Table Of ContentDIFFUSIONTENSORIMAGINGANDTHEMEASUREMENTOFDIFFUSION
TENSORSIN
BIOLOGICALSYSTEMS
By
LEIYANG
ADISSERTATIONPRESENTEDTOTHEGRADUATESCHOOL
OFTHEUNIVERSITYOFFLORIDAINPARTIALFULFILLMENT
OFTHEREQUIREMENTSFORTHEDEGREEOF
DOCTOROFPHILOSOPHY
UNIVERSITYOFFLORIDA
1999
Copyright1999
By
LeiYang
ACKNOWLEDGEMENTS
Iwouldliketothankmysupervisor,Dr.Andrew,forhiskindness,patience,and
encouragementofmygraduatecareer.Withouthim,thisdissertationwouldnothave
beenfinished.Ilearnedmuchfromhisdeepinsightsinto Physics.Iwouldalsoliketo
thankmyresearchsupervisor,Dr.Mareci,forhisgenerosityandguidance.Heledmeand
thewholeresearchgroupintothediffusionimagingarea,whichhasproducedonepaper,
twoSMRMconferenceoralpresentations,threeconferenceabstracts,andthreemore
submittedpapers.Hisexcellentideaofintroducingcoherencetransferpathwayintothe
diffusion-weightingcalculationwasthestartingpointofthenewformulaandnew
diffusiontensorimagingmethods.AlsothankstoDr.Inglisforteachingmeeverydetail
aboutNMR,givingmeinvaluablesuggestionsaboutmyresearch.Iwouldalsoliketo
givespecialthankstoDr.SullivanandtoDr.Yeltonfortakingcareofinternational
studentslikemewhowasthousandsofmilesawayfromhomeandstrugglingtosurvive
inaforeigncountry.
Iexpressmysincerethankstomanycolleagueswhohavemademystayatthe
UniversityofFloridasomethingthatIwillrememberfondlyforyears.IappreciateDr.
Wirth,Dr.Jones,Dr.Harris,XeveSilverfortheirhelpinsurgery,Dr.Briggsforletting
meusehisoffice,Dr.Fitzsimmonsforhelpingmebuildtherfcoil,DanPlantfor
hardwaresupport,andHaiquanDaiforcomputersupport.
iii
Thisthesisisdedicatedtomyfather,YuhuiYang,whosurvivedthedisasterof
theculturalrevolutionsince1967.Itwashistoleranceandlovethatsupportedmeandmy
wholefamilythroughthedarkages.
AlltheseachievementbelongtoJesusChrist,mylordandsavior.Heisalways
withme,nomatterwhathappens.MayallpraisesgotoGod!
iv
TABLEOFCONTENTS
Page
ACKNOWLEDGMENTS i«
ABSTRACT ix
CHAPTERS
1 INTRODUCTIONANDBACKGROUND 1
Introduction 1
Background 4
BrownianMotionandDiffusionDistance 4
DiffusionEffectsonNMR 5
MethodsforApparentDiffusionCoefficient(ADC)Measurement 6
Bipolargradientpulsespin-echosequence 6
Bipolargradientpulsestimulated-echosequence 7
Problemsforthesetwotechniques 7
DiffusionCoefficientasanImportantParameterinBiomedicalSystems 8
ClinicalapplicationofdiffusionMRimaging 9
UnsolvedProblem:b-ValueCalculationforAnyOrderofQuantumCoherence....9
b-Valuecalculationproblemindifferentsequence 9
b-Valuecalculationprobleminmultiplequantumcoherence 11
Conclusion 11
2 ACOHERENCETRANSFERAPPROACHTOGRADIENT
WEIGHTINGFACTORCALCULATION 17
Theory 17
SpinEvolutioninthePresenceofAnisotropicDiffusion 18
ExplicitEffectofRFPulses 21
ApplicationtoDifferentPulseSequences 23
ApplyingtheTheorytoSingleQuantumCoherenceSequences
inIsotropicCondition 24
Gradientechosequence 24
Spin-echosequence 24
Stimulcated-echosequence 25
DoubleQuantumCoherence 25
3 DIFFUSIONTENSORMETHODS 28
v
DataAcquisitionandProcessing 28
FormulasforDataAcquisition 28
DataProcessing 30
SpinEchoandStimulatedEchoDiffusionTensorImaging 30
b-MatrixofSpinEchoSequence 30
b-MatrixofStimulatedEcho 32
Experiments 34
Conclusion 36
4 FASTDIFFUSIONTENSORIMAGINGUSINGAMULTIPLE
STIMULATEDECHOSEQUENCE 41
Introduction 41
Methods 41
b-MatrixCalculationforStimulatedEchoSequence 41
GeneralLibraryforb-MatrixCalculationforStimulatedEcho 43
MultipleStimulatedEchoSequence 44
Results 46
WaterandCeleryExperiments 46
RatBraininvivoExperiments 51
5 HIGH-RESOLUTIONDIFFUSIONTENSORANDCOLORED
TRACEIMAGINGOFRATSPINALCORDINVITRO 53
Introduction 53
DiffusionTensorImaging 53
AnisotropyIndex 54
AnatomicStructureofSpinalCord 55
Graymatterofspinalcord 55
Whitematterofspinalcord 56
Methods 56
FixationofRatSpinalCord 56
DiffusionTensorImagingExperiments 56
DataAnalysis 58
Results 58
DiffusionTensorValuesofNormalSpinalCord 58
DiffusionTensorValuesofInjuredSpinalCord 59
ColorsinGrayMatterRegion 59
ColorTraceImages 59
ColorsinGrayMatterRegionofNormalRatSpinalCord 59
ColorsinWhiteMatterRegionofNormalRatSpinalCord 60
ColorTraceImagesofInjuredSpinalCord 60
TraceisanImportantParameterforDifferentNerveTissues 60
AnisotropyIndexofNormalRatSpinalCord 60
vi
AnisotropyIndexofNormalandInjuredWhiteMatterTissues 61
DiffusionTensorImagingofHumanSpinalCord 61
Conclusion 61
6 HIGH-RESOLUTIONDIFFUSIONTENSORANDCOLORED
TRACEIMAGINGOFNORMAL,HYDROCEPHALUSANDSHUNTEDRAT
BRAININVITRO 75
Introduction 75
InfantileHydrocephalus 75
ShuntTreatmentofHydrocephalus 76
WhiteMatterPathologyinHydrocephalus 76
MRImagingTechniques 77
AnatomyStructureofRatBrain 78
Methods 78
FixationoftheRatBrain 78
ShuntSurgery 78
Microimaging 78
DataProcessing 80
Results 81
DiffusionTensorValuesofNormalRatBrain 81
DiffusionTensorValuesofHydrocephalusRatBrain 81
DiffusionTensorValuesofRatBrain 81
ColorTraceImages 81
ColorinCerebralCortex 81
ColorinCorpusCallosum 82
AnisotropyIndexofWhiteMatterinNormalandHydrocephalicRatBrain 82
DiffusionTensorTraceofLateralandDorsalCortex 82
StimulatedEchoDiffusionTensorImaging 83
Conclusion 83
7 SUMMARY,INTERPRETATION,ANDCONCLUSION 98
Introduction 98
AchievementsandSignification 98
ANewFormulaforEvaluatingDiffusionWeighting 98
TwoDiffusionTensorImagingTechniques 99
DiffusionTensorImagingofNormalandInjuredSpinalCord 99
DiffusionTensorImagingofNormal,HydrocephalusandShuntedRat
Brain 100
DiffusionModelinMolecularLevel 100
FutureStudies 107
DoubleQuantumDiffusionTensorImagingandSpectroscopy 107
SpinalCordInjuryModel 107
InVivoDiffusionTensorImaging 107
Summary 107
vii
REFERENCE 109
BIOGRAPHICALSKETCH 113
viii
AbstractofDissertationPresentedtotheGraduateSchooloftheUniversityofFlorida
inPartialFulfillmentoftheRequirementsforthe
DegreeofDoctorofPhilosophy
DIFFUSIONTENSORIMAGINGANDTHEMEASUREMENTOFDIFFUSION
TENSORSIN
BIOLOGICALSYSTEMS
By
LeiYang
May1999
Chairman:E.RaymondAndrew
MajorDepartment:Physics
Thisdissertationrevisitsthetheoryofdiffusion-weightingfactorof
gradientsforanysequenceandpresentsanewcomprehensiveformulawhichnotonly
unifiesallformerresults,butalsopredictsnewresultsforunsolvedpulsesequences.
Then,onthebasisofthisnewformula,twodiffusiontensorimagingtechniqueswere
built,tested,andappliedtotheratspinalcordandbrain,thusshowingthebiologicaland
clinicalsignificanceofdiffusiontensorimaging.
Therehavebeenmanypreviousattemptstoderiveanexpressionofdiffusion-
weightingfactorofgradientsindifferentpulsesequences,butuntilnow,nobodyhas
beenabletoderiveaformulaforanydouble-quantumandmultiple-quantumcoherence
sequences,onlyunderincasehadthisproblembeensolvedexperimentally.This
dissertationintroducesanewmethodwhichnotonlyunifiesalldifferentexpressionsfor
singlequantumcoherence,butalsopredictstheexpressionsfordouble-quantumand
ix
multiple-quantumcoherencesequences.Next,usingthenewformulafordiffusion-
weightingfactor,twodiffusiontensorimagingtechniqueswerebuilt:spinechodiffusion
tensorimagingandmulti-stimulatedechodiffusiontensorimaging.TheEcho-Plan
Imaging(EPI)spinechodiffusiontensorimaginghadbeenbuiltin1994, butthemulti-
echostimulatedechodiffusiontensorimagingtechnique,alongwithBasser's EPI
stimulatedechodiffusiontensorimagingtechnique,werethefirsttwotechniquesinthe
worldthatusedstimulatedechosequenceindiffusiontensorimaging.
Inthisdissertation,diffusiontensorimagingtechniqueswerefirstappliedto
normalandinjuredratspinalcordsandbrain,colortraceimageswerepresentedwhich
clearlyshowthefiberorientationsofthespinalcordthatwerenotaccomplishedbyany
otherMRI. Wefoundthattheinjuryofthespinalcordcausesthelossofanisotropyof
whitematter,whichisconsistentwithotherresultsusingapparentdiffusioncoefficient
(ADC).Itisinterestingthatthereweresubstantialchangesindiffusioncharacteristicsin
theinjuredareawhichappearednormalbyconventionalimaging. Theseresultsimply
thatthereareconsequencesofspinalcordinjurywhichdramaticallyalteraxonstructure
butdonotchangewatercontent,soarenotdetectedbyconventionalimaging.Wefound
thatthehydrocephalusoftheratbraincausesthelossofanisotropyofwhitematter,and
hydrocephalusresultsinincreasedwatercontentinthebrainsurroundingtheventricles.
Thishasbeenconfirmedbyindependentmeasurements.
Thisisanewdirectioninthenoninvasiveinvestigationofthenormaland
abnormalbrainandspinalcordusinganewimagingtechniquetostudytissue
organization,pathologicalchanges,andrecoverywithtreatment.Thetechniquecould
ultimatelybeappliedtoclinicalsituations(inthesamewayasADCisnowbeingapplied
X