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: 8851691
• 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 2016-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8851691
• 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; cortex mapping; density; disability; follow-up; gray matter; image registration; imaging Segmentation; improved; indexing; individualized medicine; 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)

描述（由申请人提供）：炎症病变和萎缩（整体、组织特异性和区域）之间的关系被认为代表多发性硬化症（MS）中的神经变性，对于理解这种疾病的发病机制至关重要。我们假设病变的活动和空间位置驱动了多发性硬化症随后的萎缩。这一假设将通过分析 CombiRx 队列中获得的 MRI 数据得到验证。 CombiRx 是一项多中心、双盲临床试验，共有 1008 名患者入组。患者的随访时间至少为 3 年，所有患者均接受随访，直至最后一名患者于 2012 年 1 月完成随访，最多可随访 6.5 年 对一些患者来说。该队列的 MRI 数据是通过严格的 MRI 协议获得的，并且治疗分配保持不变。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) 确定皮质变薄，这是皮质病理学的度量，3) 根据使用双回波图像逐个体素确定的 T2 值评估正常脑组织的病理学，4) 确定整个大脑， 组织特异性和区域萎缩，5) 确定病变活动及其空间位置对区域萎缩的影响，并检查 MRI 测量作为疾病可能的生物标志物/预测因子的作用。图像分割将使用多光谱分割结合基于图集的技术来执行。 T2-高信号和T1-低信号病变的活动性将通过在微分同胚非线性图像配准后的不同时间点获取的图像相减来确定。将使用基于张量的形态测定法来确定区域萎缩。将使用白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，综合 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联。这种包含空间信息的策略应该能够识别疾病的稳健生物标志物/预测因子。该提案的一个独特之处在于，该分析基于一个大型且临床特征良好的队列，并在相对较长的时间内进行了跟踪，以了解炎症与神经退行性变之间的关系。缩写：CNS（中枢神经系统）； DGM（深层灰质结构）； DIR（双反转恢复）； DSI（Dice相似度指数）； DTI（扩散张量成像）； EDSS（扩展残疾状况量表）； FoE（专家领域）； GM（灰质）； ICBM（国际脑图谱联盟）； MNI（蒙特利尔神经病学研究所）； MRF（马尔可夫随机场）； MRI（磁共振成像）； MRIAP（MRI 自动处理）； MRS（磁共振波谱）； MS（多发性硬化症）； MSFC（MS功能复合材料）； MTR（磁化传输比）； NABT（正常脑组织）； NAWM（正常白质）； PD（质子密度）； RGM（区域总经理）； RRMS（复发缓解型多发性硬化症）； RWM（区域白质）； SIENAX（结构图像评估，包括标准化、萎缩（X 截面）；SPM（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（白质）