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: 8536405
• 负责人: PONNADA A NARAYANA
• 金额: $ 32.09万
• 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/8536405
• 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)

描述（由申请人提供）：炎症性病变与萎缩（全球，组织特异性和区域性）之间的关系被认为代表多发性硬化症（MS）中的神经变性（MS）对于理解这种疾病的发病机理至关重要。我们假设病变的活性和空间位置驱动了MS中随后的萎缩。该假设将通过分析在Combirx队列上获取的MRI数据来验证。 Combirx是一项多中心，双盲临床试验，有1008名参与者。患者的最低时间为3年，所有患者遵循所有患者，直到最后一名患者于2012年1月完成，最多可进行6.5年的随访 在某些患者上。该队列的MRI数据是通过严格的MRI协议获得的，并且治疗分配保持恒定。该提案的五个具体目的是：1）自动鉴定T2-hyperintense，T1-高位和GD增强病变及其空间位置，2）确定皮质稀疏是皮质病理学的量度，3）评估病理学评估病理学。在正常出现的脑组织中，基于T2值，使用双回声图像以逐素为基础确定，4）确定整个大脑，组织特异性和区域萎缩，5）确定病变活性和病变的效果它们在区域萎缩上的空间位置，并检查MRI测量的作用是该疾病的生物标志物/预测因子。图像分割将使用多光谱分割与基于ATLAS的技术结合进行。 T2-Hyperintense和T1-Hypointense病变的活性将通过在差异非线性非线性图像注册后在不同时间点获得的图像来确定。区域萎缩将使用基于张量的形态法测定。病变位置与区域萎缩之间的连通性的影响将使用白质图集进行研究。最后，复合MRI测量将与EDS（扩展的残疾状态量表）和MSFC（MS功能量表）及其各个组件相关。包括空间信息在内的该策略应允许鉴定疾病的强大生物标志物/预测因子。基于较大且临床表征良好的队列的分析随后在相对较长的时间内了解炎症与神经变性之间的关系是该建议的独特特征。缩写：中枢神经系统（中枢神经系统）； DGM（深灰质结构）； dir（双重反转恢复）； DSI（骰子相似性指数）； DTI（扩散张量成像）； EDSS（扩展残疾状态量表）；敌人（专家领域）； GM（灰质）； ICBM（国际脑图联盟）； MNI（蒙特利尔神经研究所）； MRF（马尔可夫随机场）； MRI（磁共振成像）； MRIAP（MRI自动化处理）； MRS（磁共振光谱）； MS（多发性硬化症）； MSFC（MS功能复合材料）; MTR（磁化转移比）； NABT（正常出现的脑组织）； nawm（正常出现的白质）； PD（质子密度）； RGM（区域总经理）； rrms（复发汇总MS）; RWM（区域白质）； Sienax（萎缩（X截面）的结构图像评估，包括归一化； SPM（统计参数映射）； TBM（基于张量的形态计）； toads（拓扑保存解剖分段）； VBM（VBM） ）