乳腺弥散加权成像的原理和临床应用

Diffusion-weightedImagingoftheBreast:PrinciplesandClinicalApplications,何杰2013年12月25日,乳腺弥散加权成像：原理和临床应用,Diffusion-weightedimagingisamodalitythatmakesuseofmagneticresonance(MR)imagingtodepictthediffusivityofwatermoleculesinadefinedvoxelbymeansoftheapplicationofmotion-probinggradients.ThisimagingpropertyisuniqueandprovidesadifferentcontrastmechanismthanthatobservedonconventionalT1-andT2-weightedMRimages.Evaluationofbreastimagesacquiredwithsensitizationtothediffusionofwatermoleculeshasthepotentialtoplayanadjunctroleintheassessmentofbreasttissue.DWI是一种通过运动-探测梯度磁场的应用的方式，在一个有限的像素内，利用磁共振来检测水分子弥散的方法。这种成像方式是唯一，并且与常规的T1和T2加权MR图像相比，提供一个不同的对比机制。乳腺图像的获取来源于对水分子的扩散敏感，其拥有在乳腺组织的评估中发挥辅助作用的潜力。,Introduction,Diffusion-weightedimagingwasinitiallyappliedintheclinicalsettinginthemid-1990sforthediagnosisofacutestroke.Atthattime,diffusion-weightedimagingdemonstratedahighdiagnosticutility,notonlyintheinvestigationofacutestroke,butalsoindevelopingthedifferentialdiagnosisforotherbrainabnormalities,includingtumorsandabscesses.弥散加权成像在临床上最初的应用是90年代中期对急性脑卒中的诊断，不仅用于检测急性脑卒中，而且发展到别的脑部异常病变的鉴别诊断，包括肿瘤和脓肿。,Introduction,SubsequenttechnicaladvancesinMRimaging,includingthedevelopmentofultrafastimagingsequencesandtheproliferationofarraycoilsandofimagerswithhighermagneticfieldstrength(whichincreasesignal-to-noiseratioSNRperunittime)haveledtoareductionintheimpactofmotionartifactsandtheinvestigationoforgansotherthanthebrain.在MR成像随后的技术进步，包括超快成像序列的发展和较高磁场强度阵列线圈和成像器的发展（这提高了每单位时间的信噪比），导致了运动伪影的影响的减少,Introduction,Diffusion-weightedimaginghassubsequentlybeenusedintheevaluationofdiseaseprocessesinvariousanatomiclocations(eg,chest,liver,pancreas,prostategland)thathadpreviouslynotbeenstudiedduetodifficultiesresultingfrommovementduringpatientrespiration,peristalsis,andlowinherentSNR.弥散加权成像随后被用于不同的解剖部位疾病过程的评价（如胸部，肝脏，胰腺，前列腺），这些以前从未研究过，因为病人呼吸，蠕动所导致的困难和低的信噪比。,Introduction,In1997,Englanderetaladdressedthepossibilityofapplyingdiffusion-weightedimagingtothehumanbreast.Sincethattime,clinicalstudieshavebeenundertaken,andseveralstudieshaveshowndiffusion-weightedimagingtobehighlysensitivefortheevaluationofbreastcancerandapossiblemeansofdifferentiatingbetweenbenignandmalignanttumors在1997年，Englander等人探讨了DWI应用于人体乳腺的可能性。从那时起，一些临床研究开始进行，并且一些研究表明DWI在评估乳腺癌上有高的敏感性，是一种鉴别诊断良恶性肿瘤的可能的方法。,Introduction,Asaresultofthesefindings,diffusion-weightedbreastimaginghasattractedgreaterinterestamongbreastimagers,withmanycliniciansadvocatingapplicationsbeyondjustclinicalresearch.However,theincorporationintoclinicaldecisionmakingofinformationgleanedfromdiffusion-weightedbreastimaginghasbeenslowcomparedtotheuseofinformationobtainedfromdiffusion-weightedimagingofotherorgans.由于这些发现，乳腺弥散加权成像吸引了乳腺影像学家越来越多的注意，许多医生主张应用不仅仅是临床研究。然而，与其他器官的弥散加权图像的使用相比，应用在乳腺上比较缓慢。,Introduction,Onereasonisthatthediagnosticroleofdiffusion-weightedimaginginbreastimaginghasnotbeenincorporatedintothealreadyestablishedBreastImagingandReportingDataSystemlexicon(11).ContrastmaterialenhancedbreastMRimagingiscurrentlyacceptedasthemostsensitiveimagingtechniqueforthediagnosisandstagingofbreastcancer.However,severalstudieshavenotedthatconventionalbreastMRimaging,includingT2-weightedimagingandcontrast-enhancedT1-weightedimaging,islimitedintermsofspecificityintheassessmentofbreasttumors原因之一是弥散加权成像在乳腺成像上的诊断作用还没有纳入到已经确定的BI-RADS系统中。对比增强乳腺磁共振是目前公认是最敏感的用于乳腺癌诊断和分级的成像技术。然而，然而，一些研究表明常规乳腺磁共振成像，包括T2加权像和T1对比增强磁共振在评价乳腺肿瘤的特异性方面作用有限。,Introduction,Consequently,therehasbeenconsiderableinterestinthedevelopmentofadjunctMRimagingmethodstoimprovethespecificityofdynamiccontrast-enhancedbreastMRimaging,anddiffusion-weightedbreastimagingisbeinginvestigatedforitspotentialtoimprovebreastdiseasediagnosisatthecostofasmallincreaseinexaminationtime.因此，在发展辅助磁共振成像方法用来提高动态对比增强乳腺磁共振的特异性上，引起了研究者很大的兴趣，研究者正在研究DWI乳腺成像，探讨其耗费最小的检查时间增加乳腺疾病诊断率的潜力。,Introduction,InthisPPTwediscusstheprinciplesofdiffusion-weightedimaging,offersuggestionsforoptimizingdiffusion-weightedbreastimagingtechnique,anddiscusstheclinicalimplementationofdiffusion-weightedbreastimaging.在这个PPT里，我们讨论DWI的原理，提出优化DWI乳腺成像技术的建议，并且讨论DWI乳腺成像的临床应用,Introduction,PrinciplesofDiffusion-weightedImaging,DWI的原理,ProtonDiffusioninBiologicTissue,Diffusionistherandomandthermal(Brownian)motionofwatermolecules(oranyothertypeofmolecule).Thismotionisaffectedbythelocaltissueenvironmentandthepresenceofbarriers(eg,cellmembranesandsemipermeablemembranes).Themotionofwatermoleculesismorerestrictedintissueswithahighcellulardensity弥散是水分子（或其他分子类型）的无规则的热运动（布朗运动）。这种运动受局部组织环境和障碍的影响（如细胞膜和半透膜）。组织中的水分子的运动在细胞外和细胞内空间中更受限，如果细胞密度较高或者有亲脂性细胞膜作为障碍。,ProtonDiffusioninBiologicTissue,Incontrast,themotionofwatermoleculesislessrestrictedinareasoflowcellularityorwherecellmembraneshavebeendestroyed.Alesscellularenvironmentprovidesalargerextracellularspaceforthediffusionofwatermolecules,whichmayalsofreelytransgressdefectivecellmembranestomovefromtheextracellularintotheintracellularcompartment.Therefore,thedegreeofwaterdiffusionintissueisinverselycorrelatedwithtissuecellularityandtheintegrityofcellmembranes.相比之下，水分子的运动在低的细胞密度或者细胞膜被破坏的区域受限较少。一个不完整的细胞环境为水分子的弥散提供一个大的细胞外空间，这也方面水分子从细胞外进入细胞内隔室。因此，水分子在组织中弥散的程度与组织的细胞密度和细胞膜的完整性呈负相关。,ProtonDiffusioninBiologicTissue,Diffusion-weightedimagingisusedtovisualizethedegreeofwatermoleculediffusionatinvivoMRimaging.Signalintensityatdiffusion-weightedimagingisinverselyproportionaltothedegreeofwatermoleculediffusion,whichwillbeinfluencedbythehistologicstructure;inotherwords,thesignalintensitywillimplythehistologicstructure.弥散加权成像用于在体磁共振中监测水分子扩散的程度。DWI里信号强度与水分子弥散的程度呈反比，其受组织学结构的影响；换句话说，信号强度将反映组织学结构。,ProtonDiffusioninBiologicTissue,Diffusionisquantifiedbymeasuringwhatisknownastheapparentdiffusioncoefficient(ADC)valueinsquaremillimeterspersecond,whichdefinestheaverageareacoveredbyamoleculeperunittime.TheADCvaluecanbecalculatedbyassessingthesignalattenuationthatoccursatdiffusion-weightedimagingperformedatdifferentbvalues.扩散通过测量众所周知的表观扩散系数值（平方毫米每秒）来进行定量，这被定义为每单位时间一个分子覆盖的平均面积。ADC值通过评估施加不同b值弥散加权成像的信号强度来计算。,TechnicalConsiderations,Spin-echoechoplanardiffusion-weightedimagingisthemostpopularclinicaltechniqueforgeneratingdiffusion-weightedimages.Tointroducediffusionweightingintoaspin-echoechoplanarimagingsequence,twodiffusion-sensitizinggradientsare“sandwiched”arounda180radiofrequency(RF)refocusingpulsebeforeechoplanarimagingdatacollection(Fig1).自旋回波平面扩散加权成像是目前最流行的产生弥散加权图像的临床技术。为了把弥散加权引入自旋回波平面成像序列，在回波平面图像数据收集之前，两个弥散致敏梯度夹在180度射频（RF）聚焦脉冲周围,Figure1.Graphillustratesthepulsesequenceofsingle-shotspin-echoechoplanardiffusion-weightedimaging.G=gradient,MPG=motion-probinggradient.该图说明了单次自旋回波平面弥散加权成像的脉冲序列。G=梯度，MPG=运动探测梯度,CorrelationbetweenSignalIntensity,bValue,andADCValue,SignalIntensityandbValueSignalintensityatdiffusion-weightedimagingisinfluencedbybvalueaccordingtothefollowingequation,whichismodifiedfromEquation1:SDW=SSE(expbD)(1expTR/T1)exp(TE/T2)exp(bD),(4)whereDisthediffusioncoefficient,SDWistheattenuatedspin-echosignal,SSEisthefullspin-echosignalwithoutdiffusionattenuation,andristhespindensity在弥散加权图像中，信号强度通过下面的公式受b值的影响，这个公式由公式1所改写：SDW=SSE(expbD)(1expTR/T1)exp(TE/T2)exp(bD)，在这里D是弥散系数，SDW是衰减自旋回波信号，SSE是没有任何弥散衰减的完全性自旋回波信号，r是自旋密度。,CorrelationbetweenSignalIntensity,bValue,andADCValue,Accordingtothisequation,thesignalintensityatdiffusion-weightedimagingconsistsofT2-weightedsignalanddiffusion-weightedsignal.Thelatterisemphasizedwiththeapplicationofhighermotion-probinggradients.Ontheotherhand,T2-weightedsignalwillbeemphasizedatlowerbvalues(T2shine-througheffect).Inaddition,thesignalintensityatdiffusion-weightedimagingwilldecreaseasbvalueincreases;thus,anSNRthatissufficientforlesiondetectionmustbeprovidedwhileemphasizingthecontributionfromthediffusioncoefficientalonebecauseoftheir“trade-off”relationship(Fig2)通过这个公式可知，弥散加权成像的信号强度包括T2加权信号和弥散加权信号。后者强调较高运动探测梯度的应用。另一方面，T2加权信号在低b值时比较明显（T2透射效应）。另外，弥散加权成像的信号强度将随着b值的提高而降低；因此，在提供一个足以检测出病灶的SNR的同时必须要着重弥散成分的贡献，因为它们之间的“矛盾关系”,Figure2.Diffusion-weightedimagesofaphantom,obtainedatbvaluesof1000(a),1750(b),and2000(c)sec/mm2,showhowthesignalintensityofwater(W)anddetergent(D)decreasesasbvalueincreases.Thesignalintensityofdetergentremainshighuntilb=1750sec/mm2,whereasthesignalintensityofwaterisclosetothenoiselevelatb=2000sec/mm2.Thisisbecausedetergenthasahigherviscositythanwater.水模的弥散加权图像，分别为1000(a),1750(b),and2000(c)sec/mm2，显示了水模（W）和洗涤剂模型（D）的信号强度如何降低当b值提高。洗涤剂的信号强度直到b=1750sec/mm2依旧保持很高，然而水的信号强度在b=2000sec/mm2接近于噪声水平。这是因为洗涤剂比水有更高的粘度。,CorrelationbetweenSignalIntensity,bValue,andADCValue,IdentificationofadiscretebreastlesionismandatoryforevaluatingitsADCvalue,anddoingsorequiressufficientcontrastresolutiontodifferentiatethebreastlesionfromtheadjacentbreastparenchyma.KurokiandNasucomparedthesignalintensityofthenormalmammaryglandwiththatofbreastcanceratvariousbvaluestoestablishtheoptimalbvalue.乳腺病变的鉴别是评估其ADC值，这样需要足够的对比度来鉴别诊断乳腺病变和邻近的乳腺实质。Kuroki和Nasu比较了不同b值下正常乳腺和乳腺癌的信号强度，以确定最佳的b值。,CorrelationbetweenSignalIntensity,bValue,andADCValue,Intheirstudy,abvalueof1000sec/mm2wasconsideredoptimalfordiffusion-weightedbreastimaging,sincethesignalofthenormalmammaryglandissuppressedandthesignalofbreastcancerissufficientlyhightoallowdetectionandevaluation.Ontheotherhand,theauthorsstatedthatthesignalofthemammaryglandmightnotbesuppressedatb=1000sec/mm2incasesofseverefibrocysticdisease(9),andrecentstudieshavedocumentedtheusefulnessofabvalueof1500sec/mm2.在他们的研究中，b值为1000sec/mm2被认为最适合于弥散加权乳腺成像，因为正常乳腺的信号被抑制及乳腺癌的信号足够高来用于检测和评价。另一方面，作者指出b值为1000sec/mm2时，严重的纤维囊性疾病的乳腺组织的信号将不会被抑制，最近的研究已经证明b值等于1500sec/mm2的有用性。,Figure3Ductalcarcinomainsitu(DCIS)intheleftbreast.Diffusion-weightedimagesobtainedatbvaluesof500(a),1000(b),and1500(c)sec/mm2showthatthesignalintensityofnormalbreastparenchymadecreaseswithincreasingbvalue.ThesignalintensityofDCISintherightbreast(arrows)isconspicuousrelativetothedecreasedsignalintensityofnormalbreastparenchymainb,andthesignalintensityofnormalbreastparenchymaintheleftbreastisclosetothenoiselevelinc.左侧乳腺导管原位癌（DCIS）。b值分别为500,1000,1500sec/mm2的弥散加权图显示正常乳腺实质的信号强度随着b值的升高而降低。b图中，相对于正常乳腺实质信号强度的降低，左乳导管原位癌的信号强度较显著。C图中左乳正常乳腺实质的信号强度接近于噪声水平,CorrelationbetweenSignalIntensity,bValue,andADCValue,Recentstudieshavedocumentedthatthesignaldecayfitsthemultiexponentialmodelinvivoathigherbvalues,inwhicheachcompartmenthasdifferentADCvalues.Thesimplestmodelistheintracellular-extracellularcompartmentsmodel,whichisappliedtothebrainandprostategland(Fig4)最近的研究已经证明，高b值时，在体内信号衰减适合多指数模型，在多指数模型中，每个隔室具有不同的ADC值。最简单的模型是细胞内-细胞外隔室模型，其将适用于脑和前列腺,Figure4.Simulationsofsingle-compartmentandtwo-compartmentmodelswithextracellularfreediffusionandintracellularrestricteddiffusion.GraphillustratesthecorrelationbetweenS/S0(S=signalintensitywithdiffusion,S0=signalintensitywithoutdiffusion)andbvalue,expressedasS/S0=f1(expbD1)+f2(expbD2),whereD1=extracellulardiffusioncoefficient,D2=intracellulardiffusioncoefficient,f1=extracellularvolumefraction,andf2=intracellularvolumefraction.Parameterswereasfollows:D1=1.010-3mm2/sec,D2=0.110-3mm2/sec,f1=0.7,andf2=0.3.单室模型和双室模型（细胞外自由弥散和细胞内受限弥散）。图显示了S/S0（S是弥散的信号强度，S0是没有弥散的信号强度）与b值的关系，其公式以S/S0=f1(expbD1)+f2(expbD2)表示，在这里D1是细胞外弥散系数，D2是细胞内弥散系数，f1是细胞外体积分数，f2是细胞内体积分数。参数如下：D1=1.010-3mm2/sec,D2=0.110-3mm2/sec,f1=0.7,andf2=0.3,CorrelationbetweenSignalIntensity,bValue,andADCValue,TheimportantpointisthatADCvaluescanbeinfluencedbywhichbvaluesareapplied,afactthathighlightstheneedforconsistentandstandardizedprotocols.Figure5illustratesthedecreaseinADCvaluewithachangeinbvalueinvariousdiseases.最重要的一点是，ADC值受b值的影响，这个事实强调了对扫描机器标准一致性和标准化的需要。图7显示在不同疾病随着b值的变化，ADC值的降低。,Figure5.ChangesinADCvalueversuschangesinbvalue.Diffusion-weightedimageswereobtainedatbvaluesof500,750,1000,and1500sec/mm2,andtheADCvalueateachbvaluewascalculatedfromthesignalintensityofdiffusion-weightedimagesobtainedateachbvalueandatb=0sec/mm2.AllcasesshowadecreaseinADCvaluewithanincreaseinbvalue.ADC值的改变和b值的改变。b值分别为500,750,1000,and1500sec/mm2的弥散加权图，每个b值下的ADC值由b值为0及每个b值下的弥散加权图的信号强度计算。所有的病例显示随着b值的增加，ADC值降低。,NormalBreastParenchyma,VariationinthesignalintensityandADCvalueofnormalbreastparenchymaisobservedduetonormalhormonalfluctuationsthroughoutthemenstrualcycleanddifferencesinindividualphysiologicandbiochemicalmakeup(52).Inwomenwithnormalmenstrualcycles,ADCvaluesdecreaseinweek2andincreaseduringweek4,althoughthesedifferencesdonotreachstatisticalsignificance.正常乳腺实质在信号强度和ADC值上的变化的原因是整个月经周期正常荷尔蒙波动和个体的差异。正常生理周期的女性，在第二周ADC值降低，在第四周ADC值升高，尽管这些差异没有达到统计学意义。,NormalBreastParenchyma,Thisphenomenonisthoughttobeduetoanincreaseinthewatercontentofthebreastduringthesecondhalfofthemenstrualcycle,withADCvaluesreachingapeakafewdaysbeforetheonsetofmenstruation.ThereducedADCvalueinweek2ofthemenstrualcycleisthoughttocorrelatewithreducedwatercontentinthebreastduringthistime这种现象被认为是由于月经周期的第二阶段，乳腺含水量的增加，伴随着月经前几天ADC值达到高峰。月经周期的第二周时ADC值下降被认为与乳腺在这个时期含水量的降低有关。,NormalBreastParenchyma,Ithasbeenfoundthatthereisanincreasedrateoffalse-positivefindingsatcontrast-enhancedbreastMRimagingduringweeks1and4ofthemenstrualcycle(54).Therefore,itisrecommendedthatcontrast-enhancedbreastMRimagingbeperformedduringweek2ofthecycle.目前已经发现在对比增强乳腺磁共振上，月经周期的第一周和第四周假阳性结果的发生率会增加。因此，建议在月经周期的第二周施行对比增强乳腺磁共振,NormalBr