AdvancedMedicalImagingDevelopmentsand ApplicationsforNeuroscienceResearch NationalInstitutesofHealth Bethesda,MD June9,2011 FinalMeetingReport

I. II. III. IV. V. VI. VII.

TABLEOFCONTENTS AbbreviationsUsed...2 ExecutiveSummary.............................................................................................. 3 PurposesandObjectivesoftheSymposium.......................................................4 SummaryofPresentationsandDiscussion .........................................................4 . MeetingFindings................................................................................................. 9 Conclusion..........................................................................................................10 ContactInformation .......................................................................................... 10 . Appendix1:WorkshopAgenda.........................................................................11 Appendix2:ListofWorkshopParticipants........................................................13

I. AbbreviationsUsed
AD ASLMRI BBB CBF CESTMRI CNS CSF CT dEEG dMRI DTI EEG FDGPET fMRI HCP MEG MEMRI MRI MRS ND PET RF RfMRI SPECT SPIO T1 T2 T2* TfMRI AlzheimersDisease ArterialSpinLabelingMRItechniquetoaccessCBF BloodBrainBarrier CerebralBloodFlow ChemicalExchangeSaturationTransferMRI CentralNervousSystem CerebrospinalFluid XRayComputedTomography DensearrayEEG DiffusionMRI DiffusionTensorImagingforbraintractography Electroencephalographymeasuringelectricalactivityofthebrain APETtechniqueusingF18labeledglucosetotrackglucosemetabolism AnMRImethodtoaccessbrainactivation HumanConnectomeProject Megnetoencephalography ManganeseEnhancedMRI MagneticResonanceImaging MagneticResonanceSpectroscopy NeorodegenerativeDiseases PositiveEmissionTomography Radiofrequency RestingstatefMRI SinglePhotonEmissionComputedTomography SuperParamagneticIronOxide Longitudinalrelaxationofprotonsinamagneticfield Transverserelaxationofprotonsinamagneticfield T2enhancedbyfieldnonuniformities(morepronouncedinhighfieldMRI) TaskevokedfMRI

II. ExecutiveSummary AbouttheSymposium ThissymposiumentitledAdvancedMedicalImagingDevelopmentsandApplicationsfor NeuroscienceResearchtookplaceattheNationalInstitutesofHealth(NIH)ListerHill CenterAuditoriumonJune9,2011.Themeetingwascoorganizedandsponsoredbythe NationalCenterforResearchResources(NCRR),NationalInstitutesonDrugAddiction (NIDA),NationalInstituteofMentalHealth(NIMH)andNationalInstituteofBiomedical ImagingandBioengineering(NIBIB).Twelveinvitees,eightspeakerswithmedicalimaging expertiseandfourdiscussantswithcrossboundaryexpertise,participatedinthisoneday symposium.TheaudienceconsistedofNIHprogramstaff,imagingscientistsand neurobiologistsatdifferentstagesoftheirresearchcareersfromwithinandoutsidethe NIH.Themeetinghadtwosessions,amorningsessionfocusedontechnicalaspectsof medicalimagingandanafternoonsessionontheapplicationofmedicalimagingto addresscrucialquestionsinneuroscience.Eachsessionwasfollowedbyapanel discussionandquestionsfromtheaudience. Background Neurobiologistshaveutilizedadvancedmolecularbiologicalassaysand immunohistochemistrytoidentifythecauseandprogressionofneurologicaldiseasesand disorders.However,thosetechniquesareoftenlimitedbecausetheycanonlybe performedonbiopsiedorpostmortembrainsamplesand,therefore,lacklongitudinal applicability.MedicalimagingmodalitiessuchasMRI/MRS,PET,CTandopticalimaging, aswellastheircomodalities,haveenabledrealtimevisualizationofthecentralnervous system(CNS)inlivesubjects.Becausetheydonotrequirebrainsamples,mostofthese technologiesareroutinelyusedinclinicsandofferminimallyinvasivemeanstodetect structural,metabolicandphysiologicprocessesofbrainfunctionforresearchand diagnosticpurposes.Thedevelopmentofnovelimagingtechnologyrequiresstrong knowledgeandbackgroundinchemistry,physicsandengineering.Forexample,chemists synthesizespecializedradiopharmaceuticals,contrastagentsandprobestoimprove imagecontrastanddetectcellulartargets.Engineersdesigncoils/sensorswithdifferent geometrytomaximizesignaltonoiseforspecificareasofinterest.Physicistsdevelop specializedpulsesequencesanddataprocessingalgorithmstoacquireandinterpretdata withgoodimageresolutioninordertogaininsightsintoneuralstructure,functionand activity.Numerouscollaborativeresearcheffortsbetweenneurobiologistsandimaging scientistshaveshownpromisesolvingneuroscientificproblems.Withsuchcross disciplinaryinvolvement,thesuccessofcollaborationreliesheavilyontheunderstanding, communication,andrespectamongtheinvestigators.Thereisvalueinbringingtogether neurobiologistsandimagingscientiststotalkaboutworkingtogetherasateamtobetter understandbrainfunctioninhealthyanddiseasestates. FocusofMeeting Thissymposiumbroughttogethermedicalimagingscientistsandneurobiologiststo1) explorestateoftheartmedicalimagingcapabilitiesandtheirapplicationsin 3

neuroscienceresearch,2)identifyobstaclesandproblemsassociatedwiththe collaborativeeffortsbetweenthetwodisciplines,and3)discusswaystotacklethese challenges.Presentationsweregearedtowardneurobiologistswhohaveworking knowledgeaboutmedicalimagingcapabilities. III. PurposeandObjectivesoftheSymposium 1) Provideanupdateonthestateofthecurrentmedicalimagingtechnologyfor neuroscienceresearch:presentationsaimedtogiveanoverviewofthedevelopment andbasicprinciplesofstateoftheartmethodologyusedtoimageanatomy,function, connectivityandmolecularactivitiesinhumanbrains.Thegoalwastoexpose neurobiologiststothefieldofmedicalimagingandtoequipthemwithsufficient knowledgeandvocabularytobettercommunicatewiththeimagingscientists. 2) Highlightmedicalimagingopportunitiesandapplicationinneuroscienceresearch: presentationsaimedtoshowcasethebroadapplicationsthesetechnologiescanoffer todetectbraindiseasesanddisorders.Thisprovidedanopportunityfor neurobiologiststoevaluatepotentialimagingapplicationstheycanleverageto enhancetheirresearch. 3) Exploreandencouragebettercoordinationandcommunicationforsynergistic researchcollaborationbetweenimagingscientistsandneurobiologists:discussion withthespeakersanddiscussantsoccurredduringthePanelDiscussionSessions whichincludedquestionsontherobustnessaswellaslimitation/pitfallsofmedical imagingtechnologiesandpersonalexperienceinthistypeofinterdisciplinary collaboration.Theobjectivewastocreateadialogueandcommongroundbetween thesetworesearchgroupsforbettercollaborativeefforts. IV. SummaryofPresentationsandDiscussion MorningSession:NutsandBoltsofMedicalImagingTechnologies MRIforBrainAnatomy,PhysiologyandFunctions ThispresentationprovidedanoverviewofthecontributionstoMRImethodology developmentsattheNationalResourceforQuantitativeFunctionalMRIatKennedy KriegerResearchInstituteandtheJohnsHopkinsUniversitySchoolofMedicine.Topics included: Principlesandapplicationsofdiffusiontensorimaging(DTI),whitematterfiber tracking,andthedevelopmentofthefirsthumanwhitematteratlas.Thisincludesthe firstinvivofibertrackingandthesubsequentapplicationtohumandisease.In addition,theDTItechnologyhasbeenfurtherdevelopedtogeneratedeformablebrain atlasestoinvestigatebraindevelopmentfrominfantstoadultsandtoassesswhite matterchangesindifferentpathologies.Suchnoninvasivetechnologycouldbeapplied 4

inconjunctionwithgeneticanalysisinanimalmodelsandpatientstoestablishpossible linkagebetweengenesandbraindisorders. Developmentofmethodologytononinvasivelymeasurecerebralbloodvolume. ArterialSpinLabelingMRIisonetechniqueinwhichtheprotonspinsoftheblood werelabeledbyanRFpulsebeforeenteringthebrainforMRdetection. Developmentofprotein/peptideimagingfirstinanimalsandsubsequentlyinhumans. Recentapplicationstoimageischemiaandbraintumorsandtoseparatetheeffectsof tumortreatmentfromthoseofrecurrenttumorsweredemonstrated. TheadvancementofhighmagneticfieldshumanMRIinclinicalapplication.The highestMRIfieldstrengthapprovedforclinicalusageis3tesla.Morerecently,7tesla MRIscannershavebecomeavailableforpreclinicalstudiesinhuman.TheseMRI scannershaveprovidedhigherresolution,enhancedcontrastimagingcapabilitiesto delineatemicrovasculatureofthebrain,whichwasnotdetectablebyclinically approvedMRIscanners.SomeexamplesofwholebrainhighresolutionMRIwere presentedtogetherwithsomeearlyillustrationsofapplicationstomultiplesclerosis andHuntingtonsdisease. DensearrayElectrophysiologyTechnologyforNeuralConnectivity ThispresentationshowcasedanelectrophysiologytechniquecalleddensearrayEEG (dEEG)tomeasurefunctionalactivityofhumancerebralnetworkswithmillisecond temporalresolution.Keypointswere: UnlikeconventionalEEGtechnologywithlimitednumberofelectrodesaffixedtothe scalp,dEEGtechnologyprovidesanetworkof256sensors(GeodesicSensorNet) coveringtheentireheadsurface. ThecapabilityofdEEGtechnologyinlocatingelectricalactivitywithanatomical accuracyisenhancedbyenclosingthesubjectinaphotogrammetrysystemfor geometricinformationoftheskull. Basedonskullinformation,advancedlinearinversemethodswithstatistical standardizationcangeneratedensemapsofbrainelectricalactivitieswithanatomical braincoordinates. ThealignmentofcorticalsourcepatcheswithDTItractographyisnowfeasible,andit promisesnewapproachestouncoveringthedynamicfunctionalnetworksofthe humanbrain.BeingcompatiblewithMRI,GeodesicSenorNetprovidesanadditional sourceofconnectivityinformationintheHumanConnectomeProject. Thistechnologyhasalsobeenusedtoinvestigatethesourceofdepression,neural mechanismofexpertperception,aswellastolocatetheabnormalbrainactivityin patientswithepilepsyinpreparationforneurosurgery. 5

ContrastEnhancedMRIforMolecularImaging ThepresentationprovidedabasicintroductiontocontrastenhancedMagneticResonance Imaging(MRI)formolecularimagingandpotentialapplicationsinneuroscienceresearch. Keypointswere: AsdefinedbytheSocietyforNuclearMedicinein2007,molecularimagingisthe visualization,characterizationandmeasurementofbiologicalprocessesatthe molecularandcellularlevelsinhumansandotherlivingsystems. MolecularMRIrequirestheuseofcontrastagentstoenhancetheimagecontrastof thestructureoffluidswithinthebody. MRcontrastagentsarecategorizedintoT1andT2agents.T1agentsappearbrightin T1weightedimagesand,therefore,arecalledpositivecontrastagents.T2agents appeardarkinT2weightedMRimagesandarecallednegativecontrastagents. GadoliniumhasbeenusedclinicallyasaT1agenttodetectbloodbrainbarrierleakage astheresultoftumororneurologicaldiseases. ManganeseEnhancedMRI(MEMRI)usesmanganeseion(Mn2+,ananalogtoCa2+)asa T1agenttodelineateneuronaltractsanddetectcalciumtransportandneuronal activation.Thesestudieshavebeenperformedinrodentsandnonhumanprimates. Superparamagneticironoxide(SPIO)nanoparticleshavebeenusedtoassessblood volumechangesassociatedwithbrainactivities.SPIOhasbeenusedtolabel antibodiesagainstAmyloidproteininmouseAlzheimersdisease(AD)modelto evaluateADprogression. However,thecaveatoftheseexcitingmoleculardetectioncapabilitiesisthelimitation ofcontrastagentsdeliveryacrosstheBBB.Methodstosafelyandreversiblyopenthe BBBtodeliverthecontrastagentsareneeded. PETforMolecularImaging Newdevelopmentsinpositronemissiontomography(PET)continuetoyieldunique informationonbiochemicaltransformationsandthedistributionandmovementofdrugs directlyinthelivinghumanbrainandotherorgans. TheadvancementofPETrequiresinnovationinradiotracerchemistry,particularlyin thedevelopmentofmethodsforintroducingtheshortlivedisotopesintochemical compoundsandwhicharetargetedtospecificcellularelements.Thedevelopmentof PETforneuroscienceresearchthatutilizesanimalsrequirestracersthatcanberapidly synthesizedandthathavewelldefinedkineticsandpredictablebioavailabilityin animalmodels.

 Fluorine18labeledglucose(FDG)isanacceptedradiotracerusedintheclinictotrack glucosemetabolismassociatedwithbrainactivities. Radioligandtechniquetargetingdopaminereceptorshashelpedinunderstandingthe involvementofthebraindopaminepathwayindrugaddictionandobesity.PET studiesshowedthatmanipulatingbraindopaminereceptorsreversedtheaddictive behaviorinanimalsandcouldpotentiallybeapplicableinhumans. PETimaginginhumansprovidestheopportunitytomeasurerelationshipsbetween genotype,brainchemistryandpersonality.Anexamplewasgivenonthestudyof monoamineoxidase(MAO),anenzymethatoxidizesneurotransmitters.Inhibitorsof MOAhavebeenusedtotreatdepressionandParkinsonsdisease.LowMAOA(a subtypeofMAO)genotypewasimplicatedwithantisocialbehavior.Usingradiotracer targetingMAOA,PETstudiesfoundthatitistheproteinproductofMAO,notthe genotype,whichpredictstraitaggression. AfternoonSession:ApplicationsofMedicalImagingTechnologyinBrainResearch

MRIinNeurodegenerativeDiseaseResearch Duringthepastdecade,therehasbeenanexplosioninresearchusingbrainMRI,PETand SPECTscanningtoinvestigatechangesinthebrainthatoccurduringnormalagingand progressionofneurodegenerativediseases(ND).Thesetechnologieshavealsobeenused inotherconditions,suchasdepressionandposttraumaticstressdisorders.Keypointsof thispresentationwere: ThereiscurrentlynoeffectivetreatmentthatslowstheprogressionofND.Theonly acceptablemethodtoaccuratelydiagnoseNDisbasedonpostmortembrainstaining. MRImethodologieshavebeenusedtoidentifyNDmarkersinlivingsubjects.Current methodsincludeT1,T2andT2*weightedimagingforanatomicalstructure;DTIfor neuralintegrity;ASLforbloodperfusion;andfMRI(suchasTfMRIandRfMRI)for brainfunctions. GroupstudiesofstructuralMRIhavefoundpotentialstructuralADmarkersincertain partsofthebrainssuchas1)reducedvolumesinthecortexandhippocampus,2)low bloodperfusion,and3)DTIabnormality(astheresultofdisorganizedfibers). ManyPETandSPECTimagingmethodologieshavebeenusedtodetectmolecular alterationinAD.FDGPEThasbeenusedtodetectbrainhypometabolismthatis associatedwithADsdementia.Severalnovelradiotracershavebeenusedtodetect ADinhumanssuchas1)PittsburghCompoundB(PiB)foramyloidburden,2)PK11195 formicrogliaactivities,and3)THK523fortautangles.

Standardizationinimagingmethodologiesformultisiteimageacquisitionandimage datasharingwillaccelerateourunderstandingintheprogressofADandother neurodegerativediseases. TheHumanConnectomeProject TheHumanConnectomeProject(HCP)isaneffortfundedbyNIHtocharacterizethe macroconnectomeinthebrainanditsvariabilityinhealthyadults.Keypointsofthis presentationwere: Connectomeisacomprehensivemapofneuronalconnections. AconsortiumofinvestigatorsatWashingtonUniversity,UniversityofMinnesota, UniversityofOxfordandsixotherinstitutionsrecentlybeganafiveyearprojectto characterizethehumanconnectomeinalargecohortoftwinsandtheirnontwin siblings. ImagingtechnologiesusedintheHCPincludedMRI,RfMRI,TfMRIandMEG/EEG. Thekeychallengesofthisenormousundertakingareindividualvariabilityinbrain structure,functionsandconnectivity.Informationfromthesestudiesneedstobe mappedtohighresolutionstructureMRIforgroupstudies. Understandinghumanbraincircuitryinhealthanddiseaseisagrandchallengeforthe 21stcentury.Usingadvancedcomputationalmethods,theHCPinvestigatorsconduct groupstudiestorelatebraincircuitrytobehavioralcapacitiesaswellasgenotypic data. Acompleteconnectomeatthelevelofmicroscopicfeaturesiswelloutsideour graspatthepresenttime.

ApplicationofMolecularMRItoStudiesofBrainFunction

Molecularindicesforneuronalactivationincludegeneexpression,aswellasintracellular andextracellularsignalling.NovelMRIsensorsallowingthedetectionofbrainfunctionby accessingperturbationofthemolecularindicessuchasproteins,neurotransmittersand ionsareusedinanemergingfieldcalledmolecularfMRI. AmongmanyMRIsensorsdevelopedthusfar,proteinbasedsensorsofferspecial advantagesduetooftheapplicabilityofpowerfulproteinengineeringstrategies. ThedevelopmentandoptimizationofaneurotransmittersensorusingaP456Bm3 hemedomainthatbindstodopamineforMRIdetectionofdopaminereleasewas discussed.

 ThedevelopmentandoptimizationofamagneticnanoparticlebasedMRIsensor thatdetectsintracellularcalciumsignallingassociatedwithneuronalactivationwas discussed.

PETinAddictionResearch

PETneuroimagingtechniqueshaveleadtosignificantadvancesinourunderstandingof theneurobiologyandtreatmentofdrugaddictioninhumans.Thecapabilitytoconduct parallelstudiesinnonhumanprimatesandhumansubjectsprovidesapowerful translationalapproachtolinkfindingsinhumanandanimalresearch. PEThasbeenusedtodefinetheinvivobiodistributionandpharmacokineticsofdrug abuseandrelatethesefindingstothetimecourseofbehavioraleffectsassociated withtheiraddictiveproperties. Althoughdopaminergicsystemshavebeenextensivelystudied,other neurotransmittersystemsknowntoplayacriticalroleinthepharmacologicaleffects ofabuseddrugshavebeenlargelyignoredinnonhumanprimatePETneuroimaging. Recently,therehasbeensomesuccessinimplementingpharmacologicalfMRIin awakenonhumanprimates. Nevertheless,theuniqueversatilityofPETimagingwillcontinuetocomplementthe systemslevelstrengthsoffMRI,especiallyinthecontextofnonhumanprimatedrug abuseresearch. Collectively,theresultsofPETneuroimagingstudieshaveenhancedour understandingoftheneurobiologicalbasisofstimulantaddictionandcouldhavea significantimpactoneffortstodevelopmedicationstotreatstimulantabuse. V. MeetingFindings Thefollowingpointsweremadebytheattendees,programstaff,speakersand discussantsduringthesymposium. Neurobiologistshavedifficultyinkeepingupwiththerapidprogressioninmedical imagingtechnologyduetodisparateexpertiseinthetwofields. Thereisacommunicationbarrierbetweenimagingscientistsandneurobiologistsowing toalackofunderstanding,criticalevaluationand/orappreciationbetweenthetwo disciplines.

Imagescientistspresentintricateimageswithoutasufficientvalidationthatwould requiretheinputofaneuroscientist. Imagingresearchlaboratoriesandcentersneedstandardizedcomputergenerated interpretationsofphysiologicalphenomenabasedonimagesignals. 9

Longscansareneededtoacquirehighresolutionimageswithsufficientsignaltonoise; patientsareaskedtostaystillinthescannerforanextendedperiodforimageacquisition. Suchlongscanshaverestrictedcuttingedge,highresolutionimagingmethodologiesfrom beingavailabletoroutineclinicalapplications. Thecurrentstateofmolecularimagingisdominatedbyrelativelyconservative approachessuchasPETduetoitsproximitytohumanapplications.Conversely,molecular MRIisprogressingslowlybecauseofitslimitedapplicationtohumans. Minimallyinvasiveopticalimagingtechniques,althoughlimitedindepthpenetration, haveledtomajoradvancesinourknowledgeofintracellularandmulticellularsignaling processesinbrain. Thereisaneedtodevelopsensitiveandtargetspecificprobesinotherimagingmodalities thatcanbeusedtoimagemoleculareventsinthebrainnoninvasively. TheBloodBrainBarrierremainsaformidableobstacletoovercomeinadvancing molecularimagingresearchforclinicalapplicationandindrugdiscoveryforbrain diseases.

VI. Conclusion Medicalimagingtechnologyencompassesmanymodalitiesandallowsinvivovisualization ofstructure,functionandphysiologyofthebrain.Methodologydevelopmentsforthese modalitiesrelyonindepthunderstandingofchemistry,physicsandengineering.Recent advancesinmedicalimagingtechnologyhavebroughtourviewabouthowthewhole brainworkstoanewlevelasdemonstratedbyourspeakers. Thepresentationsinthisonedaysymposiumdidnotcomprehensivelycoverthe complexityofmedicalimagingtechnologyandtheunderlyingprinciples.Wehopethese overviewsencourageneurobiologistsandimagingscientiststoworkasteamsto understandhealthyanddiseasedbrains. VII. ContactInformation ChristinaLiu,Ph.D.,P.E. DivisionofBiomedicalTechnology NationalCenterforResearchResources Phone:3014350905 Email:christina.liu@nih.gov FormoreinformationaboutNCRR,pleasevisitncrr.nih.gov. 10

Appendix1: SymposiumAgenda ______________________________________________________________________________

7:458:15a.m. 8:158:20a.m. 8:208:30a.m. Registration WelcomeRemarks BarbaraAlving,M.D.,director,NationalCenterforResearchResources Introduction ChristinaLiu,Ph.D.,P.E.,NationalCenterforResearchResources

SessionI:NutsandBoltsofMedicalImagingTechnologies Chair:DaYuWu,Ph.D.,NationalInstituteonDrugAbuse 8:309:10a.m. MRIforBrainAnatomy,PhysiologyandFunctions PetervanZijl,Ph.D.,JohnsHopkinsUniversityandNationalResourcefor QuantitativeFunctionalMRI 9:109:50a.m. DenseArrayElectrophysiologyTechnologyforNeuralConnectivity DonTucker,Ph.D.,UniversityofOregonandElectricalGeodesics,Inc. 9:5010:05a.m. Break 10:0510:45a.m. ContrastEnhancedMRIforMolecularImaging RobiaG.Pautler,Ph.D.,BaylorCollegeofMedicine 10:4511:25a.m. PETforMolecularImaging JoannaFowler,Ph.D.,BrookhavenNationalLaboratory 11:25a.m.12:15p.m.PanelDiscussions Moderator:YantianZhang,Ph.D.,NationalInstituteofBiomedicalImagingand Bioengineering PanelMembers: AllanReiss,M.D.,StanfordUniversity VinodMenon,Ph.D.,StanfordUniversity EngLo,Ph.D.,MassachusettsGeneralHospital/HarvardMedicalSchool ScottSmall,M.D.,ColumbiaUniversity 12:151:00p.m. Lunch SessionII:ApplicationsofMedicalImagingTechnologyinBrainResearch Chair:MichaelF.Huerta,Ph.D.,NationalInstituteofMentalHealth MRIinNeurodegenerativeDiseaseResearch 1:001:40p.m.

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MichaelWeiner,M.D.,UniversityofCalifornia,SanFranciscoandNational CenterforImagingofNeurodegenerativeDiseases 1:402:20p.m. TheHumanConnectomeProject DavidVanEssen,Ph.D.,WashingtonUniversityinSt.Louis

2:202:35p.m.Break ApplicationofMolecularMRItoStudiesofBrainFunction 2:353:15p.m. AlanJasanoff,Ph.D.,MassachusettsInstituteofTechnology 3:153:55p.m. PETinAddictionResearch LeonardHowell,Ph.D.,EmoryUniversityandYerkesNationalPrimateResearch Center 3:554:40p.m. PanelDiscussions/ClosingRemarks Moderator:ChristinaLiu,Ph.D.,P.E.,NationalCenterforResearchResources PanelMembers: AllanReiss,M.D.,StanfordUniversity VinodMenon,Ph.D.,StanfordUniversity EngLo,Ph.D.,MassachusettsGeneralHospital/HarvardMedicalSchool ScottSmall,M.D.,ColumbiaUniversity

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Appendix2:ListofParticipants(inalphabeticalorder) ______________________________________________________________________________
SpeakersandDiscussants Name JoannaS.Folwer,Ph.D. LeonardL.Howell,Ph.D. AlanJasanoff,Ph.D. EngH.Lo,Ph.D. VinodMenon,Ph.D. RobiaG.Pautler,Ph.D. AllanL.Reiss,M.D. ScottA.Small,M.D. DonTucker,Ph.D. DavidC.VanEssen,Ph.D. PeterC.M.vanZijl,Ph.D. MichaelW.Weiner,M.D. Email fowler@bnl.gov lhowell@emory.edu jasanoff@mit.edu lo@helix.mgh.harvard.edu menon@stanford.edu rpautler@bcm.edu areiss1@stanford.edu sas68@columbia.edu dtucker@egi.com vanessen@wustl.edu pvanzijl@jhu.edu Michael.Weiner@ucsf.edu

OrganizationCommitteeMembers Name Email MichaelF.Huerta,Ph.D. mhuert1@mail.nih.gov ChristinaHLiu,Ph.D.,P.E. christina.liu@nih.gov DavidShurtleff,Ph.D. dshurtle@mail.nih.gov DaYuWu,Ph.D. wudy@nida.nih.gov YantianZhang,Ph.D. yantian.zhang@nih.gov

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