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ObjectiveVolumetriccontrast-enhancedultrasound(VCEUS)imaginghasthepotentialtomonitorchangesinrenalperfusionfollowingvascularinjury.容積超聲造影顯像可以作為一種監(jiān)測(cè)血管損傷后腎臟灌注變化的潛在手段。CurrentmethodsforquantifyingAKIaresearchingforbio-markersindicativeofkidneyinjurysuchaspositivefluctuationsinserumcreatinine.However,serumcreatininelevelslackthesensitivityandspecificitynecessaryforearlydetection.DuetothenephrotoxicnatureofbothCTandMRcontrastagents,otherstandardperfusionimagingmodalitiesarenotsuitablefordiagnosisandmonitoringofAKI.目前確診AKI的方法主要通過(guò)尋找血液中腎臟損害的生物標(biāo)志物，例如血肌酐水平升高。但是血肌酐缺乏早期診斷的敏感性及特異性。由于CT及MR造影本身存在腎毒性，而其他標(biāo)準(zhǔn)灌注顯像模式不適合診斷及監(jiān)測(cè)AKI。VCEUScouldprovideamoredetailedideaoftheactualpercentageofischemictissueresultingfromthisrenalcomplicationbyidentifyingregionsofischemictissue.通過(guò)鑒別缺血組織區(qū)域，腎臟造影能夠?qū)τ捎谀I臟并發(fā)癥造成的缺血組織的實(shí)際百分比提供更加細(xì)致的理念。ThefocusofthispaperistoinvestigatetherepeatabilityandrobustnessofVCEUSimagingfortrackingperfusionchangesinthehealthyandinjuredkidney.這篇文章主要致力于觀察超聲造影顯像追蹤正常及受損腎臟灌注變化的可重復(fù)性及穩(wěn)定性。二MethodVCEUSutilizesaseriesofplanarimageacquisitions,capturingthenon-linearsecondharmonicsignalfrommicrobubble(MB)contrastagentsflowinginthevasculature.Tissueperfusionparameters(peakintensity,IPK;time-to-peakintensity,TPK;wash-inrate,WIR;areaundercurve,AUC)werederivedfromtime-intensitycurvedatacollectedduringinvitroflowphantomstudiesandinvivoanimalstudiesofhealthyandinjuredkidney.容積超聲造影通過(guò)一系列的二維圖像采集，捕捉流入脈管系統(tǒng)的微氣泡造影劑形成的非線性二次諧波信號(hào)。在體外流速模型及體內(nèi)正常/受損腎臟的動(dòng)物研究中，收集來(lái)自時(shí)間-強(qiáng)度曲線的組織灌注參數(shù)（峰強(qiáng)度、達(dá)峰值強(qiáng)度時(shí)間、內(nèi)洗率、曲線下面積）。Fortheflowphantomstudies,eithertheconcentrationofMBcontrastagentwasheldconstant(10μL/L)withvaryingvolumetricflowrates(10,20,and30mL/min)ortheflowratewasheldconstant(30mL/min)andthecontrastagentconcentrationwasvaried(5,10,and20μL/L).在體外流速模型研究中，保證微氣泡濃度穩(wěn)定（10μL/L），改變?nèi)莘e流速率（10,20,and30mL/min），或者保證流速穩(wěn)定（30mL/min），改變微氣泡濃度(5,10,and20μL/L)。Animalstudieswereperformedusingeitherhealthyratsorthosethatunderwentrenalischemia-reperfusioninjury.Aseriesofrenalstudieswereperformedusinghealthyrats(N=4)whiletheangleofthetransducerwasvariedforeachVCEUSimageacquisition(referenceor0°,45°,and90°)toassessifrepeatedrenalperfusionmeasureswereisotropicandindependentoftransducerposition.Bloodserumbiomarkersandimmunohistologywereusedtoconfirmacutekidneyinjury.動(dòng)物研究應(yīng)用健康小鼠及遭受缺血再灌注的小鼠來(lái)完成。用正常小鼠完成一系列腎臟研究，每次超聲造影圖像采集的傳感器角度是多變的（參考角度為0°、45°、90°），以便評(píng)估重復(fù)的腎臟灌注方法是等向性的，其獨(dú)立于傳感器方位。血漿生物標(biāo)記物及免疫組織學(xué)用來(lái)確診急性腎損害。三Results1.FlowphantomresultsrevealedalinearrelationshipbetweenMBconcentrationsinjectedintotheflowsystemandtheIPK,WIR,andAUCperfusionmeasures(R2>0.56,P<0.005).Further,therewasalinearrelationshipbetweenchangesinvolumeflowrateandtheTPK,WIR,andAUCmetrics(R2>0.77,P<0.005).1.血流模型結(jié)果提示注射入流速系統(tǒng)的微泡濃度與峰強(qiáng)度、內(nèi)洗率及曲線下面積呈線性相關(guān)（R2>0.56，P<0.005）。另外，容積流率變化值與時(shí)間流速峰值、內(nèi)洗率、曲線下面積度量值呈線性相關(guān)(R2>0.77,P<0.005)。圖1a顯示固定容積流速，改變微泡造影劑濃度所形成的時(shí)間-強(qiáng)度曲線。三條時(shí)間強(qiáng)度曲線均在同一時(shí)間達(dá)到了峰強(qiáng)度。Figure1ashowstime-intensitycurvesforthreedifferentMBconcentrationsforafixedvolumetricflowrate.Allthreetime-intensitycurvesreachtheirpeakintensityatthesametimepoint。Thederivedperfusionparametersfromtime-intensitycurvedata(i.e.,IPK,TPK,WIR,andAUC)aredescribedinFigure1a.從時(shí)間強(qiáng)度曲線中可以得出IPK/TPK/WRI/AUC等灌注參數(shù)。IPKrevealedalinearrelationshipwiththeconcentrationofcontrastagentused(Figure2e,R2=0.56,P<0.001),asdidWIR(Figure2g,R2=0.75,P<0.005)andAUC(Figure2h,R2=0.93,P<0.001).TPK(Figure2b,R2=0.93,P<0.001),WIR(Figure2c,R2=0.92,P<0.001),andAUC(Figure2d,R2=0.77,P<0.005)hadlinearrelationshipswithchangesinflowrate.therewasalsonosignificantchangeinTPKwithrespecttocontrastconcentration(Figure2f,P>0.85)aswellasIPKwithrespecttoflowspeed(Figure2a,P>0.06).2.Nosignificantdifferencewasfoundbetweenthetransducerangleduringdataacquisitionandanyofthederivedrenalperfusionmeasures(P>0.60).2.數(shù)據(jù)獲取期間傳感器角度與所有腎臟灌注參數(shù)之間無(wú)顯著性相關(guān)性(P>0.60)。Figure3illustratesthetimeintensitycurvesobtainedatdifferenttransducerorientations:0°(origin),45°,and90°.Importantly,astrongcorrelationwasfoundbetweentimeintensitycurvesacquiredatthevarioustransducerscanningangles(ρ>0.98,P<0.001).圖3為傳感器在0°、45°及90°三個(gè)不同角度所獲得的時(shí)間強(qiáng)度曲線。從圖中可以看出不同傳感器角度獲得的時(shí)間強(qiáng)度曲線存在顯著相關(guān)性。Figure4describestheperfusionparametersversuschangesinimageacquisitionangle.Therewasnostatisticaldifferencebetweenallthreeanglesinanyofthefourparametersinvestigated(P>0.48).圖4提示灌注參數(shù)與接收器角度變化之間的關(guān)系。從圖中可以看出四個(gè)灌注參數(shù)與與傳感器角度無(wú)統(tǒng)計(jì)學(xué)差異(P>0.48)。3.Afterinductionofrenalischemia-reperfusioninjuryinaratanimalmodel(N=4),VCEUSimagingoftheinjuredkidneyrevealedaninitialreductioninrenalperfusionwhencomparedtocontrolanimalsfollowedbyaprogressiverecoveryofvascularfunction.3.建立老鼠腎臟缺血再灌注損害動(dòng)物模型后，與持續(xù)血管功能恢復(fù)的對(duì)照組動(dòng)物模型組相比，受損腎臟的容積超聲造影圖像顯示腎臟灌注顯著降低。Figure5depictstherelativedifferencebetweenthepercentchangeofthemeanvaluesforeachoftheperfusionmeasurementobtainedincontrolkidneysandthosesubjectedtoacuteischemicconditions.EarlyUSmeasurementsindicatethatperfusionwasconsiderablylowerintheinjuredkidneys.圖5描述對(duì)照組腎臟及缺血再灌注腎臟組兩組間每個(gè)灌注值的均數(shù)值變化的相對(duì)偏差。早期提示灌注的超聲參數(shù)，腎損傷組較對(duì)照組明顯下降。尤其是灌注參數(shù)IPK，在第5小時(shí)是最不同的，在48小時(shí)是最相似的。這組數(shù)據(jù)說(shuō)明，與對(duì)照組相比，術(shù)后腎損害組存在低灌注，在48小時(shí)時(shí)出現(xiàn)有限的再灌注。其它灌注參數(shù)也有相似結(jié)果，與對(duì)照組相比，TPK、WIR及AUC在5小時(shí)或24小時(shí)時(shí)達(dá)到峰值差異，在48小時(shí)時(shí)逐步增加到對(duì)照組參數(shù)相似值。Thiswasalsosupportedbyserumcreatininelevels,asshowninFigure6,wheretherewasapeakinthedifferencebetweenmeanserumcreatininevaluesfromcontrolratsandratssubjectedtoischemicinjuryatthe24-hrtimepointandthenhadpartiallyrecoveredby48hr.圖6中血漿肌酐水平能支持上述結(jié)果，在24小時(shí)時(shí)，對(duì)照組小鼠及缺血再灌注小鼠肌酐水平均數(shù)差值達(dá)到最大，在48小時(shí)時(shí)有部分恢復(fù)。四DiscussionEnhancingmethodsfordetectingseverityofAKIhasthepotentialofimprovingpatientoutcomebyincreasingtheinformation,knowledgeandunderstandingofhowtotreatthedisease.ThestrategiesinvestigatedhereareintendedtosupplementcurrentmethodstogainamoreinformativedescriptionofAKIwhereportionsofthetissuebecomeis-chemic.通過(guò)優(yōu)化提高探知AKI嚴(yán)重性的方法，增加對(duì)怎樣治療AKI的信息、知識(shí)和理解，為提高患者預(yù)后提供可能性。本文目的是為目前的方法提供補(bǔ)充，以便對(duì)由缺血造成的AKI提供更加詳盡的描述。五ConclusionAcutekidneyinjuryisaseriousdiseaseinneedofmoremethodstohelpdiagnos