胶质瘤基因表达与影像学之间的联系——文献回顾及展望ppt课件.pptx

胶质瘤基因表达与影像学之间的联系胶质瘤基因表达与影像学之间的联系文献文献回顾及展望回顾及展望北京市神经外科研究所STAR MARKERS AND COMMON IMAGINGStar markers:-MGMT -IDH1 -EGFR -1p/19q -TP53 -Ki-67 -PTEN -MIB-1 -Others -TypesCommon imaging:-T1/T2 -T1+-FLAIR -CBV -DTI/DWI -DCE-MR -MRS -PET -SPECTIDH11p/19qEGFRP53MGMTT1/T2 1.Albert Lai,et al 2011 2.Carrillo,J.A.,et al 2012 3.Metellus,Philippe,et al 2010 1.Metellus,Philippe,et al 2010 2.Megyesi JF,et al 2004 3.Kim JW,et al 2011 1.Diehn,Maximilian,et al 2008 2.Shazeeb MS,et al 2011 3.Mu,Ketao，et al 2015 1.Wang,Y Y,et al 2014 2.Wang,Y Y,et al 2015 1.Carrillo JA,et al 2012 2.Sunwoo L,et al 2013 3.Ahn,Sung Soo,et al 2014 FLAIR 1.Ellingson BM,et al 2013 2.Metellus,Philippe,et al 2010 3.Pope,W.B,et al 2012 1.Metellus,Philippe,et al 20101.Ellingson BM,et al 2013 1.Liu C,et al 2012 1.Ellingson BM,et al 2013T1+1.Albert Lai,et al 2011 2.Ellingson BM,et al 2013 3.Metellus,Philippe,et al 2010 1.Metellus,Philippe,et al 20101.Ellingson BM,et al 2013 1.Sunwoo L,et al 2013 2.Ahn,Sung Soo,et al 2014 3.Ellingson BM,et al 2013DTI 1.Tan,W L,et al 2014 1.Ahn,Sung Soo,et al 2014DWI(ADC)1.Sunwoo L,et al 2013 CBVMRS 1.Pope,W.B,et al 2012DCE-MRI 1.Ahn,Sung Soo,et al 2014PETSPECTSTAR MARKERS AND COMMON IMAGINGPTENMIB-1Ki-67OthersTypesT1/T2 1.Jamshidi N,et al 2012 2.Gevaert,Olivier,et al 2014 3.Fan,Xing,et al 2015 1.Naeini KM,et al 2013FLAIR 1.Liu C,et al 2012 1.Gevaert,Olivier,et al 2014 T1+DTI 1.Bell,C.et al 2014 DWI(ADC)1.Zikou,A.K.,et al 2012CBV 1.Zikou,A.K.,et al 2012 MRS 1.Yu TG,et al 2015DCE-MRI PETSPECTSTAR MARKERS AND COMMON IMAGINGMGMTMGMT1 1、水肿很少出现甚至不会出现在甲基化的肿瘤周围、水肿很少出现甚至不会出现在甲基化的肿瘤周围4。2 2、MGMTMGMT状态需要纹理特征分析才能够建立与状态需要纹理特征分析才能够建立与MRIMRI特征的联系特征的联系8、9。3 3、MGMTMGMT与与ADCADC呈正相关，呈正相关，ADCADC与与PFSPFS呈正相关呈正相关10。4 4、M MG GM MT T甲甲基基化化的的肿肿瘤瘤容容易易出出现现在在左左侧侧颞颞叶叶，而而M MG GM MT T非非甲甲基基化化的的肿瘤更倾向于长在右侧半球肿瘤更倾向于长在右侧半球3 。5 5、MGMTMGMT非甲基化和非甲基化和EGFREGFR扩增的肿瘤容易生长在右侧岛叶，丘脑，扩增的肿瘤容易生长在右侧岛叶，丘脑，颞叶并向侧脑室后部室管膜下区延伸颞叶并向侧脑室后部室管膜下区延伸10。6 6、非非甲甲基基化化的的M MG GM MT T肿肿瘤瘤在在T T1 1增增强强和和T T2 2/F FL LA AI IR R像像上上比比M MG GM MT T甲甲基基化化的肿瘤强化面积大的肿瘤强化面积大3。PROBABILISTIC RADIOGRAPHIC ATLAS OF GLIOBLASTOMA PHENOTYPESB.M.Ellingson.et al,AJNR,2013MGMT promoter methylated tumors occur more frequently in the left temporal lobet-valuePrediction of methylguanine methyltransferase promoter methylation in glioblastoma using dynamic contrast-enhanced magnetic resonance and diffusion tensor imagingSungSoo Ahn.et al,J Neurosurg,2014DCE-MRI permeability parameters:Ktrans may serve as a potential imaging biomarker to predict MGMT methylation status in glioblastoma.CORRELATION OF APPARENT DIFFUSION COEFFICIENT VALUES MEASURED BY DIFFUSION MRI AND MGMT PROMOTER METHYLATION SEMIQUANTITATIVELY ANALYZED WITH MS-MLPA IN PATIENTS WITH GLIOBLASTOMA MULTIFORME methylated MGMTUn-methylated MGMTT1WADCThe mean ADC revealed a positive relationship with MGMT promoter methylation ratioLeonard Sunwoo et al,Journal MRI,2012IDH1IDH11 1、IDH1IDH1突变的肿瘤好发于额叶而且肿瘤细胞临近脑室下区突变的肿瘤好发于额叶而且肿瘤细胞临近脑室下区3，3。2 2、用标准的、用标准的MRIMRI特征就可预测特征就可预测IDH1IDH1的表达状态的表达状态4。3 3、在在D DT TI I相相中中，利利用用部部分分异异向向分分数数和和A AD DC C可可以以在在星星形形细细胞胞胶胶质质瘤瘤中监测中监测IDH1 R132HIDH1 R132H的突变情况的突变情况5。4 4、随随着着年年龄龄上上升升，I ID DH H1 1突突变变减减少少，肿肿瘤瘤更更容容易易长长在在岛岛叶叶并并且且1p/19q1p/19q均表现为阴性均表现为阴性6。RELATIONSHIP BETWEEN TUMOR ENHANCEMENT,EDEMA,IDH1 MUTATIONAL STATUS,MGMTPROMOTER METHYLATION,AND SURVIVAL IN GLIOBLASTOMAAll IDH1 mutant tumors were non-contrast enhancing tumor positive,and most were located in the frontal lobe.J.A.Carrillo et al,AJNR,2012DETECTING ISOCITRATE DEHYDROGENASE GENE MUTATIONS IN OLIGODENDROGLIAL TUMORS USING DIFFUSION TENSOR IMAGING METRICS AND THEIR CORRELATIONS WITH PROLIFERATION AND MICROVASCULAR DENSITYFAADCIDH1(-)IDH1(+)Ji Xiong et al,Journal MRI,2015This study demonstrated that the MaxFA and MinADC are useful DTI parameters for differentiating Oligodendroglial Tumors with and without IDH mutations.CAN DIFFUSION TENSOR IMAGING NONINVASIVELY DETECT IDH1 GENE MUTATIONS IN ASTROGLIOMAS?A RETROSPECTIVE STUDY OF 112 CASESThis study demonstrates that DTI metrics have potential ability to distinguish astrogliomas with IDH1 mutation from those without mutation.FAADCIDH1(-)IDH1(+)W.L.Tan et al,AJNR,2014NON-INVASIVE DETECTION OF 2-HYDROXYGLUTARATE AND OTHER METABOLITES IN IDH1 MUTANT GLIOMA PATIENTS USING MAGNETIC RESONANCE SPECTROSCOPYWater-suppressed proton(1H)MRS provides a non-invasive measure of 2-HG in gliomas,and may serve as a potential biomarker for patients with IDH1 mutant brain tumors.IDH1mutantWild-typeWhitney et al,J Neurooncol,2013EGFREGFR1 1、E EG GF FR R扩扩增增和和E EG GF FR R-突突变变的的G GB BM M普普遍遍出出现现在在左左颞颞极极延延伸伸到到左左岛岛叶区域叶区域3。2 2、E EG GF FR R过过表表达达的的G GB BM M对对比比增增强强体体积积更更大大10 但但与与P PT TE EN N，1 10 0号号染染色色体单倍体或多倍体的体单倍体或多倍体的GBMGBM相比并没有明显的差异相比并没有明显的差异3。3 3、E EG GF FR R通通过过表表达达E EG GF FR R-促促进进胶胶质质母母细细胞胞瘤瘤微微血血管管形形成成。目目前前的的研研究究只只停停留留在在通通过过顺顺磁磁性性氧氧化化铁铁合合成成的的E EG GF FR R共共轭轭体体检检测测E EG GF FR R受受体体水平和通过水平和通过diTyr-GdDTPAdiTyr-GdDTPA观察观察EGFREGFR的表达水平的表达水平11、12。PROBABILISTIC RADIOGRAPHIC ATLAS OF GLIOBLASTOMA PHENOTYPESEllingson et al,AJNR,2013EGFR amplified and EGFR variant 3-expressing tumors occurred most frequently in the left temporal lobe.TARGETED SIGNAL AMPLIFYING ENZYMES ENHANCE MAGNETIC RESONANCE IMAGING OF EGFR EXPRESSION IN AN ORTHOTOPIC MODEL OF HUMAN GLIOMA3T MR can reveale EGFR expression through diTyr-GdDTPAMohammed et al,Cancer Res,20121P/19Q1P/19Q1p/19q1p/19q缺失的间变性少突胶质细胞瘤在缺失的间变性少突胶质细胞瘤在T1/T2T1/T2上表现为边缘上表现为边缘不规则，不均匀强化，呈浸润状态的异缘信号不规则，不均匀强化，呈浸润状态的异缘信号7，7。LOWER APPARENT DIFFUSION COEFFICIENTS INDICATE DISTINCT PROGNOSIS IN LOW-GRADE AND HIGH-GRADE GLIOMAA threshold mean ADC value could predict the 1p/19q codeletion and identify low-risk LGGs.J W Kim et al,J Neurol Neurosurg Psychiatry,2011PREDICTION OF OLIGODENDROGLIAL HISTOLOGY AND LOH 1P/19Q USING DYNAMIC 18FFET-PET IMAGING IN INTRACRANIAL WHO GRADE II AND IIIGLIOMASLOH 1p/19qNon-LOH 1p/19qNathalie L et al,Neuro-oncology,2012RELATIONSHIP BETWEEN RADIOLOGICAL CHARACTERISTICS AND COMBINED 1P AND 19Q DELETION IN WORLD HEALTH ORGANIZATION GRADE III OLIGODENDROGLIAL TUMOURSJ W Kim et al,J Neurol Neurosurg Psychiatry,2011Significant relationships between the 1p19q codeletion and magnetic resonance image characteristics in oligodendroglial tumours such as frontal location,an indistinct tumour border.1p19qcodeletion Intact 1p19qKI-67KI-67用用SeedlinkSeedlink方法可以成功找到方法可以成功找到Ki-67Ki-67的热点的热点16。COMPARISON OF MULTIPLE PARAMETERS OBTAINED ON 3T PULSED ARTERIAL SPIN-LABELING,DIFFUSION TENSOR IMAGING,AND MRS AND THE KI-67 LABELING INDEX IN EVALUATING GLIOMA GRADINGSignificant correlations were observed between the Ki-67 index and the mean,maximum,and minimum ADC,Cho/Cr,and lactate/Cr ratios.IIIVH.Fudaba et al,AJNR,2014CORRELATION OF DIFFUSION TENSOR,DYNAMIC SUSCEPTIBILITY CONTRAST MRI AND 99MTC-TETROFOSMIN BRAIN SPECT WITH TUMOUR GRADE AND KI-67 IMMUNOHISTOCHEMISTRY IN GLIOMAThis study showed that the findings on perfusion MRI and brain SPECT with99mTc-Tetrofosmin were most closely correlated with Ki-67 index.Ki-672%Ki-6730%George A et al,Clinical Neurology and Neurosurgery,2014FRACTIONAL ANISOTROPY AND TUMOR CELL DENSITY OF THE TUMOR CORE SHOW POSITIVE CORRELATION IN DIFFUSION TENSOR MAGNETIC RESONANCE IMAGING OF MALIGNANT BRAIN TUMORSDTI(FA and MD)show positive correlation with Ki-67 labeling indexManabu Kinoshita et al,NeuroImage,2008DIFFUSION TENSOR AND DYNAMIC SUSCEPTIBILITY CONTRAST MRI IN GLIOBLASTOMAA significant correlation was observed between Ki-67 index and ADC,FA ratio,rCBV and rMTT.Anastasia K et al,Clinical Neurology and Neurosurgery,2012AMIDE PROTON TRANSFER IMAGING OF ADULT DIFFUSE GLIOMAS:CORRELATIONWITH HISTOPATHOLOGICAL GRADESTogao O et al,Neuro Oncol,2013There were positive correlations between Amide proton transfer(APT)signal intensity(SI)and Ki-67 LI(P.01,R0.43).COMPARISON OF 4-METHYL-11CTHIOTHYMIDINE(11C-4DST)AND 3-DEOXY-3-18FFLUOROTHYMIDINE(18F-FLT)PET/CT IN HUMAN BRAIN GLIOMA IMAGING-Yasunori Toyota et al,EJNMMI Research,2015PET/CT find that a significant correlation between the Ki-67 labeling index and the tumor-to-normal tissue uptake ratio of 11C-4DST and 18F-FLTP53P531 1、P53P53突变的胶质母细胞瘤更容易在额叶临近侧脑室喙部延伸区突变的胶质母细胞瘤更容易在额叶临近侧脑室喙部延伸区域生长域生长13。2 2、P53P53突变型低级别胶质瘤与左侧颞叶中部和右侧颞叶前部高表突变型低级别胶质瘤与左侧颞叶中部和右侧颞叶前部高表达相关达相关14。3 3、胶质瘤的、胶质瘤的MRIMRI纹理特征与纹理特征与MIB-1MIB-1和和P53P53有直接的关系，现在已经有直接的关系，现在已经能够找到检测能够找到检测MIB-1MIB-1的方法，但是对的方法，但是对P53P53现在还没有有效的检测手现在还没有有效的检测手段段15。注：注：1 1、2 2均使用均使用Voxel-based neuroimaging analysisVoxel-based neuroimaging analysisMAPPING P53 MUTATIONS IN LOW-GRADE GLIOMA:A VOXEL-BASED NEUROIMAGING ANALYSISWang Y et al,AJNR,2015Using quantitative neuroimaging analyses find there is a correlation between tumor location and p53 status.TOWARDS MIB-1 AND P53 DETECTION IN GLIOMA MAGNETICRESONANCE IMAGE:A NOVEL COMPUTATIONAL IMAGE ANALYSIS METHODChenbin Liu et al,Phys.Med.Biol,2012This study proposes a novel method to detect the expression status of MIB-1 and p53 non-invasivelyCORRELATION OF L-METHYL-11C-METHIONINE(MET)UPTAKEWITH L-TYPE AMINO ACID TRANSPORTER 1 IN HUMANPET/CT:Maximum standardized uptake value(SUVmax)correlates with L-Type amino acid transporter 1 LAT1 expression in the tumor in newly diagnosed gliomas.Shuichi Okubo et al,J Neurooncol,2010展望1 1、目目前前对对于于胶胶质质瘤瘤等等级级、胶胶质质瘤瘤生生长长位位置置与与影影像像学学，分分子子遗遗传传学关系的研究比较完善。但对学关系的研究比较完善。但对PTENPTEN，TERTTERT这两个这两个“明星明星”基因的基因的相关报道较少。已经报道的相关报道较少。已经报道的“明星明星”基因也需要进行实验验证。基因也需要进行实验验证。2 2、对对于于胶胶质质瘤瘤边边界界与与基基因因的的关关系系尚尚不不明明确确。目目前前的的影影像像学学手手段段不能准确地描绘胶质瘤边界。不能准确地描绘胶质瘤边界。3 3、对对于于肿肿瘤瘤形形状状，影影像像学学征征象象（坏坏死死，水水肿肿等等）与与基基因因之之间间相相关性的研究出于初级阶段，可进行相应尝试。关性的研究出于初级阶段，可进行相应尝试。4 4、目目前前的的研研究究已已经经涉涉及及用用影影像像学学方方法法区区分分间间叶叶型型的的G GB BM M，但但对对其其他亚型的区分方法尚不可知。他亚型的区分方法尚不可知。5 5、对、对MRSMRS的应用现在只停留在的应用现在只停留在LAC,CHO,CrLAC,CHO,Cr，NAANAA，TMATMA这五种物这五种物质的研究上，对于能否运用新物质的波谱进行研究尚不可知。质的研究上，对于能否运用新物质的波谱进行研究尚不可知。参考文献1 1、Phillips Phillips HS,HS,Kharbanda Kharbanda S,S,Chen Chen R,R,et et al.al.Molecular Molecular subclasses subclasses of of high-grade high-grade glioma glioma predict predict prognosis,prognosis,delineate delineate a a pattern pattern of of disease disease 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