肾灌注的容积超声造影显像-医学课件

一

ObjectiveVolumetriccontrast-enhancedultrasound(VCEUS)imaginghasthepotentialtomonitorchangesinrenalperfusionfollowingvascularinjury.容积超声造影显像可以作为一种监测血管损伤后肾脏灌注变化的潜在手段。CurrentmethodsforquantifyingAKIaresearchingforbio-markersindicativeofkidneyinjurysuchaspositivefluctuationsinserumcreatinine.However,serumcreatininelevelslackthesensitivityandspecificitynecessaryforearlydetection.DuetothenephrotoxicnatureofbothCTandMRcontrastagents,otherstandardperfusionimagingmodalitiesarenotsuitablefordiagnosisandmonitoringofAKI.目前确诊AKI的方法主要通过寻找血液中肾脏损害的生物标志物，例如血肌酐水平升高。但是血肌酐缺乏早期诊断的敏感性及特异性。由于CT及MR造影本身存在肾毒性，而其他标准灌注显像模式不适合诊断及监测AKI。VCEUScouldprovideamoredetailedideaoftheactualpercentageofischemictissueresultingfromthisrenalcomplicationbyidentifyingregionsofischemictissue.通过鉴别缺血组织区域，肾脏造影能够对由于肾脏并发症造成的缺血组织的实际百分比提供更加细致的理念。ThefocusofthispaperistoinvestigatetherepeatabilityandrobustnessofVCEUSimagingfortrackingperfusionchangesinthehealthyandinjuredkidney.这篇文章主要致力于观察超声造影显像追踪正常及受损肾脏灌注变化的可重复性及稳定性。二MethodVCEUSutilizesaseriesofplanarimageacquisitions,capturingthenon-linearsecondharmonicsignalfrommicrobubble(MB)contrastagentsflowinginthevasculature.Tissueperfusionparameters(peakintensity,IPK;time-to-peakintensity,TPK;wash-inrate,WIR;areaundercurve,AUC)werederivedfromtime-intensitycurvedatacollectedduringinvitroflowphantomstudiesandinvivoanimalstudiesofhealthyandinjuredkidney.容积超声造影通过一系列的二维图像采集，捕捉流入脉管系统的微气泡造影剂形成的非线性二次谐波信号。在体外流速模型及体内正常/受损肾脏的动物研究中，收集来自时间-强度曲线的组织灌注参数（峰强度、达峰值强度时间、內洗率、曲线下面积）。Fortheflowphantomstudies,eithertheconcentrationofMBcontrastagentwasheldconstant(10μL/L)withvaryingvolumetricflowrates(10,20,and30mL/min)ortheflowratewasheldconstant(30mL/min)andthecontrastagentconcentrationwasvaried(5,10,and20μL/L).在体外流速模型研究中，保证微气泡浓度稳定（10μL/L），改变容积流速率（10,20,and30mL/min），或者保证流速稳定（30mL/min），改变微气泡浓度(5,10,and20μL/L)。Animalstudieswereperformedusingeitherhealthyratsorthosethatunderwentrenalischemia-reperfusioninjury.Aseriesofrenalstudieswereperformedusinghealthyrats(N=4)whiletheangleofthetransducerwasvariedforeachVCEUSimageacquisition(referenceor0°,45°,and90°)toassessifrepeatedrenalperfusionmeasureswereisotropicandindependentoftransducerposition.Bloodserumbiomarkersandimmunohistologywereusedtoconfirmacutekidneyinjury.动物研究应用健康小鼠及遭受缺血再灌注的小鼠来完成。用正常小鼠完成一系列肾脏研究，每次超声造影图像采集的传感器角度是多变的（参考角度为0°、45°、90°），以便评估重复的肾脏灌注方法是等向性的，其独立于传感器方位。血浆生物标记物及免疫组织学用来确诊急性肾损害。三Results1.FlowphantomresultsrevealedalinearrelationshipbetweenMBconcentrationsinjectedintotheflowsystemandtheIPK,WIR,andAUCperfusionmeasures(R2>0.56,P<0.005).Further,therewasalinearrelationshipbetweenchangesinvolumeflowrateandtheTPK,WIR,andAUCmetrics(R2>0.77,P<0.005).1.血流模型结果提示注射入流速系统的微泡浓度与峰强度、內洗率及曲线下面积呈线性相关（R2>0.56，P<0.005）。另外，容积流率变化值与时间流速峰值、內洗率、曲线下面积度量值呈线性相关(R2>0.77,P<0.005)。图1a显示固定容积流速，改变微泡造影剂浓度所形成的时间-强度曲线。三条时间强度曲线均在同一时间达到了峰强度。Figure1ashowstime-intensitycurvesforthreedifferentMBconcentrationsforafixedvolumetricflowrate.Allthreetime-intensitycurvesreachtheirpeakintensityatthesametimepoint。Thederivedperfusionparametersfromtime-intensitycurvedata(i.e.,IPK,TPK,WIR,andAUC)aredescribedinFigure1a.从时间强度曲线中可以得出IPK/TPK/WRI/AUC等灌注参数。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.数据获取期间传感器角度与所有肾脏灌注参数之间无显著性相关性(P>0.60)。Figure3illustratesthetimeintensitycurvesobtainedatdifferenttransducerorientations:0°(origin),45°,and90°.Importantly,astrongcorrelationwasfoundbetweentimeintensitycurvesacquiredatthevarioustransducerscanningangles(ρ>0.98,P<0.001).图3为传感器在0°、45°及90°三个不同角度所获得的时间强度曲线。从图中可以看出不同传感器角度获得的时间强度曲线存在显著相关性。Figure4describestheperfusionparametersversuschangesinimageacquisitionangle.Therewasnostatisticaldifferencebetweenallthreeanglesinanyofthefourparametersinvestigated(P>0.48).图4提示灌注参数与接收器角度变化之间的关系。从图中可以看出四个灌注参数与与传感器角度无统计学差异(P>0.48)。3.Afterinductionofrenalischemia-reperfusioninjuryinaratanimalmodel(N=4),VCEUSimagingoftheinjuredkidneyrevealedaninitialreductioninrenalperfusionwhencomparedtocontrolanimalsfollowedbyaprogressiverecoveryofvascularfunction.3.建立老鼠肾脏缺血再灌注损害动物模型后，与持续血管功能恢复的对照组动物模型组相比，受损肾脏的容积超声造影图像显示肾脏灌注显著降低。Figure5depictstherelativedifferencebetweenthepercentchangeofthemeanvaluesforeachoftheperfusionmeasurementobtainedincontrolkidneysandthosesubjectedtoacuteischemicconditions.EarlyUSmeasurementsindicatethatperfusionwasconsiderablylowerintheinjuredkidneys.图5描述对照组肾脏及缺血再灌注肾脏组两组间每个灌注值的均数值变化的相对偏差。早期提示灌注的超声参数，肾损伤组较对照组明显下降。尤其是灌注参数IPK，在第5小时是最不同的，在48小时是最相似的。这组数据说明，与对照组相比，术后肾损害组存在低灌注，在48小时时出现有限的再灌注。其它灌注参数也有相似结果，与对照组相比，TPK、WIR及AUC在5小时或24小时时达到峰值差异，在48小时时逐步增加到对照组参数相似值。Thiswasalsosupportedbyserumcreatininelevels,asshowninFigure6,wheretherewasapeakinthedifferencebetweenmeanserumcreatininevaluesfromcontrolratsandratssubjectedtoischemicinjuryatthe24-hrtimepointandthenhadpartiallyrecoveredby48hr.图6中血浆肌酐水平能支持上述结果，在24小时时，对照组小鼠及缺血再灌注小鼠肌酐水平均数差值达到最大，在48小时时有部分恢复。四DiscussionEnhancingmethodsfordetectingseverityofAKIhasthepotentialofimprovingpatientoutcomebyincreasingtheinformation,knowledgeandunderstandingofhowtotreatthedisease.ThestrategiesinvestigatedhereareintendedtosupplementcurrentmethodstogainamoreinformativedescriptionofAKIwhereportionsofthetissuebecomeis-chemic.通过优化提高探知AKI严重性的方法，增加对怎样治疗AKI的信息、知识和理解，为提高患者预后提供可能性。本文目的是为目前的方法提供补充，以便对由缺血造成的AKI提供更加详尽的描述。五ConclusionAcutekidneyinjuryisaseriousdiseaseinneedofmoremethodstohelpdiagnos