBIQUITINNATION IS JECT WILL
HAVE THEIR OWN CT AND MR WILL
IDENTIFY THE INTERIOR INSULA,
WILL KNOW THE DEPTH OF IT, THE
DEPTH OF THE TRANSDUCER AND THIS
IS HOW THE GENERAL TARGETING
STRATEGY WORKS.
OKAY, THESE ARE SOME OF OUR
EARLIER RESULTS HOT OFF THE
PRESSES, AND SO THIS IS SOME
DATA BEFORE LIFU.
AND SO WHEN YOU DELIVER A HEAT
PAIN STIMULUS TO THE HAND, YOU
WILL ACTIVATE THIS HIERARCHICAL
NO SUSCEPTIVE SOPHISTICATED MAT
O SENSORY NETWORK AND YOU CAN
GET S1, SOPHISTICATED MAT O
SENSORY CORTEX, WE DO GET CONTRA
LATERAL AND IPSA LATERAL INSULA,
THALAMUS AND ACC, SO WHAT I'M
SHOWING ON THE RIGHT.
ON THE TOP THIS IS THE RAW DATA,
BOLD DATA FROM THE LEFT INSULA,
HIGHLIGHTED HERE IN THE WHITE
CIRCLE, AND EVERY TIME THE
STIMULUS, STIMULUS IS
REPRESENTED, THE STIMULUS
STORYOT HAND IS REPRESENTED BY
EACH 1 OF THOSE RED VERTICLE
LINES AND THEN THE TRACE BELOW
IS THE AVERAGE HEMODYNAMIC
RESPONSE FOR THE LEFT INSULA.
SO WHEN YOU DIRECT TO THE DIRECT
INSULA, WHAT HAPPENS?
THIS HAPPENS.
WE HAD MASSIVE SIGNAL
ATTENUATION AND YOU CAN SEE FROM
A--FROM THE RAW DATA AND ALSO
FROM THE AVERAGE TRACE THAT WE
DO GET A MASSIVE INHIBITION AND
THAL CASE, IN THIS SUBJECT.
SO THE OTHER THING WE'RE
INTERESTED IN IS DOES THIS HAVE
BEHAVIORIAL RELEVANCE.
SO THE 2 BARS ON THE LEFT, THIS
IS THE AVERAGE PAIN RATING ON
THE LEFT AND THEN AFTER THE
INTERVENTION ON THE RIGHT AND WE
HAVE A SLIGHT DECREASE IN THE
PAIN RATING IS WHAT WE'RE REALLY
INTERESTED IN DOING NOW IS
LOOKING AT HOW DOES THE
BEHAVIORIAL DATA RELATE TO THE
BOLD DATA AND SO THAT'S WAWE'RE
SHOWING HERE AS THIS IS THE RAW
DATA FROM THE LEFT ANTERIOR
INSULA, SO THIS IS A SMALL RI
SPHERE AND THAT'S THE RAW BOLD
DATA IN BLACK AND THIS IS THE
BEHAVIOR DATA, THE BUTTON
PROCESS FROM AFTER EACH
STIMULUS, SO, IT'S NOT
CONCLUSIVE IF THERE'S ANY STRONG
RELATIONSHIP BETWEEN THE
BEHAVIORIAL RESULTS AND THE RAW
BOLD DATA FOR EITHER THE INSULA
OR THE PRIMARY SOPHISTICATED MAT
O SENSORY CORTEXAS BUT WE'RE
LOOKING AT DIFFERENT WAYS TO
LOOK AT THIS DAT AND POTENTIALLY
USING THE DEHAIEVERRIAL DAT AS 1
OF OUR REGRESSORS TO TEASE A BIT
OF THIS OUT.
SO THE OTHER THING WE'RE
INTERESTED IN S&P LOOKING AT
CORRELATION BETWEEN THESE AREAS
AND THESE TASK POSITIVE AREAS IN
THE SOPHISTICATED MAT O SENSORY
HIERARCHY, WHAT IS IT DOING NOT
ONLY TO ACTIVITY AND THE
ANTERIOR INSULA BUT ALSO IN
THESE RELATED CONNECTED AREAS,
SO THIS IS A CORRELATION MATRIX
OF SOME OF OUR TASK POSITIVE
AREAS WE'RE INTERESTED IN, AND
SO WE HAVE BEFORE ULTRASOUND ON
THE LEFT, AND THEN POST ULTRA
SOUND IN THE MIDDLE AND THEN
THERE'S THE DIFFERENCE PLOT ON
THE RIGHT AND I THINK WHAT'S
INTERESTING IS THAT THE BIGGEST
DIFFERENCE BETWEEN PREAND POST
WITH THIS SUBJECT WAS FOR LEFT
INSULA CONNECTIVITY AND OHM IN
THE LEFT INSULA CONNECTIVITY,
WHERE WE DELIVER DIFFERENCES IN
CONNECTIVITY WITH THE PRIMARY
SOPHISTICATED MAT O SENSORY
CORTEX AND THE ANTERIOR SING
LATTERY CORTEX.
THIS IS DATA FROM ANOTHER
SUBJECT.
IT'S BEFORE LIFE, ON THE LEFT
AND THEN AFTER, A LIFU ON THE
RIGHT AND ONCE WITH AGAIN CAN
YOU SEE THAT THE STIMULUS DOES
RECRUIT THE INSULA AND IN THIS
CASE IT'S HEAVILY RECRUITED THE
AMYGDALA IN THIS SUBJECT AND
THEN AFTER ULTRASOUND, IF THE
INSULAR ACTIVITY HAS BEEN
ATTENUATE AND THEN THERE'S SOME
CHANGES, SLIGHT ATTENUATION OF
THE AMYGDALA AND OTHER NETWORKS
SUGGIEST THAGOREAN LIFU MIGHT
HAVE AN INHIBITORY EFFECT ON
THIS NETWORK.
THAL CASE, WE DID NOT SEE THE
DIFFERENCE FOR THE PAIN RATING
AND WE'RE CURRENTLY, LOOKING AT
THE RELATIONSHIP OF THE PAIN
RATING WITH THE RAW DATA TO SEE
WHAT THE RELATIONSHIP IS IF ANY.
SO, I'VE KEPT ALL MY DATA HERE
TO WHAT WE'VE DONE IN ULTRASOUND
WITH BOLD IMAGING AND WE HAVE, 2
SUBJECTS NOW, WHAT WE HAVE OVER
30 SUBJECTS NOW THAT I'VE DONE
EEG AND I DON'T HAVE THAT DATA
NOW BUT WE DO HAVE VERY ROBUST
BEHAVIORIAL EFFECTS IN THE GROUP
LEVEL AND EEG DATA I'M ONLY
SHOWING YOU A COUPLE SUBJECTS
HERE AND HOPEFULLY HAVE THAT
RELATIONSHIP WITH OUR BOLD DATA
AS WELL.
AND SO THE OTHER THING WE'RE
INTERESTED IN, AND I THINK YAN
POINTED THIS OUT QUITE WELL IS
THE MAJOR BARRIER TO ULTRASOUND
IS THE SKULL.
SO WE'RE VERY INTERESTED IN I
THINK SOME OF THESE OTHER
NEUROMODLATTORY TECHNIQUES ARE
ALSO UNDERSTANDING THE DOSING
AND HOW MUCH ENERGY IS NEEDED TO
GET THESE TYPES OF EFFECTS.
AND SO WE'RE REALLY INTERESTED
IN LOOKING AT METRICS OF THE
SKULL TO HELP US INDICATE HOW
MUCH ENERGY IS GETTING IN THERE
AND WHERE THE ENERGY IS GOING.
SO WE COLLECT CTs AND MR
IMAGING ON ALL OUR SUBJECTS SO
WHAT WE'RE ABLE TO DO IS WE'RE
ABLE TO IMAGE THE BONE QUITE
WELL AND WE CAN PARSE IT INTO
THE CORTICALE AND FOLLICULAR
LAYERS AND THEN WHAT WE CAN DO
IS DRIVE THIS SKULL DENSITY
RATIO METRIC AND SO, THE METRIC
IS USED WITH HIGH INTENSITY
PROTOCOLS TO INDICATE WHETHER
THE SUBJECT IS APPROPRIATE FOR
LIFU ISHT VENTION BECAUSE IF YOU
ARE--IF YOU'RE SKULL DENSITY
RATIO IS AN APPROPRIATE, CAN YOU
GET INCREASED HEATING FROM HIGH
ENERGY AND SO THAT'S NOT
CONDUCIVE, IT'S NOT CONDUCIVE TO
SAFE INTERVENTIONS, AND SO WE'RE
CURRENTLY LOOKING AT WHAT ARE
THE SKULL DENSITY RATIOS OF OUR
PARTICIPANTS?
WHAT IS THE RELATIONSHIP OF THAT
TO HOW MUCH DOSING IS GETTING IN
AND WHETHER IT'S HAVING A BOLD
EFFECT OR A BEHAVIORIAL EFFECT?
AND ALSO INTERESTED IN THE
THICKNESS OF THE BONE, BUT WE'VE
PREVIOUSLY SHOWN THAT THICKNESS
ALONE DOES NOT ACCOUNT FOR THE
PRESSURE IN THE HEAD OR SOME OF
THESE BOLD RESPONSES BECAUSE
BONES NOT HOMOGEANIOUS SO THE
THICKNESS IS NOT A GOOD
PREDICTOR OF THE NG THAT'S
GETTING IN THE HEAD.
SO CAN YOU SEE HERE FROM SOME OF
OUR MODELS, I'M POINTING OUT TO
HOW MUCH PREDICTED LOSS CAN YOU
GET.
SO WE'RE DELIVERING 700-PASCALS
OUTSIDE THE HEAD, AND I THINK
THE CURRENT STATE OF THE FIELD,
I'M HAPPY TO DEBATE THIS WITH
ANYONE WHO MAY OR MAY NOT KNOW,
BUT WE DON'T ACTUALLY KNOW WHAT
PRESSURE IS TOO LOW OR WHAT IS
OPTIMAL DOSING FOR ULTRASOUND
YET SO THESE ARE THINGS WE'RE
TRYING TO FIGURE OUT RIGHT NEW
IS HOW MUCH PRESSURE IN THE HEAD
DO WE NEED TO GET THE SUSTAINED
ROBUST RELIABLE EFFECTS.
AND WITH THAT I WOULD LIKE TO
THANK MY LAB, PAST AND PRESENT
AND ALSO THE INSTITUTIONS THAT
I'VE COLLABORATED WITH AND SOME
OF MY FUNDING PARTNERS AND I'M
HAPPY TO ANSWER ANY QUESTIONS.
[ APPLAUSE ]
>>QUESTIONS FOR WYNN?
>>ALL RIGHT, YAN, HIT ME.
>>I HIT THE CHANGES IN
FUNCTIONAL CONNECTIVITY
INTRIGUING, WERE THEY OBSERVED
ALSO IN THE SECOND SUBJECT?
>>YES, BUT IN DIFFERENT AREAS
AND SO THAT SUBJECT HAD A
DIFFERENT KIND OF LIFU PROAND I
THINK THIS WAS BROUGHT UP IN THE
ISSUE OF NEUROMOD, IS WHAT IS
THE CURRENT STATE OF THE SUBJECT
OR HOW WOULD THE RECEPTOR
[INDISCERNIBLE] INTERVENTION OR
TESTING AND SO IN THAT CASE WE
DID NOT SEE A SIMILAR
RELATIONSHIP.
WE DID SEE CHANGES AFTER LIFU
BUT IT WAS BT SPECIFIC TO THAT
INSULA ACC, AND IT THEY HAD A
LOT MORE CONNECTIVITY IN THE
AMYGDALA AND THAT SHOWED
DIFFERENTIAL RESULTS SO I THINK
WE'RE REALLY INTERESTED ON THE
SINGLE SUBJECT EFFECTS AND HOW
THEY CONTRIBUTE TO GROUP
EFFECTS.
BUT AS I THINK EVERYONE KNOWS
THESE SINGLE SUBJECTS ARE
DIFFERENT.
AT LEAST BETWEEN THOSE 2
SUBJECTS NOW, WASN'T THE SAME.
>>DR. CHEN?
NGREAT TALK.
THANK YOU SO MUCH.
I HAVE 2 QUESTIONS, YOU
MENTIONED THE BEHAVIOR SO CAN
YOU JUST PLEASE TELL A BIT MORE,
DID YOU GET THAT BEHAVIOR READ
OUT BEFORE OR WITH THE MAGNET
OR--
>>INSIDE THE MAGNET DURING THE
SCAN SO PULSE DELIVERED ON THE
HAND AND THEN A CERTAIN WINDOW
TO RESPOND AFTERWARDS.
>>AND THE SECOND QUESTION IS
HAVE YOU LOOKED AT YOU KNOW
AFTER THE FIRST OF THE INSULA,
YOU SEE THE DECREASING MEDULLAR,
AND HAVE YOU LOOKED AT THE
CONNECTIVITY CHANGE AFTER?
>>YEAH, SO MY STUDENT ANDREW
WILL PRESENT A LOT OF THE
CONNECTIVITY DATA TO THAT
SHORTLY TODAY.
>>THANK YOU.
>>HI, JUST QUICK QUESTION, DID
YOU SAY THAT THERE WAS TO YOUR
TASTE NOT A GOOD COMMERCIAL
SOLUTION FOR MR COMPATIBLE
[INDISCERNIBLE] AND THEN YOU HAD
TO BUILD YOUR OWN?
>>SO I DIDN'T--I MISSED THAT.
>>IS THERE TO DATE AN
MR-COMPATIBLE [INDISCERNIBLE] OR
YOU HAVE TO BUILD YOUR OWN IF
YOU REALLY WANT TO
BE--COMPATIBLE?
>>THIS DATA IS FROM A
COMMERCIAL TRANSDUCER AND SO WE
DID NOT DELIVER ULTRASOUND WHILE
THEY WERE IN THE SCANNER, SO
THIS DAT IS NOT CONCURRENT, BUT
YES, OUR PAST DATA WE ENDED UP
MAKING OUR OWN TRANSDUCERS THAT
WERE MR COMPATIBLE SO IF WE WANT
TO DO CONCURRENT FMRI, WE JUST
FOUND THAT SOME COMMERCIAL
TRANSDUCERS, NOT ALL, I KNOW
THERE'S SOME THAT WORK BUT, WHEN
THEY SELL YOU AN MR COMPATIBLE
TRANSDUCER, IT IS MR SAVE BUT
THEY DON'T HAVE ANY ANY IN
WHETHER IT HAS ARTIFACT OR NOT.
SO WE FOUND A LOT OF THESE MR
SAFE TRANSDUCERS, DO HAVE A LOT
OF ARTIFACT AND SO WE ENDED UP
JUST BUILDING OUR OWN.
>>ONE MORE QUESTION.
WOULD YOU EXPECT THAT THE HIGHLY
FOCAL STIMULATION OF A
SUBPORTION OF INSULA WOULD HAVE
A MAJOR IMPACT ON THE
PERCEPTION?
IT'S QUITE IMPRESSIVE TO SEE
SOME IN SUBJECT NUMBER 1.
WHERE I AM AIMING TO--HAVE YOU
CONSIDERED STIMULATING MULTIPLE
OF THESE TARGETS, MAYBE LARGER
PORTION, MAYBE BILATERAL AND
MAYBE THE FELLOW [INDISCERNIBLE]
TO REALLY--
>>I THINK IT'S A GOOD POINT WE
ALWAYS TALK ABOUT THE VALUE OF
LIFE IS HOW SPECIFIC IT IS BUT
IT'S QUITE A POSSIBILITY THAT
IT'S TOO SPECIFIC SO IT DOES
LEAVE TO YOU SOME TARGETING
ISSUES AND SO, YES, WE FIRST
THOUGHT CAN WE GET A
DIFFERENTIAL EFFECT BETWEEN
AMPI, BUT BILATERAL MIGHT BE
BETTER BUT IN THIS CASE, THIS S
THE FIRST FORAY INTO THAT BUT
YES, I WOULD BE INTERESTED IN
SEEING THAT AS MORE IS BETTER
THAT KIND OF THING.
>>LET'S THANK DR. LEGON.
>>THANK YOU.
>>[ APPLAUSE ]
>>OUR NEXT SPEAKER IS
DR. JACEK, DMOCHOWSKI, FROM THE
CITY COLLEGE OF NEW YORK.
HE'S CURRENTLY AN ASSOCIATE
PROFESSOR AND TODAY HE WILL TALK
TO US ABOUT THE MRI OF
NEAR-INFRARED OPTICAL
MODULATION.
>>THANK YOU YAN, I'M JACEK, I'M
AT THE CITY COLLEGE OF NEW YORK
AND TODAY I WILL TALK ABOUT A
TYPE OF BRAIN SIMULATION THAT I
DON'T THINK WE'VE HEARD ABOUT
YET TODAY.
OPTICAL MODULATION IS ACTUALLY
NOT THE PREFERRED NOMENCLATURE
BUT IT IS THE TITLE OF THIS
TALK.
UNFORTUNATELY FOR ME I DON'T
HAVE ANY DISCLOSURES.
SO WHAT IS PHOTO BIOMODDULATION?
SO FIRST OF ALL, THIS USED TO BE
CALLED LOW LEVEL LASER THERAPY,
SO ALSO HAS BEEN REFERRED TO AS
COLD LACER.
PHOTO BIOMODDULATION IS NOW I'VE
HEARD, THERE WAS LIKE A GROUP OF
EXPERTS IN THIS FIELD THAT ALL
DECIDED TO COME TOGETHER 1 DAY
AND DECIDE ON THIS BEING THE
HOPEFUL ULTIMATE NAME OF THIS
TECHNOLOGY SO AS WITH MANY
THINGS IN MEDICINE, IT WAS
DISCOVERED ACCIDENTALLY IN THE
60S.
A HUNGARIAN PHYSICIAN HAD AN
IDEA THAT HE COULD CURE CANCER
WITH RAISER RADIATION.
AND SO HE ASKED HIS PHYSICIST,
THIS WAS IN HUNGARY, I BELIEVE,
ASKED HIS PHYSICIST COLLEAGUE TO
BUILD HIM A LASER SPECIFYING
SOME INTENSITY THAT HE WANTED TO
WORK WITH.
UNFOR THEINATELY, AND THEY ONLY
DISCOVERED THIS AFTER THE FACT,
THAT THE LASER HE GOT FROM HIS
COLLEAGUE HAD A MUCH LOWER
INTENSITY THAN HE HAD INTENDED
TO USE.
AND HE DID NOT, SO, YOU KNOW THE
EXPERIMENT WAS VERY STRAIGHT
FORWARD, IT WAS 2 GROUPS OF
MICE, HALF GOT THE LASER
THERAPY, THE OTHER HALF DIDN'T
AND THERE WAS NO EFFECT ON THE
CANCER PROGRESSION, BUT HE DID
NOTICE THAT THE MICE THAT GOT
TREATED WITH THE LASER, THEIR
HAIR WOULD GROW BACK MORE
QUICKLY.
YOU KNOW THE MICE HAD TO BE
SHAVED FOR THESE EXPERIMENTS AND
SO THAT WAS KIND OF THE GENESIS
OF PHOTO BIOMODDULATION.
AND UNFORTUNATELY AS WITH MANY
FIELDS THAT HAVE A LOW BARRIER
TO ENTRY, THERE HAVE BEEN MANY,
WELL WHAT I'M CALLING HERE IS
LESS THAN RIGOROUS REPORTS IN
THIS FIELD, SO THIS IS NOT A
FIELD THAT YOU WANT TO GET INTO
FOR THE PRESTIGE BECAUSE THERE
ARE SOME PRETTY YEAH, PRETTY
PSEUDOSCIENTIFIC REPORTS OUT
THERE.
BELIEVE IT OR NOT OUT OF ALL
THOSE PICTURES I BELIEVE THAT
THE ONLY 1 OF THESE PICTURES
THAT IS ACTUALLY FDA APPROVED IS
THE BASEBALL CAP.
THAT IS--IT'S AN FDA APPROVED
TREATMENT FOR MALE PATTERN
BALDNESS.
BUT WHAT I'M TRYING TO SAY HERE
IS THAT, THIS IS AN AREA, PHOTO
MODULATION IS NOT JUST ABOVE THE
BRAIN, I'LL BE TALKING TO YOU
ABOUT THE SUBSET OF THIS THAT IS
DIRECTED AT THE BRAIN, BUT THAT
FACET, THAT I'M INTERESTED IN,
IS VERY RECENT.
SO, REALLY JUST IN THE LAST 10,
15 YEARS HAS PHOTO BIO
MODULATION BEEN SERIOUSLY
INVESTIGATED IN THE CONTEXT OF
COGNITIVE FUNCTION, PSYCHIATRIC
APPLICATION.
SO TRANSFERRING OF PHOTO
BIOMODDULATION, YOU KNOW THE
DEFINITION, IT'S HARD TO EVEN
COME UP WITH A VERY SPECIFIC
DEFINITION.
I DEFINE IT HERE AS THE
NONINVASIVE APPLICATION OF LOW
LEVELS OF NEAR INFRARED LIGHT
THROUGH THE BRAIN.
SO WHAT IS LOW LEVEL?
SO IF YOU'RE FAMILIAR WITH
POWER, YOU KNOW POWER
MEASUREMENTS AND BRAIN
STIMULATION, THE POWER OF THITE
LIGHT COMING OUT OF THAT LASER
IS GENERALLY A COUPLE HUNDRED
MILLI WATTS AND THE PERCENTAGE
OF THAT THAT ACTUALLY PENETRATES
TOWARDS THE BRAIN SURFACE,
DEPENDS BUT IT'S IN THE ORDER OF
A FEW%, AND SO IF YOU SHINE 300
MILLI WATTS AT THE HEAD, YOU
WILL GET 3-6 MILLI WATTS IN THE
BRAIN.
SO THAT'S A GOOD WAY OF DEFINING
LOW LEVEL HERE IS IT'S AN
INTENSITY THAT DOESN'T HEAT THE
BRAIN OR HOPEFULLY DOESN'T HEAT
THE BRAIN AND IT CAN BE DOABLE
WITH LASERS OR LIGHT EMITTING
DIODES, THE ONLY ADVANTAGE OF
THE LASER, THERE'S NOTHING
SPECIAL ABOUT COHERENT LIGHT, IN
THIS SENSE, CAN YOU DO
EVERYTHING THAT IS DONE WITH
LASERS WITH LEDs, IT'S JUST
HARDER TO GET 300 MILLI WATTS
OUT OF AN LED, THAN IT IS WITH A
MONOCHROMEATIC LASER.
SO THE REASON PEOPLE USE LASERS
HERE IS JUST A CONVENIENCE OF
DELIVERING THAT MUCH LIGHT, YOU
KNOW, EFFICIENTLY.
SO I THINK IF THERE'S 1 THING
THAT YOU REMEMBER FROM THIS TALK
IS THAT PHOTO MODULATION IS
DIFFERENT THAN TMS AND TDCS AND
ALL THOSE ASSETS.
IT'S NOT TRYING TO MAKE NEURONS
FIRE AT ALL OR NOT DIRECTLY AT
LEAST.
IT'S TARGETING THE BI ONY
ENERGETIC PATHWAYS, PATHWAYS.
AND SO, THE TARGET HERE IS NOT
MEMBRANE POTENTIAL, BUT IT'S HOW
MUCH ENERGY, ATP NEURONS HAVE AT
THEIR DISPOSAL.
SO I'M IN THE A BIOLOGIST SO I'M
PROBABLY NOT THE BEST PERSON TO
TRY TO EXPLAIN TO YOU THE
BIOPHYSICS OF PHOTO
BIOMODDULATION BUT THE KEY
MOLECULE, THE KEY ABSORBER HERE
AND AGAIN, THIS IS BACKED BY A
LOT OF GOOD--ACTUALLY
EXPERIMENTS, HOWEVER, YOU'RE
STILL A LOT OF DEBATE HERE AS TO
WHAT THE PRECISE MECHANISM IS,
LIGHT, THE INTERACTION BETWEEN
LIGHT AND BIOLOGICAL TISSUE IS
ALWAYS SUPER COMPLICATED AND
IT'S VERY HARD TO GET STRAIGHT
ANSWERS BUT CYTOCHROME C-OX DACE
IS AN ENZYME IN THE ELECTRON
TRANSPORT CHAIN OF THE
MITOCHONDRIAL RESPIRATION CYCLE.
SO IT'S THE THEORY IS THAT
PHOTONS IN THE INFRARED LIGHT
HAVE THE RIGHT ENERGY LEVEL TO
BE ABSORBED BY CCO AND THAT
BASICALLY SPEEDS UP THAT
CELLULAR RESPIRATION PROCESS, IT
SPEEDS UP, YOU KNOW THE CHEMICAL
REACTIONS THAT ARE ULTIMATELY
PRODUCING ATP WHICH IS A GOOD
THING.
ESPECIALLY IF, THERE IS AN
IMBALANCE IN ATP.
THERE ARE OTHER HYPOTHESIS OUT
THERE, 1 IS THAT, NITRIC OXIDE
IS ASSOCIATED AND THAT CAN
BE--THAT CONTRIBUTOR OF BASAL
DILATION, SO THERE'S THE BLOOD
FLOW HYPOTHESIS IS STILL OUT
THERE.
IT'S STILL A POTENTIAL WAY THAT
PHOTO BIOMODDULATION EXERTS
WHATEVER EFFECTS IT DOES EXERT.
BUT THERE IS A LOT OF EVIDENCE
THAT SHINING THE INFRARED LIGHT
ON CELLS, BASICALLY INCREASES
THE COMSUMPTION OFOX GENERATED
AND AS A RESULT, GLUCOSE
METABOLISM AND THERE'S LOTS OF
INVITRO, AND ANIMAL WORK THAT
DOCUMENTING THE INCREASED
PRODUCTION OF ATP, WITH PHOTO
BIOMODDULATION.
AGAIN, I JUST WANT TO MAKE IT
CLEAR THAT KIND OF THE BASIC
SCIENCE STUDIES HERE ARE
ACTUALLY PRETTY SOUND.
IT'S MORE ON THE APPLICATION
SIDE THAT I THINK THERE'S A LOT
OF, SOME, YEAH, LESS THAN
RIGOROUS INVESTIGATION REPORTS
OUT THERE.
SO 1 THING ABOUT THIS FIELD
THAT'S INTERESTING IS THAT A LOT
OF THE PHYSIOLOGICAL EFFECTS
THAT HAVE BEEN DOCUMENTED HAVE
BEEN DONE IN MICE, AND SO THIS
IS A--I GENERAL TREND IN
NEUROMODDULATION THAT GETTING
EFFECTS, SHOWING EFFECTS, IS A
LOT EASIER IN THE RODENT AND I
THINK THAT'S PRIMARILY BECAUSE
OF THE--JUST THE ANATOMY DOESN'T
SCALE UNIFORMLY FROM RODENT TO
HUMAN.
IT'S JUST, YOU KNOW IF YOU NEED
300 MILLI WATTS TO REACH THE
HUMAN BRAIN, THEN AND THE HUMAN
BRAIN IS LET'S SAY, I DON'T KNOW
10 TIMES BIGGER THAN THE MOUSE
BRAIN, YOU WILL NEED LESS THAN
30 MILL WATTS TO REACH THE MOUSE
BRAIN, THE ANATOMY IS MORE
FAVORABLE AND SO THERE MAY BE
OTHER REASONS WHY, AND SO
SHOWING THESE KINDS OF EFFECTS
IN HUMANS HAS BEEN MORE
CHALLENGING.
I MEAN, EVEN JUST BECAUSE IT'S
NOT EASY TO MEASURE CEREBRAL
BLOOD FLOW OR ATP PRODUCTION IN
THE HUMAN BRAIN.
SO THATIA KIND OF THE MOTIVATION
FOR OUR WORK.
AND SO, MY VIEW HERE IS THAT MRI
CAN BE VERY VALUABLE FOR FULL
BRAIN STIMULATION IN THIS CASE,
FOR PHOTO BIOMODDULATION AND THE
REASON IS THAT MRI, ALLOWS US TO
ACTUALLY SEE WHAT'S GOING ON
WHEN YOU STIMULATE THE BRAIN
WITH LIGHT.
SO IT PERMITS A NONINVASIVE
SPATIALLY RESOLVED READ OUT OF
THE ACUTE AND ALSO THE AFTER
EFFECT OF THE HUMAN BRAIN TO FET
O BIOMODDULATION AND SO,--PHOTO
BIOMODDULATION AND HERE'S THE
PICTURE OF WHAT MOST OF OUR
EXPERIMENTS HAVE LOOKED LIKE.
WE GENERALLY HAVE BEEN
SIMULATING HEALTHY HUMAN
PARTICIPANTS AT REST AND MOST
OFTEN THE MOST RIGHT FRONTAL
POLE.
I DON'T HAVE GREAT EXPLANATION
FOR WHY WE CHOSE THE RIGHT
FRONTAL POLE, THE FOREHEAD IS
MOSTLY BECAUSE THERE'S NO HAIR
THERE SO THERE'S 1 LESS
POTENTIAL SOURCE OF VARIABILITY
BECAUSE YOU DON'T HAVE THE
SCATTERING AND THE RIGHT SIDE,
THERE'S REALLY NO REASON.
WE COULD HAVE GONE WITH THE LEFT
BUT YOU WOULD NEED TWICE AS MANY
SUBJECTS IF YOU WANTED TO
RANDOMIZE THE HEMISPHERE THAT
YOU'RE TARGETING.
YOU KNOW I'VE NEVER SEEN ANY
EVIDENCE FOR LIKE A HEMISPHERIC
IN THE RESPONSE TO THIS TYPE OF
STIMULATION.
SO THE QUESTIONS THAT WE'VE BEEN
TRYING TO ANSWER FOR THE LAST 2
YEARS, ON NUMBER 1 IS CAN YOU
MODULATE FUNCTIONAL CONNECTIVITY
WITH PBM AND TO ANSWER THAT
WE'VE BEEN USING MULTIECHO BOLD
SEQUENCES.
ALSO MR GIVES US THE OPPORTUNITY
TO DO THERMOGENESIS ORDER OF
MICRONSETRY WHICH IS REALLY NICE
AND WE'VE USED THAT TO ANSWER
THE REQUESTY OF WHETHER PHOTO
BIOMODDULATION INCREASES BRAIN
TEMPERATURE AND MOST RECENTLY,
WE'VE BEEN USING SPECROSCOPY, SO
PHOSPHOROUS MAGNETIC RESONANCE
SPECROSCOPY TO TRY TO ANSWER THE
KEY QUESTION HERE WHICH IS ARE
YOU ACTUALLY MODULATING ATP IN
THE HUMAN BRAIN WITH THIS.
>>ALL RIGHT, LOOKS LIKE I HAVE
8 MINUTES SOPHISTICATED I HAVE
TO--HERE'S A--I DON'T WANT TO
ALL TOO MUCH ON THE APPROACH BUT
JUST SO YOU UNDERSTAND WHAT
ARE--HOW OUR EXPERIMENTS ARE
CONDUCTED.
THEY'RE ALMOST ALWAYS LIKE THIS,
BEFORE, DURING AND AFTER.
WHERE BEFORE AND AFTER THERE'S
NO STIMULATION AND DURING THERE
IS, WELL, THIS IS FOR THE--THIS
IS OUR EXPERIMENTAL TIMING
DIAGRAM FOR THE FMRI STUDIES
THAT WE DID, SO BASICALLY A VERY
LONG BOLD SCAN, WE'RE IN THE
MIDDLE OF THAT SCAN, WE
STIMULATE THE PATIENTS WITH THE
LASER, AND THE READ OUT HERE IS
FUNCTIONAL CONNECTIVITY WHICH IS
JUST CORRELATION, ACTUALLY, IT'S
CORRELATION BETWEEN DIFFERENT
PARTS OF THE BRAIN, AND THERE'S
LOTS OF EVIDENCE, A TON OF
EVIDENCE, ACTUALLY THAT THIS IS
AN IMPORTANT THING TO STUDY.
INFORMATION PROCESSING IS
DISTRIBUTED AND YOU KNOW BRAIN
STATE AND PATTERN OF
CONNECTIVITY, YOU KNOW THEY'RE
ALMOST 1 AND THE SAME, THERE'S
JUST A PROBLEM WITH A LOT OF
EVIDENCE TO SUGGEST THAT A LOT
OF YOUR EXPERIENCE IS ROOTED IN
JUST WHICH PARTS OF THE BRAIN
ARE RIGHT NOW COMMUNICATING WITH
EACH OTHER, SO, THIS WAS A
NATURAL PLACE TO LOOK FOR
EFFECTS.
SO WHAT I'M GOING TO SHOW YOU
HERE, YOU WILL SEE A BUNCH OF
INFLATED COTTERISS AND THE COLOR
YOU WILL SEE ON THE CORTEX WILL
TELL YOU HOW STRONGLY THAT PART
OF THE BRAIN IS CONNEBTED TO THE
RIGHT FRONTAL POLE WHICH IS WHAT
WE'RE STIMULATING.
SO CONNECTIVITY IS KIND OF HARD
TO SHOW.
SO THIS IS BEFORE STIMULATION,
SO AGAIN, WE'RE STIMULATING THE
RIGHT FRONTAL POLE AND THE COLOR
HERE, THE MORE YELLOW, THE MORE
CONNECTED, THE REGION IS, AND
THEN THIS IS--THAT WAS BEFORE,
THERE IS DURING, CAN YOU SEE
HOPEFULLY, IF YOU AGREE WITH ME,
THAT IT'S BRIGHTER AND THEN THIS
IS AFTER.
SO, IT'S NOT--NOT QUITE AS
BRIGHT, BUT THERE'S STILL
SOMEWHAT BEEN AFFECTED AND THIS
IS NOW THE RIGHT HEMISPHERE.
SO I'LL SHOW YOU ON THE NEXT
SLIDE, KIND OF THE WHOLE BRAIN
VIEW OF THIS PREDICTURE.
IN A COLOR MATRIX, SO
ESSENTIALLY WHAT'S HAPPENING IS
THAT THERE'S THE CONNECTIVITY
WITH THE REGION THAT HAS BEEN
STIMULATE SIDE GOING UP.
ESPECIALLY DURING ILLUMINATION
AND IT DOESN'T SEEM TO BE, IT
SEEMS TO BE RATHER GLOBAL, SO
HERE, NOW, THESE ARE THE
CONNECTIVITY MATRIXES, SO
QUADRABBITS ARE HEMISPHERES, THE
MORE RED THE MORE CONNECTIVITY.
WE PARCELLATE THE BRAIN HERE
INTO 150 REGIONS OF INTEREST AND
WE LOOK AT CONNECTIVITY MEASURED
BEFORE DURING AND AFTER
ILLUMINATION SO, I WILL CUT TO
THE CHASE, IT DOESN'T LOOK LIKE
ACTUALLY IN THE A, B, C, AND
DOESN'T LOOK LIKE THERE'S MUCH
GOING ON IF YOU DO A
SUBTRACTION, YOU SUBJECT THESE,
YOU DO SEE AN INCREASE AND
WHAT'S REASSURING RATHER IS THAT
THE QUADRANT THERE AND PANEL
THAT HAS THE LEAST RED IS THE
CONNECTIONS BETWEEN THE LEFT
HEMISPHERE AND THESE ARE THE
CONNECTIONS WITHIN THE
NONSIMMULATED HEMISPHERE, SO
THAT'S SOMEWHAT OF A VALIDATION
AND YOU SEE THE EFFECTS IS
LARGELY GONE AFTERWARDS, SO IT
DOES SEEM, THIS INCREASE IN
CONNECTIVITY DOES SEEM TO BE
MOSTLY AN ACUTE PHENOMENON, IN
TERMS OF TIME COURSE, SO I DON'T
HAVE TIME TO GET INTO WHY WE DID
MULTIPLE ECHOES, BUT WE DID DO
MULTIPLE ECHOES, MOST TO TRY TO
DISAMBIGUATE BLOOD FLOW ANDOX
GENERATEDDATION WHICH IS MUCH
HARDER THAN WE THOUGHT IT WOULD
BE, BUT ECHO 3 HERE IF YOU LOOK
AT THE TIME COURSE, THE VERT
AXIS IS CONNECTIVITY, HORIZONTAL
ACCESS IS TIME AND HOPEFULLY YOU
WILL AGREE WITH ME THAT
SOMETHING IS HAPPENING AT THE
TIME OF STIMULATION WHICH HERE
IS AT THE 5 MINUTE MARK.
THERE'S ACTUALLY A SHARP DECLINE
RIGHT WHEN YOU TURN ON THE LASER
AND THEN, A RAPID ASCENT TO
HIGHER BASE LINE LEVEL.
SO IT DOES SEEM TO BE LARGELY
WITH THIS EFFECT, I APPROXIMATE
UTR IT IN QUOTATIONS THERE
BECAUSE BOLD IS SLOW.
WHEN I SAW THIS, THIS MADE ME
BELIEVE THAT THERE IS ACTUALLY
SOMETHING REAL HERE WE ALSO HAVE
THERAPY AND MOMETRY, I WILL
REALLY CUT TO THE PUNCH LINE
HERE WE HAD A PHASE DIFFERENT
SEQUENCE, BASICALLY LOOKS AT THE
TEMPERATURE FREQUENT,
TEMPERATURE DEPENDENT ATOM AND
WE DIDN'T SEE ANY DIFFERENCE.
WE DID A SHAM CONDITION HERE,
BUT WE DIDN'T SEE ANY DIFFERENCE
IN THE TEMPERATURE OF THE
SIMULATOR REGION OR ANYWHERE
ELSE IN THE BRAIN AT ALL.
AND SO, THIS WAS AGAIN REALLY
MOSTLY A VALIDATION OF THE FACT
THAT THE AMOUNT OF LIGHT THAT
WE'RE PUTTING INTO THE BRAIN IS
NOT ENOUGH TO PRODUCE A
RESOLVABLE INCREASE IN
TEMPERATURE.
OORK AND THE MOST RECENT STUDY
THAT STILL ISN'T PUBLISHED BUT
HOPEFULLY NEXT TIME WE GIVE THIS
TALK WILL BE, USING PHOSPHOROUS
MRS AND I WAS THINKING HOW DO I
EXPLAIN THIS BAZ THE PHYSIC
SYSTEM NOT STRAIGHT FORWARD BUT
I CAME UP WITH THIS SEQUENCE AND
ENERGY METABOLITES CONTAIN
PHOSPHOROUS AND THE PHOSPHOROUS
HAS A SPIN, THIS ISOTOPE HAS A
SPIN AND SO IT'S ACCESSIBLE TO
MR, AND SPECIFICALLY PHOSPHOROUS
MRS IS WOQUANTIFYING DIFFERENT
MOLECULES THAT CONTAIN
PHOSPHOROUS AND SO FOSTER NURSED
FOCUSED ON KRE TINSA TIEN AND
ATP ARE REALLY IMPORTANT FOR
ENERGY AND METABOLISM AND WITH
MRS WE'RE ABLE TO MEASURE THOSE
AND OBVIOUS EXPERIMENT IS TO DO
THIS BEFORE, DURING AND AFTER
PHOTO BIOMODDULATION, SO HERE
ARE SOME PICTURES IN THE
SCANNER, WE DO WHOLE BRAIN MRS,
THE VOXELS ARE BIG, 1 AND HALF
CENTIMETERS, AND THE PICTURE ON
THE RIGHT IS A PICTURE OF A
SPECTRUM, SO THE HEIGHT HEIGHT
OF THE PEEK SYSTEM THE HIGHER
THE CONCENTRATION, SO WE WANT TO
CARE ABOUT THE RELATIVE,
BASICALLY WE CARE ABOUT THE 3
PIECES ON THE RIGHT, THOSE ARE
THE ATP GROUPS AND THE BIG PEEK
IN THE MIDDLE, THAT'S PC R,
BASED ON THE REFERENCE, LIKE A
STORAGE, OF ENERGY, SO WE'RE
LOOKING TO SEE WHETHER THESE
PEEK HEIGHTS ARE MODULATED BY
PHOTO BIOMODDULATION, SO THE
EXPERIMENT WAS SAME AS BEFORE.
THE ONLY DIFFERENCE IS THAT IT
TAKES 10 MINUTES TO COME UP WITH
1 OF THESE SPECTRA, SO WE DID 10
MINUTES BEFORE AND 10 MINUTES
DURING AND 10 MINUTES AFTER.
SO FOR EVERY SUBJECT WE HAVE AND
EVERY VOXEL WE HAVE 3 OF THESE
SPECTRA AND WE LOOK AT DUE TO
HEIGHTS OF THOSE PEAKS DIFFER.
BECAUSE THIS ACTIVITIES AND
PROJECTED, COVID TOTALLY
KILLED--TRIED TO KILL THIS
PROJECT SO WE HAD TIME TO DO
SOMETHING THAT DIDN'T REQUIRE US
GOING INTO THE CAMPUS SO WE DID
SOME MODELING AND THE 1 THINK
THIS I WAS ABLE TO DO WAS
FINALLY FIGURE OUT WHAT IS--WHEN
YOU STIMULATE WHAT WE THOUGHT
WAS THE RIGHT FRONTAL POLE WHERE
DOES THE LIGHT ACTUALLY GET
ABSORBED.
WELL IT TURNS OUT IF YOU BELIEVE
MCX WHICH IS A GREAT TOOL, THAT
THE MOST OF THE ABSORPTION IS
ACTUALLY HAPPENING IN THE
ORBITAL GYRUS AND I THINK THE
REASON IS THE FOREHEAD ON MOST
PEOPLE'S ACTUALLY SLOPED SO WHEN
YOU PUT SOMETHING KIND OF NORMAL
TO THE SURFACE, IT'S ACTUALLY
ALREADY IN A MORE DOWNWARDS AND
IT'S A LOT OF IT GOES RIGHT
ABOVE THE EYE.
SO THAT BECAME KIND OF OUR ROI.
AND WE WERE ABLE TO DO THIS
BECAUSE WE WERE STUCK AT HOME
WITH SOMETHING TBU SOFTWARE.
ALL RIGHT.
BECAUSE I DON'T WANT TO GO OVER
TIME, WHAT I WILL SAY IS, YES I
THINK THERE'S AN EFFECT, NO I
DON'T THINK IT'S A SLAM DID YOU
THINK BUT I DEFINITELY DO WHEN I
LOOKED AT, SO THE AXIS ON THE
LEFT RESHAM AND POST, PRESTEM
AND POST, AND THE VERTICALAXIS
HERE IS THE RATIO OF ATP.
IF THE RATIO GOES DOWN, ATP'S
GOING UP AND THE IMPORTANT LOT
IS THE SECOND PLOT THERE, WHAT
YOU SEE HERE IS THAT BASICALLY
ALL THE SUBJECTS, GYRATIONS
GOING DOWN DURING AND AFTER,
ACTIVE STIMULATION, COMPARED TO
SHAM.
SO IT'S--YOU KNOW IT'S A
MODULATION OF THE DYNAMICS OF
ATP.
THAT WE SAW IN OUR COHORT.
WE DID NOT SEE THIS AND I'M
SHOWING YOU 1 OFFTARGET REGION
HERE, THIS IS JUST ILLUSTRATED.
THIS IS THE LEFT INTRA PARIETAL
SULKUS FOR EXAMPLE.
SO YES THERE WAS AN EFFECT, SO
SIGNIFICANT EFFECT ON ATP, BUT
IT'S--IT'S--YOU NEED TO COMPARE
IT THE SHAM CONDITION
CONNECKATIVITY INCREASED BY
1 PERCENT, AND THIS CONSIDERED
THIS TO BE A BRAIN WIDE EFFECT
IN TERMS OF HOW THIS HAPPENS AND
THIS OCCURRED TO ME THAT ALL
BRAIN STIMULATION, AT THE END
ADDING ENERGY AND THE BRAIN
LIGHTER OR MECHANICAL
STIMULATION, IT'S ENERGY AND THE
DIFFERENCE IS HOW IT'S
TRANSDUCED, THIS IS JUST ANOTHER
SUBSTANTIATION OF THAT, WE'RE
GIVING THE BRAIN MORE ENERGY AND
THE HYPOTHESIS HERE IS THAT THAT
ENERGY IS BEING USED TO BRING
THE PATTERN OF CONNECTIVITY
CLOSER TO WHATEVER THE BRAIN
WANTS, WE DO HAVE THEFS IS
CHANGING ATP
CONCENTRATION--THOSE 2 SYSTEMS
HAVE TONS OF FEEDBACK, IT'S A
PESSIMISTIC BULLET BUT P31 MRS
WHICH I STILL THINK IS AN
AMAZING TOOL THAT YOU CAN
MEASURE ATP IN THE BRAIN, BUT I
WILL SAY IT'S SLOW, IT'S NEARBY,
AND IT HAS LOW SNR, OTHER THAN
THAT IT'S GREAT.
THANK YOU.
BIG SHOUT OUT TO DUKE
[INDISCERNIBLE] AND RYAN AND
TAUGHT ME HOW TO DO ALL THIS MRI
SEQUENCES.
THANK YOU.
[ APPLAUSE ]
>>THANK YOU.
THAT WAS VERY ENTERTAINING.
JUST A SUGGESTION, I THINK
YOU'VE BEEN LOOKING IN HEGHTY
HUMAN BRAINS, IT'S INTERESTING
BECAUSE THE MECHANISM THAT
YOU'RE LOOKING AT IS
BIOENERGETICS AND 1 SUGGESTION
WOULD BE IF YOU APPLY THIS IN A
CLINICAL STUDY, PARKINSONS IS A
DISEASE WHERE IT'S IMPORTANT, I
KNOW YOU MENTIONED RODENT
MODELS, SO IN PARKINSON'S
DISEASE, ABNORMALITY HAS BEEN
SHOWN IN MITOCHONDRIA, THEY'VE
BEEN SHOWN TO BE CHANGES IN THE
ATP AND THE REGION YOU'RE
TARGETING WHICH IS THE FRONTAL
POLE IS THE ORBITAL IS THE AREA
THAT IS RELEVANT IN PARKINSONS
SO THIS COULD BE CLINICALLY
APLIBLABLE.
MORE SPECIFICALLY ABOUT
QUESTIONS ON THE SITE, I'M JUST
WONDERING HOW LONG DO YOU EXPECT
THESE EFFECTS TO LAST FOR, I
KNOW IMMEDIATELY YOU WERE SAYING
22ndS BUT BIOLOGICALLY ?
>>I CAN'T KEEP THEM IN THE
SCANNER MORE THAN 6 OR 8
MINUTES.
HONESTLY, I THINK THAT THE ATP
EFFECT LASTED AT LEAST 10
MINUTES AFTERWARDS.
I CAN'T ANSWER YOU WITH ANY
DATA, IT'S A CRITICAL QUESTION,
WHAT I ALWAYS SAY IS THE
LIKELIHOOD OF GETTING LASTING
EFFECTS WILL GO UP WITH REPEATED
APPLICATION, RIGHT?
AND SO I'M NOT A BIG BELIEVER
THAT 1 SHOT BRAIN STIMULATION
WILL INCREASE YOUR MOOD FOR A
MONTH LIKE SOME PEOPLE HAVE
CLAIMED, BUT BUT I THINK THAT--I
THINK THAT THE CIRCUITRY IS
THERE TO PRODUCE A PLASTIC
EFFECT BUT I IMAGINE THAT WE
WILL HAVE TO REPEAT THE
STIMULATIONS FOCUSED ON GET IT.
>>GREAT, THANKS.
>>THANK YOU.
>>LET'S THANK DR. DMOCHOWSKI,
AGAIN.
OUR NEXT SPEAKER IS DR. KIM
BUTTS PAULEY, SHE'S A PROFESSOR
IN RADIO LOGICAL SCIENCES AT
STANFORD UNIVERSITY AND SHE WILL
BE TALKING ABOUT MRI BASED
VERIFICATION OF TRANSCRANIAL
ULTRASOUND STIMULATION TARGETING
WITH 2 SPECIFIC TARGETS.
>>THANK YOU CROSS LINKING I
WANT TO TALK ABOUT HOW WE USE
TRANSCRANIAL SIMULATION TO
HUMANS.
-SORRY, THE FLUORESCENCE MOVES
AROUND WITH A FOCUS INTERESTING,
ANYWAY, LET ME GET PAST THAT AND
TALK ABOUT THE MRI.
OKAY, SO YAN AND WYNN, SET UP
VERY NICELY 1 OF THE BIGGEST
PROBLEMS FOR US WHICH IS THE
CULL.
SO IF YOU HAVE A THIN AND
HOMOGEANIOUS SKULL, THEN MAYBE
YOU GET ABOUT HALF THE INTENSITY
ACROSS THE SKULL.
YOU COULD HAVE A LESS GOOD
SCENARIO HERE WHERE YOU HAVE A
THICK AND HOMOGEANIOUS AND YOU
WILL AND CORTICALE BONE AND YOU
GET MAYBE LIKE 20% OF THE
INTENSITY SCROOSES THE SKULL BUT
THERE COULD ACTUALLY BE MORE
COMPLICATED CASES SO THESE
ARE--I'M SHOWING YOU IMAGES HERE
THAT ARE CT IMAGES HERE OF
DIFFERENT SUBJECTS THAT ARE
TREATED FOR ESSENTIAL TREMOR FOR
ULTRASOUND AND IF YOU LOOK AT
THESE SKULLS THERE'S A LOT OF
HETEROGENERATED AITY IN THE
THICKNESSS, AS WELL AS THE
COMPOSITION, AND FOR EXAMPLE,
LIKE I--I MIGHT ASK YOU WELL
WHICH 1 YOU THINK IS THE LEAST
TRANSMISSIVE TO ULTRASOUND, AND
YOUR EYE IS PROBABLY DRAWN TO
THIS 1 OVER HERE, AND PARTLY
BECAUSE IT'S VERY THICK BONE,
BUT ALSO BECAUSE I SHOWED IT ON
THE LAST SLIDE BUT IT TURNS OUT
THAT THIS 1 UP HERE IS ACTUALLY
50% LESS THAN MISSIVE AND IT'S
BECAUSE IT HAS ALL THAT BONE,
WHICH IS WHAT WYNN WAS ALLUDING
TO IS IN PRESENTATION, WHEN YOU
HAVE A LOT OF BONE, IT'S NOT
TRANSMISSIVE.
SO THESE REALLY SHOW YOU THE
VARIATIONS BETWEEN SUBJECTS IN
THE CT PICTURES BUT I SORT OF
MISLED YOU A LITTLE BIT WHEN I
SAID I WAS SHOWING YOU ALL THESE
CT PICTURES BUT IT ACTUALLY
TURNS OUT THAT 1 OF THESE ROWS
IS MRI PICTURES OF SKULLS, SO
NOW I MIGHT ASK YOU WHICH ROW DO
YOU THINK THAT IS, BUT RATHER
THAN GIVE YOU A QUIZ BECAUSE I
DON'T HAVE THAT MUCH TIME AND I
HAVE A LOT I WANT TO COVER, I
WILL TELL YOU IT'S THE LAST ROW,
AND SO THESE ARE UTE IMAGES OF
DIFFERENT SKULLS AND IN CASE YOU
DON'T BELIEVE ME, THERE'S THE
ACTUAL IMAGES, A LITTLE BIT OF
VARIATION WAS USED, I DON'T
REALLY GO INTO THAT.
BUT MRI PICTURES OF THE SKULL
ARE GETTING BETTER AND BETTER
ALL THE TIME.
THERE WERE BEAUTIFUL PICTURES
AND THIS SET RIGHT HERE SHOW
YOU, YOU CAN ALSO USE THOSE FOR
LOOKING FOR CALCIFICATIONS WHICH
COULD BE VERY USEFUL TO US.
OKAY, SO WHAT DO WE WANT TO DO
WITH THOSE?
ONE OF THE THINGS WE HAVE TO DO
IS ASSESS THE ATTENUATION AND
BASE ABERRATIONS CORRECTIONS
WHICH WAS ALLUDED TO EARLIER, SO
I HAVE A COUPLE OF ANIMATIONS
HERE THAT SHOW YOU WHAT THE
ISSUE IS, SO IF WHAT YOU HAVE IS
YOUR BEAM GOING THROUGH
HOMOGENERATED YIEWS SKULL, THEN
YOU SEE THE OTHER SIDE IS THAT
THE WAVE FRONTS ARE ALL IN FACE
AND THAT'S IN CONTRAST TO THE
SITUATION NOW WHERE IF YOU HAVE
YOUR WAVE FRONTS COMING THROUGH,
A SKULL THAT IS VARIABLE
THICKNESS, SO IT'S NOW GOING TO
HIT THE SKULL, THOSE WAVE FRONTS
WILL SPEED UP AS THEY GO THROUGH
THE SKULL BECAUSE IT'S VARIABLE
THICKNESS THEY COME OUT ON
DIFFERENT PHASES ON THE OTHER
SIDE.
SO NOW WE HAVE THE SITUATION
WHERE OUR BEAM WAS--I DIDN'T
MEANINAR TO PLAY AGAIN WAS
INITIALLY END FACE AND THEN, IT
WAS COHERENT AND THEN IN THE END
IT WAS INCOHERENT OR OUT OF FACE
SO IF YOU LOOK OVER HERE YOU CAN
SEE IT'S A HIGH PRESSURE POINT
AND A LOW PRESSURE POINT AND
WHAT DOES THAT DO, SO IF YOU
HAVE A BEAM WHICH IS NOT
ABNORMALITIESERATED AND MORE AND
MORE ABERRATION LOOKS LIKE THAT.
AND SO WHAT IF YOU SAY THESE
SKULLS OVER HERE YOU MIGHT HAVE
SIGNS THAT ARE A LITTLE BIT
ABNORMALITIESERATED AND OVER
HERE VERY ABNORMALITIESERATED
THIS IS AGAIN WHAT WYNN
MENTIONED AND THIS IS AN
INTERESTING CASE BECAUSE IT MAY
NOT BE VERY ABNORMALITIESERATED
BUT IT WOULD BE REFRACTED
MEANING IT WON'T BE WHERE YOU
THINK IT IS.
SO MY POINT HERE WAS THAT MRI
CAN DO A GOOD JOB OF
DIAGONALLING YOU NOT JUST ABOUT
THE ABSORPTION OF THE
ATTENUATION BUT ALSO THE
ABERRATION CORRECTIONS AND THE
IDEA HERE IS THAT IF YOU CAN
CALCULATE WHAT THE PHASES SHOULD
BE THROUGH ANY PORTION OF SKULL,
CAN YOU PREPHASE THE ELEMENTS IN
ORDER TO MAKE SURE THE BEAM IS
COHERENT AT THE FOCUS.
OKAY, SO TO PROVE THAT POINT, MY
STUDENT STEVE YOUNG DID THIS
WITH THE INSIGHT TRANSDUCER, HE
HAD 3 DIFFERENT SKULLS AND HE
DID THIS VERY CAREFUL SET UP
WHERE HE PUT THE SKULLS IN THE
TRANSDUCER AND HE HAS A
HYDROPHONE RIGHT HERE AND HE CAN
TURN THE TRANSDUCER ON AND GET A
PICTURE OF THE FOCAL SPOT AND IN
THE ABSENCE OF ANY PHASE
CORRECTION, YOU SEE SOMETHING
THAT LOOKS LIKE THAT SO THE
INTENSITY IS A BIT LOW AND ON
AVERAGE IT'S A BIT LOW COMPARED
TO THE SITUATION WHERE YOU WERE
TO DO THE BEST CORRECTION YOU
COULD THAT MEANS YOU WOULD
CALCULATE THE PHASES WITH THAT
HYDROCONE AS YOU TURN ON 1
ELEMENT OF A TIME, YOU COULD
CYCLE THROUGH ALL THE ELEMENTS
AND CALCULATE THOSE PHASES ARE
AND YOU CORRECT FOR THAT AND
THAT'S THE BEST YOU CAN DO AND
SO, THAT'S WHAT I'M GOING TO
GIVE OVER HERE WITH A NORMALIZED
TO THAT 1 SO IT'S A VALUE OF 1.
OKAY, WHERE AM I GOING WITH
THIS?
I WANTED TO TELL YOU ABOUT MRI
VERSUS CT.
SO THE IDEA NOW IS IF YOU TAKE
YOUR MRI PICTURE OF THE SKULL
AND SAY LET'S CALCULATE WHAT
THAT PHASE TERM SHOULD BE, YOU
DO THAT FOR THE PATHS AND YOU
THEN YOU GET A PICTURE OF THE
FOCAL SPOT AS MEASURED AND YOU
CAN DO THAT WITH CT AS WELL AND
HOW DO THEY COMPARE, OOPS, SORRY
ABOUT THAT, NIGH NEED TO GO
BACKWARDS.
AND THEN WHAT YOU SEE, THE
COMPARISON IS THAT ACROSS THE 3
OTHER SKULLS ON AVERAGE THEY ARE
EQUIVALENT.
THEY GIVE YOU AN EQUIVALENT OF
FOCAL SPOT, AT THE--THIS WAS
JUST 1 OF THOSE 3 SKULLS BUT ON
AVERAGE ACROSS THE 3, THEY'RE
EQUIVALENT SO MRI CAN BE USE
INDEED PLACE OF CT.
OKAY, SO THAT'S 1 PLACE, 1 OF
THE 3-POINTS I WANTED TO
DISCUSS.
THE SECOND 1 IS CAN MRI BE USED
TO MAKE A MEASUREMENT.
SO, WE TALKED A BIT ABOUT WELL,
YOU COULD CALCULATE WITH THE
PHASE IS, YOU COULD DO A BEAM
SIMULATION BUT COULD YOU MAKE A
MEASUREMENT OF WHAT ACTUALLY
REACHES THE BRAIN AND THEN WHAT
CAN THAT TELL US.
SO, WE DID A STUDY, LARGE ANIMAL
STUDY, WITH THE FRY BROTHERS DID
BACK IN THE 1950SALY WE DID IT
ACROSS THE INTACT SKULL IN THE
SHEEP AND WE SONICATED LGN WHILE
THERE WERE FLASHING LIGHTS ON
THE SHEEP MODEL HERE.
WE DID THIS WITH THE INSIDE
TRANSFACIC TRANSDUCER, 500
KILOHERTZ WHICH IS GREAT, NOT
SUITABLE FOR HUMAN USE BUT WE
WERE ABLE TO USE IT FOR THIS
STUDY.
THE SHEEP MODEL AGAIN HAS A THIN
AND HOMOGEANIOUS SKULL AND WE
AFFIXED THE TRANSDUCER TO THE
TOP OF THE MR HEAD COIL.
WE HAD TO USE THE HEAD COIL
BECAUSE IT WOULD ACCOMMODATE THE
SHEEP NOSE AND YOU CAN SEE THE
LED FLASHING LIGHTS HERE ON THE
SHEEP.
OKAY, SO WE PUT THEM IN THE MR
UNDERANESTHESSIA AND FIGURED OUT
WHERE THE LGN WAS AND WE
COULDN'T FIND THE RIGHT CLAIM IN
ORDER TO DO THAT STUDY SO WE
REFER TODAY BACK TO PUTTING
ELECTRODES BACK ON THE
SUBCUTANEOUSLY OVER THE VISUAL
CORTEX AS WELL AS FRONTAL PART
OF THE BRAIN AND THEN OUR
PARADIGM WENT LIKE THIS,
SOPHISTICATEDY THEY WERE AN
THESAURUS THISITIZED DOING THE
E, G AS WE FLASHING LIGHTS IN
ORDER TO MEASURE THE POTENTIAL
WHICH WOULD BE 240 MINUTES
PERIOD FOLLOWED BY 2-3 MIN
PERIODS OF SONIC CONTROL
LOCATION SO WE HAD AN ACTIVE
CONTROL, DURING THAT PERIOD
THERE WAS 1 THAT WAS ONLY LIGHT
ONLY AND 1 THAT WAS ULTRASOUND
ONLY, BUT I WILL SHOW YOU THE
RESULTS FROM THE LIGHT ONLY.
AND SO THAT MEANS IT'S A BIT
MORE LIKE AN OFFLINE PROTOCOL IN
THAT THE ULTRASOUND HAD BEEN ON
DURING OTHER--ANOTHER 152nd
PERIOD BUT WE WEREN'T LOOKING
RIGHT AFTER THE ULTRASOUND.
AND THE HEART RATE AND
TEMPERATURE MAINTAINED CONSTANT
WHICH IS SORT OF LIGHTENING UP.
SOPHISTICATED OKAY, SO THIS
LOOKS AS IF OUR FOCAL SPOT
LOOKED LIKE AND WE DID THE
SIMULATIONS AND THEN WE DID AN
PICTURE SO WE'RE ABLE TO GET A
PATIENTS IN THE CLINIC UPPER OF
THE FOCAL SPOT SO I WANT TO TAKE
TIME TELLING YOU ABOUT MRRP, AND
THE WAY WE USE IT AT THE TIME
WAS SORT OF VERIFYING OUR
TARGET, WELL 2 THINGS FIRST OF
ALL WAS THE EQUIPMENT WORKING,
THAT WAS IMPORTANT TO KNOW.
YES WE GOT AN ULTRASOUND INTO
THE BRAIN AND IS IT WHERE WE
PRESCRIBED IT TO BE?
BECAUSE IT'S ENTIRELY POSSIBLE
IN A SKULL THAT WASN'T THIN AND
HOMOGEANIOUS IT MAY HAVE BEEN
DISPLACED AS I MENTIONED BEFORE
BUT HERE IT GAVE US THE LOCATION
WHERE WE WANTED IT SO THAT WAS
GREAT.
SO JUST A BIT OF A DIGRESSION AS
TO HOW THIS WORKS.
WHEN YOU TURN ULTRASOUND ON,
THERE WILL BE ABSORPTION OF
MOMENTUM, YOU LOOK AT THE FOCUS,
THEY WILL ABSORB AND THEN I WILL
DISPLACE AS CAN YOU SEE THERE,
SO WITH MRI WHAT HAPPENS IS THAT
WE TURN THE ULTRASOUND ON,
DURING THE APPLICATION OF A
MAGNETIC FIELD GRADIENT.
SO WHEN WE DO THAT NOW, WE THINK
ABOUT PROTONS, SPINS ABOVE
PROTONS THEY WILL MOVE TO A
HIGHER MAGNETIC FIELD, THEY WILL
ACCUMULATE PHASE DEPENDING ON
THE DISTANCE THAT THEY MOVED AND
NOW WHAT WE'VE DONE IS WE
ENCODED INTO THE PHASE WHAT THAT
DISPLACEMENT WAS.
IN OTHER WORDS WE ENCODED TO THE
FACE WHAT THE INTENSITY OF THE
ULTRASOUND IS.
SO THIS WAS SORT OF A SIMPLE
IMPLEMENTATION, WE DON'T USE
SOMETHING WIGHT THAT SIMPLE.
WE USE SOMETHING QUITE LIKE
THIS, IT HAS A LOWER B-VALUE SO
WE HAD BETTER SIGNAL TO NOISE.
THAT'S WHAT OUR EXVIVO PICTURE
LOOKED LIKE AND THEN FOR ANY
PARTICULAR SET UP, AS YOU
INCREASE THE POWER ON THE
TRANSDUCER, THEN YOU GET MORE
DISPLACEMENT AND SO, THIS IS
JUST SAYING AS WE HAVE MORE
INTENSITY, AND WE TURNED IT UP,
THE POWER AND WE GET MORE
DISPLACEMENT.
SO THE REQUESTY IS, CAN WE
MEASURE DISPLACEMENT AND BACK
OUT THE INTENSITY OR EFFECT?
SO THE EFFECT WE WERE LOOKING AT
WAS IN THE SHEEP.
WE WERE LOOKING AT REDUCTION IN
THE VISUALLY EVOKED POTENTIAL SO
THIS IS THE ANIMALS, THIS IS
JUST 1 OF THEM SHOWING YOU THE
TRACE THERE, SO THE BASE LINE IS
IN BLUE, WE WERE LOOKING AT THE
DIFFERENCE BETWEEN THE N70 AND
THE P100 PEAKS AND SEEING WHEN
WE WERE SONICATING LGN THAT WAS
REDUCED.
JUST LOOKING OVER A NUMBER OF
ANIMALS, HERE'S THE SHAM ANIMALS
AND ON AVERAGE THERE'S NO
DIFFERENCE AND IN THE 1S WE WERE
SONICATING, THERE WAS A
REDUCTION AND WE WERE SONICATING
IT AT ACTIVE CONTROL AND THIS IS
JUST IN THE BAR GRAPH OF THAT
SAME DATA AS WELL AND THESE 2
LGN TIME POINTINGS TOGETHER IN
THE 3 CONTROLS THERE.
OKAY, SO WE SEE A REDUCTION AND
DOES THE MRR, TELL US ABOUT THE
REDUCTION?
IN THIS PLOT WE HAVE THE
REDUCTION IN THE VISUALLY
REVOKED POTENTIAL SO HERE WE SEE
THE SITUATION WHERE THERE'S
LOWER SKULL ATTENUATION, THERE'S
MORE DISPLAYMENT AT THE FOCUS
AND THAT'S WHERE WE HAD A BIGGER
REDUCTION IN THE VISUALLY EVOKED
TO PENTINE REGIMENNIAL, OVER
HERE THERE'S HIGHER SKULL
ATTENUATION, LESS DISPLACEMENT
AND LESS OF A REDUCTION, SO THIS
IS REALLY NICE BECAUSE NOT ONLY
WOULD IT TELL US, YES, IT'S
WORKING AND THE SPOT IS WHERE WE
THINK IT SHOULD BE, BUT IT ALSO
TELLS US HOW MUCH INTENSITY
WE'RE ACTUALLY GETTING INTO THE
SKULL AS OPPOSED TO KIND OF
SIMULATING JUST ENOUGH.
AND THEN THEREFORE, HOW MUCH OF
A MODLATTORY EFFECT DO YOU THINK
WE'RE GOING TO GET.
OKAY, SO THE THIRD THING I WANT
TO TALK ABOUT TODAY IS A BIT ON
THE AUDITORY COMPOUND AND THEN
MRI WILL PLAY A ROLE HERE TWICE
SO THE STORY HERE IS THAT FIRST
OF ALL IT'S BEEN A COUPLE YEARS
SINCE WE WERE SORT OF REAWAKENED
TO THE ISSUE THAT ULTRASOUND CAN
BE HEARD.
AND SO, IF YOU HAVE AN
ULTRASOUND ENVELOPE THAT LOOKS
LIKE THIS WITH A RECK TANGLE
THEN IT'S A RECENT PUBLICATIONS,
SHOWED THAT IN RODENTS, THAT
COULD BE HEARD AND THEN WE
FOLLOWED UP WITH A PUBLICATION
THAT SHOWED IF YOU SMOOTH YOUR
WAVE FORMS, AND YOU DON'T HAVE
FREQUENCY, IMPLEMENTS THAT
OVERLAP IN THE HOUSE HEARING
RANGE THEN IT DOESN'T INVOLVE
THE PERIPHERAL AUDITORY SYSTEM,
OKAY, SO NOW, IN 2022, WE 2
WEEKS AGO HAD THE FOCUS
ULTRASOUND MODULATION CONFERENCE
AND THERE'S A FAIR AMOUNT OF
FOCUS ON THE ISSUE OF THE
AUDITORY COMPOUND IN HUMANS SO 2
OF THE LABS THERE, LEONARD AND
[INDISCERNIBLE] WERE BOTH
SHOWING THAT IF YOU USED A WAVE
FORM THAT HAS THESE SQUARE
COMPONENTS, THEN IT'S GOING TO
AFFECT AN ONLINE TASK THAT HAS
ATTENTION EFFECT.
AND THEN ALSO THE IMPLICATION IS
THAT IF THERE'S GOING TO BE A
TREATMENT THAT WILL HAVE A
PLACEBO EFFECT THEN THAT COULD
BE EFFECTIVE AS WELL.
ALL RIGHT, SO, WHEN I WAS ON
SEBATICLE THIS SUMMER I SPENT A
MONTH WITH [INDISCERNIBLE] AND
WE DID A PILOT STUDY AND IN THIS
STUDY WE STUDIED 7 SUBJECTS
WHERE WE,A PLIED A RECTANGULAR
WAVE FORM LIKE THIS, THAT WAS
20-SECONDS LONG AND THIS 1
LOOKED RAMPED UP AND THIS IS
WHAT THE POWER SPECTRA LOOKS
LIKE.
SO IN THE RECTANGULAR WAVE FORM
THERE'S PREQUENCY COMPONENTS
ACROSS THE HEARING RANGE,
HEARING IS DEFINED AS 32-HERTZ,
2/16 KILOHERTS.
SO WE HAVE A REDUCTION HERE IN
THE FREQUENCY COMPONENTS THAT
HUGH MANS ARE MOST SENSITIVE TO
FROM 1 TO 41 KILL HERTZ TO 1
KILL HERTZ AND THERE'S REDUCTION
OF MAGNITUDE IN THE POWER
SPECTRUM SO WHAT HAPPENED WITH
OUR SUBJECTS.
AS I MENTIONED WE HAD 7 SUBJECTS
AND WE WOULD INCREASE, WE
INTERSPERSED THESE TO IN A
RANDOM ORDER AND WE INCREASE
INDEED LOWERED THE PRESSER LEVEL
AND ASKED THEM WHEN WHO RAISED
THEIR HAND WHEN THEY HEARD
SOMETHING AND HERE WE'RE
PLOTTING THE DETECTION THRESHOLD
SO THIS IS FOR THE RECTANGULAR
PULSES SHOWN HERE WITH ALL THE
FREQUENCY COMPONENTS HERE SAYS
KROO THE RAIRVELG SO YOU SEE THE
DETECTION THRESHOLD IS A LOW
PRESSURE, AND THEN WITH THE
SMOOTHED WAVE FORM IT INCREASES
ON AVERAGE THE DETECTION
THRESHOLD WITH PRESSURE.
SO THAT WAS REALLY GREAT SAYING
THAT YOU KNOW THIS CAN REALLY
REDUCE THE AUDITORY COMPOUND IF
YOU SMOOTH THE FORM IN RODENTS,
THE SAME THING HAPPENS FOR
HUMANS AS WELL.
SO THAT'S REALLY GREAT.
I DO WANT TO POINT OUT THE FACT
THAT WHILE MRI IS VERY USEFUL,
CAN BE USED FOR LOTS OF THINGS,
IF, MRI, FOR EXAMPLE, THAT I
JUST MENTIONED, THAT THIS
AUDITORY ISSUE IS VERY
PROBLEMATIC FOR MRI, IT'S
ALREADY A LOUD ENVIRONMENT AND
THEN WE'RE TALKING ABOUT
APPLYING ULTRASOUND WHICH CAN BE
HEARD ESPECIALLY IF YOU DO
SOMETHING LIKE A 1 KILOHERTZ
RECTANGULAR PULSE LINGS THAT ARE
INCREDIBLE LOAMACYY LOUD AND TO
TOP IT ALL OFF, IT'S ESPECIALLY
PROBLEMATIC BECAUSE IF YOU WEAR
EAR PLUGS THE CONDUCTED SOUND IS
A THOUSAND TIMES LOUDER, SO IT'S
VERY PROBLEMATIC FOR MRI IN
TERMS OF SAFETY.
IT'S ALSO ANOTHER POINT I WANTED
TO POINT OUT HERE IS THAT IT'S
ACTUALLY VERY INTERESTING, SO
THIS PARTICULAR WAVE FORM WAS A
LITTLE BIT COMPLEX, IT SOUNDED
MORE LIKE A--ACTUALLY PLAYED 3
IN A ROW, 2 OR 300 MILLISECONDS
APART SO IT SOUNDED LIKE
TSH-TSH-TSH.
SO THIS JUST RESULTED IN A VERY
HIGH PITCH.
HIGHER PITCH THAN THE ENVELOPE
OF THAT WAVE FORM WOULD HAVE
SUGGESTED BUT THAT IS WELL
CORROBORATED WITH THE LITERATURE
THAT THERE IS A FREQUENTLY
HIPITCH.
AND WE LOOK AT THIS DATA OVER
HERE, IT WAS VERY INTERESTING
BECAUSE AGAIN, THE SUBJECTS
REPORTED THIS HIGH PITCH AND ALL
OF THESE SUBJECTS, WELL I SHOULD
SAY, 6 OUT OF THE 7 WERE WERE
TESTED AND HAD NORMAL HEARING
AND THE PURPOSE WHO HAD THE BEST
HEARING WAS THE LIGHT PLURIBU
AND THEN THEY COULD NOT HEAR
THAT HIGH PITCH.
SO THERE'S A LOT OF VARIABILITY
IN TERMS OF COULD HEAR WHAT.
AND THEN, LASTLY IT WAS VERY
INTERESTING BECAUSE I WAS ABLE
TO LOOK BACK, 5 OF THE 7
SUBJECTS HAD BONE MRIs AND I
WAS ABLE TO LOOK BACK AND SEE
HOW THORS THRESHOLD DETECTION
RELATED TO SKULL THICKNESS AND
YOU CAN SEE THAT THE DETECTION
THRESHOLD WAS HIGHER WHEN THEY
HAD A THICKER SKULL.
SO MOST LIKELY THAT'S TELLING US
THAT WELL, THERE'S 2
POSSIBILITIES, EITHER THE
THICKER SKULL DIDN'T SORT OF
RESONATE TO THE ULTRASOUND IN
THE SAME WAY OR THAT WHAT THEY
HEAR WITH THAT HIGH PITCH IS
BECAUSE THE ULTRASOUND IS
GETTING THROUGH AND THEN IT'S
SORT OF VIBRATING THE TISSUES
AND THAT'S GOING IN VIA TISSUES
MAYBE THROUGH THE INTURNOVERRAL
AUDITORY CANAL BUT THERE'S I
LITTLE HERE WE HAVE STOCK
EXCHANGE STUDY AND IN TERMS OF
BONE CONDUCTION AND WILL END UP
BEING VERY INTEREST.
OKAY, SO I WOULD LIKE TO
CONCLUDE NOW.
MR SKULL IMAGING CAN BE
EQUIVALENT TO CT, WITH THE GOOD
PICTURES WE'RE SEEING, IT COULD
BE USED TO SCREEN FOR KAGZ
ESKSS, MRR FEE WILL BE A VERY
IMPORTANT TECHNIQUE TO ASSESS
LOCATION AND ALSO PROVIDE A
MEANS TO ELECTRIC AT THE DOSE
ACTUALLY DREVERRED INTO THE
BRAIN IN ORDER TO GET A SENSE OF
THE DOSE RESPONSE AND THEN
LASTLY, NOT LISTED HERE, WE DO
NEED TO BE CAREFUL OF THE
AUDITORY COMPOUND, NOT JUST FOR
THE COMPOUND FOR THE TASK BUT
ALSO IN TERMS OF SAFETY AND THE
AUDITORY EFFECTS WITH ULTRA
SOUND COULD BYE-BYE A SAFETY
ISSUE.
--BECOME A SAFETY ISSUE.
I THINK I'M OUT OF TIME.
DO WANT TO ADVERTISE THE FOCUS
ULTRASOUND MODULATION CONFERENCE
IN 2023.
WE AS A MULTIDISCIPLINARY
CONFERENCE FOCUSING ON
MECHANISMS, NEUROSCIENCE AND
CLINICAL APPLICATIONS AND
TECHNICAL ADVANCEMENTS.
I WOULD LIKE TO ACKNOWLEDGE MY
GROUP, FUNDING AND MY CENTERS.
THANK YOU IF YOU HAVE QUESTIONS,
I AM HAPPY TO ANSWER THEM AT
THIS TIME.
>>[ APPLAUSE ]
>>QUESTIONS FOR DR. PUTTS
PAULEY.
>>GREAT TALK.
DID YOU--HOW WELL DO YOUR
DISPLACEMENT MEASUREMENTS
CORRELATE WITH ATTENUATION
MEASUREMENTS FROM ANY KIND OF
ACOUSTIC MODELS WHETHER THEY
CORRELATE THAT WAS 1 WAY TO
MEASURE IT, SO HOW WELL DID
THOSE WORK?
>>THEERGT OF THEM CORRELATED
WITH IT EITHER, SO SINCE THERE
WAS A GOOD CORRELATION BETWEEN
THE DISPLACEMENT, YOU BELIEVE
THOSE MORE THAN WE BELIEVE THE
OTHER 2 METRICS.
ANOTHER QUESTION?
>>HOW WELL DO YOU THINK IF YOU
DID AN OFFLINE ULTRA ULTRASOUND
MAKE GET THE PREDATORY ISSUES?
>>HOW MUCH OFFLINE DO YOU THINK
I WOULD RSKT AFFECTED FOR IT.
>>YEAH.
>>I'M NOT SURE, THAT MIGHT BE
SOMETHING FOR THE CLINICAL
SCIENTISTS TO FIGURE OUT.
I THINK IT WOULD BE INTERESTING
TO FIND OUT.
, THANK YOU.
>>GREAT.
TALK I HAVE A QUESTION ABOUT
YOUR AUDITORY CONFOUND.
IF YOU LOOKED AT THE AUDITORY
CORTICALE RESPONSE AND HOW THAT
MAYBE CORRELATE TO THE
DETECTION?
OR ANY WAY AND THAT GIVES TOO
ABOUT WHETHER THAT'S LIKE BONE?
>>SO WE HAVEN'T DONE THAT IN
HUMANS, WE HAVE DONE SOME WORK
IN THE MOUSE WITH THE CALCIUM I
WAS TELLING YOU THERE AND WOOF
BEEN MAINLY LOOKING AT THE
SMOOTH WAVE FORMS BECAUSE WE
WANT TO TO STAY AWAY FROM THE
AUDITORY CONFOUNDS, WE HAVE DONE
JUST A TOKEN NUMBER WITH A
RECTANGULAR WAVE FORM IS IT
SEEMS SORT OF ON THE SURFACE AND
QUANTITATE THAT AND THAT THE
FLUORESCENCE RESPONSE WE SEE IS
VERY HIGHLY CORRELATED TO THE
PRESSURE TIMES THE SQUARE ROOT
OF THE DURATION OF THE PULSE,
AND SO THAT HOLDS FOR BOTH WHEN
YOU LOOK AT THE LOCUST.
>>YOU SAW MAYBE REDUCTION OF
THE VP, STRONGER EFFECT FOR THE
STRONGER DISPLACEMENT, THAT IS
QUITE IMPRESSIVE TO ME AND 1
THING THAT WE CAN OBSERVE ACROSS
THE 3 TALKS TODAY, AT LEAST
BECOME AN OBSERVATION TO ME WAS
THE INHIBITION IN RESPONSE TO
THE ULTRASOUND.
SO, WE MIGHT START THINKING OF
WHY WE SEE THESE INHIBITORY
EFFECTS IN THESE CASES, AND YOU
HAVE ANY THOUGHTS ON THAT.
>>YEAH, THERE'S A FAIR AMOUNT
OF WORK GOING ON RIGHT NOW,
LOOKING AT RODESSENTS WITH THE
CALCRUM IMAGING OF WHERE THEY
MAKE A GCAMP MODIFICATION, I
SHOULD SAY ME AND OTHERS ARE ON
EXCITATORY CELLS AND INHIBITORY
CELLS AND IT'S ACTUALLY VERY
INTERESTING THAT IT SORT OF A
RESPONSE DEPENDS ON THE MAKE UP
OF THE CELLS IN DIFFERENT PARTS
OF THE BRAIN.
SO THE CORTEX FOR EXAMPLE WHERE
HAVE YOU BOTH AND YOU SEE A BIG
RESPONSE AND YOU POLIT IT OUT,
IT SEEPS LIKE THE INHIBITORY
CELLS HAVE SORT OF A DECREASE
AND MAYBE THE INTERPRETATION
THEN IS THAT THE INHIBITORY
CELLS ARE SHUTTING DOWN, THE
EXCITATORY CELLS, HAVE A BIG
RESPONSE, SO I THINK A LOT OF IT
HAS TO DO WITH THE CELL MAKE UP,
IN THAT WHEN WE THINK ABOUT IF
SOMETHING'S EXCITATORY OR
INHIBITOR, WE HAVEN'T TAKEN THAT
INTO ACCOUNT AND I THINK WE
THINK BACK ON THEKS SIGHTATTORY
AND INHIB THORS ORT WE SHOULD
PROBABLY TRITE TO DISAMBIGUATE
THAT BEFORE WE MAKE CONCLUSIONS.
MAYBE WE SHOULD
REINREPRESENTATION AT THE TIME
OUR LITERATURE.
>>ADDITIONAL QUESTIONS FOR
DR. BUTTS-P A ULY?
ALL RIGHT.
GREAT LETS THANK THE DOCTOR
AGAIN.
[ APPLAUSE ]
>>ALL RIGHT, I'M BASTIAN AND I
WILL START THE PROFFERED PAPERS
ORAL SESSION.
I WOULD LIKE TO REMIND THE
SPEAKERS TO USE THIS SLIDE, IF
YOU DON'T HAVE THE SLIDE, SAY IT
OUT LOUD.
AND FINALLY IF
AURORE NIEWENHUYS, IF YOU ARE
HERE PLEASE UPLOAD YOUR PAPER IF
YOU ARE NOT HERE WE WILL MOVE
ON.
AND RIGHT NOW WE WILL HEAR FROM
HARRIET LEA-BANKS AND SHE WILL
TALK ABOUT MRI-GUIDED
TRANSCRANIAL FOCUSED ULTRASOUND
FOR ANESTHETIC DELIVERY IN THE
BRAIN.
>>HELLO, DISCLAIMER AND
PROFESSORS THOSE THAT ARE USED
IN THIS WORK.
THIS IS A REAL COLLABORATIVE
EFFORT BETWEEN A GROUP OF
SCIENTIST DEPARTMENT AND SUNNY
BROOK AND THE ALSO THE DIVISION
OF NEUROSURGERY AND OUR
COLLEAGUES IN NEUROSURGERY ARE
ABSOLUTE EXPERTS IN DEEP BRAIN
STIMULATION BUT ARE NOW LOOKING
FOR A NONINVEIGHS ALTERNATIVE
METHOD TO EITHER EXCITE OR
INHIBIT SPECIFIC PARTS OF THE
BRAIN AND WORK WE'VE BEEN
INVOLVED IN LOOKS AT USING NANO
PARTICLES TO DELIVER ANESTHETIC
AGENTS IN SPECIFIC REGIONS OF
BRAIN GUIDED AND TARGETED WITH
MRI GUIDED TRANSCAIN ARIAL
FOCUSED ULTRASOUND.
AS WE'VE HEARD ALREADY TODAY,
MANY TIMES FOCUSED ULTRASOUND
ALONE IS ABLE TO MODULATE
NEURONAL ACTIVITY.
BUT PREVIOUSLY, WE'VE SHOWN THAT
YOU CAN USE ULTRASOUND TO
TRIGGER THE RELEASE OF
ANESTHETICS IN THE BRAIN, IN
PARTICULAR, WE'VE BEEN LOOKINGA
THE ANESTHETIC AGENT PENTIUM
BARB TOLL-LIKE RECEPTOR WHEN
LOOEDED INTO THE DROPLETS, THESE
LIQUID FILLED NANO DROPLETS,
THEY UNDERGO VAPORIZATION, THEY
TRANSFORM FROM A LIQUID NANO
PARTICLE INTO A GASEOUS
MICROBUBBLE.
AND AS THEY UNDERGO THIS
PROCESS, NOT ONLY DO THEY EMIT
UNIQUE ACOUSTIC EMISSIONS WE CAN
DETECT IN REALTIME THEY ALSO
OFFLOAD ANY DRUG THEY MIGHT BE
CARRYING IN THEIR SHELL FOR
EXAMPLE, FOR EXAMPLE
AN ANESTHETIC AGENT. AND WE'VE
BEEN ACIAL TO SHOW IF WE TRIGGER
THIS MOTORIZATION, IN 1 HALF OF
THE MOTOR CORTEX, WE CAN SEE A
ROBUST AND SUSTAINED MOTOR
SENSORY DEFICIT WHICH LASTS UP
TO 2 HOURS AFTER TREATMENT AND
THIS IS PERHAPS THE
BEGENERATEDDING OF COMPATTING
THOSE LIMITATIONS AROUND USING
FOCUS ULTRASOUND FOR
NEUROMODDULATION AND TYPICALLY
THOSE TRANSIENT EFFECTS PERHAPS
BY USING ULTRASOUND TO DELIVER
AN AGENT THAT HAS A LONGER
LASTING EFFECT, WE CAN SUSTAIN
AND ENHANCE THE PERSISTENCE OF
ULTRASOUND FOR NEUROMODDULATION.
TO GIVE YOU A BIT OF BACKGROUND
ABOUT THESE NANO DROPLETS,
THEY'RE RELATIVELY TIGHTLY SIZE
DISTRIBUTED WITH A DIAMETER OF
200 NONE O METERS BUT WHEN THEY
UNDERGO VAPORIZATION THEY
TRANSFORM INTO 1 MICRON SIZED
MICROBUBBLES.
THIS IS OF A TYPICAL SIZE AT
LEAST BOTH IN CLINICAL
DIAGNOSTIC IMAGING AND FOR BLOOD
BRAIN BARRIER IMAGING, WE SEE
THAT THIS VAIBORRIZATION PROCESS
IS PRESSURE DEPENDENT AND
DEPENDING ON THE FORMULATION
OFLET DROPMENTS AND THE
FREQUENCY WE USE AS WE RAMP UP
THE ULTRASOUND PRESSURE, WE SEE
THIS DISTINCT THRESHOLD BY THOSE
DROPLETS VAIBORRIZE, THEY EMIT
THESE EMISSIONS AND ALSO WE FIND
THOSE ACOUSTIC EMISSIONS MAP TO
THE EXTENT OF DRUG RELEASES
THAT'S OCCURRING.
AS I MENTIONED THIS VAPORIZATION
THRESHOLD IS ALSO RELATIVE AND
ALSO DEPENDENT ON FREQUENCY.
WE FIND THAT HIGHER FREQUENCIES,
TYPICALLY FOR THIS FORMULATION
REQUIRE HIGHER ULTRASOUND
PRESSURES.
SO HOW DO WE ACHIEVE THIS IN
VIVO, WELL WE'RE USING THIS MRI
GUIDED TRANSCRANIAL AND SINGLE
METROPOLITAN TRANSDUCER WHICH
WE'RE DRIVING THIRD HARMONIC
FREQUENCY AND IN THE CENTER OF
THERE IS A HYDROPHONE, A SECOND
TRANSDUCER THAT'S LISTENING BACK
TO ANY EMITTED ACOUSTIC FROM
THAT FOCAL REGION.
THE RAT HERE IS PLACED AND THE
HEAD IS--SO YOU CAN SEE HERE
THAT THE CENTRAL LOCATION OF
THAT MR IMAGE WAS CO REGISTERED
TO THE WELLICATION OF THE
ULTRASOUND FOCUS, WE'RE ABLE TO
GET ACCURATE TARGETING OF OUR
ULTRASOUND FOCUS WITHIN THE
BRAIN.
IN TERMS OF TREATMENT, WE'RE
USING A SIMPLE ULTRASOUND
PULSING SCHEME, 10 MILLI SECOND
BURSTS, PULSE EVERY SECOND FOR A
DURATION OF 5 MINUTES.
DISP THOSE DROPLETS ARE
DELIVERED THROUGH IV.
PREVIOUSLY THE WORK I'VE SHOWN
YOU HAS BEEN WITH THE INTACT
BLOOD BRAIN BARRIER, NOTHING HAS
CHANGED IN TERMS OF THE
COMPETITION OF THE BRAIN.
WE'VE BEEN USING SMALL LIP
OPHILIC AGENTS THAT ARE ABLE TO
CROSS THE BLOOD-BRAIN BARRIER SO
RECENTLY WE DELIVERED CO
DELIVERING MICROBUBBLES
ALONGSIDE NANO DROPLETS TO SEE
IF THIS EFFECT COULD BE ENHANCED
AND SUSTAINED FURTHER.
SO IN THIS SCHEMATICIME SHOWING
YOU 4 SEQUENTIAL EEVENLGT EVENTS
THAT HAPPEN DURING OUR PROTOCOL.
SO FFORTLY WE'RE INJECTING
MICROBUBBLES AND NANO DROPLETS
TOGETHER IN THE RAPS, WE THEN
VERIFIED THAT WE'RE ABLE TO
ACHIEVE BLOOD BRAIN BARRIER
OPENING, SO HERE YOU CAN SEE
SOME OF THOSE UNIQUE AKOWOF
THETIC EMISSIONS THAT WE ONLY
DETECT WHEN WE HAVE DOUBLES
PRESENT, HARMONIC FREQUENCIES
WITHIN ULTRASOUND SPECTRA,
BUBBLES RESPOND AT MUCH LOWER
PRESSURES THAN NANO DROPLETS, SO
LEER WE'RE USING A LOW PRESSURE
ULTRASOUND SONICATION, SO YOU
EXCITE THE MICROBUBBLES, THE
DYNAMICALLY RESPONDING IN SIZE
AND THEY'RE OPENING UP THOSE
TIGHT JUNCTIONS INCREASING THE
PERMIABILITY OF THE BLOOD BRAIN
BARRIER.
WE VERIFIED THE BLOOD BRAIN
BIRRIER SURFACESSIER HAS BEEN
CHANGED IN SOME WAY BOTH THROUGH
MRI CONTRAST ENHANCED
IMPEDIMENTSAGING, THIS IS AN
AGENT WE INJECT OR THROUGH EVANS
BLUE FOR HISTOLOGICAL APPROACH,
BOTH OF THESE ARE 2 DYES WITH AN
INTACT BRAIN BEAR AREA WOULD NOT
BE SEEN IN THE BRAIN TISSUE.
THIRDLY WE WAIT FOR THOSE
MICROBUBBLES TO WASH OUT.
TYPICALLY THIS ONLY TAKES A
MINUTE BUT TO BE SAFE WE'RE
USING A 20 MINUTE DURATION TO
INSURE THOSE MICROBUBBLES ARE
WASHED OUT IN CIRCULATION.
WE APPLY A SECOND LOW PRESSURE
SONICATION TO VERIFY THAT THAT'S
HAPPENED AND YOU CAN SEE HERE
THAT WE'RE ONLY SEEINGA I
REFLECTION OF THE FUNDAMENTAL
THERE, NONE OF THOSE EXCITING
HARMONIC EMISSIONS, 30 MINUTES
LATER WE WANT TO SEE HAVE WE
THEREFORED NANO DROPLETS INTO
THE BRAIN TISSUE, IS ANYTHING
STILL ACOUSTICALLY ACTIVE IN
THAT REGION.
NOW AT THIS TIME POINT IF WE
SONICATE THE OTHER HEMISPHERE, A
MEMORY RESPONSEIS FEAR THAT
HASN'T BEEN OPENED WE DON'T SEE
CEREBELLUMS SIGHTING ACOUSTIC
EMISSIONS, HOWEVER WHEN WE
SONICATE AT A HIGHER PRESSURE,
REQUIRED FOR VAPORIZATION, THAT
OPEN BRAIN REGION WE SEE THIS
REAPPEARANCE OF THE HARMONIC
EMISSIONS LETTING US KNOW
ACTIVITY IS OCCURRING.
HOWEVER IS ANY DRUG BEING
RELEASED OR ANY AMOUNT OF DRUG
BEING RELEASED IN THE BRAIN
REGION.
BEFORE I GOET TO THAT ISSUES LET
ME RECAP THE WAYS IN WHICH WE'RE
USING MRI IN THIS STUDY FOR
TARGETING FOR TREATMENT MAPPING
TO VERIFY THAT WE ARE INCREASING
THE PERMIABILITY OF THE BLOOD
BRAIN BARRIER AND FOR SAFETY
ASSESSMENT AND OF COURSE WE
FOLLOW THAT UP WITH VARIOUS
HISTOLOGICAL STUDIES.
AT THE CELLULAR LEVEL WHAT'S
GOING ON THEN WHEN WE DELIVER
THIS ANESTHETIC INTO THE BRAIN,
USING CFOSTER NURSED EXPRESSION
WE'RE ABLE TO MAP WHETHER THE
NEURONAL FIRING IS TAKING PLACE
AND HAS IT CHANGED AT ALL
RELATIVE TO UNSONICATED REGIONS.
AND WE FIND WHEN WE DON'T HAVE
THE DRUG ON BOARD IN THOSE NANO
DROPLETS AT LEAST IN THE MOTOR
CORTEX WE SEE ANP CRISE IN
CFOSTER NURSED EXPRESSION IN
THAT REGION.
HOWEVER WHEN WE SUCCESSFULLY
DELIVER THE PENTINE REGIMEN O
BARBIT OL, WE UNDERSTAND
SOMETHING'S HAPPENING AT A
CELLULAR LEVEL BUT WHAT ABOUT AT
A BEHAVIORIAL LEVEL?
WELL WE'RE USING RATS, PAINTING
THEIR FEET AND HAVE THEM WALK
ALONG AN ENCLOSER, WHILE IT'S A
SIMPLE TEST, IT'S A SENSITIVE
WAY OF DETECTING CHANGES IN
SENSORY MOTOR BEHAVIOR AND WE
CAN SEE, THAT AFTER SUCCESSFULLY
DELIVERING PENTINE REGIMEN O
BARBITAL TO 1 HALF OF THE MOTOR
CORTEX WE SEE AN INREECE IN THE
ASYMMETRIC MOTOR FUNCTION.
HOWEVER THE TAKE HOME MESSAGE I
WOULD LIKE TO SHARE WITH YOU
HERE IS IN THE CASE OF THE OPEN
BLOOD BRAIN BARRIER, WE'RE ABLE
TO ACHIEVE AN EQUIVALENT LEVEL
OF SENSORY MOTOR DEFICIT BUT
WITHOUT A THIRD OF THE DRUG
DOSE.
SO BY HAVING THE BLOOD BRAIN
BARRIER OPEN DURING THIS
PROCEDURE, WE'RE ABLE TO CUT
DOWN ON THE AMOUNT OF ANESTHETIC
REQUIRED TO ACHIEVE THIS MOTOR
DEFICIT BY A THIRD MPLET SO IN
CONCLUSION WE'RE EXPLORING HOW
THESE ULTRASOUND NANO DROPLETS
MIGHT BE A WAY TO ADAPT A
NEUROMODDULATION TOOL WITH MRI
GUIDED ACHIEVED ULTD RASOUND AND
ACHIEVING THROUGH THIS SMALL
18thS.
WE'VE SHOWN THAT THIS
VAPORIZATION SHOWS THE RELEASE
OF THE DRUG AND ALSO AN EMISSION
OF UNIQUE ACOUSTICS WHICH WE CAN
DETECT IN REALTIME AS A WAY BOTH
TO LOOK AT--SORRY TREATMENT
EFFICACY AND ALSO TREATMENT
SAFETY.
AND THE OPEN THE BLOOD BRAIN
BARRIER WITH THE MICROSOUND AND
MICROBUBBLES WITH THE POTENTIAL
STRATEGY TO DELIVER THESE
DROPLETS INTO THE BRAIN WHERE
THEY SEEM TO REMAIN AKOWOF
THEICALLY ACTIVE FOR AT LEAST 30
MINUTES AFTER INJECTION.
SO IN THE FUTURE I'M LEARNING
MRI TECHNIQUES, BUT WE MAY
INVESTIGATE INVOLVING IN THIS
WORK, I LOOK FORWARD TO LEARNING
MORE FOR THE NEXT COUPLE OF DAYS
AND WE'RE LOOKING FORWARD TO THE
FEATURE WHERE WE'RE ALREADY
STARTING TO APPLY THIS PLATFORM
TO SERL NEUROLOGICAL AND
PSYCHIATRIC DISORDERS WITH OUR
MARTENERS IN NEUROSURGERY.
THANK YOU VERY MUCH FOR
LISTENING.
AND THANK ALL THOSE INVOLVED IN
THIS WORK.
>>HI, THANK YOU FOR THE TALK.
I WAS WONDERING, ARE YOU LIMITED
IN THE SIZE OF THE DROPLETS,
THAT YOU COULD USE FOR THIS
TECHNIQUE?
>>SO SORRY FROM TERMS OF
FABRICATION BY TUNING THE RATIO
OF THE SHELL MATERIAL TO THE
CORE MATERIAL WE DO HAVE QUITE A
LARGE RANGE OF DROPLETS THAT CAN
BE FABRICATED HOWEVER, IN TERMS
OF SAFETY, WE ARE AWARE THAT YOU
GET THIS 5 TIMES EXPANSION IN
DIAMETER IF WE'RE INJECTING
THESE AGENTS INTO THE
VASCULATURE, WE WANT TO INSURE
IT THAT THEIR RESULT IN SIZE
WILL NOT BE CAUSING ANY DAMAGE
IN TERMS OF GASEOUS VOLUME.
SO WE HAVE SETTLED ON THE SIZE
OF 200-NANOMETERS IN DIAMETER
BECAUSE IT'S COMPARABLE TO THE
MICROBUBBLE SIZE WE USE
CLINICALLY.
>>THE EXCITATION GIVEN THE
EMPTY NANO PARTICLES IS QUITE
INTRIGUING TO ME, WHAT DO YOU
THINK IS HAPPENING?
>>YEAH, IT'S AN EXCELLENT
QUESTION.
MICROBUBBLES HAVE HAD THE SAME
EFFECT, WE THINK AS PROFESSOR
CANNED WHAT WAS TALKING
DIFFERENT REGIONS OF THE BRAIN
WE KNOW ARE GOING TO HAVE
DIFFERENT RESPONSE DEPENDING ON
THEIR NEURONAL COMPOSITION WE
SEE DIFFERENT EFFECTS WHEN WE
SEE CENTRAL BRAIN REGIONS BUT I
WOULD SUGGEST IT'S A MECHANICAL
EFFECT AS THAT VAPORIZATION
PROCESS IS HAPPENING WITH THE
MICROBUBBLES, THEY UNDERGO THIS
VOLUMETRIC EXPANSION, WHICH CAN
PULL AND PRESSURE ON THIS.
>>DO YOU THINK IT'S PUSHING ON
THE ENDOTHELIAL WALL OR SOME
KIND OF WAVE LOCALLY INTO THE
BRAIN?
>>VERY INTERESTING QUESTION.
I THINK PROBABLY THE MECHANICAL
EFFECTS ARE DOMINATING IN THAT
SCENARIO, WE ALSO KNOW THAT
FLUID EFFECTS AROUND THAT
VOLUMETRICALLY ARE CHANGING CAN
BE VERY STRONG THE VELOCITIES IN
THE FLUID AROUND BUT SECONDARY
RADIATION FORCES MAY ALSO BE
COMING INTO PLAY, THAT WAS AN
INTERESTING POINT.
THANK YOU.
>>CAN YOU TALK A LITTLE BIT
ABOUT HUMAN TRANSLATION, IT
SEEMS SUPER SMART TO TALK ABOUT
MICROBUBBLES.
I MEAN DO YOU THINK IT'S
SOMETHING THAT COULD BE USED
RELATIVELY SOON IN HUMANS?
WHAT ARE THE MAIN BARRIERS?
CAN YOU SPEAK ON THAT?
>>YEAH, THANK YOU.
I'VE BEEN--BUILDING ON SOME OF
THE REALLY EXCELLENT WORK THAT
MANY OF YOU PARTICULARLY
DR. [INDISCERNIBLE] THERE, DOING
MANY OF THESE NEW NOW PHASE 1
PHASE 2 CLINICAL TRIALS USING
MICROBUBBLES FOR BLOOD BRAIN
BIRRIER SURFACESSIER OPENING WE
KNOW THAT THAT PORTION OF THE
WORK IS BEING REALLY WELL
CLINICALLY USED AND CLINICALLY
TOLERATED WITH NO ADVERSE SIDE
EFFECTS.
THE INFUSION GROUP WOULD BE VERY
SIMILAR, THE COMPETITION OF NANO
DROPLET SYSTEM ALMOST IDENTICAL,
THEY'RE JUST IN A LIQUID STATE
RATHER THAN A GAS STATE SO WE
IMAGINE THINGS LOAMACYIC
REGULATORY APPROVAL WOULD
PROBABLY BE RELATIVELY SIMPLE.
YES, I THINK THERE'S CERTAINLY
POTENTIAL FOR THIS AND I THINK
THE SYSTEMS ARE THERE AND READY
TO BE USED FOR THESE PLATFORMS.
>>GREAT.
LET'S THANK THE SPEAKER AGAIN.
COMPREHEND.
>>THE NEXT SPEAKER IS ANDREW
STROHMAN, HE WILL TALK ABOUT LOW
INTENSITY FOCUSED ULTRASOUND TO
THE LEFT HUMAN DORSAL ANTERIOR
INSULA ALTERED
SALIVA--SALIVAIENCE NOTEBOOK
WORK BOLD SIGNALS DURING RESTING
AND PAIN CERTAINLY--CERTAINLY
VOAKED STATES IN AN INTENSITY
DEPENDENT FASHION.
>>HELLO, EVERYBODY MY NAME IS
ANDREW STROHMAN AT THE FRALIN
BIOMEDICAL RESEARCH INSTITUTE AT
VTC IN VIRGINIA, WE WILL LOOK AT
THE ABILITY TO ALTER NETWORK
FUNCTIONAL CONNECTIVITY AND
INTENSITY DEPENDENT FASHION AND
I HAVE NO FINANCIAL CONFLICTS OF
INTEREST.
QUICKLY WE WILL TALK ABOUT
BRIEFLY REITERATING THE ROLE OF
INSULA IS PAIN, GOING OVER THE
PROTOCOLS AND METHODS AND THE
RESULTS OF 2 OF THESE ARE ROI
CONNECTIVITY ANALYSIS AND VOXEL
AND FINALLY [INDISCERNIBLE].
SO YOU SAW THIS SLIDE EARLIER.
JUST TO RITY IT CAN BE
SUBDIVIDED INTO ANTERIOR AND AND
INTERIOR SECTIONS, IT INTEGRATES
THESE BOTTOM UP SIGNALS WITH TOP
DOWN COGNITIVE EMOTIONAL PAIN
SIGNALS THROUGH A COMMUNICATION
WITH A VARIETY OF STRUCTURES
NOTABLY THE HYPOTHALAMUS AND THE
AMYGDALA.
AS YOU SAW PREVENTIVELY FROM
SOME OF THE MODELING WE'VE DONE
HERE, CAN YOU SEE FREE WATER
TANK DATA LAID OVER TO SCALE ON
A STRUCTURAL MRI SHOWING WE HAVE
SINGLE GYRATE ISOLATION WITH
LIFU.
ON THE SIM NOLL IS ITED ON THE
SIGNATURE OF PHYSICAL PAIN, THE
AUTHORS IDENTIFIED POORLY AND
ANTICORRELATED REGIONS WITH
TRANSIENT HEAT PAIN.
NOTABLYTHEY SAW THAT THE
ANTERIOR INSULA AND SINGULATE
HAD HIGH INTENSITY TO HEAT PAIN
VERSUS OTHER NONPAINFUL
STIMULATIONS.
AN ADDED FEATURE OF THE DORSAL
ANTERIOR INSULA AND THE ANTERIOR
SINGULATE IS THAT THEY SERVE AS
CORD NOTES IN THE RESPONSE,
WHICH IS IMPORTANT FOR SWITCHING
WITH THE DEFAULT NET,OT LEFT AND
THE CORTEX AS WELL AS THE
EXECUTIVE NETWORKOT RIGHT WITH
THE POSTERIOR GIVING--YOUERAL
AND LATERAL CORTEX.
IT'S A FURTHER NONAPOPTOTICET
THAT THESE NETWORK RESPOND
DYNAMICALLY TO PAIN.
PREVIOUSLY, IN NONHUMAN
PRIMATES, SUCH AS LEONARD
HAGUEIN HAVE SHOWN IN NONHUMAN
PRIMATES THAT THE RESTING STATE
FUNCTIONAL CONNECTIVITY CAN BE
ALTERED WITH LIFU APPLICATION,
SO YOU CAN SEE HERE, THEY
APPLIED LIFU TO THE SINGULAR, OR
THE AMYGDALAs A THE SEED
REGIONS OF INTEREST SHOWING THEY
ARE ABLE TO ALTER RESTING
FUNCTIONAL CONNECT AND THAT
LEADS US TO THE NEXT QUESTION IS
LIFU, TO THE LEFT DAI, MODULATE
THESE RESTING STATE FUNCTIONAL
CONNECTIVITY METRICS IN REASON
YOJS TO THE FMRI NEURAL PAIN
BASED SIGNATURES.
SO FOR ROI-ROI ANALYSIS WE
WANTED TO SEE IF IT WOULD
DECREASE SALIVA--SALIVAIENCE
FUNCTIONAL NETWORK CONNECTIVITY
AND AS WELL AS SEEING RESTING
STATE SALIENCE CONNECTIVITY WITH
THE AMYGDALA AND THE
HYPOTHALAMUS.
NEXT WE WANT TO SEE IF THERE WAS
ANY CHANGES IN THE INTRA PLAY
BETWEEN THOSE 3 NETWORKS WE SAW
EARLIER SO WE HYPOTH CISED THAT
IT WILL DECREASE NETWORK
CONNECTIVITY AND THESE 2 REGIONS
OF INTEREST ISSUES AS WELL AS
THE COG 95ATIVE EXECUTIVE
NOTEBOOK WORK AGAIN USE THE
BILATERAL AND LATERAL PREFRONTAL
CORTEXS, FINALLY FOR THE FOURTH
HYPOTH THAT WE HAVE VARYING
INTENSITIES, WE WILL ALTER THE
RESTING STATE NETWORK FUNCTIONAL
CONNECKIVITYITY.
WE FOLLOW THIS UP, WITH THE
VENTURES BEING THE LEFT DORSAL
INSULA AND HYPOTHESIS THAT WE
DECREASE THESE ASSOCIATE WIDE
THE FMRI SIGNATURE.
FOR PROTOCOLS AND POETIC RAM
TERS THIS FOCUSED TRANSDUCER TO
THE LEFT EAI, USING OUR
NAVIGATION SYSTEM AND USED THE
REGISTERS AND CTs ARE THE
PURPOSE OF OUR MODELING.
RIGHT HERE, HERE THE PARAMETERS
FOR THE STUDY, THESE HAVE BEEN
USED SERL TIMES AND CONSISTENTLY
SHOWN TO PRODUCE ACTIVITY, THAT
VERGES ON INHIBITION.
I WILL USE AGAIN I SAW THE SLIDE
AND DR. LIGON'S TALK, THIS IS
THE BASIC OUTLINE FOR OUR FMRI
STUDY, HE LOOKEDDA THE HEAT
EVOKED STIMULI AND THE COUNTER
BALANCE RESTING STATE SCANS WE
DID ON EITHER SIDE OF OUR
PREPOST LIFE DESIGN AND AGAIN
OUR RESTING STATE FUNCTIONAL
CONNECTIVITY WITH THE REGIONS OF
INTEREST THAT WE JUST DEFINED.
SO, FOR OUR ROI TO ROI NETWORK
FUNCTIONAL CONNECTIT ANALYSIS WE
RESULTS HERE WITH THE MAP,
LOOKINGA THE FIRST HYPOTHESIS OF
DECREASING SALIENCE IN THE
NETWORK, CAN YOU SEE HERE THAT
WHEN YOU GROAP BOTH TOGETHER, WE
CAN SEE THAT CONTRARY TO WHAT WE
WOULD ASSUME, WE WILL SEE
DECREASED CONNECKATIVITY OF THE
THE ACCWITH THE BI LAT AMYGDALA
AND THE HYPOTHALAMUS.
FOLLOWING UP YOU CAN SEE THAT
THESE NETWORKS ARE IN GREEN AND
OTHERS IN BLUE AND YOU CAN SEE
WE HAVE DECREASED FRONTAL CORTEX
AND INCREASES IN THE FRONTAL
CORTEX NODE WITH THE BILATERAL
AMIC DUALA AND THE HYPOTHALAMUS.
ALL OF THESE DIFFERENT
INTENSITIES, ATTRIBUTING TO THE
EFFECTS AND WE FOLLOW THIS UP BY
TAKING THE EXACT SAME ANALYSIS
AND STRATIFYING IT BASED ON
INTENSITY.
SO LOOK AGAIN REVISITING THE
FIRST HYPOTHESIS WITH THE
RESTING ESTATE CONNECTIVITY.
YOU CAN SEE AT THE LOWER
INTENSITY WE DO SEE DECREASED
CONNECTIVITY BETWEEN THE LEFT AI
AND THE RIGHT AI AND THIS IS NOT
SEEN IN THE HIGHER INTENSITY.
LOOKING AGAIN WITH THE SECOND
HYPOTHESIS, IT'S THE OPPOSITE,
IT'S LOWER INTENSITY WE DID NOT
SEE THE EFFECTS AT THE HIGH
EXPOSURE TO RADIATION WE DID SEE
THE INCREASE BETWEEN THE ACCAND
REGIONS OF INTEREST.
AND LOOKING AT THE INTERPLAY
TWEEZE THEEN NETWORKS WE SEE
THAT THE HIGHER INTENSITY WE
HAVE THE DECREASED INTENSITY
WITH WHERE THIS IS NOT SEEN AT
THE LOWER IPT GREATER TENSITY.
--LOWER INTENSITY.
FINALLY, THE LEFT REGION OF
INTEREST AND WE SAW DECREASED
CREATIVITY WITH THE PREKUHNIOUS,
AND LOOKING BACK ON THE
SIGNATURE OF PAIN, THE LEFT
PREKUHNIOUS IS 1 OF THE
ANTICORRELATED REGIONS WITH
THESE TRANSIENT HEAT STIMULI.
AND SO CONCLUSIONS, FOR ROI-ROI
ANALYSIS WE SHOW THAT THE LEFT
AI DECREASES FUNCTIONAL
CONTHECTATIVITY WITH THE RIGHT
AI, AND DECREASES FUNCTIONAL
CONNECTIVITY BETWEEN THE RADIOIT
AND LEFT PREFRONTAL CORTEXS.
TO THE LEFT AI THIS IS INCREASES
FUNCTIONAL CONNECTIVITY OF THE
ACCAND MEDIATE PREFONTAL CORTEX
WITH THE HYPOTHALAMUS AND THE
BILATERAL AMYGDALA AND FINALLY
BOTH INTENSITIES SLEEP APNEA AND
OBESITYEM TO CONTRIBUTE TO THE
OBSERVED WHOLE GROUP EFFECTS.
FINALLY, LIFU TO LEFT DAI
INCREASES FUNCTIONAL
CONTECTATIVITY OF THE ACCAND
BOTH INTENSITIES DIFFERENTIALLY
CONTRIBUTE TO THE OBSERVED WHOLE
GROUP.
AND DECREASES CONNECTIVITY WITH
THE LEFT PREKUHNIOUS.
THANK YOU SO MUCH, THANK YOU TO
EVERYONE WHO WORKED ON THIS AND
I WILL TAKE QUESTIONS.
>>[ APPLAUSE ]
>>QUESTIONS?
WHEN YOU DID YOUR ROI ANALYSIS
WAS THIS OVER SINGERLE SUBJECTS
OR AVERAGED OVER THE 8 SUBJECTS.
>>AVERAGED.
>>ROI AND AVERAGE, AND YOU
DIDN'T SHOW, THERE WERE NO LINES
BETWEEN SOME OF THE ROIs IS
THAT BECAUSE YOU SAW NOTHING OR
BECAUSE YOU--IT WAS NOT
SIGNIFICANT WITH THE SIGNIFICANT
CHANGE?
>>YEAH, YOU DIDN'T SEE THEM
BECAUSE THEY WERE NOT
SIGNIFICANT.
>>OKAY.
ALL RIGHT IF THERE ARE NO OTHER
QUESTIONS, LET'S THANK THE
SPEAKER AGAIN..
[ APPLAUSE ]
SO FINALLY IS AURORE HERE?
YEAH?
SURE.
OKAY, GO AHEAD.
>>GOOD AFTERNOON, EVERYONE.
SO, I AM PASCAL [INDISCERNIBLE]
BASED OUT OF BELGIUM, THIS
PROJECT IS FINANCED BY THE
REGION SO THAT'S FOR DISCLOSURE,
IN BELGIUM WE MAKE CHOCOLATE, WE
MAKE BEER BUT WE ALSO BUILD
NEUROSTIMMULATORS AND THAL CASE,
IT'S A NOCT URNAL STIMULATOR AND
IT IS DESIGNED FOR ACTIVE
STIMULATION AND STIMULATION
DURING MRI AND FMRI.
FOR THOSE WHO DON'T KNOW WHAT IT
IS OR SMALL REMINDER OF A
NEUROSTIMMULATOR AT LEAST, IN
THIS CASE, IT'S AN IMPLANTABLE
NEUROSTIMMULATOR.
SO IT'S BASICALLY VERY SIMILAR
TO WHERE BASE MAKER EXCEPT
THAT'S STIMULATING SO THEY ARE
ALMOST ALL BUILT IN THE SAME WAY
WHERE YOUR ELECTRONICS AND
BATTERY ARE INSIDE.
YOU HAVE WIRES, COMING OUT OF
THE TITANIUM CASING AND THEY GO
TO AN CERTAINLY--CERTAINLY LECT
RODE AND THE ELECTRODE IS NEXT 1
OR BRAIN TISSUE.
AND ALL THIS METASELL A PROBLEM,
IT'S A PROBLEM, IT'S A RISK WHEN
YOU GO TO MRI.
YOU CAN HAVE IMPLANT MOVEMENT
AND ON THE IMAGE YOU CAN SEE
THAT YOU HAVE THE MAGNET OF THE
COCHLEAR IMPLANT WHICH IS RIPPED
OFF BY ITSELF, CAN YOU HAVE
IMPLANTING, IT CAN BE HEATING,
CAN YOU HAVE BURN DURING AN MRI
SECTION, CAN YOU HAVE IMPLANT
MALFUNCTION DUE TO MAGNETIC
FIELD OR INTERACTION AND MRI
IMAGE ARTIFACT GAVES VERY POOR
IMAGE.
IF YOU WANT TO PLACE A
NEUROSTIMMULATOR ON THE MARKET,
YOU NEED TO ASSESS ITS MRI
SAFETY.
AND YOU DO THAT USING SPECIFIC
STANDARD AND AFTER TESTING THE
MRI CONDITIONS THAT DURING
RADIOLOGISTS HAS TO APPLY TO BE
SAFE.
AND UNDER THESE CONDITIONS, THEY
ARE RELATED TO BODY REGIONS THAT
ARE [INDISCERNIBLE], THEY
RELATED TO THE FACT THAT THEY
HAVE TO BE SWITCHED OFFER DURING
THE MRI SESSION, THE REACT TO
THE FACT THAT THE SCAN DURATION
MIGHT BE LIMITED, OR MIGHT BE
LIMITED AND CHANGING SOIN CREASE
THE TIME OF THE PEOPLE THERE AND
THE RADIOLOGISTS AND YOU ALSO
HAVE PATIENTS AT RISK AND MOST
OF THE TIME MOST PEOPLE WHO ARE
NOT UNIVERSITY STUDENTS, REGULAR
PATIENTS THEY DON'T WANT TO MAKE
MRI WITH SOMEONE WITH AN
IMPLANT.
SO WE WANTED TO CHANGE
TAKEN--THEY FACT.
AND AS I SAID, METEDDAL IS THE
PROBLEM, SO THE IDEAS ARE EASY,
METAL IS THE PROBLEM SO LET'S
REMOVE THE METAL.
IT WAS NOT THAT EASY, WE A LOT
OF RECOMMEND, WE HAVE A GREAT
TEAM AND WE SUCCEEDED TO DO SO
AND I WILL PRESENT YOU WITH THAT
NEUROSTIMMULATOR THAT WE
ATTRIBUTED AND THE 1 YOU SEE ON
THE SLIDE IS THE
NEUROSTIMMULATOR THAT IS
SUPPLIED FOR VAGUS STIMULATION,
AND YOU IMPLANT IT IN THE CHEST
REGION AND THEN YOU HAVE TO LEAD
THAT GOING TO THE ELECTRODE AND
THE ELECTRODE IS WRAPPED ARK
ROUND IN THIS CASE, THE AND THIS
SEIZURE EFFECT, THAT WILL BE
FEPILEPSY TREATMENT.
AND IT IS A NEUROSTIMMULATOR SO
YOU DON'T SEE ANY TITANIUM
CASING ANYWHERE, SO THE
ELECTRONIC IS INSIDE GLASS INCAP
SURVEYSALATION, WE REPLACE THE
WIRES CAN OPTICAL FIBERS AND
CUSTOM OPTICAL FIBERS WE BUILT
THEM FROM SCRATCH TO BE
COMPATIBLE TO BE FIT FOR
IMPLANTATION AND THE
NEUROSENSORS, SO SENDING THOSE
UP TO THE ELECTRODE.
IN THIS CASE, WE STILL
STIMENTULATING QUICKER WAYS OR
WE HAVE TO CONVERT BACK TO THE
OPTICAL PARALYSIS TO ANOTHER
[INDISCERNIBLE] AND WE DO THAT
WITH [INDISCERNIBLE] CELL THAT
IS CONVERTING THE OPTICAL ENERGY
TO [INDISCERNIBLE].
AND THEN WE ASSESSED THAT EVENT
FOR MRI SAFETY BECAUSE WE WANT
TO PLACE IT ON THE MARKET.
AND WE FOUND THAT WE GOT NO
[INDISCERNIBLE] DUE TO THE
CANNED WHAT ELEBT RODE WE HAVE
NO AMOUNT OF FUNCTION AND THE
GENERATORS AND DURING ANY KIND
OF MRI SEQUENCES MEANING IT IS
FRUITFUL WITH FMRI AND BIG RISK
IS EATING AND IN THIS CASE, WE
HAVE NO MORE THAN 2-DEGREES
EVERYWHERE FOR THE IMPLANTABLE
PATH, TO THE DEGREE SO 3.60 RISK
FAHRENHEIT AND EVEN THE ELEBT
RODE WHICH IS THE MOST SENSITIVE
PART, EVEN IF EATING IS
NEGLIGIBLE.
TALKING ABOUT [INDISCERNIBLE]
QUALITIES, WE STILL HAVE SOME
METAL PARTS, SO WE HAVE THAT DID
YOU THE DEFECT IS QUITE LIMITED
AND THE BRAIN IMAGING CAN BE
PERFECT.
AND AS A RESEARCHER WE HAVE
CONDITION THAT NEED TO BE
APPLIED SO AT 1.5, THERE'S NO
SCAN TRANSMISSION, NO CHANGE, NO
TIME LIMITATION, NO LIMIT
AITIONZOT MODE OR BODY SCAN AND
WE HAVE NO LEAD FOR THIS WITHY
NEED TO THIS FOR THE TERM WHERE
THIS CASE CAN BE THE PROBLEM AND
IN THIS CASE, THERE WILL BE
THERE AND THERE IS NO PROBLEM.
AND AS A CONCLUSION, WHAT WE DID
WAS TO BUILD THE
NEUROSTIMMULATOR, WE BUILD IT
FOR VAGUS STIMULATION BUT THE
TECHNOLOGY PLATFORM, IT CAN BE
APPLIED TO ANY KIND OF
NEUROSTIMMULATION PIECE,
ESPECIALLY DEEP BRAIN
STIMULATION IN THIS CASE, WHERE
IT'S A BIG ADVABTAGE BUT ALSO WE
REMOVED THE INTAKE CELLS, WE
HAVE AN IMPLANT QUICKLY READY
FOR OPTICAL IMAGES O GENETICS
AND IN THE NEAR DISTANT FUTURE,
ALSO DIRECTOR OF THE
[INDISCERNIBLE] STIMULATION.
AND @ MOMENT WE ARE STUDYING THE
POTENTIAL BY O MARKERS FOR
STIMULATION.
AND THERE IT IS.
AND THAT WAS OF COURSE DUE TO A
GREAT TEAM WHERE SOME OF THEM
ARE PRESENT HERE AND I WANT TO
THANK YOU FOR ALL THE WORK THAT
DID FOR THE PAST 6 YEARS.
THANK YOU.
[ APPLAUSE ]
MCAN YOU HAVE IT ON DURING MRI.
WOULD MRI IMPACT THE EFFICIENCY
OF THE THERAPY?
>>SO THAT'S THE WHYED, WE GO TO
MRI, WE SIMULATE AND AT THE SAME
TIME CAN YOU SEE WHAT'S
HAPPENING IN THE BRAIN.
>>SO THE IPG IS IMPLANT IN THE
BODY.
>>IT IS IMPLANTED THERE.
>>IT CAN HAVE IT ON.
>>IN THE CHEST.
>>YEAH.
>>AND YOU GO TO EXTERNAL SYSTEM
WHICH IS BASICALLY
[INDISCERNIBLE] OPTICS AS WELL
GOING OUT OF THE MRI OR
KD--SALLY LAWEDDER DALE.
>>JUST CURIOUS LIKE RF FIELD,
GRADIENT FIELDS FROM THE MRI,
WITH THAT IMPACT OF
FUNCTIONALITY OF THE IPG.
I KNOW IT'S A SAFE, BUT I WAS
WONDERING DOES IT IMPACT ANY
THERAPY?
FUNCTIONAL--
>>FUNCTIONALLY [INDISCERNIBLE].
SO THAT'S STANDARD WE NEED TO
FOLLOW.
IT'S A NICE STANDARD FOR THAT,
IT'S GOOD GUIDANCE, IT'S
PROVIDING ANY KIND OF AREA
[INDISCERNIBLE] WORST CASE MRI
SEQUENCES AND EACH 1 FOR THE
FUNCTIONAL, WITHOUT ANY PROBLEM.
AND WHAT WE DID IS TO BE OF
COURSE THE EXTERNAL SYSTEM TO
COMMUNICATE OUTSIDE THE MRI RULE
AND WE STIMULATE AT THE SAME
TIME YOU CAN RECORD THE MRI
SEQUENCES.
>>THANK YOU.
>>I THINK I MAY HAVE MISSED IT,
I'M CONFUSED.
WHAT IS THE MECHANISM OF ACTION
HERE, LOOK ARE YOU TALKING ABOUT
OPTICAL IMAGES O GENETICS?
SO IS THIS SOMETHING THAT
INVOLVES INJECTION OF A DRUG TO
PENTACLIALLY GENETIC ALTERATION
OR THIS IS LIKE GENETIC--
>>THIS THE 1 I PRESENTED TO YOU
IS NORMAL STIMULATION, WE--WE
REGULARLY STIMULATE THE NERVE
BUT WHAT I WAS SAYING ON THE
PLATFORMS WE CAN REMOVE, WHEAR I
SAID WHICH IS ON TOP OF GH1, AND
WE WANT TO IMPLANT TO DELIVER A
PARTICULAR PROCESS THAT OR A
PARTICULAR OBSERVATION THAT WE
CAN QUICKLY DO [INDISCERNIBLE]
NEUROSIMMULATOR TO NEUROSCIENCE.
>>OKAY, VERY GOOD.
>>YOUR IPG I THOUGHT WAS QUITE
SMALL.
IS THERE ANY KIND OF BATTERY
SORT OF INNOVATION GOING ON
HERE.
>>JPG IS SMALL, AND I WOULD
LIKE IT TO BE EVEN SMALLER AND
EFFECTIVELY IT'S SMALL BECAUSE
THE BATTERY IS ALSO SMALL, BUT
IT'S A RECHARGEABLE BATTERY.
AND THE IDEA WE TALKED ABOUT
THERE IS THAT, WE WANT TO BE
ABLE TO MAKE THE ALGORITHMIC
SIDE FOR SENSING INSIDE AS
COMPLEX AS WE WERE, SO WE DON'T
WANT OUR LIMITATION TO LIMIT THE
FUNCTIONALITY OF THE DEVICE.
>>LOOK FORWARD TO UPDATES.
>>OKAY, WELL, THEN,--
>>SORRY.
>>[INAUDIBLE ]
>>IF YOU HAVE PUT A TYPE ON
YOUR ROOF, BASICALLY YOU GET SUN
LIGHT, AND YOU CONVERT ABOUT MAX
NULL TWEBT PERSON, MEANING THAT
INSIDE [INDISCERNIBLE] EACH
PERSON WILL [INDISCERNIBLE].
IF YOU DO THAT, BASICALLY YOU
HAVE THE SAME--AND THE OPTICAL
GO TO THE [INDISCERNIBLE] OF
COURSE AND THAT 1 IS SMALLER,
IT'S VERY, VERY SMALLER.
BUT IT'S NOT LIKE UPON WE HAVE
RANKED [INDISCERNIBLE] OTHER
PHOTO ITSELF AND WE GOT AROUND
60 PERSON OF CONVERSION.
WE STILL HAVE ABOUT 40 PERSON OF
THAT [INDISCERNIBLE] WHICH IS
CONVERTED TO [INDISCERNIBLE] BUT
IT'S VERY LIMITED, IT'S ONLY THE
[INDISCERNIBLE] STIMULATION, I
HAVE DONE IT A FEW TIMES.
OKAY.
>>ALL RIGHT.
THANK YOU VERY MUCH.
THANK YOU FOR SUCH A GREAT
SESSION.
[ APPLAUSE ]
>>SO WE RESUME AT 4:30
>>WELCOME TO THE
FOURTH AND LAST SESSION FOR
TODAY.
THIS WILL BE THE ORWILLA
PRESENTATION OF ABSTRACTS.
WE WILL HAVE A LINE UP OF 5
SPEAKERS.
AND OUR FIRST SPEAKER IS
MATTHIEU, DAGOMMER, WHO WILL
TALK ABOUT HIS OPTICAL IMAGES
MIATION OF DEEP LEARNING
STRATEGY FOR ESTIMATION OF
CORTICAL PORS ONITY MAP FROM MRI
T1-WEIGHTED IMAGES.
>>SO I HAVE NOTHING TO DECLARE.
SO AS YOU KNOW, TRANSCRANIAL
ULTRASOUND IS A PROMISING
NEUROSTIMMULATION TECHNIQUE,
IT'S NONINVASIVE, IT REACHES
DEEP IN THE BRAIN AND HAS BEEN
DEVELOPED AND VALIDATED IN
ANIMAL STUDIES.
HOWEVER, TRANSLATION TO HUMANS
IS STILL DIFFICULT BECAUSE OF
SCATTERING AND OBSTRUCTION BY
THE SKULL.
SO HERE'S AN EXAMPLE OF THE
SIMULATION IN ORDER TO, YOU HAVE
A DUCER--SO, ACOUSTIC
[INDISCERNIBLE], PEEK INTENSITY
FALLS INSIDE TARGET OF INTEREST,
NOW, IF PEOPLE SCHEDULE BETWEEN
THOSE IN AND THE TARGET, YOU SEE
THE STRONG LEAD, AND ATTENUATE,
SO, SO TAKING INTO,A COUNT IS
CRITICAL FOR THOSE ACCURATE,
HOWEVER, A MAIORITY OF ONGOING
CLINICAL STUDIES STILL DO NOT
MODEL THIS CAUSE, SO HERE'S AN
EXAMPLE OF THAT ONGOING MGH
STUDY, OR GETTING THE RIGHTS
WITH THE ENVELOPE USING THE
TARGET LINE UP STRATEGY SO THESE
ARE SIMULATIONS PERFORMED
RETROSPECTIVELY ON THE SUBJECTS
AND AS YOU CAN SEE HERE ON THIS
MAP, WE HAVE BLACK CIRCLE
REPRESENTING THE AMYGDALA AND WE
CAN SEE THAT WE'RE ABLE TO REACH
THE TARGET, HOWEVER, FOR OTHER
SUBJECTS, WE MISS TARGETS.
AND WE REALIZE, IF WE HIT THE
TARGET, WE ONLY GET 30% OF
MEASHTS.
THE THING IS FORTUNATELY WE HAVE
WELL ESTABLISHED METHODS,
NUMERICAL METHODS TO TAKE INTO
ACCOUNT THIS CAUSE AND THOSE
STIMULATIONS RELYOT MAPS AND
THIS IS THE TYPICAL WORK FLOW TO
PERFORMANCE SIMULATIONS: FIRST
WE PERFORM A CT SCAN, WE THEN
EXTRACT THE MAP, WE DERIVE
ACOUSTIC PARAMETERS AND THEN WE
FEED THESE ACOUSTIC PARAMETERS
TO THE SIMULATION, THE PROBLEM
OF THE FLOW CHART IS THAT CT
SCAN EXPOSES THE SCAN THROUGH
IONIZING RADIATION AND THE THING
WE CARE ABOUT IN THE END IS THE
PERS ONITY MAP SO HOW CAN WE
OBLIGATIONS STAIN THE MAP IN A
DIFFERENT WAY.
WELL IN THIS STUDY, WE WANT TO
DEVELOP A TOOL TO ESTIMATE,
VELOCITY FROM MRI, SO YOU'RE
LOOKING AT A PATIENT, AND THIS
IS THE EQUIVALENT PORS ONITY
MAP.
NOW LET'S LOOK AT THE MRI.
AS CAN YOU SEE THERE IS VERY
LITTLE CONTRAST AROUND THE
SKULL.
HOWEVER, IF WE CHANGE THE
SATURATION, WE CAN SEE CLEARLY
THAT THE INFORMATION ABOUT
POROSITY IS THERE, SO WHAT WE
NEED IS AN IMAGE TO IMAGE TO
IMAGE TRANSLATION METHOD AND WE
KNOW THAT DEEP LEARNING IS WELL
SUITED FOR THIS SO WE PROPOSED A
APPROACH TO GO OVER THE PROBLEM
AND WE WERE INSPIRED BY OTHER
SIMILAR STUDIES.
SO BEFORE I DIVE INTO DEEP
LEARNING, I WILL TALK ABOUT
POROSITY, IT IS AT PLACENTAS
BASED SO IT CONSISTS IN
AVERAGING MRI CT PAIRS FOR FOR
MULTIPLE SUBECTOMYOSIN JUDGES.
AS YOU CAN SEE ON THE IMAGE THE
POROSITY, 1 PART IS VERY BLURRY
SO THE POROSITY IS VERY QUITE
DIRT EXPE WE LOST INFORMATION
BECAUSE OF THE AVERAGING
PROCESS.
IN THIS STUDY WE USED POROSITY
AS A CONFIRMATION FOR OUR METHOD
BUT WE DID NOT USE IT DIRECTLY.
SO NOW LET'S TALK ABOUT DEEP
LEARNING SO WHAT WE WANT TO DO
IS TO CREATE A GENERATOR THAT'S
TAKES AND INPUTS AN MRI MESSAGE
AND THE MAP.
HOW TO--SO THE WAY TO DELIVER
THIS TO TRAIN THAT KIND OF MODEL
IS TO COMPARE THE GENERATED
POROSITY WITH THE ACTUAL
POROSITY MAP AND TO GIVE
FEEDBACK TO THE GENERATOR TO
TRAIN IT.
SO THIS IS THE VERY SIMPLE,
SIMPLEST GENERATED MODEL WE CAN
HAVE.
IF WE REFINE A LITTLE BIT, WE
CAN ADD DISCRIMINATOR WHICH IS A
TYPE OF NETWORK, THAT'S ABLE TO
TELL THE DIFFERENCE BETWEEN
GENERATED AND THE REAL POROSITY
MAPS AND THIS ALLOWS TO GIVE
MORE REFINED FEEDBACK TO THE
GENERATOR.
NOW STARTING FROM THIS
ARCHITECTURE, WE CAN TRY TO
CHANGE THE TARGETS, SO WAWE TRY
TO DO WAS REPLACING THE POROSITY
BY THE SQUARE ROOT OF POROSITY
IN ORDER TO BOOST THE POROSITY
CONTRAST.
WE ALSO TRIED DIFFERENT TYPES OF
GENERATOR.
WE TRIED TO USE DIFFERENT LOSS
FUNCTIONS AND WE TRY TO CHANGE
THE INPUT SO, 1 THING WE DID WAS
TO STACK THE IMAGE WITH WHAT I
STALK BODY A FEW SLIDES BEFORE
AND CREATE A 2 CHANNEL IMAGE.
WE ALSO TRIED DIFFERENT PROTEIN
STRATEGIES USING 3D BATCHES, THE
IDEA REMAINS THE SAME.
THE IDEA IS TO INCREASE THE SIZE
OF THE DATA SET AND TO INCREASE
THE MEMBER OF WEIGHT OF THE
MODEL.
FINALLY, SO ANOTHER METHOD WE
USED WAS CALLED [INDISCERNIBLE]
MASK AND THE IDEA WAS TO MASK
OUTPUTS FROM THE GENERATOR IN
ORDER TO FORCE THE GENERATOR TO
RESTRICT THE LEARNING OF THE
MODEL TO PIXELS INSIDE THE SKULL
MASK THROUGH A--YEAH,--NOW LET'S
TALK ABOUT ANOTHER METHOD WE USE
WITH THE MODEL, IT CONSISTS IN
DAISY CHAINING THE SIMILAR
MODELS IN A ROPE AND ANY MODEL
IN THIS SERIES, THE PREVIOUS
OUTPUT, THE OUTPUT OF THE
PREVIOUS MODEL.
SO QUICK WORD ABOUT THE DATA WE
USED WE HAD 1 MILLIMETER IOWAS O
TROPIC MRI OBTAINED WITH MP RED
SEQUENCE, WE HAD CLINICAL STEMS,
WE HAD A TOTAL OF 15 SUBJEKS, TO
REGISTERED [INDISCERNIBLE], WE
USED 13 SUBJECTS FOR TRAINING, 1
FOR VALIDATION AND 1 FOR TEST,
SO NOW LET'S TALK ABOUT THE
RESULTS SO WHAT YOU SEE HERE,
S&P OUR VALIDATION, SO THE
ERROR, MODELS ON VALIDATION
SETS, AND ON THE Y-AXIS YOU HAVE
THE ABSOLUTE ERROR AND THE
RESPONSE TO THE AVERAGE RAB
ABSOLUTE PIXEL ERROR AND ON THE
X-AXIS YOU HAVE THE RESPONSE
THAT RESPONDS TO DEEP LEARNING
MODEL ITERATIONS.
AS YOU CAN SEE THE 2 CURVES
CONVERSE TOGETHER SO THERE IS
NOT A BIG GROUP BETWEEN THIS
PORS ONITY AND THE POROSITY
TARGET.
NOW WE TROO TO USE THE
GENERATORS AND TRY TO TYPES OF
INPUT.
MRI OR MRI COMPIN ONS WITH
SPECIFICITY.
SO WE HAD 4 CONFIGURURATIONS IN
TOTAL.
WE CONCLUDED THAT THE BEST
CONFIGURURATION WAS TO USE
RESNET AND NO PC T.
WE ALSO TRIED DIFFERENT
COMBINATIONS AND IT TURNED OUT
THAT THE BEST CONFIGURURATION
WAS TO USE L1 PRESENTER FOR LOSS
FUNCTION.
NOW, CHARGING THE INPUT SIZE HAS
DRAMATIC IMPACT ON THE
PERFORMANCES AS WE CAN SEE, THE
3D CROPPINGS, YIELDED THE BEST
RESULTS.
SO WE USED 3 CROPPINGS.
THREE PATCHES.
REGARDING THE OTHER CONTEXT
MODEL, WE CONCLUDED THERE WAS
LITTLE PERFORMANCE INCREASE,
HOWEVER, IT DID NOT OUTWEIGH THE
COMPUTATIONAL COST OF TRAINING
SELF-MODELING IN A ROW SO WE DID
NOT CURE IT IN THE FINAL MODEL.
NOW, THE PROPAGATION IN THE MASK
IS A METHOD THAT YIELDED BETTER
RESULTS IN 2 D MODELS AND 3D
MODELS.
SO WE DID IT IN THE FINAL MODEL.
SO THE PROPOSED MODEL INN CLUEDS
A GENERATOR, 3D PATCHES, THE
TARGET IS THE POROSITY, IT'S
STRAINED USING [INDISCERNIBLE]
AND [INDISCERNIBLE], AS YOU CAN
SEE ON THESE BAR PLOT, THE
PERFORMANCE OF THE PC T ONLY WAS
12%, THE [INDISCERNIBLE] WHICH
WAS THE STANDARD IMAGE TO IMAGE
ALGORITHM PERFORMED SLIGHTLY
BETTER BELOW 12% AND OUR MODEL
RETURNS AN ERROR SO ON THE TEST,
SORRY, OF 5.8% OF THE POROSITY.
SO WE HAVE A SIGNIFICANT
IMPROVEMENT WITH RESPECT TO THE
REFERENCE METHODS.
SO FOR NOW LET'S TACK A LOOK AT
THE OUTPUTS FROM OUR MODEL.
SO WHAT YOU HAVE HERE IS THE MRI
AND THEN THE PIXTOP IX AND THE
ERROR OF THE MODEL IS LOWER ON
THIS SLIDES.
SO THIS IS ANOTHER VIEW ON THE
SLICE WITH THE SAME CONCLUSION
AND ON THE SAGITTAL SLICE AGAIN
WITH THE SAME CONCLUSION.
SO TO SUM UP, WE OPTIMIZED A
DEEP LEARNING METHOD FOR MRI TO
PROVIDE THE ESTIMATION, THE
PURPOSE INCLUDES THE RESONATE
GENERATOR, 3D BATCHES, TARGET
THE POROSITY AND USES 1% TO LOSS
AND BIM.
OUR PROPOSED APPROACH HAS LESS
THAN 6% ERROR, AND IT'S A 2
TIMES PERFORMANCE IMPROVEMENT
COMPARED TO PC T AND THE
STANDARD DEEP LEARNING ALGORITHM
AND FINALLY THIS ENABLES FAST
SIMULATIONS FOR TFUS NAVIGATION.
THANK YOU VERY MUCH FOR YOUR
ATTENTION AND I'M HAPPY TO TAKE
ANY QUESTIONINGS.
[ APPLAUSE ]
>>ANY QUESTIONS?
>>THANK YOU VERY MUCH FOR THE
PRESENTATION, WE KNOW THAT L1
AND L2 NORMS PROVIDE YOU SOME
INSIGHT INTO THE LOSS FUNCTIONS
AND ABOUT THE PERFORMANCE OF
YOUR MATING, MY QUESTION IS DID
YOU HAVE A CHANCE TO COMPARE
YOUR FINDINGS WITH THE GROUP FOR
FUTURE SIMILARITIES IN THE INDEX
MATRIX, SO DID YOU CHECK THAT
PARAMETERS IN PROCESSING
PARAMETERS?
>>WE DID CHECK THOSE METRICS, I
ASSUME WE'RE TALKING ABOUT
STRUCTURAL SIMILARITY, RIGHT?
WE DID USE IT.
BUT WE DECIDED TO STICK TO
ABSOLUTE HERROR, YOU KNOW IN AN
EFFORT TO REALLY FOCUS ON THE
PIXEL ERROR.
>>IN TERMS OF LOSS FUNCTIONS L1
AND L2 ARE KIND OF GROUND ROOTS
IN THE IMAGE PROCESSING SITE BUT
ONCE YOU COMPETED YOUR
PREDICTIONS, DID YOU HAVE A
CHANCE TO COME PAIR YOUR
PREDICTIONS AND THE GRANT ROOTS
IN TERMS OF SSIM OR FSIM?
DO YOU HAVE FOR EXAMPLE, 90% OF
SIMILARITY THROUGH
[INDISCERNIBLE] OR 95% OF
SIMILARITY TO [INDISCERNIBLE]
>>SO, FROM MEMORY, I THINK THE
SSEM WAS AROUND 1997%, SOMETHING
LIKE THAT.
THANK YOU.
>>WELCOME.
>>ALL RIGHT, THANK YOU VERY
MUCH MATTHIEU.
>>OUR NEXT SPEAKER IS
DR. NOREEN BUKHARI-P A RLAKTURK,
SHE WILL TALK ABOUT ENGAGEMENT
TO DEEP BRAIN NETWORK AS A
PREDICTOR BIOMARKER FOR CLINICAL
PRESPONSE TO TMS.
>>GOOD AFTERNOON, CAN EVERYBODY
HEAR ME.
I'M FROM DUKE UNIVERSITY.
I'VE HAD A GOOD TIME AT THIS
CONFERENCE SO FAR, IT'S BEEN
FOCUSED MOSTLY ON THE
TECHNOLOGICAL DEVELOPMENT I'M A
NEUROLOGIST AND SCIENTIST SO I
WILL DISCUSS SPECIFICALLY ABOUT
THE APPLICATION OF TMS AND
FUNCTIONAL MRI TO ADVANCE
THERAPY FOR PATIENTS WITH NURRA
O LODGE CALIFORNIA DISORDERS
DEBINNING WITH FOCAL HAND
DYSTONIA.
I HAVE NO CONFLICTS OF INTEREST
OR DISCLOSURES.
DYSTONIA IS AN INVOLUNTARY
GESTURE, IT CAN INVOLVE THE
WHOLE BODY OR IT CAN BE FOCAL TO
A LIMB SUCH AS THE HAND.
PATIENT WHO ARE GENERALIZED ARE
WHEELCHAIR BOUND AND BED BOUND
AND OVERALL VERY DEBILITATING.
THERE ARE CURRENTLY NO DISEASE
MODIFYING THERAPY FIST ANY
MOVEMENT DISORDERS, SPECIFICALLY
DYSTONIA HERE, AND SYMPTOMS VARY
FROM PATIENT TO PATE.
WE KNOW FROM KRINICAL AND
PRECLINICAL STUDIES IN THIS
DISORDER THAT THE PROBLEM WITH
DYSTONIA IS A PROBLEM OF BRAIN
CIRCUITRY, AND SPECIFICALLY OF
BRAIN CONNECTIVITY.
THEREFORE TMS, TRANSCRANEIO
MAGNETIC STIMULATION KNOWN TO
PLAY A ROLE IN MODIFYING BRAIN
CIRCUITRY AND BRAIN PLASTICITY
BECOMES AN IDEAL APPROACH TO TRY
TO DEVELOP NEW THERAPY FOR THESE
PATIENTS.
ONE OF THE KEY LIMITATIONS OF
TMS THOUGH, IS IT ONLY ACTIVATES
AND MODIFYS NEURONS THAT ARE
LESS THAN 1 CENTIMETER.
NOW THERE HAVE BEEN PRIOR
STUDIES OF TMS, TMS STUDIES IN
PATIENTS WITH FOCAL HAND DISTONE
RAW DATA AND THEY HAVE SHOWN
SOME TRANSIENT BENEFIT, SO WHAT
CAN WE LEARN FROM THESE INITIAL
7 STUDIES.
THERE ARE 5 OF THE STUDIES THAT
SHOWED THAT MULTIPLE SESSIONS OF
REPETITIVE TMS IN PATIENTS WITH
FOCAL HAND DYSTONIA, LED TO
CLINICAL IMPROVEMENT AFTER TMS
WAS APPLIED AT THE PREMOTOR
CORTEX.
WITH THE STUDY THAT SHOWED THE
LONGEST EFFECT WAS 2-3 WEEKS AND
THAT WAS SHOWN WHEN TMS WAS
APPLIED AT THE PRIMARY SO MAT O
SENSORY CORTEX.
AND SO, THUS FAR WHEN WE KNOW IS
THAT TMS ISSUE, REPETITIVE TMS
APPLICATION AND FOCAL DYSTONIA
DOES SHOW A TRANSIENT BENEFIT
AFTER APPLICATION AT THE
PREMOTOR AND SOPHISTICATED MAT O
SENSORY CORTEX.
BUT HOW DO WE PROLONG THIS
EFFECT.
HOW DO WE DEVELOP A LONG LASTING
THERAPY, A QUESTION THAT IS
APPLICABLE IN THE NEUROLOGICAL
BUT ALL THE CLINICAL DISEASE
MODELS.
SO WORK BY OTHERS IN ANOTHER
DISEASE MODEL IS HAS ACTUALLY
LED US TO AN ADVANCEMENT,
SPECIFICALLY JOEL VOSS' GROUP
HAS SHOWN THAT WHEN TMS IS SAW
PLIED AT THE SUPERIOR PARIETAL
CORTEX IT LEAD TO DEEP BRAIN
MODIFICATION OF THE HIPPOCAMPUS.
THEY SHOWED THAT CHANGES IN
FUNCTIONAL BRAIN CONNECTIVITY
CAN LEAD TO IMPROVEMENT IN
MEMORY SO THIS LED US TO ASK THE
QUESTION THAT WHAT IS THE KEY
DIFFERENCE, WHAT IS THE KEY DEEP
BRAIN NEST WORK TO TARGET
PATIENTS WITH DYSTONIA AND SO
MULTIPLE GROUPS HAVE ACTUALLY
SHOWN THAT BASAL GANGLIA IS A
KEY DEEP BRAIN REGION THAT IS
ABNORMALITIES SNRORMAL IN
PATIENTS WITH FOCAL DYSTONIA.
THIS IS A SEMINOLE PAPER FROM
JOEL PEARL MATTERS GROUP AT WASH
U.
AND THAT I HAVE SHOWN SEVERAL
PATIENTS SHOW A KEY DEFACT IN
THE KEY REGION OF THE BASAL
GANGLIA.
AND SPECIFICALLY IT'S A DEE
CREASE IN BASAL GANGLIA ACTIVITY
AND FUNCTIONAL MRI.
OUR GROUP HAS ALSO SHOWN, THAT
THE ABNORMALITY IN PATIENTS WITH
FULL DYSTONIA ALSO OCCURS
PRIMARILY AT THE BASAL GANG
LIAISON AWHAT WE'RE SHOWING
ADDITIONALLY IS THAT ACTIFORT,
THE FUNCTIONAL BRAIN ACTIVITY IS
STAYED DEPENDENT AND IT CHANGES
DEPENDING ON WHETHER THE
ACTIVITY OCCURS ON THE ON BLOCK
OF WRITING OR THE OFF BLOCK.
DETAILTHIS STUDY WILL BE
DISCUSSED TOMORROW BY DR. ANDREW
MICHAEL, BUT THIS FINDING BY OUR
GROUP AND OTHERS ACTUALLY FORM
THE FUNDAMENTAL BASES FOR OUR
HYPOTHESIS WHICH WAS WHICH BASAL
AREA WILL HELP PATIENTS WITH
DYSTONIA AND OUR HOPE IS THAT BY
MODIFYING THE BASAL GANG LIAISON
A WE CAN DEVELOP A LONG LASTER
THERAPY.
SO WE'VE HOPE TO BE ABLE TO
DELIVER TMS AND WE FOCUS ON THE
PREMOTOR CORTEX AND THE PRIMARY
SOPHISTICATED MAT O SENSORY
CORTEX, HYPOTHESISSING THAT THE
TRANSIENT BENEFIT MAY HAVE BEEN
DUE TO SOME MODIFICATION OF THIS
DEEP BRAIN REGION SO WE APPLY 10
MRTMS, AND WE PATIENT WITH FOCAL
HAND DYSTONIA AT THE PREMOTOR
CORTEX OF THE PRIMARY
SOPHISTICATED MAT O SENSORY
CORTEX.
WE ALSO DELIVERED
[INDISCERNIBLE] AT THE PREMOTE
CORCORTEX IN THESE PATIENTS.
OUR STUDY WAS DOUBLE BLINDED AND
SHAM CONTROLLED AND IMPORTANTLY
WE DID A RANDOMIZED ORDER OF TMS
DELIVERY WHERE ALL SUBJECTS
RECEIVED ALL 3 TMS CONDITIONS IN
A CROSS OVER DESIGN.
NOW THE TMS IN ORDER TO MEASURE
THE EFFECT OF THIS TMS STUDY, WE
ACTUALLY TOOK BEHAVIORIAL
MEASUREMENTS AT BASE LINE, AND
THEN IMMEDIATELY AFTER THE TMS
SESSION, WE ALSO TO LOOK AT THE
BASAL GANGLIA ACTIVITY WE
PERFORMED TASK FUNCTIONAL MRI.
NOW IN ORDER TO INSURE THAT WE
WERE TARGETING A REGION OF
INTEREST, WHICH IS PRIMARILY THE
MOTOR NETWORK WE USE AN APPROACH
CALLED THE MOTOR TEST
SYNCHRONIZED TMS DELIVERY WHICH
MEANS WE DELIVERED TMS IN 4
BLOCKS OF SIM USE, ALTERNATED BY
4 BLOCKS OF A TASK THAT WAS REEL
KEEPSAKES VABT TO PATIENTS WITH
DYSTONIA, WHICH IS A MOTE OAR
LEARNED TASK SUCH AS WRITING.
AND SO 1 OF THE CHALLENGE I
DON'T NEED TO TELL THIS GROUP IS
THE TECHNICAL VARIABLE,
BIOLOGICAL VARIABILITY.
SO TO ASK A BIOLOGICAL QUESTION,
WE WANTED TO OPTIMIZE THE
TECHNICAL DELIVERY OF TMS.
SO WE WORK WITH OUR COLLEAGUES
IN FUNCTIONAL MRI AND OUR
COLLEAGUES IN TMS ENGINEERING TO
OPTIMIZE AND REALLY INSURE MORE
PRECISE DELIVERY OF THIS TMS.
SO WE BEGAN BY GETTING A
FUNCTIONAL MRI ON PATIENTS WITH
FOCAL HAND DYSTONIA AS A BASE
LINE TO DEVELOP OUR BRAIN LINE
TARGETING.
SO SPECIFICALLY SUBJECTS
COMPLETED A T1 MRI.
AND THIS KNOW THEY COMPLETED A
TASK FMRI TO THE WRITING TASK TO
IDENTIFY FUNCTIONAL BRAIN
ACTIVITY.
WE THEN OVERLAY THE MNIAT
LAS PINTAS FOR THE PREMOTOR TEXT
AND ULTIMATELY WE IDENTIFIEDED
HIGHEST WE HAVE SCORE WITHIN THE
FORMULA METER TO LESS THAN 1
CENTIMETER DANCE FROM THE
SUPERFICIAL CORTEX.
WHICH ALLOWED US TO DEVELOP A
SMALL 2 VOXEL MASK, WE THEN TOOK
THE FUNCTIONAL BRAIN TARGETED
MASK AND WE WORK OUR COLLEAGUES
IN ENGINEERING, PARTICULARLY
DR. PETER [INDISCERNIBLE] GROUP,
HIS GROUP HAS SHOWN THAT TO
OPTIMIZE AND MAXIMIZE THE
ELECTRIC FIELD AT THE CORTICALE
GYRUS OF INTEREST, YOU WANT TO
DELIVER TMS COIL IN AN
ORIENTATION THAT MACK MYSELFS
THE LANGUAGE FIELD TANGENTIAL TO
THE COTTERICALLY GYRUS.
SO USING THAT PRINCIPLE WE WORK
TOGETHER TO BASICALLY DEVELOP A
TMS TARGETED ANALYSIS PIPELINE.
AND THE GOAL WAS TO ABLE TO RUN
A COMPUTATIONAL SIMULATION IN
SOFTWARE THAT ALLOWED US TO
DETERMINE WHICH IS THE OPTIMAL
COIL ORIENTATION ON THE SCALP
THAT COULD MASS MIKES THE
ELECTRIC AT FIELD AT THE
CORTICALE GYRUS SO THE ULTIMATE
GOAL AND OUTPUT WAS BASIC LE A
SCALP TARGETING THAT ALLOWED US
TO BE ABLE TO MAXIMIZE ELECTRIC
FIELD AT THE CORTICALE GYRUS,
THAT DATA WAS THEN INPUT AND ON
THE DAY, 1 MORE THING IS THAT ON
THE DAY OF THE TMS STIMULATION,
WE THEN ADJUST THAD SCALP
TARGETING BASED ON THE HAIR
THICKNESS OF THE SUBJECT.
AND THIS INFORMATION WAS PUT
INTO A NEURONAVIGATION SOFTWARE
AND THEN COMPLETED THE STUDY,
AND THE FIRST QUESTION WE WANTED
TO KNOW WAS HOW WELL DID WE DO
IN THE RECEIVED ELECTRIC FIELD
AT THE CORTICO GYRUS OF INTEREST
IN ORDER TO ANSWER THE QUESTION
BIOLOGICALLY, WE NEED TO BE ABLE
TO DELIVER EQUAL AMOUNTS OF
ELECTRIC FIELD ACROSS BOTH
ACTIVE CORTICALE TARGETS AND SO
WE LOOKEDDA THE THAT AND IN FACT
WE HAVE NO DIFFERENCE IN THE
RECEIVED ELECTRIC FIELD AT THE
PRIMARY SOPHISTICATED MAT O
SENSORY OR PRO MOTOR CORTEX IN
PATIENTS WITH FOCAL HAND
DYSTONIA, SO THEN WE ASKED THE
QUESTION, WELL HOW DID OUR
PATIENTS DO BEHAVIORIALLY AFTER
1 SESSION OF REPETITIVE TMS.
AND WHAT WE SAW WAS THAT TMS
DELIVERED IN A SINGLE SESSION
ACTUALLY LED TO A SIGNIFICANT
REDUCTION IN BEHAVIOR OF
DYSTONIA, IN PATIENTS WHO
RECEIVED ACTIVE TMS OR PREMOTOR
PRIMARY SOPHISTICATED MATE O
SENSORY TORTEX AND WE ASKED HOW
DO WE DO IN TERMS OF FUNCTIONAL
BRAIN ACTIVITY, DO WE MODIFY THE
BASAL GANGLIA AND IT WAS A
SURPRISE TO US AS WELL AS HOW
MUCH BENEFIT WE ACTUALLY
DELIVERED, WE SAW THAT PATIENT
WHO IS HAVE TMS DELIVERED AT THE
SOPHISTICATED MAT O SENSORY
CORTEX SO A INCREASE WITH BOLD
ACTIVITY IN THE PATIENTS
COMPARED TO THOSE WHO RECEIVE
ACTIVE TMS AS A PREMOTOR OR
SHAM.
SO IN CONCLUSION I'VE SHOWN YOU
THAT REPETITIVE TAMERICA S CAN
ALLOW FOR MODIFICATION OF DEEP
BRAIN NETWORK AND THAT RTMS AND
THE PRIMARY SENSORY CORTEX
IMPROVE DISTONNIC BEHAVIOR BUT
IT'S SPECIFICALLY THE 10-HERTZ,
A CONCEPT WE CAN SAY IS TARGET
ENGAMEMENT AND FUTURE STUDIES
ARE NEEDED TO SELECTIVE
ENGAGEMENT OF BASE AT GANGLIA
COULD SERVE AS A PREDICTIVE
BIOMARKER BUT CLINICAL RESPONSE
TO OUR TMS AND THEREFORE ALLOW
US TO DEVELOP A TARGETED THERAPY
THAT WOULD BE LONG LASTING IN
THESE PATIENTS AND FIEBDING FROM
THE STUDY COULD OVERALL INFORM
THE DESIGN AND DEVELOPMENT OF
NONINVASIVE NEUROMODDULATION
WITH PATIENTS WITH DYSTONIA,
WITH THAT I AM HAPPY TO TAKE ANY
QUESTIONS, I WORK WITH A LARGE
GROUP OF PEOPLE AND FORTUNATE TO
HAVE TECHNICAL EXPERTS TO
COLLABORATE WITH SO THANK YOU
VERY MUCH.
>>DO WE HAVE ANY QUESTIONS?
STHRKS YOU TALKED SO FAST I
MIGHT HAVE MISSED IT.
SO DID YOU END UP GETTING A
LASTING IMPROVEMENT IN THE
PATIENTS WITH DYSTONIA.
>>YES, SO THE BENEFIT I WAS
SHOWING IN THE BEHAVIOR SIDE WAS
MEASURED IMMEDIATELYOT DAY OF,
HOWEVER, WE ACTUALLY WERE ASKING
OUR PATIENTS THE SAME QUESTION,
WHAT WAS SURPRISING IS HOW LONG
THEY WERE REPORTING THE BENEFITS
SO OUR PATIENTS REPORTED
BENEFITS THAT LASTED UP TO A
MONTH AND 1 PATIENT SAID IT
NEVER REOCCURRED.
SO WE'VE HAD TO DO ADVANCED
ANALYSIS TO SEE WHAT WAS
CONSISTENT WAS THAT PATIENTS WHO
HAD LONG LASTING BENEFIT ENDED
UP HAVING AT THIS TIME AT THE
PRIMARY SOPHISTICATED MAT O
SENSORY CORTEX, ENDED UP
RECEIVING TMS AT THE CORTEX,
SUGGESTING THAT MAYBE ACTIVATION
OF DIFFERENT TYPES OF PLASTICITY
RESPONSES, WHEREAS TMS AT THE
ACTIVE PRIMARY SOPHISTICATED MAT
O SENSORY CORTEX MAY BE
ACTIVATING A LONG-TERM
PLASTICITY RESPONSE COMPARED TO
THOSE WHO WERE RECEIVING, THE
TMS CONDITION AT THE PREMOTOR
CORTEX.
THANK YOU VERY MUCH DR. BUKHARI.
[ APPLAUSE ]
>>NEXT UP, DR. DEBILY FROM THE
UNIVERSITY OF HOSPITAL OF
STRASBOURG.
>>THANK YOU CAN YOU HEAR ME?
I AM A PSYCHIATRIC DOCTOR IN THE
CENTER HOSPITALLIER UNIVERSITY
DESTRASBOURG, IN FRANCE, I WANT
TO TALK ABOUT THE VALIDATION OF
A BIOMARKER IN THE DIAGNOSIS OF
PERIODIC CATATONYA, I HAVE NO
DECLARATIONS.
SO FIRST WHAT ARE WE TALKING
ABOUT WE ARE TALKING ABOUT A
SUBTYPE OF SCHIZOPHRENIA, WHICH
IS WITH THE PATIENT AND HAS
RECEIVED [INDISCERNIBLE] WITH
ACCLIMATION OF THE RESIDUAL
SYMPTOMS, IT'S A POLYMORPHIC
PRESENTATION AND THESE 2-POINTS
WILL BE VERY IMPORTANT LATER.
AND ALL RIGHT BEEN BY 2 TEEMSOT
FMRI, TO WONDER WHAT ARE THE
ORIGIN EVER THE BRAIN WHICH
CAUSES THE SYMPTOMS.
BUT THIS GROUP EFFECT AND WE
WANTED TO MAKE A TODAY ABOUT
SINGLE PATIENT IMAGES.
SO WE WROTE A PROTOCOL WITH
ACQUISITION OF [INDISCERNIBLE]
CONTRAST.
EVERY PATIENT HAS A 3 SCAN WITH
2 MEASURE, 1 WAS AT TEOF 9.7
MILLI SECONDS AND 1 WAS 21 MILLI
SECONDS.
WE FOCUSED ON THE SAME 2 ORIGINS
OF INTEREST, L-PMAND L-SMA AND
EACH PATIENT HAD IT'S OWN MRI
COMPARED TO IT, AND THE DAILY
BASIS THEA BASE OF CONTROLLED
SUBJECT TO MAKE [INDISCERNIBLE]
THE BRAIN [INDISCERNIBLE].
>>WE USE THE BIOSCAN MODEL
WHICH ALLOW US TO MAKE
MODULARIZATION OF THE
SENSITIVITY AND SPECIFICITY.
AND WE--WHICH ALLOWS A
POSSIBILITY TO MAKE THE
[INDISCERNIBLE] UPDATES FOR THE
[INDISCERNIBLE] EVERY TIME WE
RECRUIT A NEW [INDISCERNIBLE].
WE USE PRIOR DATA AND IT GIVES
YOU MORE REPRESENTATIVE OF THE
RESULT, WITH THE BELIEF OF THE
SENSITIVITY AND THE HER EDITTITY
OF THIS VALUE IS A TRUE 1.
WE MADE THE FIRST PROOF OF
CONCEPT 2 D WITH A SAMPLE.
OUR METHOD OF ACQUISITION HAS
HAD HIGH ACRASESY AND HIGH
KD--SALLY WHICH MADE IT REALLY
RELIABLE MEASUREMENT.
THE FIRST 1 IS PRIOR CATATONYA
23, AND 26 PATIENTS WITH NOVEL
OR PHENOTYPE OF MENTAL DISEASES,
WE HAD A SENSITIVITY OF 98% AND
A SPECIFICITY OF 8% WITH A
NORMATIVE PRIOR.
THIS FIRST PROOF OF CONCEPT, WE
LEARNED 2 THINGS.
FIRST, OUR WORK SEEMS TO BE
SPECIFIC, BECAUSE THE OTHER
PATIENT WITH ANOTHER FORM OF
[INDISCERNIBLE] SEEMS TO HAVE
IT.
ALSO, OUR BIOMARKERS SEEMED TO
BE SENSITIVE TO A PATIENT WITH A
MOTOR IMPAIRMENT INCLUDING THE
REQUIRED MOTOR IMPAIRMENT LIKE
MULTIPLE SCLEROSIS OR LEG
INJURIES.
WE DECIDED TO USE OUR DATA WITH
ANOTHER EXAMPLE, THE DATA WAS
WEIGHTED INDEX AND WE INCLUDED
13 PATIENT [INDISCERNIBLE] AND A
PATIENT WITH ANOTHER PHENOTYPE.
WE THEN HAD A SENSITIVITY OF 77
PERSON AND A PATIENT WITH 78%.
PATIENTS WITH MORE UNCLEAR
DIAGNOSIS AND DIAGNOSTIC
CORRECTIONS, THEY MAKE ALLOW US
TO MAKE A CORRECTION OF THE
DIAGNOSIS.
WE DECIDED TO MAKE AN UPDATE OF
THE ABILITY OF OUR BIOMARKER
EXCLUDING THE PATIENT WITH MOTOR
IMPAIRMENT AND TAKING A FULL
DATA SET WITH THE
[INDISCERNIBLE] PRIOR, AND THEN
WE THEN HAD SENSITIVITY OF 82%
AND SPECIFICITY OF 98%.
SO, WE HAVE INCENTIVE AND
SPECIFIC BIOMARKER.
COMBINED WITH THE CLINICAL EXAM
NATION, IT HAS A GOOD
[INDISCERNIBLE], AND A GOOD
PARTICIPATORY [INDISCERNIBLE],
SO FOR EXAMPLE, IF YOU TAKE THE
PATE WITH THE SSD DIAGNOSIS,
WITHOUT BIOMARKER THEY HAVE
PROBABILITY OF 14% TO HAVE
PERIODIC CATATONIA, IF THEY HAVE
A POSITIVE BIOMARKER THEY HAVE A
PROBABILITY OF 73% TO HAVE A
CATATONYA, AND IF THEY HAVE A
NEGATIVE BIOMARKER, THE
PROBABILITY HOLDS TO 3%.
WE WILL NOW REPLICATE OUR
FURTHER STUDY INCLUDING MORE
PHENOTYPES OF MENTAL INJURY, AND
WE CAN NOW IN OUR MODEL, ALLOW
US TO MAKE [INDISCERNIBLE]
THAT,A LOW US TO WEIGH THE DATA
FOR EACH PROTOCOL.
WE ARE NOW MAKING DIAGNOSIS FOR
[INDISCERNIBLE] - AS I SAID IT'S
A MOLECULAR PRESENTATION OF THE
SYMPTOMS SO IT'S A HUGE AREA FOR
PATIENTS WITH THE MORE SYMPTOMS,
THERE IS NO ACHE, OR STRATEGY
WITH THE FOLLOW UP OF THE
[INDISCERNIBLE] AND WE ARE NOT
ABLE TO MAKE BETTER RESEARCH ON
THE CATATONYA, FOR EXAMPLE, WE
ACTUALLY CORTICALE USING THIS
BIOMARKER ON THE TARGET FOR THE
TMS STIMULATION, AND WE OBTAINED
A HUGE EVALUATION OF THE
PATIENTS MORE THAT WE COULD HOPE
WITH ONLY A PHARMAICOLOGGIC
TREATMENT AND STIEMENTS BETTER
BY [INDISCERNIBLE].
WE WILL NOW USE THE BIOMARKER TO
REDEFINE THE PHENOTYPE OF THE
CATATONYA.
USING A RIGOROUS APPROACH, YOU
USE THE BIOMARKER FOR THE
PATIENT WITH A MORE BOUNDARY
PATIENT WITH EARLY ONSET,
DIAGNOSIS, I DON'T HAVE THE SAME
CLINICAL PRESENTATION OF THE
OTHER AND WE CAN WITH THE
TECHNOLOGY AND OUR BIOMARKER,
REDEFINE THIS PHENOTYPES AND
CONFIRM IT WITH ANATOMY
[INDISCERNIBLE].
I WOULD REALLY LIKE TO THANK THE
[INDISCERNIBLE] TEAM WITHOUT
WHOM I WOULD NOT BE ABLE TO MAKE
THIS PRESENTATION
ESPECIALENTIALLY
[INDISCERNIBLE].
AND ALSO THE TEAM OF THE
STRASBOURG, AND THE
NEUROMODDULATION CENTER.
THANK YOU FOR YOUR ATTENTION.
[ APPLAUSE ]
>>HI, NICE PRESENTATION.
WHY WAS THE--WAS THE LONG TE
NEEDED?
YOU SHOWED THERE WAS A
CORRELATION BETWEEN THE 2 ISL,
WAS IT NEEDED AFTER LONG T?
>>THREE?
>>ARE WHY DO YOU NEED 2?
>>ONE IS MORE IMPORTANT THAN
THE OTHER AND THE OTHER IS
SPECIFIC.
IN THE 1970S LIKE THE
[INDISCERNIBLE] ACQUISITION, BUT
THE 21 SIGNAL IS NOR SENSITIVE
AND WE HAVE BIOMARKERS WITH THE
A COMBINATION OF THE BOTH, TO
THE TARGET SO THE CONTEXT AND
[INDISCERNIBLE] IN THE 2
ACQUISITION, AND THE COMPOSITION
OF THE 4 FACAS RAM TERS MADE THE
BY O MARKER, THE POSITIVITY OF
THE BIOMARKER.
>>ARE THERE ANY OTHER
QUESTIONS?
IF NOT WE WILL MOVE TO THE NEXT
SPEAKER.
THANK YOU VERY MUCH.
[ APPLAUSE ]
DR. JEANJEAN FROM THE UNIVERSITY
HOSPITAL OF STRASBOURG.
>>HELLO EVERYBODY, MY NAME IS
LUDOVIC, DORMEGNY-JEANJEAN, AND
I WILL TALK TO YOU ABOUT OUR
WORK ON PERSONALIZING TARGETING
IN RTMS USING ASL IN DEPRESSION,
AND IT'S APPLICATION TO THE
DEPRESSIVE DISORDER.
SO I WILL NOW SAY A SENTENCE NOW
[INDISCERNIBLE] WE NEED TO
REFINE OUR EQUIPMENT
[INDISCERNIBLE].
IN THE FIELD OF TMS, IN THIS WAY
WE CAN [INDISCERNIBLE] THE
ONE-SIZE-FITS-ALL APPROACHES AND
IMPROVE EFFICACY.
WE DO THAT BECAUSE OF BIRTH AS
ANNOT ME OF FUNCTION AND
VIABILITY OF THE BRAIN BUT
PATHOPHYSIOLOGICAL
HETEROGENERATED AITY OF
DEPRESSION AND THE OTHER
CIRCUITRY DISORDERS.
WE PROPOSE TO USE TMS TARGETING
TO RUES IT FOR ROBUSTNESS AND
[INDISCERNIBLE] BETWEEN THESE.
AND WE USE FOR THESE TODAY, VERY
CLOSE WITH THE 1 PRESENTED BY
[INDISCERNIBLE] AND USE IT TO
DEFINE ANOMALY AND A SET OF
CONTROL--ABNORMALITIES VERSUS
CONTROLS AND ALSO PERSONALIZE
THAT WITH THE REBALANCE
PERFUSION ABNORMALITIES AND THEN
THERE IS A PARTICULAR BIOMARKER,
IF WE,A ASSESSES IT
[INDISCERNIBLE], WOO CAN USE IT
AS IT MAY NOT COME AND READY
WITH YOUR [INDISCERNIBLE].--WE
SEEM TO BE LESS NEUROLOGIC
FUNCTION [INDISCERNIBLE] WE WE
ARE ALSO DIFFERENT TO THE WORK
ABOUT REBALANCING
[INDISCERNIBLE] BECAUSE WE USE
MORE ACCURATE AND MORE
REPRODUCIBLE MEANS AND WE--WE
ARE NOT LIMITED TO A SINGLE
PURPOSE THAT [INDISCERNIBLE]
DEFICIT TARGET.
WE CONDUCTED A PILOT STUDY WITH
THE COURSE OF A DESIGN WITH
EQUIPMENT TMS, CLASSIC TMS,
TARGETING THE DORSAL
[INDISCERNIBLE].
AND POST CONNECTOR STIMULATION.
FOR [INDISCERNIBLE] WE USE
STIMULATION OF ACTIVATION AND
LOOK FOR CONSISTENCY WITHIN THE
BRAIN AND WE USE [INDISCERNIBLE]
POSITIONING.
THERE IS A CHANGE OF DEFINITION
IN [INDISCERNIBLE] AND
[INDISCERNIBLE], DEVELOP WELL
AND [INDISCERNIBLE] BECAUSE OF
THE 2 SHORT AREA, THE THRESHOLD
BETWEEN THOSE 2.
JUST A LITTLE BIT MORE ABOUT THE
DATA PROCESSING WE USE, THE
[INDISCERNIBLE] CONTRAST FOR
EACH EQUIPMENT AND THEN COMPARE
EACH OF THIS INTEREST, WE'VE
[INDISCERNIBLE] WITH THOSE
[INDISCERNIBLE].
THIS WAY, WE KIND HAVE BEEN
SPECIFIC TYPE OF SPECIFIC OF
EQUIPMENT FOLLOWING
[INDISCERNIBLE] OF THIS
CONTRAST.
WE USE THE [INDISCERNIBLE]
BETWEEN THE 2 MOBILITYS OF THESE
AND BETWEEN THE [INDISCERNIBLE].
AND WE INCLUDED 22 PATIENTS
[INDISCERNIBLE] AND WE HAVE
EFFUSION [INDISCERNIBLE] WITH
MANY POSSIBILITY OF TARGETING
AND THANKS TO THE ROBOTIC
PLACEMENT WE WERE ABOUT TO REACH
UP TO 18 TARGET SECTION.
IN THIS CASE, WE HAVE THE NUMBER
OF [INDISCERNIBLE] BETWEEN
TARGETS AND THE NUMBER OF
[INDISCERNIBLE] BETWEEN
SESSIONS.
TMS INDUCED SPECIFIC LOCALIZED
DECREASED SDF IN THE BRAIN
HEMISPHERE, IT WAS THE EARLY
TREATMENT TO INDUCE THIS TYPE OF
[INDISCERNIBLE] PROPHETIC.
AND IT WAS IN [INDISCERNIBLE]
INVOLVED IN [INDISCERNIBLE]
PROCESSES.
AND TO CONCLUDE IMAGING INN
DUCED SPECIFIC EFFECT ON THE
RCBF, WHICH IS RTMS OR TDCS,
[INDISCERNIBLE] AND THAT FURTHER
WORK FOR INTERPRETATION AND
[INDISCERNIBLE].
THIS IS AN ALTERNATIVE WAY TO
PERSONALIZE THE RTMS, DIFFERENT
TO CONNECTIVITY BASED ON
[INDISCERNIBLE] BUT NOT
MANDATORY [INDISCERNIBLE].
AND [INDISCERNIBLE] TODAY AND
WAS NOT SIGNIFICANT IN OUR STUDY
BECAUSE IT WAS [INDISCERNIBLE].
BUT THE NEXT DAY, IT WOULD BE TO
[INDISCERNIBLE] STUDY WITH
BETTER DESIGN TO THANK
[INDISCERNIBLE] CORRELATES OF
[INDISCERNIBLE] METRIC AND WE
SHOULD PAY PARTICULAR ATTENTION
TO PATIENT WITH A REEMINENT
[INDISCERNIBLE] PROCESS
[INDISCERNIBLE].
I WANT TO THANK OUR TEAM WE ARE
LUCKY TO WORK WITH
[INDISCERNIBLE] AND I THANK YOU
IF ARE YOUR ATTENTION.
[ APPLAUSE ]
>>ARE THERE ANY WEB CONNECTEDS
FOR THE SPEAKER?
I HAVE A QUESTION.
SO THE ASL MEASUREMENTS ARE THEY
GIVING YOU THE TARGETS FOR TMS?
>>YES.
>>DO HAVE YOU AN EXPLANATION
FOR THE MECHANISM, WHAT BY?
>>WE DO NOT TAKE
[INDISCERNIBLE] ABOUT UNDERLYING
MECHANISM BECAUSE WE MADE AS FEW
ASSUMPTION AS POSSIBLE ABOUT
MECHANISM BUT JUST, SEEKING TO
REBALANCE OKAY, THANK YOU.
ANY OTHER WEB CONNECTEDS.
ANY OTHER QUESTIONS, OKAY, IF
NOT WE WILL MOVE TO THE NEXT
SPEAKER.
THANK YOU.
[ APPLAUSE ]
NEXT UP WE HAVE HONG MING LI
FROM THE UNIVERSITY OF
PENNSYLVANIA.
>>GOOD AFTERNOON EVERYONE,
UNFORTUNATELY HONG MING LI WAS
NOT ABLE TO JOIN THIS MEETING SO
I WILL MAKE THIS PRESENTATION.
SO WE WILL START WITH THE SLIDES
SHE PROVIDED TO SPEED UP THE
PLACEMENT OF ELECTRONIC FIELD.
I HAVE NO CHRIS DISCLOSURES.
SO FOR ELECTRIC FIELD MODELING,
WHAT MATTERS IS THE LEARNING FOR
FAST OPTICAL IMAGES MIEDZATION
FOR TMS COIL PLACEMENT, SO
RELATIVELY FASTER OF
OPTIMIZATION FOR PLACEMENT.
IN RECENT YEARS, [INDISCERNIBLE]
HAVE SPEED UP THE DEEP FIELD
MODELING, SO INCLUDING NASA TO
HELP SIMPLIFY THIS, BUT
PARTICULARLY DEEP LEARNING HAVE
DEMONSTRATED THAT
[INDISCERNIBLE] PERFORMANCE TO
SPEED UP THE OPTIMIZATION, SO
THIS CAN GENERATE SOLUTIONS BY
DIRECT LEARNING FROM ELECTRONIC
FIELD THAT GENERATED BY OTHER
TYPES OF MEDICINE LIKE FEM,
HOWEVER THIS METHOD KIND OF TO
PROVIDE DEEP LEARNING MASS WERE
NOT DESIGNED FOR DIRECT STARTS,
THE POSITIVE DECREASED IN THE
DEEP FIELD MODELING.
SO GET THIS STARTED WITH THE
PROVIDE THE DEEP LEARNING METHOD
TO DIRECT [INDISCERNIBLE]--CAN
GENERATE AN ELECTRONIC FIELD
THAT'S LOOSE AND USING ANY
REASON.
THIS IS SELF-CONTAINED,
KD--SALLY WADIFFERENT FROM THIS,
IN, AND DEEP LEARNING MASS, THAT
HAVE TO USE ALL THE TYPES OF
[INDISCERNIBLE] TO GENERATE DATA
OF ELECTRONIC FIELD.
SO THIS IS OVER THE FRAMEWORK OF
THE [INDISCERNIBLE], GIVEN ANY
INPUT CONSISTENT E-FIELD MODEL
AND EFIELD GENERATED BY MASK
COIL.
OUR MASK IS APPLIED TO
AUTOMYSELF DEEP LEARNING NEURAL
NETWORK TO GENERATE ELECTRONIC
SCALE UP TO MINIMIZE LOST PARTS
AND ON THE MODEL YOU DON'T
OPTIMIZE IT, THE MODEL CAN
DIRECTLY APPLY TO NEW DATA TO
GENERATE ELECTRONIC FIELD OF
THESE EVENTS THERE FOR THE
[INDISCERNIBLE].
>>OR UPON THAT, THE STANDARD
UNIT, NETWORK ARCHITECTURE TO
USE IT AND THE NETWORKS THAT
COMPUTERS ARE ELECTRONIC FIELD
SO BASICALLY WE WANT INPUT AND
CONDUCTING AND PRIME THE FIELD
THAT OUR METHOD CAN DIRECTLY
GENERATE THAT ELECTRONIC
POTENTIAL AND THE CAN ALSO
COMPUTE GRADIENT OF THIS
POTENTIAL TO GENERATE THE
ELECTRONIC FIELD.
WE HAVE [INDISCERNIBLE] METHOD
ON OUR [INDISCERNIBLE] WITH 100
IMAGE OR THE HIGH QUALITY
[INDISCERNIBLE] TO THE MRI
IMAGE, THUS WE DON'T HAVE
[INDISCERNIBLE] FOR THE FIELD SO
WE COMPARED OUR FEM SOLUTIONS IS
USING THE SAME NAMES.
SO THE MODEL ON THE 100 SUBJECTS
AND THE VARIED MODEL TO THE 25
SUBSETS.
SO 1 IS VERY DIFFERENT SETTINGS
OF [INDISCERNIBLE] PLACEMENT.
BECAUSE FIRST EVALUATE THE MASS
FOR THE COIL PLACE AT A LOCATION
[INDISCERNIBLE].
THE RIGHT FIGURE SHOWS SOLUTION
GENERATED BY FEM AND THE DEEP
LEARNING MASK FOR DIFFERENT
SUBSET.
THIS RESULTS INDICATES THAT
THOSE ARE GENERATED SIMILAR
ELECTRONIC FIELDS.
IS A SMALL DIFFERENCE, THE SPEED
OF OUR [INDISCERNIBLE] DEPEND ON
THE SPECIAL AND HEAD MODEL.
THE HEAD MODEL WAS A CUBIC
[INDISCERNIBLE] AND WE WERE
ASKED DO CONSIDER ELECTRONIC
FIELD FOR 25-SECONDS.
SO WE ALSO TEST THE MODEL ON
THAT DATA WITH COIL PLACED AT
THE SAME PLACE BUT INDIFFERENT
DIRECTION.
WE ALSO UPON [INDISCERNIBLE]
MODEL WITH THE PLACEMENT WITH A
DIFFERENT DIRECTION AND MOUNT
FOR DIFFERENT PLACE.
SO ALL THOSE RESULTS,
EXPERIMENTS HAVE [INDISCERNIBLE]
DEMONSTRATED THAT DEEP LEARNING
MASK CAN GENERATE ELECTRONIC
FIELD COMPARABLE TO FEM
SOLUTIONS.
HOOVER, THIS, IS THE COMMITTEE
WERE A RESULTS FOR THE
COMPARISON BETWEEN FEM SOLUTIONS
IS THE DEEP LEARNING SOLUTIONS.
ON THE GRAY MATTER, THE PLAQUE
MATTER, READINGS, THE
CORRELATION BETWEEN THOSE 2, THE
2 SOLUTIONS WERE UP FOR 4984,
AND THE DIFFERENCE, WAS AS SMALL
AS A POINTER 0, OF COURSE, THE
PERFORMANCE WAS DIFFERENT AT
DIFFERENT SETTINGS OF THE COIL
PLACEMENT, BUT ALL THIS METHODS,
ALL THESE RESULTS HAVE
DEMONSTRATED THAT THE DEEP
LEARNING MASS CAN GENERATE IT,
SOLUTIONS TO COMPARABLE TO THE
FEM'S MASTER, WE KNOW THE FEM
SOLUTIONS ARE NOT
[INDISCERNIBLE] AND THE SUBSET
TO CERTAIN AREAS SO WE ALSO
COMPARED IT TO THE DEEP LEARNING
MASS TO THESE FEM BASED ON
SEVERITY MODEL.
THESE RESULT INDICATORS THAT THE
DEEP LEARNING ACTUALLY CAN
ATTENUATE SLIGHT BETTER ACCURACY
THAN THE STANDARD FEM.
SO, IN SUMMARY OUR STUDY SHOWS
THAT THE STEPS PROVIDED CAN
GENERATE A ELECTRONIC FIELD
COMPARABLE TO FEM MASS, HOWEVER,
ONGOING RESEARCH FOCUS ON MODEL
OPTIMIZATION, INCLUDING TRAINING
MODEL ON THE LARGER BETA SAMPLE
AND AUTOMYSELF THE
[INDISCERNIBLE], AND
OPTIMIZATION [INDISCERNIBLE].
THANK YOU FOR YOUR ATTENTION.
[ APPLAUSE ]
>>THERE ARE ANY QUESTIONS?
OKAY, I HAVE A QUICK, QUESTION,
SO HOW LONG DOES IT TAKE TO
OPTIMIZE WITH CNIBS?
>>I'M SORRY?
>>HOW LONG DOES IT TAKE TO
OPTIMIZE FOR CNIPS, YOU SAID
WITH DEEP LEARNING IT TAKES A
SECOND?
>>DEPENDS ON YOUR USE, IT TAKES
ABOUT 10-SECONDS.
HOWEVER, THERE ARE IMPAIRMENTS.
>>OKAY.
ANY QUESTIONS?
OKAY, IF NOT, I THINK WRAPPING
UP THE SESSION, THANK YOU ALL
FOR ALL THE SPEAKERS.
[ APPLAUSE ]