fmri在功能性慢性內(nèi)臟痛研究中的進(jìn)展課件

fMRI在功能性慢性內(nèi)臟痛研究中的應(yīng)用和進(jìn)展

TheapplicationandprogressoffMRIinthestudyoffunctionalchronicvisceralpain

xxx重點(diǎn)實(shí)驗室

JiangsuProvincekeyLabofxxx14級研究生：xxx

導(dǎo)師：xxx教授

綜述報告結(jié)語與展望fMRI在CRD實(shí)驗動物中的應(yīng)用fMRI在臨床IBS病人中的應(yīng)用及進(jìn)展目錄fMRI與功能性慢性內(nèi)臟痛背景簡介

一、二、三、四、一、fMRI與功能性慢性內(nèi)臟痛背景簡介

1.2fMRI歷史194619731992199119771990取得了臨床MRI掃描器的專利；Mansfield使用回波成像(EPI)序列更快的得到圖像FelixBloch和EdwardPurcell分別發(fā)現(xiàn)了核磁共振(NuclearMagneticResonance)現(xiàn)象Lauterbur提出NMR可以用來成像Ogawa通過T2加權(quán)像觀察到BOLD效應(yīng)

Belliveau首次通過對比機(jī)制觀察到功能圖像

Ogawa&Kwong發(fā)表了通過BOLD信號成像的結(jié)果1.3fMRI簡介

功能性磁共振成像（functionalMagneticResonanceImaging，fMRI）：是利用磁振造影來測量神經(jīng)元活動所引發(fā)之血液動力的改變。目前主要是運(yùn)用在研究人及動物的腦或脊髓。capillary含氧血紅蛋白去氧血紅蛋白BloodOxygenLevelDepend1.4功能性慢性內(nèi)臟痛簡介

功能性慢性內(nèi)臟痛（Functionalchronicvisceralpain）：是一種以腹痛或腹部不適,伴或不伴排便習(xí)慣改變?yōu)樘卣鞯奈改c功能性疾病,癥狀至少持續(xù)3個月,但結(jié)腸組織未見明顯病理學(xué)變化。功能性慢性內(nèi)臟痛IBSCRD1.4.2情緒-覺醒網(wǎng)絡(luò)（emotional–arousalnetwork）

和皮層處理網(wǎng)絡(luò)（cortical–modulatorynetwork）Fig.2.Cortical-affectivecircuiteffectiveconnectivitymodel.J.S.Labusetal.Pain(2013)情緒-覺醒環(huán)路:

杏仁核、藍(lán)斑復(fù)合體、嘴側(cè)/膝下/膝上扣帶回等；皮層處理環(huán)路:前額葉皮質(zhì)、眶顳額葉皮質(zhì)等。

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

MaleFemaleZ.Wangetal.,Pain(2009)1.4.3內(nèi)臟刺激腦部環(huán)路聯(lián)系二、fMRI在臨床IBS病人中的應(yīng)用IBS組在給予安慰劑后接受直腸刺激的腦區(qū)激活Figure.5.Rectaldistension-inducedneuralactivationinthecingulatecortex(A)andthesomatosensorycortex(S1/S2,B).JuliaSchmidetal.,Neurogastroenterology(2015)MCC、島葉、丘腦、杏仁核PCCS1、小腦S2S1、S2IBS組和對照組接受直腸刺激后的腦區(qū)激活Figure6.Majorsitesofactivationdifferencesbetweenirritablebowelsyndrome(IBS)andhealthycontrolsubjects.C.L.Kwanetal.,Neurology(2005)對照組和IBS組接受直腸刺激誘導(dǎo)的腦區(qū)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感覺運(yùn)動皮質(zhì)、vmPFC運(yùn)動皮質(zhì)

SMAthalamus,SMA,下頂葉對照組和IBS組島葉和扣帶回種子區(qū)的功能聯(lián)系Figure9.(AandB)FunctionalconnectivityoftheinsulaseedsinthecontrolandIBSgroupsduringliminalstimulation.(CandD)ThesameintheaMCC(incontrols)andpACC(inIBSpatients)seedsduringliminalstimulation.(EandF)GroupcomparisonsofinsularandcingulatefunctionalconnectivitybetweencontrolsandIBSpatients.(IBSVS.controls:dmPFC,vmPFC,dlPFC,andPCC)dlPFCIBS組和對照組在情緒認(rèn)知過程中的性別差異Fig.10.Sexdifferences(IBS+HC)forME-MF(ME-MF=matchingemotion–matchingform).J.S.Labusetal.Pain(2013)Fig.11.DiseaseandsexdifferencesforME-MF.IBS女性病人腦區(qū)注意力相關(guān)網(wǎng)絡(luò)的fMRIC.S.HUbbardetal.,NeurogastroenterolMotil(2015)Figure12。StatisticalTmapsfortheregionofinterestanalysesforthealtering,orienting，andexecutivecontrolconditionsoftheAttentionNetworkTest(ANT).

目前關(guān)于IBS的fMRI研究主要集中在靜息態(tài)、不同條件直腸刺激下的腦區(qū)變化，便秘型和腹瀉型差異、性別差異，安慰劑效應(yīng)、痛覺期待因素、注意力因素、不同的干預(yù)治療措施對IBS腦區(qū)變化的影響。近年來，關(guān)于IBS在情緒、認(rèn)知、情感處理中的進(jìn)展得到了關(guān)注，為探討情感體驗成分在疼痛的作用中提供了更多的依據(jù)和思考。三、fMRI在實(shí)驗動物中的應(yīng)用雄性S-D大鼠在接受不同壓力下CRD刺激后的腦區(qū)激活J.Lazovicetal.,NeurogastroenterolMotil(2005)Figure14.AxialfMRIimagesoftheratbrainatthepressuresof40mmHg(A)60mmHg(B)and80mmHg(C),ofthesameanimal.amygdalaHypothalamus（PVN）NTStrigeminalnucleus雄性F344大鼠腦內(nèi)杏仁核植入皮質(zhì)酮對內(nèi)臟刺激的fMRI變化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局部腦血流（regionalcerebralbloodflow，rCBF）顯像Fig.18.Comparisonofchangesinregionalcerebralbloodflow-relatedtissueradioactivityinresponseto60-mmHgcolorectaldistensioninfemaleandmalerats.Z.Wangetal.,Pain(2009)從認(rèn)知神經(jīng)科學(xué)的角度，研究人腦對復(fù)雜任務(wù)的解決固然重要，但復(fù)雜任務(wù)刺激不利于臨床應(yīng)用；多數(shù)研究都集中在孤立腦區(qū)的激活與否，沒有考慮腦區(qū)之間的相互關(guān)系，即忽略了區(qū)域之間時間上的關(guān)聯(lián)性；通過激活腦區(qū)的功能相關(guān)性，可以為神經(jīng)生物學(xué)、分子生物學(xué)、藥理學(xué)和行為學(xué)治療等提供更有指導(dǎo)意義的思路；研究表明臨床上關(guān)于IBS的中樞認(rèn)知處理過程在疾病的發(fā)生發(fā)展中具有重要作用，但受倫理學(xué)、治療干預(yù)尤其是腦區(qū)等的限制，其發(fā)展受到一定的阻礙；由于模型構(gòu)建、小動物磁共振實(shí)驗裝置等的限制，目前關(guān)于fMRI在功能性慢性內(nèi)臟痛實(shí)驗動物上的研究甚少，生命早期CRD作為IBS病人的經(jīng)典模型之一，開展此慢性內(nèi)臟痛動物實(shí)驗，實(shí)現(xiàn)與臨床科研之間的生物轉(zhuǎn)化亟待解決。參考文獻(xiàn)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,Ga?F,etal.Placeboanalgesiainpatientswithfunctionalandorganicabdominalpain:AfMRIstudyinIBS[J].Gut,2014,64(3).20.C.S.Hubbard,J.Hong,Z.Jiang,etal.Increasedattentionalnetworkfunctioningrelatedtosymptomseveritymeasuresinfemaleswithirritablebowelsyndrome[J].Neurogastroenterology&Motility,2015,27(9):1282–12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