fmri在功能性慢性内脏痛研究中的进展课件

fMRI在功能性慢性内脏痛研究中的应用和进展

TheapplicationandprogressoffMRIinthestudyoffunctionalchronicvisceralpain

江苏省xxx重点实验室

JiangsuProvincekeyLabofxxx14级研究生：xxx

导师：xxx教授

综述报告结语与展望fMRI在CRD实验动物中的应用fMRI在临床IBS病人中的应用及进展目录fMRI与功能性慢性内脏痛背景简介

一、二、三、四、一、fMRI与功能性慢性内脏痛背景简介

计算机体层成像(CT)20世纪50~60年代70~80年代80~90年代19世纪末20世纪初

X线放射诊断学正电子发射成像(PET)单光子发射体层成像(SPECT)磁共振功能成像〔FMRI〕超声成像(USG)核素γ闪烁成像(γ-scintigraphy)计算机体层成像(CT)磁共振成像(MRI)数字血管减影(DSA)1.1医学影像学开展简史

1.2fMRI历史194619731992199119771990取得了临床MRI扫描器的专利；Mansfield使用回波成像(EPI)序列更快的得到图像FelixBloch和EdwardPurcell分别发现了核磁共振(NuclearMagneticResonance)现象Lauterbur提出NMR可以用来成像Ogawa通过T2加权像观察到BOLD效应

Belliveau首次通过对比机制观察到功能图像

Ogawa&Kwong发表了通过BOLD信号成像的结果1.3fMRI简介功能性磁共振成像〔functionalMagneticResonanceImaging，fMRI〕：是利用磁振造影来测量神经元活动所引发之血液动力的改变。目前主要是运用在研究人及动物的脑或脊髓。capillary含氧血红蛋白去氧血红蛋白BloodOxygenLevelDepend1.4功能性慢性内脏痛简介功能性慢性内脏痛〔Functionalchronicvisceralpain〕：是一种以腹痛或腹部不适,伴或不伴排便习惯改变为特征的胃肠功能性疾病,病症至少持续3个月,但结肠组织未见明显病理学变化。功能性慢性内脏痛IBSCRD与内脏伤害性感受处理息息相关的三个环路：

Emerana.Mayeretal.,Gastroenterology(2006)C稳态传入网络包括：臂旁核、丘脑、岛叶、dACC等。稳态传入网络〔homeostatic-afferentnetwork〕Figure1.Ascendingprojectionsofhomeostaticafferents.(B)Spino-thalamo-corticalsystem.(C)Corticalmodulationofhomeostaticafferentinputtothecentralnervoussystem.1.4.2情绪-觉醒网络〔emotional–arousalnetwork〕

和皮层处理网络〔cortical–modulatorynetwork〕Fig.2.Cortical-affectivecircuiteffectiveconnectivitymodel.J.S.Labusetal.Pain(2021)情绪-觉醒环路:

杏仁核、蓝斑复合体、嘴侧/膝下/膝上扣带回等；皮层处理环路:前额叶皮质、眶颞额叶皮质等。

Fig.3.Sexdifferencesinactivationofthehomeostaticafferent,emotional–arousal,andcortical–modulatorynetworksinresponsetonoxiousvisceralstimulation.

MaleFemaleZ.Wangetal.,Pain(2021)1.4.3内脏刺激脑部环路联系二、fMRI在临床IBS病人中的应用IBS患者与正常人之间脑局部一致性(ReHo)的差异Figure4.

ReHodifferencesbetweenIBSpatientsandcontrols.J.KEetal.,NeurogastroenterolMotil(2021)中央后回、丘脑、小脑蚓、顶叶aMCC、pACC、sACC、vm/dl/vlPFCIBS组在给予抚慰剂后接受直肠刺激的脑区激活Figure.5.Rectaldistension-inducedneuralactivationinthecingulatecortex(A)andthesomatosensorycortex(S1/S2,B).JuliaSchmidetal.,Neurogastroenterology(2021)MCC、岛叶、丘脑、杏仁核PCCS1、小脑S2S1、S2IBS组和对照组接受直肠刺激后的脑区激活Figure6.

Majorsitesofactivationdifferencesbetweenirritablebowelsyndrome(IBS)andhealthycontrolsubjects.C.L.Kwanetal.,Neurology(2005)对照组和IBS组接受直肠刺激诱导的脑区激活Figure7.(A–D)BrainactivationincontrolsandIBSpatientsduringsubliminalandliminalrectaldistensions.(E)Seedregionsdefinedintheanteriorinsula(left)andaMCC(right)basedonrectaldistension-inducedactivationinthe

controlgroup.(F)Seedregionsdefinedsimilarlyinthebilateralanteriorinsula(left)andpACC(right)intheIBSpatientgroup.X.LIU，NeurogastroenterolMotil(2021)PCC、PAGaMCC、insula、dmPFC、caudate,andPAG感觉运动皮质、vmPFC运动皮质

SMAthalamus,SMA,下顶叶组内、组间激活功能区的比较Figure8.(A)Comparisonofbrainactivationbetweensubliminalandliminalstimulationconditionsinthecontrolgroup.(B)ThesameintheIBSpatientgroup.(C)GroupcomparisonofbrainactivationbetweencontrolsandIBSpatientsduringsubliminalstimulation.(D)Thesameduringliminalstimulation.对照组和IBS组岛叶和扣带回种子区的功能联系Figure9.(AandB)FunctionalconnectivityoftheinsulaseedsinthecontrolandIBSgroupsduringliminalstimulation.(CandD)ThesameintheaMCC(incontrols)andpACC(inIBSpatients)seedsduringliminalstimulation.(EandF)GroupcomparisonsofinsularandcingulatefunctionalconnectivitybetweencontrolsandIBSpatients.(IBSVS.controls:dmPFC,vmPFC,dlPFC,andPCC)dlPFCIBS组和对照组在情绪认知过程中的性别差异Fig.10.

Sexdifferences(IBS+HC)forME-MF(ME-MF=matchingemotion–matchingform).J.S.Labusetal.Pain(2021)Fig.11.DiseaseandsexdifferencesforME-MF.IBS女性病人脑区注意力相关网络的fMRIC.S.HUbbardetal.,NeurogastroenterolMotil(2021)Figure12。

StatisticalTmapsfortheregionofinterestanalysesforthealtering,orienting，andexecutivecontrolconditionsoftheAttentionNetworkTest(ANT).健康成年人接受直肠扩张刺激的纤维束联系Fig.13.Connectionsbetweenthemainareasactivatedduringvisceralperception.X.Moissetetal.,EuropeanJournalofPain(2021)目前关于IBS的fMRI研究主要集中在静息态、不同条件直肠刺激下的脑区变化，便秘型和腹泻型差异、性别差异，抚慰剂效应、痛觉期待因素、注意力因素、不同的干预治疗措施对IBS脑区变化的影响。近年来，关于IBS在情绪、认知、情感处理中的进展得到了关注，为探讨情感体验成分在疼痛的作用中提供了更多的依据和思考。三、fMRI在实验动物中的应用雄性S-D大鼠在接受不同压力下CRD刺激后的脑区激活J.Lazovicetal.,NeurogastroenterolMotil(2005)Figure14.AxialfMRIimagesoftheratbrainatthepressuresof40mmHg(A)60mmHg(B)and80mmHg(C),ofthesameanimal.amygdalaHypothalamus（PVN）NTStrigeminalnucleusFigure15.AxialfMRIimagesoftheratbrainduringtherectalballoonstimulationatthepressureof60mmHg(A)and80mmHg(B),ofthesameanimal.SCPAGthalamusCblHiIL、PL雄性F344大鼠脑内杏仁核植入皮质酮对内脏刺激的fMRI变化Figure16.SpecificnucleiactivatedinratswithCORT(AandC)micropelletsbutnotactivatedinratswithCHOL(BandD)〔A、B：40mmHgor；C、D：60mmHg〕.Figure17.Specificnucleiactivatedby60mmHgCRDbutnotat40mmHgCRDinratswitheitherCORT(CandD)orCHOL(AandB)(A、C:60mmHg;B、D:40mmHg).AnthonyC.Johnsonetal.,PlosOne(2021)Wistar大鼠接受CRD的SPECT局部脑血流〔regionalcerebralbloodflow，rCBF〕显像Fig.18.Comparisonofchangesinregionalcerebralbloodflow-relatedtissueradioactivityinresponseto60-mmHgcolorectaldistensioninfemaleandmalerats.Z.Wangetal.,Pain(2021)目前关于fMRI在CRD模型所致慢性内脏痛的实验尚未开展。接受急性结直肠内脏刺激的动物在fMRI中的研究也较少，重复刺激和单次刺激的差异与否，不同的给药途径，不同药物的干预等都存在较大的科研价值。当然fMRI活体动物成像麻醉对实验存在一定的影响，但活体成像后动物可以继续进行分子生物学等实验，在一定程度上降低了实验相关性数据的个体差异和组间、组内差异，由此关于CRD模型在fMRI中的根底研究亟待开展。四、结语与展望从认知神经科学的角度，研究人脑对复杂任务的解决固然重要，但复杂任务刺激不利于临床应用；多数研究都集中在孤立脑区的激活与否，没有考虑脑区之间的相互关系，即忽略了区域之间时间上的关联性；通过激活脑区的功能相关性，可以为神经生物学、分子生物学、药理学和行为学治疗等提供更有指导意义的思路；研究说明临床上关于IBS的中枢认知处理过程在疾病的发生开展中具有重要作用，但受伦理学、治疗干预尤其是脑区等的限制，其开展受到一定的阻碍；由于模型构建、小动物磁共振实验装置等的限制，目前关于fMRI在功能性慢性内脏痛实验动物上的研究甚少，生命早期CRD作为IBS病人的经典模型之一，开展此慢性内脏痛动物实验，实现与临床科研之间的生物转化亟待解决。参考文献1.Lazovic,J,Wrzos,H.F,Yang,Q.X,etal.Regionalactivationintheratbrainduringvisceralstimulationdetectedbyc-fosexpressionandfMRI[J].Neurogastroenterology&Motility,2005,17(4):548–556.2.Annalisa,DalLago,AlbertoE,Minetti,Pietro,Biondetti,etal.Magneticresonanceimagingoftherectumduringdistension.[J].DiseasesoftheColon&Rectum,2005,48(6):1220-1227.3.KwanCL,DiamantNE,PopeG,,etal.Abnormalforebrainactivityinfunctionalboweldisorderpatientswithchronicpain.[J].Neurology,2005,65(8):1268-1277.4.LawalA,KernM,SidhuH,etal.Novelevidenceforhypersensitivityofvisceralsensoryneuralcircuitryinirritablebowelsyndromepatients.[J].Gastroenterology,2006,130(1):26–33.5.JohnsonAC,BrentM,JelenaL,etal.BrainActivationinResponsetoVisceralStimulationinRatswithAmygdalaImplantsofCorticosterone:AnfMRIStudy[J].PlosOne,2021,5(1)::e8573.6.LarssonMBO,KirstenT,CraigAD,etal.BrainResponsestoVisceralStimuliReflectVisceralSensitivityThresholdsinPatientsWithIrritableBowelSyndrome[J].Gastroenterology,2021,142(3):463-472.7.KeszthelyiD,TroostFJ,MascleeAA.Irritablebowelsyndrome:methods,mechanisms,andpathophysiology.Methodstoassessvisceralhypersensitivityinirritablebowelsyndrome.[J].AmericanJournalofPhysiologyGastrointestinal&LiverPhysiology,2021,303(2):G141-54.8.ElsenbruchS,KotsisV,BensonS,etal.Neuralmechanismsmediatingtheeffectsofexpectationinvisceralplaceboanalgesia:AnfMRIstudyinhealthyplaceborespondersandnonresponders[J].Pain,2021,153(2):382-90.9.Jui-YangH,KilpatrickLA,JenniferL,etal.PatientswithChronicVisceralPainShowSex-RelatedAlterationsinIntrinsicOscillationsoftheRestingBrain[J].JournalofNeuroscience,2021,33(29):11994-12002.10.LabusJS,ArpanaG,KristenC,etal.Sexdifferencesinemotion-relatedcognitiveprocessesinirritablebowelsyndromeandhealthycontrolsubjects.[J].Pain,2021,154(10):2088–2099.11.ZhuX,ZhuX,ChenW,etal.TheApplicationofFunctionalMagneticResonanceImaginginanInfantRatModelofIrritableBowelSyndrome[J].GastroenterologyResearch&Practice,2021,2021(5):637-645.12.TownerRA,SmithN,SaundersD,etal.ContrastEnhancedMagneticResonanceImagingasaDiagnosticTooltoAssessBladderPermeabilityandAssociatedColonCrossTalk:PreclinicalStudiesinaRatModel[J].JournalofUrology,2021,193(4):1394-1400.13.X.Liu,A.Silverman,M.Kern,etal.Excessivecouplingofthesaliencenetworkwithintrinsicneurocognitivebrainnetworksduringrectaldistensioninadolescentswithirritablebowelsyndrome:apreliminaryreport[J].Neurogastroenterology&Motility,2021.14.MakinTR,FilippiniN,DuffEP,etal.Network-levelreorganisationoffunctionalconnectivityfollowingarmamputation[J].Neuroimage,2021,28:217–225.15.IcenhourA,LanghorstJ,BensonS,etal.Neuralcircuitryofabdominalpain-relatedfearlearningandreinstatementinirritablebowelsyndrome[J].Neurogastroenterology&Motility,2021,27(1):114–127.16.SegerdahlAR,MelvinM,OkellTW,etal.Thedorsalposteriorinsulasubservesafundamentalroleinhumanpain.[J].NatureNeuroscience,2021,18(4).17.SchmidJ,BingelU,RitterC,etal.Neuralunderpinningsofnocebohyperalgesiainvisceralpain:AfMRIstudyinhealthyvolunteers.[J].Neuroimage,2021,120:114–122.18.KeJ,QiR,LiuC,etal.Abnormalregionalhomogeneityinpatientswithirritablebowelsyndrome:Aresting-statefunctionalMRIstudy[J].Neurogastroenterology&Motility,2021.19Schm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