胶质瘤基因表达与影像学之间的联系文献回顾及展望课件

中国脑胶质瘤图谱计划中国脑胶质瘤图谱计划 胶质瘤基因表达与影像学之间的联系 文献回顾及展望 北京市神经外科研究所 中国脑胶质瘤图谱计划 Star markers and Common imaging Star markers: -MGMT -IDH1 -EGFR -1p/19q -TP53 -Ki-67 -PTEN -MIB-1 -Others -Types Common imaging: -T1/T2 -T1+ -FLAIR -CBV -DTI/DWI -DCE-MR -MRS -PET -SPECT 中国脑胶质瘤图谱计划 IDH11p/19qEGFRP53MGMT T1/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 2010 1.Ellingson BM,et al 2013 1.Liu C,et al 2012 1.Ellingson BM,et al 2013 T1+ 1.Albert Lai,et al 2011 2.Ellingson BM,et al 2013 3.Metellus, Philippe,et al 2010 1.Metellus, Philippe,et al 2010 1.Ellingson BM,et al 2013 1.Sunwoo L,et al 2013 2.Ahn, Sung Soo,et al 2014 3.Ellingson BM,et al 2013 DTI 1.Tan, W L,et al 2014 1.Ahn, Sung Soo,et al 2014 DWI(ADC) 1.Sunwoo L,et al 2013 CBV MRS 1.Pope, W. B,et al 2012 DCE-MRI 1.Ahn, Sung Soo,et al 2014 PET SPECT Star markers and Common imaging 中国脑胶质瘤图谱计划 PTENMIB-1Ki-67OthersTypes T1/T2 1.Jamshidi N,et al 2012 2.Gevaert, Olivier,et al 2014 3.Fan, Xing,et al 2015 1.Naeini KM, et al 2013 FLAIR 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 2012 CBV 1.Zikou, A. K.,et al 2012 MRS 1.Yu TG,et al 2015 DCE-MRI PET SPECT Star markers and Common imaging 中国脑胶质瘤图谱计划 MGMT 1、水肿很少出现甚至不会出现在甲基化的肿瘤周围4 。 2、MGMT状态需要纹理特征分析才能够建立与MRI特征的联系8、9 。 3、MGMT与ADC呈正相关，ADC与PFS呈正相关10。 4、MGMT甲基化的肿瘤容易出现在左侧颞叶，而MGMT非甲基化的 肿瘤更倾向于长在右侧半球3 。 5、MGMT非甲基化和EGFR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10 。 6、非甲基化的MGMT肿瘤在T1增强和T2/FLAIR像上比MGMT甲基化 的肿瘤强化面积大3 。 中国脑胶质瘤图谱计划 Probabilistic Radiographic Atlas of Glioblastoma Phenotypes B.M. Ellingson. et al, AJNR,2013 MGMT promoter methylated tumors occur more frequently in the left temporal lobe 中国脑胶质瘤图谱计划 t-value Prediction of methylguanine methyltransferase promoter methylation in glioblastoma using dynamic contrast-enhanced magnetic resonance and diffusion tensor imaging SungSoo Ahn. et al, J Neurosurg ,2014 DCE-MRI permeability parameters: Ktrans may serve as a potential imaging biomarker to predict MGMT methylation status in glioblastoma. 中国脑胶质瘤图谱计划 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 MGMT Un-methylated MGMT T1WADC The mean ADC revealed a positive relationship with MGMT promoter methylation ratio Leonard Sunwoo et al, Journal MRI ,2012 中国脑胶质瘤图谱计划 IDH1 1、IDH1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、用标准的MRI特征就可预测IDH1的表达状态4。 3、在DTI相中，利用部分异向分数和ADC可以在星形细胞胶质瘤 中监测IDH1 R132H的突变情况5。 4、随着年龄上升，IDH1突变减少，肿瘤更容易长在岛叶并且 1p/19q均表现为阴性6。 中国脑胶质瘤图谱计划 Relationship between Tumor Enhancement,Edema,IDH1 Mutational Status,MGMTPromoter Methylation, and Survival in Glioblastoma All IDH1 mutant tumors were non-contrast enhancing tumor positive, and most were located in the frontal lobe. J.A. Carrillo et al, AJNR ,2012 中国脑胶质瘤图谱计划 Detecting Isocitrate Dehydrogenase Gene Mutations in Oligodendroglial Tumors Using Diffusion Tensor Imaging Metrics and Their Correlations With Proliferation and Microvascular Density FAADC IDH1(-) IDH1(+) Ji Xiong et al, Journal MRI ,2015 This study demonstrated that the MaxFA and MinADC are useful DTI parameters for differentiating Oligodendroglial Tumors with and without IDH mutations. 中国脑胶质瘤图谱计划 Can Diffusion Tensor Imaging Noninvasively Detect IDH1 Gene Mutations in Astrogliomas? A Retrospective Study of 112 Cases This study demonstrates that DTI metrics have potential ability to distinguish astrogliomas with IDH1 mutation from those without mutation. FAADC IDH1(-) IDH1(+) W.L. Tan et al, AJNR ,2014 中国脑胶质瘤图谱计划 Non-invasive detection of 2-hydroxyglutarate and other metabolites in IDH1 mutant glioma patients using magnetic resonance spectroscopy Water-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-type Whitney et al, J Neurooncol ,2013 中国脑胶质瘤图谱计划 EGFR 1、EGFR扩增和EGFR-突变的GBM普遍出现在左颞极延伸到左岛 叶区域3 。 2、EGFR过表达的GBM对比增强体积更大10 但与PTEN，10号染色 体单倍体或多倍体的GBM相比并没有明显的差异3 。 3、EGFR通过表达EGFR-促进胶质母细胞瘤微血管形成。目前的 研究只停留在通过顺磁性氧化铁合成的EGFR共轭体检测EGFR受体 水平和通过diTyr-GdDTPA观察EGFR的表达水平11、12 。 中国脑胶质瘤图谱计划 Probabilistic Radiographic Atlas of Glioblastoma Phenotypes Ellingson et al, AJNR , 2013 EGFR amplified and EGFR variant 3- expressing tumors occurred most frequently in the left temporal lobe. 中国脑胶质瘤图谱计划 Targeted signal amplifying enzymes enhance magnetic resonance imaging of EGFR expression in an orthotopic model of human glioma 3T MR can reveale EGFR expression through diTyr-GdDTPA Mohammed et al, Cancer Res, 2012 中国脑胶质瘤图谱计划 1p/19q 1p/19q缺失的间变性少突胶质细胞瘤在T1/T2上表现为边缘 不规则，不均匀强化，呈浸润状态的异缘信号7，7。 中国脑胶质瘤图谱计划 Lower apparent diffusion coefficients indicate distinct prognosis in low-grade and high-grade glioma A threshold mean ADC value could predict the 1p/19q codeletion and identify low-risk LGGs. J W Kim et al, J Neurol Neurosurg Psychiatry, 2011 中国脑胶质瘤图谱计划 Prediction of oligodendroglial histology and LOH 1p/19q using dynamic 18FFET-PET imaging in intracranial WHO grade II and IIIgliomas PET: FET-uptake was signifi cantly higher in gliomas with 1p/19q codeleted, compared with noncodeleted. LOH 1p/19q Non-LOH 1p/19q Nathalie L et al, Neuro-oncology, 2012 中国脑胶质瘤图谱计划 Relationship between radiological characteristics and combined 1p and 19q deletion in World Health Organization grade III oligodendroglial tumours J W Kim et al, J Neurol Neurosurg Psychiatry, 2011 Significant relationships between the 1p19q codeletion and magnetic resonance image characteristics in oligodendroglial tumours such as frontal location, an indistinct tumour border. 1p19q codeletion Intact 1p19q 中国脑胶质瘤图谱计划 Ki-67 用Seedlink方法可以成功找到Ki-67的热点16 。 中国脑胶质瘤图谱计划 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 Grading Significant correlations were observed between the Ki-67 index and the mean, maximum, and minimum ADC, Cho/Cr, and lactate/Cr ratios. IIIV H. Fudaba et al, AJNR, 2014 中国脑胶质瘤图谱计划 Correlation of diffusion tensor, dynamic susceptibility contrast MRI and 99mTc-Tetrofosmin brain SPECT with tumour grade and Ki-67 immunohistochemistry in glioma This study showed that the fi ndings on perfusion MRI and brain SPECT with99mTc-Tetrofosmin were most closely correlated with Ki-67 index. Ki-67 2% Ki-67 30% George A et al, Clinical Neurology and Neurosurgery, 2014 中国脑胶质瘤图谱计划 Fractional anisotropy and tumor cell density of the tumor core show positive correlation in diffusion tensor magnetic resonance imaging of malignant brain tumors DTI(FA and MD) show positive correlation with Ki-67 labeling index Manabu Kinoshita et al, NeuroImage, 2008 中国脑胶质瘤图谱计划 Diffusion tensor and dynamic susceptibility contrast MRI in glioblastoma A signifi cant correlation was observed between Ki -67 index and ADC, FA ratio, rCBV and rMTT. Anastasia K et al, Clinical Neurology and Neurosurgery, 2012 中国脑胶质瘤图谱计划 Amide proton transfer imaging of adult diffuse gliomas: correlationwith histopathological grades Togao O et al, Neuro Oncol, 2013 There were positive correlations between Amide proton transfer (APT) signal intensity (SI) and Ki-67 LI (P.01,R0.43). 中国脑胶质瘤图谱计划 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, 2015 PET/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-FLT 中国脑胶质瘤图谱计划 P53 1、P53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13 。 2、P53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14 。 3、胶质瘤的MRI纹理特征与MIB-1和P53有直接的关系，现在已经 能够找到检测MIB-1的方法，但是对P53现在还没有有效的检测手 段15 。 注：1、2均使用Voxel-based neuroimaging analysis 中国脑胶质瘤图谱计划 Mapping p53 Mutations in Low-Grade Glioma: A Voxel- Based Neuroimaging Analysis Wang Y et al, AJNR, 2015 Using quantitative neuroimaging analyses find there is a correlation between tumor location and p53 status. 中国脑胶质瘤图谱计划 Towards MIB-1 and p53 detection in glioma magnetic resonance image: a novel computational image analysis method Chenbin Liu et al, Phys. Med. Biol, 2012 This study proposes a novel method to detect the expression status of MIB-1 and p53 non- invasively 中国脑胶质瘤图谱计划 Correlation of L-methyl-11C-methionine (MET) uptake with L-type amino acid transporter 1 in human PET/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 中国脑胶质瘤图谱计划 展望 1、目前对于胶质瘤等级、胶质瘤生长位置与影像学，分子遗传 学关系的研究比较完善。但对PTEN，TERT这两个“明星”基因的 相关报道较少。已经报道的“明星”基因也需要进行实验验证。 2、对于胶质瘤边界与基因的关系尚不明确。目前的影像学手段 不能准确地描绘胶质瘤边界。 3、对于肿瘤形状，影像学征象（坏死，水肿等）与基因之间相 关性的研究出于初级阶段，可进行相应尝试。 4、目前的研究已经涉及用影像学方法区分间叶型的GBM，但对其 他亚型的区分方法尚不可知。 5、对MRS的应用现在只停留在LAC, CHO, Cr，NAA，TMA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。 中国脑胶质瘤图谱计划 参考文献 1、Phillips HS, Kharbanda S, Chen R, et al. Molecular subclasses of high-grade glioma predict prognosis, delineate a pattern of disease progression, and resemble stages in neurogenesis. Cancer cell. 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