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DiffusionalKurtosisImaging DKI 1 Contents DWI diffusionweightedimaging DTI diffusiontensorimaging DKI diffusionkurtosisimaging 2 DWI原理 MR图像的信号组织T1 T2驰豫时间 H1的密度 分子弥散运动DWI图像利用扩散敏感梯度脉冲将水分子弥散效应扩大 来研究不同组织中水分子扩散运动的差异 3 DWI评估弥散的参数 通过两个以上不同弥散敏感梯度值 b值 的弥散加权象 可计算出弥散敏感梯度方向上水分子的表观弥散系数 apparentdiffusioncoefficientADC ADC In S低 S高 b高 b低 弥散敏感系数 b 值 r2 2g2 3 b值的取值范围为0 10000s mm2 较大的b值具有较大的弥散权重 对水分子的弥散运动越敏感 并引起较大的信号下降 但b值越大 图像信噪比也相应下降 如果b值太小 易受T2加权的影像 产生所谓的T2透射效应 T2shinethrougheffect 一般来说用大b值差的图像测得的ADC值较准确 故侧ADC值时宜选较高b值和较大的b值差ADC反映了水分子的扩散运动的能力 指水分子单位时间内扩散运动的范围 越高代表水分子扩散能力越强 4 均质介质中可以水分子的自由运动为各向同性 即在各个方向上的弥散强度大小一致 弥散张量D描述为球形 沿磁共振的三个主坐标的特征值为 1 2 3在脑白质中由于髓鞘的阻挡 水分子的弥散被限制在与纤维走行一致的方向上 具有较高的各向异性 此时弥散张量可表示为椭球形 其特征值 1 2 3 最大特征值对应的方向与经过该体素的纤维束走行平行 5 defectsofDTI ConventionalDTIfailstofullyutilizetheMRdiffusionmeasurementsthatareinherenttotissuemicrostructure DTIcomputesapparentdiffusivitybasedontheassumptionthatdiffusionweighted DW MRsignalhasamonoexponentialdependenceonthediffusionfactor b value DTIimplicitlyassumesthatwatermoleculediffusionoccursinafreeandunrestrictedenvironmentwithaGaussiandistributionofdiffusiondisplacement 6 defectsofDTI Inbiologicaltissue complexcellularmicrostructuresmakewaterdiffusionahighlyhinderedorrestrictedprocess Non monoexponentialdecaysareexperimentallyobservedinbothwhitematterandgraymatter Moreover thesimplifieddescriptionofthediffusionprocessinvivobya2nd order3DdiffusivitytensorpreventsDTIfrombeingtrulyeffectiveincharacterizingrelativelyisotropictissuesuchasGM EveninWM theDTImodelcanfailifthetissuecontainssubstantialcrossingordivergingfibers 7 defectsofDTI Asaresult DTIquantitationisb valuedependentandDTIfailstofullyutilizethediffusionmeasurementsthatareinherenttotissuemicrostructure 8 Kurtosis Kurtosisherereferstotheexcesskurtosisthatisthenormalizedandstandardizedfourthcentralmomentofthewaterdisplacementdistribution ItisadimensionlessmeasurethatquantifiesthedeviationofthewaterdiffusiondisplacementprofilefromtheGaussiandistributionofunrestricteddiffusion providingameasureofthedegreeofdiffusionhindranceorrestriction fourthcentralmoment 四阶中心距 主要用来衡量随机分布变量的分布在均值附近的陡峭程度SincethedeviationfromGaussianbehaviorisgovernedbythecomplexityofthetissuewithinwhichthewaterisdiffusing thisexcessdiffusionalkurtosiscanberegardedasameasureofatissue sdegreeofstructure 9 OtheradvantagesofDKI Meankurtosis MK theaverageapparentkurtosisalongalldiffusiongradientencodingdirections hasbeenmeasuredanddemonstratedtoofferanimprovedsensitivityindetectingdevelopmentalandpathologicalchangesinneuraltissuesascomparedtoconventionalDTI Inaddition directionalkurtosisanalysishasbeenformulatedtorevealdirectionallyspecificinformation suchasthewaterdiffusionkurtosesalongthedirectionparallelorperpendiculartotheprinciplewaterdiffusiondirectionasdeterminedbythe2nd orderdiffusiontensor 10 DKIprovidesahigher orderdescriptionofrestrictedwaterdiffusionprocessbya2nd order3Ddiffusivitytensor DTasinconventionalDTI togetherwitha4th order3Dkurtosistensor KT 11 Conditions Themethodisbasedonthesametypeofpulsesequencesemployedforconventionaldiffusion weightedimaging DWI buttherequiredbvaluesaresomewhatlargerthanthoseusuallyusedtomeasurediffusioncoefficients Inthebrain bvaluesofabout2000s mm2aresufficient Atleast15non collinearandnon coplanardirectionsarerequiredtoconstructKT 12 DKIvsq spaceimagingtechniques DKIhasacloserelationshiptoq spaceimagingtechniques q spaceimagingmethodshaveindeedrecentlybeenemployedtoestimatediffusionalkurtosis Theprincipaldifferencebetweenthemisthatq spaceimagingseekstoestimatethefulldiffusiondisplacementprobabilitydistributionratherthanjustthekurtosis Asaconsequence q spaceimagingismoredemandingintermsofimagingtimeandgradientstrengths MeasuringthediffusionalkurtosisrequiresonlymodestincreasesinbvaluesAndDKIislessdemandingintermsofhardwarerequirementsandpostprocessingeffort 13 Kurtosistensor KT derivedparameters MK meankurtosis MKisameasureoftheoverallkurtosis Itdoesnothaveanydirectionalspecificity MK的大小取决于感兴趣区内组织的结构复杂程度 结构越复杂非正态分布水分子扩散受限越显著 MK也即越大K Axialkurtosis andK Radialkurtosis canbedefinedasthekurtosisparallelandperpendiculartotheprinciplediffusioneigenvector e1 K 越大表明在该方向非正态分布水分子扩散受限越明显 反之则表明扩散受限越弱FAK fractionalanisotropyofkurtosis SimilartoFAinDTI theanisotropyofdirectionalkurtosiscanbeconvenientlydefinedasFAKKA越小即表示越趋于各向同性扩散 若组织结构越紧密越规则 KA越大 14 DKIparametricmaps 15 DKIparametricmaps TypicalDKI derivedparametricmapsfromasinglesliceofa invivo b formalin fixedadultratbrainsandc anormalhumansubject male 44yearsold Axialdiffusivity radialdiffusivity meandiffusivity MD axialkurtosis K radialkurtosis K meankurtosis MK fractionalanisotropy FA directionallyencodedcolourFA DEC FA andfractionalanisotropyofkurtosis FAK mapsarecomputedfromDKImodel 16 DKIparametricmaps For a rawDWIswereacquiredbySEEPIwithTR TE 3000 30 3ms 5 17ms slicethickness 1mm FOV 30 30mm2 datamatrix 128 128 zerofilledto256 256 NEX 4 6b values 0 0 0 5 1 0 1 5 2 0and2 5ms m2 andalong30directionsusing7Tscanner 17 DKIparametricmaps For b rawDWIswereacquiredwiththesameparametersasthoseforinvivoexceptTE 34 3ms 9msandb valuesof0 0 1 0 2 0 3 0 4 0and5 0ms m2 Alargerb valuerangewasusedinexvivoexperimentduetothegenerallylowerdiffusivities 18 DKIparametricmaps For c rawDWIswereacquiredbySEEPIwithTR TE 2300 109ms slicethickness 2mm FOV 256 256mm2 datamatrix 128 128 NEX 2 6b values 0 0 0 5 1 0 1 5 2 0and2 5ms m2 andalong30directionsusinga3TSiemensscanner 19 DKIparametricmaps HigherMKisfoundinWM indicatingagenerallyhigherdegreeofdiffusioncomplexityandrestrictionintheWMstructures ItcanbeseenfromthedirectionalkurtosismapsthatsuchhighMKinWMismainlycontributedbyK Thissuggeststheexistenceofheterogeneityandrestricteddiffusioninaxonalstructures BothMKandK exhibitstrongcontrastbetweenWMandGMstructures 20 DKIparametricmaps BothMKandK exhibitstrongcontrastbetweenWMandGMstructures PositivemeananddirectionalkurtosesareobservedinbothWMandGM indicatingfasterDWsignaldecayatlowerb valuesandrestricteddiffusionenvironmentinbothWMandGMunderinvivoandformalin fixedconditions 21 DKIshowsageneraldecreaseindiffusivityandincreaseinkurtosisinWMandGMofthefixedbrains Thebreakdownsofneurofilamentsandmicrotubulescausedbyfixativesarebelievedtoproducemorediffusionbarriersandhenceleadtothe decreaseandK increase Otherfixationeffectssuchastissueshrinkage decreaseinmembranepermeability increaseinaxonalpackingdensityandreductionofextracellularspaceinparenchymaalsolikelycontributetothesignificant decreaseandK increase 22 Directionalkurtosisanalysisoffixedexperimentalautoimmuneencephalitis EAE spinalcord TheinflammatoryneurodegenerativediseaseEAEischaracterizedbybothaxonallossanddemyelinationInrecentDKIstudies therearepromisingresultsofusingMKtodetectchangesinnormalorpathologicalneuraltissueHowever asanaverageofkurtosesalongallthediffusiondirections MKcanlosesensitivityandspecificityinprobingdirectionalchangesofpathologicaltissue 23 EAEspinalcord K isfoundtobesignificantlyincreasedand decreasedinthelesionarea reductionislikelyduetocytoskeletalperturbationordebrisformationwhentheaxonalstructuresbreakdownInaddition increaseswhereasK decreaseslikelybecauseofthedemyelinationandaxonallossthatalsoleadtolessdiffusionrestrictioninradialdirection 24 EAEspinalcord ThedirectionallyaveragedMDandMKarefoundtobelesssensitivetoEAEpathologyduetotheoppositetrendsofdiffusivityandkurtosischangesinaxialandradialdirection 25 MonitoringpostnatalbrainmaturationbyconventionalDTI CC corpuscallosum 胼胝体 EC externalcapsule 外囊 CP cerebralpeduncle 大脑脚 AC anteriorcommissure 前联合 CT cerebralcortex 脑皮质 HP hippocampus 海马 CPu caudateputamen 新纹状体 26 MonitoringpostnatalbrainmaturationbyconventionalDTI Thesensitivityof indetectingratbrainWMmaturationisgenerallyobservedtobethehighestatlowb valueAtrelativelylowb values theapparentdiffusivityisprimarilycontributedfromthefastwaterdiffusionactivitiesinextracellularspacethatdependonbothcellularmicrostructureandmembranepermeability Theuseoflowb valuecanbestdetectthesechanges Thehigh sensitivityatlowb valueobservedinthecurrentstudysuggeststhealterationsofthesefastwaterdiffusionactivitiesalongaxonaldirectionduringbrainmaturation Suchalterationsmayresultfromtheincreaseinpackingdensityoffiberbundlesandaxons axonaldiameterincrease changesinneurofibrils andincreasedcomplexityofextracellularmatrix 27 MonitoringpostnatalbrainmaturationbyconventionalDTI Whereasthatof isthehighestathighb valueThediffusionchangesprobedinWMusinghighb valuesareascribedmoretotheslowwatermoleculediffusionparticularlyalongtheradialdirectionwhentraversingthemembranesandmyelinsheathsThehighsensitivityof athighb valueindetectingbrainmaturationshowninthefigurelikelyreflectstheseWMmicrostructuralchanges includingmyelinationandaxonaldensityanddiameterchangesduringpostnatalbraindevelopment 28 MonitoringpostnatalbrainmaturationbyconventionalDTI FAquantitationisalsoaffectedbytheb valueanditsabilityindetectingbrainmaturationalchangesvariesamongdifferentstructures 29 MonitoringpostnatalbrainmaturationbyDKI Figure7ashowsthatthesensitivityoffittingallthemulti b valueDWIstoDTImodelisgenerallysimilartothatofemployingamediumb value b 1 5ms m2 showninFigure6InFigure7b thegeneralandcontinualkurtosisincreasewithageisobserved indicatingthatmorediffusionrestrictionoccursduringbrainmaturationinbothWMandGMstructures TheDKI deriveddiffusivityandkurtosisindicesarehighlysensitivetobraindevelopmentalchanges 30 MonitoringpostnatalbrainmaturationbyDKI Both andK ofWMarefoundtoincreaseswithage whichmayarisefromvariousbiologicaleventsduringearlypostnatalbrainmaturation Theincreaseofdiffusivitycanbecausedbyaxoplasmicflowduringthemyelinationperiodneuronallossandaxonalpruningthatshortenstheaxonlengthcanleadtoanincreaseofrestriction 31 MonitoringpostnatalbrainmaturationbyDKI TheincreaseofK inWMislikelyascribedtothemyelinationandmodificationofaxonalstructuresthatincreasesrestrictionintheradialdirection DKIanalysisalsorevealsthatdiffusionrestrictionintherelativelyisotropicGMincreaseswithage ThismayreflectthemoredenselypackedstructuresandthedendriticarchitecturalmodificationinGM 32 DTIVSDKIinmonitoringpostnatalbrainmaturation WhenthereisalargeK theestimateddiffusivityinconventionalDTIshowsalargediscrepancywiththediffusivityestimatedinDKIap
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