Herranz Elena, Giannì Costanza, Louapre Céline, Treaba Constantina A, Govindarajan Sindhuja T, Ouellette Russell, Loggia Marco L, Sloane Jacob A, Madigan Nancy, Izquierdo-Garcia David, Ward Noreen, Mangeat Gabriel, Granberg Tobias, Klawiter Eric C, Catana Ciprian, Hooker Jacob M, Taylor Norman, Ionete Carolina, Kinkel Revere P, Mainero Caterina
Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Boston, MA.
Harvard Medical School, Boston, MA.
Ann Neurol. 2016 Nov;80(5):776-790. doi: 10.1002/ana.24791. Epub 2016 Oct 25.
In multiple sclerosis (MS), using simultaneous magnetic resonance-positron emission tomography (MR-PET) imaging with C-PBR28, we quantified expression of the 18kDa translocator protein (TSPO), a marker of activated microglia/macrophages, in cortex, cortical lesions, deep gray matter (GM), white matter (WM) lesions, and normal-appearing WM (NAWM) to investigate the in vivo pathological and clinical relevance of neuroinflammation.
Fifteen secondary-progressive MS (SPMS) patients, 12 relapsing-remitting MS (RRMS) patients, and 14 matched healthy controls underwent C-PBR28 MR-PET. MS subjects underwent 7T T2*-weighted imaging for cortical lesion segmentation, and neurological and cognitive evaluation. C-PBR28 binding was measured using normalized 60- to 90-minute standardized uptake values and volume of distribution ratios.
Relative to controls, MS subjects exhibited abnormally high C-PBR28 binding across the brain, the greatest increases being in cortex and cortical lesions, thalamus, hippocampus, and NAWM. MS WM lesions showed relatively modest TSPO increases. With the exception of cortical lesions, where TSPO expression was similar, C-PBR28 uptake across the brain was greater in SPMS than in RRMS. In MS, increased C-PBR28 binding in cortex, deep GM, and NAWM correlated with neurological disability and impaired cognitive performance; cortical thinning correlated with increased thalamic TSPO levels.
In MS, neuroinflammation is present in the cortex, cortical lesions, deep GM, and NAWM, is closely linked to poor clinical outcome, and is at least partly linked to neurodegeneration. Distinct inflammatory-mediated factors may underlie accumulation of cortical and WM lesions. Quantification of TSPO levels in MS could prove to be a sensitive tool for evaluating in vivo the inflammatory component of GM pathology, particularly in cortical lesions. Ann Neurol 2016;80:776-790.
在多发性硬化症（MS）中，我们使用¹¹C-PBR28同步磁共振-正电子发射断层扫描（MR-PET）成像技术，对18kDa转位蛋白（TSPO）的表达进行定量分析，TSPO是活化小胶质细胞/巨噬细胞的标志物，分析其在皮质、皮质病变、深部灰质（GM）、白质（WM）病变及正常外观白质（NAWM）中的表达情况，以研究神经炎症在体内的病理及临床相关性。
15例继发进展型MS（SPMS）患者、12例复发缓解型MS（RRMS）患者及14例匹配的健康对照者接受¹¹C-PBR28 MR-PET检查。MS患者接受7T T2*加权成像以进行皮质病变分割，并进行神经学和认知评估。使用标准化摄取值和分布容积比的归一化60至90分钟测量¹¹C-PBR28结合情况。
相对于对照组，MS患者全脑¹¹C-PBR28结合异常增高，增幅最大的部位是皮质、皮质病变、丘脑、海马及NAWM。MS的WM病变中TSPO增加相对较小。除皮质病变中TSPO表达相似外，SPMS患者全脑¹¹C-PBR28摄取高于RRMS患者。在MS中，皮质、深部GM及NAWM中¹¹C-PBR28结合增加与神经功能障碍及认知功能受损相关；皮质变薄与丘脑TSPO水平升高相关。
在MS中，神经炎症存在于皮质、皮质病变、深部GM及NAWM中，与不良临床结局密切相关，且至少部分与神经退行性变有关。不同的炎症介导因素可能是皮质和WM病变积累的基础。MS中TSPO水平的定量分析可能是体内评估GM病理学炎症成分的敏感工具，尤其是在皮质病变中。《神经病学纪要》2016年；80：776 - 790。
