Anatomical Distribution of Pathology in MS

描述(由申请人提供)： 本研究旨在探讨脑血流灌注在多发性硬化症(MS)病变负担和疾病进展中的作用。脑部血流良好的区域是否更有可能从炎症和/或脱髓鞘活动中恢复？这种倾向是否会转化为病变持续存在的解剖学盛行？多发性硬化症(MS)患者的临床病程、预后和治疗反应是高度可变和难以预测的。临床亚型复发缓解(RR)和继发性进展型(SP)分别被认为是MS病程的早期和晚期。然而，这些阶段的进展和它们之间的转化在个体之间可能会有很大的差异，而且病理差异的特征很差。我们假设，持续的组织损伤是由于解剖和生理敏感区域的病变发展所致，在这些区域，环境限制或禁止正常的修复过程(例如，炎症的消退、髓鞘的再生)。我们将专门测试大脑中血流良好的区域是否更有可能从多发性硬化症的损害中恢复，从而在疾病进展过程中减少持续性损害。为此，我们将比较早期(RR)和晚期(SP)MS患者病变的空间分布，并将这两组患者的病变分布特征作为正常脑血流灌注的函数。拟议的工作将在一大批MS患者按临床亚型分层(n=1,607 RR，n=495 SP)的回顾数据集上进行。该项目将提供有关MS早期和晚期白质病变的空间特异性以及这些分布如何与正常的健康血流模式相关的重要信息。

DESCRIPTION (provided by applicant): This research proposal aims to investigate the role of cerebral perfusion in the development of lesion burden and disease progression in multiple sclerosis (MS). Are well perfused regions of the brain are more likely to recover from inflammatory and/or demyelinating activity? Would such propensity translate into an anatomical prevalence of lesion persistence? The clinical disease course, prognosis, and response to treatment in patients with multiple sclerosis (MS) are highly variable and difficult to predict. The clinical subtypes of relapsing-remitting (RR) and secondary progressive (SP) are considered the early and late phases respectively of the MS disease course. Yet progression within these phases and conversion between them can vary greatly among individuals, and the pathological differences are poorly characterized. We hypothesize that sustained tissue damage results from lesion development in regions of anatomical and physiological susceptibility in which the environment is restrictive or prohibitive to normal reparative processes (e.g. resolution of inflammation, remyelination). We will specifically test if well perfused regions of the brain are more likely to recover from MS damage and therefore result in fewer persistent lesions over the course of disease progression. To this end, we will compare the spatial distribution of lesions in early (RR) and late (SP) MS patients and characterize lesion distribution in these two groups as a function of normal cerebral perfusion. The proposed work will be carried out on a retrospective dataset of a large cohort of MS patients stratified by clinical subtype (n = 1,607 RR, n = 495 SP). This project will provide important information regarding the spatial specificity of white matter lesions in the early and late stages of MS and how these distributions relate to the normal pattern of healthy perfusion.