預(yù)測及評價化療療效ApparentDiffusionCoefficient:PotentialImagingBiomarkerforPredictionandEarlyDetectionofResponsetoChemotherapyinHepaticPro.Xiaopeng臨床腫瘤學(xué)市腫瘤防BeijingCancerPekingUniversitySchoolofBeijingInstituteforCancerDiffusionWeighted- DiffusioniscausedbyrandommolecularTheamountofdiffusionisdeterminedbydiffusionDiffusionWeighted- Diffusion-weightedimaging(DWI)istheonlymethodtoproberandommicroscopicmotionofwaterprotonsonaperpixelbasisinvivoDiffusionWeighted-測量組織的擴(kuò)散系數(shù)受到眾多因素影響，例 Themeasurementofthediffusioncoefficientinvivomaybeaffectedbyfactorsotherthantruediffusion,e.g.temperature,perfusion,magneticsusceptibilityinthetissue,orotherkindsofmotionThetermapparentdiffusioncoefficient(ADC)ratherthandiffusioncoefficientisusedDiffusionWeighted-TheADCisstronglyaffected分子黏滯性(molecular細(xì)胞內(nèi)外膜結(jié)構(gòu)的通透性 permeabilityofmembraneseparatingtheintra-and組織／細(xì)胞結(jié)構(gòu)的方向(thedirectionalityoftissuecellularstructuresthatimpedewaterHernethAM,GuccioneS,BednarskiM.EurJRadiol2003;45:208–213.KauppinenRA.NMRBiomed2002;15:6–17.ChenevertTL,StegmanLD,TaylorJM,etal.JNatlCancerInstLyngH,HaraldsethO,RofstadEK.MagnResonMedDiffusionWeighted-ClincialUnderstandingofnormalandCharacterizingfocalanddiffuseMonitoringtherapy化療／放病灶TheCNRofHCCwashigherDWIthanin TheCNRofHCCwashigherinDWIthanin與鑒IchikawaT,etal.AJR,ChanJH,etal.AbdomImaging,2001,26(2):161-Cyst

HemangiomaADC=1.21×10-3

HCC肝細(xì)胞ADC=0.94×10-3 ThresholdADCvalueforthediagnosisofIchikawa以5.5×10-3mm2/sIchikawaT,etal.AJR,1998,170(2):397-402KimT,etal.AJR,1999,173(2):393-8.TaouliB,etal.Radiology,2003,226(1):71-療效 Kamel:DWIcouldbeusefultoolsinassessmentoftumorresponseafterKamelIR,JVascIntervRadiol,2006;17,3:505-療效KamelIR,JVascIntervRadiol,2006;17,3:505-療效 Theilmann:Atotalof13patientswithmetastaticbreastcancerand60measurableliverlesionsweremonitoredbydiffusionMRIafterinitiationofnewcoursesofchemotherapy治療早期ADC值與腫瘤對治療反映具有明顯相可以通過DWI預(yù)測乳癌肝轉(zhuǎn)移瘤diffusionMRIcanpredictresponseearlyTheilmannRJ,etal.Neoplasia,2004,6(6):831-TheilmannRJ,etNeoplasia,療效 Hepaticmetastasesarethemostcommonmalignantneoplasmoftheliverandmostofthemarerelatedwithgastrointestinalcancer化療是最為常用的治ChemotherapyisroutinelyusedtomanagetheandimprovetheDWOnlyfewofthemfocusedontheuseofDW-MRIfordetectingtheresponseofcolorectalandgastrichepaticmetastasestochemotherapy.WagnerAD,GrotheW,HaertingJ,etal.JClinOncol2006;24:2903-Our研究Theaimofthisstudyistoevaluatetheabilityoftheapparentdiffusioncoefficient(ADC)topredictresponsetochemotherapyinpatientswithcolorectalandgastrichepaticmetastases.材料 trymetastasesfromgastrointestinal肝內(nèi)至少一個可測病灶withaminimumofonelivermetastasesmeasuringthan1 KPS評分Karnofskyperformancescale(KPS)>scheduledtoinitiateanewchemotherapy材料 Theprotocolinourstudywasapprovedbyourinstitutionalreviewboard,andinformedconsentwasobtainedfromallpatients.材料 MRIbaselineandthenat3,7and42daysafterthebeginningof1.5-TMRscanner(SignaExciteII;GEMS,Milwaukee,WI,USA)T1WI,T2WI,DWI(b=0,800sec/mm2材料 專業(yè)工作站(AW4.2GEMS,USAFunctool軟件GEMS,USA)測量病灶大小、ADClesionsizeand計(jì)算ADC升高率:percentageADC%ΔADCN=(ADCN－ADCB)/ADCB大小退縮率：Tumorsizechanges（%ΔV42%ΔV42=(VB–V42)/V病灶反應(yīng)性評估23例患者8723patientsevaluated,atotalof87 各監(jiān)測點(diǎn)監(jiān)測病灶數(shù)NumberoflesionsscanedateachtimeNumberNumberTotalDayDayDayCharacteristicorCharacteristicor CharacteristicorNumberof 748411-Numberof748411-NumberoflivermetastaticFemale: Primary9Colorectal9Well 5531 axel+5531 axel+ axel+Cisplatin+5-Capecitabine+Irinotecan+CalciumNumberofpriorchemotherapyPoorly Gastric y 4Poorly4MeanonsetofMeanonsetoflivermetastasisaftertheprimarytumordiagnose(range)[months]11Thirty-eightlesionsrespondedtochemotherapyand49did化療各監(jiān)測點(diǎn)病灶平 umdiameterofrespondingandnonrespondinglesionsateachtimepointofDayDayDay

mm(+

mm(+

p化療各監(jiān)測點(diǎn)病灶平均ADCADCvaluesinrespondingandnonrespondinglesionsateachtimepointofp10-10-DayDayDay,化療中，兩組病灶平均ADC值均明顯升高（F反應(yīng)良好F反應(yīng)不良=5.512，P<0.001反應(yīng)良好組在化療中各個時間點(diǎn)平均應(yīng)不良組（F167P0001）3days：25.4%vs.7.2%；7days：26.2%vs.大小退縮率弱相關(guān)(Day3,r-value=0.344,p=0.004;Day7,r-value=0.423,p<0.001).AweakbutsignificantpositivecorrelationwasobservedbetweenpercentagereductioninlesionsizeandpercentageADCincreaseatDays3and7(Day3,r-value=0.344,p=0.004;Day7,r-value=0.423,p<0.001).AnearlyincreaseinmeanADCsandlowpre-therapymeanADCsinhepaticmetastasesfromgastricandcolorectalcarcinomasmaybeapredictorofresponsetochemotherapy.相關(guān)基礎(chǔ)研Theuseoftheapparentdiffusioncoefficient(ADC)ofwateracquiredbydiffusion-weighted(DW)MRIasasurrogatemarkeroftissuecellularityispotentiallyItiswidelyheldthattumorADCvaluesincreasefollowingsuccessfultreatment,reflectingareductionincellulardensityandbarrierstowatermotion.相關(guān)基礎(chǔ)研AnumberofanimalandcellmodelshaveindicatedthatincreasesinADCwereassociatedwithtreatment-inducedtumorregression,suchas兔VX2腫瘤模型：ADC值可反映不同區(qū)域病理差異,壞死區(qū)ADC值明顯高周邊無壞死區(qū)域VX2RabbitLiverTumorMode：ADCvaluesatthenecroticcoreofeachtumorweresignificantlygreaterthatattheviableperipheryofeachcorrespondingJieDeng,etal.InvestRadiol2006;41:相關(guān)基礎(chǔ)研d等發(fā)現(xiàn)兔腫瘤模型ADCGeschwind:ADCsweresignificantlygreaterintheareaoftumornecrosisthanintheareaofviabletumorinVX2tumorrabbitsmodelafterTACE. presenceofgreateramountsofextracellularwaterwithinthenecroticregioncausedbycelllysisandleakiercellmembranesthatcannolongercompartmentalizewatermolecules,whichallowfreediffusiontotakeplaceshrinkageofapoptoticcells,whichwouldresultinanincreaseinextracellularwaterGeschwindJF,etal.JVascIntervRadiol,2000,11(10):1245-.Inthecontrolanimal,theareaoftumornecrosisisidentifiedasabrightzone,reflectingincreaseddiffusionofwatermoleculescausedbybreakdownofcellmembranes.Awell-definedrimoflowsignalisalsoidentified,reflectingintactcellmembranesandrestrictionofwatermolecules,consistentwithviabletumorcells.Inthetreatedanimal,signalthroughoutthetumorishomogenousandbrighterthaninnormalmuscletissue,indicatingnearlycompletenecrosis.GeschwindJF,etal.JVascIntervRadiol,2000,11(10):1245-Our ChangesofADCvaluesandPathologicalParametersinMurineTumorAfter結(jié)果療后ADC值亦較前減低:4、8小時組腫瘤，鏡 ADCvaluefallingearlyaftertherapy(4,8,12h)isassociatewithedema,vascularcongestion,hemorrhageanddegenerationofthecellulose結(jié)果4小時ADC值變化率：-TheADCchangesinfourhoursaftertherapy-17.64%HEstain:Vascularengorgement結(jié)果8小時ADC值變化率：-TheADCchangesineighthoursaftertherapy45.94%HEstain:cellularedema12小時組ADC值變化率：-TheADCchangesintwelvehoursaftertherapy:- HEstain:Vascularengorgement,hemorrhageseriouslyand結(jié)果ADCvalueshavecertaincorrelationswithapoptosisindex(AI)andthepercentageofproliferation(PI)withinthetumortissue:ADCchangeshavemoderatepositivecorrelationwithapoptosispercentageandmoderatenegativecorrelationwithproliferationpercentage;theinitialADCvalueisnegativecorrelatedwithapoptosisandpositivecorrelatedwithproliferation.療前Pre-therapy

療后Post-therapy Ki67

TUNEL結(jié)果CorrelationinADCchangesandapoptosisADCchangesADCchangesPearsonSig.(2-N PearsonN

.

1.結(jié)果CorrelationinADCchangesandpr