fMRI在功能性慢性內臟痛研究中的應用和進展

TheapplicationandprogressoffMRIinthestudyoffunctionalchronicvisceralpain

xxx重點實驗室

JiangsuProvincekeyLabofxxx14級研究生：xxx

導師：xxx教授

綜述報告結語與展望fMRI在CRD實驗動物中的應用fMRI在臨床IBS病人中的應用及進展目錄fMRI與功能性慢性內臟痛背景簡介

一、二、三、四、一、fMRI與功能性慢性內臟痛背景簡介

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分別發現了核磁共振(NuclearMagneticResonance)現象Lauterbur提出NMR可以用來成像Ogawa通過T2加權像觀察到BOLD效應

Belliveau首次通過對比機制觀察到功能圖像

Ogawa&Kwong發表了通過BOLD信號成像的結果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元活動所引發之血液動力的改變。目前主要是運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功能性慢性內臟痛簡介

功能性慢性內臟痛（Functionalchronicvisceralpain）：是一種以腹痛或腹部不適,伴或不伴排便習慣改變為特征的胃腸功能性疾病,癥狀至少持續3個月,但結腸組織未見明顯病理學變化。功能性慢性內臟痛IBSCRD1.4.2情緒-覺醒網絡（emotional–arousalnetwork）

和皮層處理網絡（cortical–modulatorynetwork）Fig.2.Cortical-affectivecircuiteffectiveconnectivitymodel.J.S.Labusetal.Pain(2013)情緒-覺醒環路:

杏仁核、藍斑復合體、嘴側/膝下/膝上扣帶回等；皮層處理環路:前額葉皮質、眶顳額葉皮質等。

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

MaleFemaleZ.Wangetal.,Pain(2009)1.4.3內臟刺激腦部環路聯系二、fMRI在臨床IBS病人中的應用IBS組在給予安慰劑后接受直腸刺激的腦區激活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的腦區激活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感覺運動皮質、vmPFC運動皮質

SMAthalamus,SMA,下頂葉對照組和IBS組島葉和扣帶回種子區的功能聯系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女性病人腦區注意力相關網絡的fMRIC.S.HUbbardetal.,NeurogastroenterolMotil(2015)Figure12。StatisticalTmapsfortheregionofinterestanalysesforthealtering,orienting，andexecutivecontrolconditionsoftheAttentionNetworkTest(ANT).

目前關于IBS的fMRI研究主要集中在靜息態、不同條件直腸刺激下的腦區變化，便秘型和腹瀉型差異、性別差異，安慰劑效應、痛覺期待因素、注意力因素、不同的干預治療措施對IBS腦區變化的影響。近年來，關于IBS在情緒、認知、情感處理中的進展得到了關注，為探討情感體驗成分在疼痛的作用中提供了更多的依據和思考。三、fMRI在實驗動物中的應用雄性S-D大鼠在接受不同壓力下CRD刺激后的腦區激活J.Lazovicetal.,NeurogastroenterolMotil(2005)Figure14.AxialfMRIimagesoftheratbrainatthepressuresof40mmHg(A)60mmHg(B)and80mmHg(C),ofthesameanimal.amygdalaHypothalamus（PVN）NTStrigeminalnucleus雄性F344大鼠腦內杏仁核植入皮質酮對內臟刺激的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)從認知神經科學的角度，研究人腦對復雜任務的解決固然重要，但復雜任務刺激不利于臨床應用；多數研究都集中在孤立腦區的激活與否，沒有考慮腦區之間的相互關系，即忽略了區域之間時間上的關聯性；通過激活腦區的功能相關性，可以為神經生物學、分子生物學、藥理學和行為學治療等提供更有指導意義的思路；研究表明臨床上關于IBS的中樞認知處理過程在疾病的發生發展中具有重要作用，但受倫理學、治療干預尤其是腦區等的限制，其發展受到一定的阻礙；由于模型構建、小動物磁共振實驗裝置等的限制，目前關于fMRI在功能性慢性內臟痛實驗動物上的研究甚少，生命早期CRD作為IBS病人的經典模型之一，開展此慢性內臟痛動物實驗，實現與臨床科研之間的生物轉化亟待解決。參考文獻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):1282–1294.21.肖偉波,張強,張曄,等.第一疼痛和第二疼痛的神經影像學研究[J].中國疼痛醫學雜志,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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