Lesion Activity and Atrophy in Multiple Sclerosis: Analysis of Multi-center MRI

多发性硬化症的病变活动性和萎缩：多中心 MRI 分析

• 批准号: 8433698
• 负责人: PONNADA A NARAYANA
• 金额: $ 33.25万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2017-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8433698
• 关键词: Abbreviations; Anti-Inflammatory Agents; Anti-inflammatory; Appearance; Atlases; Atrophic; Biological Markers; Brain; Brain Mapping; Clinical; Clinical Trials; Computer software; Data; Data Analyses; Demyelinating Diseases; Development; Diffusion Magnetic Resonance Imaging; Disease; Distant; Double-Blind Method; Enhancing Lesion; Enrollment; Event; Fiber; Human; Image; Image Analysis; Individual; Inflammation; Inflammatory; Institutes; International; Lesion; Location; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Maps; Measures; Microscopic; Multiple Sclerosis; Nature; Nerve Degeneration; Neuraxis; Neurologic; Pathogenesis; Pathology; Patients; Play; Process; Progressive Disease; Protons; Publishing; Recovery; Relapsing-Remitting Multiple Sclerosis; Reporting; Resolution; Role; Structure; Techniques; Testing; Time; Tissues; Treatment Protocols; United States National Institutes of Health; Weight; base; brain tissue; cohort; density; disability; follow-up; gray matter; image registration; imaging Segmentation; improved; indexing; morphometry; tool; white matter

DESCRIPTION (provided by applicant): The relation between inflammatory lesions and atrophy (global, tissue-specific, and regional) that is thought to represent neurodegeneration in multiple sclerosis (MS) is of fundamental importance in understanding the pathogenesis of this disease. We hypothesize that the activity and spatial location of the lesions drive the subsequent atrophy in MS. This hypothesis will be verified by analyzing the MRI data acquired on the CombiRx cohort. CombiRx is a multi-center, double blinded clinical trial with 1008 enrolled patients. Patients are being followed over a minimum period of 3 years with all patients followed until the last patient completes in January 2012 allowing for up to 6.5 years of follow up on some patients. MRI data on this cohort is acquired with a rigorous MRI protocol and the treatment assignments have remained constant. The five specific aims of this proposal are: 1) automatic identification of T2-hyperintense, T1- hypointense, and Gd enhancing lesions and their spatial location, 2) determine the cortical thinning that is a measure of cortical pathology,3) assess the pathology in the normal appearing brain tissue based on the T2 values, determined on a voxel-by voxel basis using the dual echo images, 4) determine the whole brain, tissue specific, and regional atrophy, and 5) determine the effect of lesion activity and their spatial location on the regional atrophy and examine the role of MRI measures as possible biomarkers/predictors of the disease. The image segmentation will be performed using the multi- spectral segmentation in combination with the atlas-based techniques. Activity of both T2-hyperintense and T1- hypointense lesions will be determined by subtracting images acquired at different time points following diffeomorphic nonlinear image registration. Regional atrophy will be determined using the tensor based morphometry. The effect of connectivity between the lesion location and regional atrophy will be investigated using the white matter atlas. Finally composite MRI measures will be correlated with both EDSS (extended disability status scale) and MSFC (MS functional scale) and their individual components. This strategy that includes spatial information should allow identification of robust biomarkers/predictors of the disease. The analysis based on a large and clinically well characterized cohort followed over a relatively long period of time to understand the relationship between inflammation and neurodegeneration is a unique feature of this proposal. Abbreviations: CNS (central nervous system); DGM (deep gray matter structures); DIR (double inversion recovery); DSI (Dice similarity index); DTI (diffusion tensor imaging); EDSS (extended disability status scale); FoE (field of expert); GM (gray matter); ICBM (international consortium for brain mapping); MNI (Montreal Neurologic Institute); MRF (Markov random field); MRI (magnetic resonance imaging); MRIAP (MRI Automated Processing); MRS (magnetic resonance spectroscopy); MS (multiple sclerosis); MSFC (MS functional composite); MTR (magnetization transfer ratio); NABT (normal appearing brain tissue); NAWM (normal appearing white matter); PD (proton density); RGM (regional GM); RRMS (relapsing remitting MS); RWM (regional white matter); SIENAX (Structural Image Evaluation, including Normalization, of Atrophy (X-sectional); SPM (statistical parametric mapping); TBM (tensor based morphometry); TOADS (Topology preserving Anatomical Segmentation); VBM (voxel based morphometry); WM (white matter) PUBLIC HEALTH RELEVANCE: Multiple sclerosis (MS) is the most common demyelinating disease in humans and is characterized by focal inflammation and neurodegeneration. This application will investigate the relation between inflammation and neurodegeneration by analyzing the MRI data acquired longitudinally on a large cohort of clinically well characterized MS patients. Understanding this relation is expected to improve patient management by customizing treatment and conducting more efficient clinical trials.

描述（由申请人提供）：炎症性病变和萎缩（整体、组织特异性和区域性）之间的关系被认为代表多发性硬化（MS）中的神经变性，对于理解该疾病的发病机制至关重要。我们假设病变的活动性和空间位置驱动MS中随后的萎缩。该假设将通过分析CombiRx队列中获得的MRI数据进行验证。CombiRx是一项多中心、双盲临床试验，入组了1008例患者。对患者进行至少3年的随访，所有患者随访至2012年1月末例患者完成随访，随访时间长达6.5年 一些病人。该队列的MRI数据是通过严格的MRI方案获得的，治疗分配保持不变。该提案的五个具体目标是：1）自动识别T2高信号、T1低信号和Gd增强病变及其空间位置，2）确定作为皮质病理学测量的皮质变薄，3）基于T2值评估正常外观脑组织中的病理学，所述T2值使用双回波图像在逐个体素的基础上确定，4）确定全脑、组织特异性和区域性萎缩，和5）确定病变活动及其空间位置对区域性萎缩的影响，并检查MRI测量作为疾病的可能生物标志物/预测因子的作用。将使用多光谱分割结合基于图谱的技术进行图像分割。T2-高信号和T1-低信号病变的活动性将通过减去在非线性图像配准后不同时间点采集的图像来确定。将使用基于张量的形态测定法确定局部萎缩。将使用白色物质图谱研究病变位置和区域萎缩之间的连通性的影响。最后，复合MRI测量将与EDSS（扩展残疾状态量表）和MSFC（MS功能量表）及其各个组成部分相关。这种包括空间信息的策略应该允许识别疾病的稳健的生物标志物/预测因子。基于一个大型的临床特征良好的队列的分析，在相对较长的时间内进行，以了解炎症和神经退行性变之间的关系，这是该提案的独特之处。缩略语：CNS（中枢神经系统）（深灰质结构）;双反转恢复（Dice相似指数）扩散张量成像（扩展残疾状态量表）（专家领域）;全球机制（灰质）;洲际弹道导弹国际脑绘图协会蒙特利尔神经病学研究所（马尔可夫随机场）磁共振成像（MRI自动处理）（磁共振光谱学）多发性硬化（MS功能复合材料）磁化传递比（外观正常的脑组织）（正常出现的白色物质）（质子密度）（区域全球机制）;区域资源管理系统复发缓解型MS（区域白色物质）; SIENAX萎缩的结构影像评价，包括标准化（X-断层）（统计参数映射）; TBM（基于张量的形态测量）; TOADS（拓扑保留解剖分割）; VBM（基于体素的形态测量）; WM（白色物质） 公共卫生相关性：多发性硬化症（MS）是人类最常见的脱髓鞘疾病，其特征在于局灶性炎症和神经变性。本申请将通过分析在临床上充分表征的MS患者的大队列中纵向采集的MRI数据来研究炎症和神经退行性变之间的关系。了解这种关系有望通过定制治疗和进行更有效的临床试验来改善患者管理。