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

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

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,症状至少持续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IBSCRD1.4.2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(2013)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(2009)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组在给予安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(2015)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-inducedactivationinthecontrolgroup.(F)Seedregionsdefinedsimilarlyinthebilateralanteriorinsula(left)andpACC(right)intheIBSpatientgroup.X.LIU，NeurogastroenterolMotil(2015)PCC、PAGaMCC、insula、dmPFC、caudate,andPAG感觉运动皮质、vmPFC运动皮质

SMAthalamus,SMA,下顶叶对照组和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(2013)Fig.11.DiseaseandsexdifferencesforME-MF.IBS女性病人脑区注意力相关网络的fMRIC.S.HUbbardetal.,NeurogastroenterolMotil(2015)Figure12。StatisticalTmapsfortheregionofinterestanalysesforthealtering,orienting，andexecutivecontrolconditionsoftheAttentionNetworkTest(ANT).

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，安慰剂效应、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）NTStrigeminalnucleus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(2010)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(2009)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；研究表明临床上关于IBS的中枢认知处理过程在疾病的发生发展中具有重要作用，但受伦理学、治疗干预尤其是脑区等的限制，其发展受到一定的阻碍；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,2010,5(1)::e8573.6.LarssonMBO,KirstenT,CraigAD,etal.BrainResponsestoVisceralStimuliReflectVisceralSensitivityThresholdsinPatientsWithIrritableBowelSyndrome[J].Gastroenterology,2012,142(3):463-472.7.KeszthelyiD,TroostFJ,MascleeAA.Irritablebowelsyndrome:methods,mechanisms,andpathophysiology.Methodstoassessvisceralhypersensitivityinirritablebowelsyndrome.[J].AmericanJournalofPhysiologyGastrointestinal&LiverPhysiology,2012,303(2):G141-54.8.ElsenbruchS,KotsisV,BensonS,etal.Neuralmechanismsmediatingtheeffectsofexpectationinvisceralplaceboanalgesia:AnfMRIstudyinhealthyplaceborespondersandnonresponders[J].Pain,2011,153(2):382-90.9.Jui-YangH,KilpatrickLA,JenniferL,etal.PatientswithChronicVisceralPainShowSex-RelatedAlterationsinIntrinsicOscillationsoftheRestingBrain[J].JournalofNeuroscience,2013,33(29):11994-12002.10.LabusJS,ArpanaG,KristenC,etal.Sexdifferencesinemotion-relatedcognitiveprocessesinirritablebowelsyndromeandhealthycontrolsubjects.[J].Pain,2013,154(10):2088–2099.11.ZhuX,ZhuX,ChenW,etal.TheApplicationofFunctionalMagneticResonanceImaginginanInfantRatModelofIrritableBowelSyndrome[J].GastroenterologyResearch&Practice,2014,2014(5):637-645.12.TownerRA,SmithN,SaundersD,etal.ContrastEnhancedMagneticResonanceImagingasaDiagnosticTooltoAssessBladderPermeabilityandAssociatedColonCrossTalk:PreclinicalStudiesinaRatModel[J].JournalofUrology,2014,193(4):1394-1400.13.X.Liu,A.Silverman,M.Kern,etal.Excessivecouplingofthesaliencenetworkwithintrinsicneurocognitivebrainnetworksduringrectaldistensioninadolescentswithirritablebowelsyndrome:apreliminaryreport[J].Neurogastroenterology&Motility,2015.14.MakinTR,FilippiniN,DuffEP,etal.Network-levelreorganisationoffunctionalconnectivityfollowingarmamputation[J].Neuroimage,2015,28:217–225.15.IcenhourA,LanghorstJ,BensonS,etal.Neuralcircuitryofabdominalpain-relatedfearlearningandreinstatementinirritablebowelsyndrome[J].Neurogastroenterology&Motility,2015,27(1):114–127.16.SegerdahlAR,MelvinM,OkellTW,etal.Thedorsalposteriorinsulasubservesafundamentalroleinhumanpain.[J].NatureNeuroscience,2015,18(4).17.SchmidJ,BingelU,RitterC,etal.Neuralunderpinningsofnocebohyperalgesiainvisceralpain:AfMRIstudyinhealthyvolunteers.[J].Neuroimage,2015,120:114–122.18.KeJ,QiR,LiuC,etal.Abnormalregionalhomogeneityinpatientswithirritablebowelsyndrome:Aresting-statefunctionalMRIstudy[J].Neurogastroenterology&Motility,2015.19SchmidJ,LanghorstJ,GaßF,etal.Placeboanalgesiainpatientswithfunctionalandorganicabdominalpain:AfMRIstudyinIBS[J].Gut,2014,64(3).20.C.S.Hubbard,J.Hong,Z.Jiang,etal.Increasedattentionalnetworkfunctioningrelatedtosymptomseveritymeasuresinfemaleswithirritablebowelsyndrome[J].Neurogastroenterology&Motility,2015,27(9):1282–1294.21.肖伟波,张强,张晔,等.第一疼痛和第二疼痛的神经影像学研究[J].中国疼痛医学杂志,2011(6):366-369.22.PetersenGL,FinnerupNB,KasperG,etal.Expectationsandpositiveemotionalfeelingsaccompanyreductionsinongoingandevokedneuropathicpainfollowingplacebointerventions.[J].Pain,2014,155(12):2687–2698.23.KatjaW,MarkusP,IreneT.Neurocognitiveaspect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