Anatomical Distribution of Pathology in MS

本研究旨在探讨脑灌注在病变负荷发展中的作用， 多发性硬化症（MS）的疾病进展。大脑中灌注良好的区域更容易从 炎症和/或脱髓鞘活性？这种倾向是否会转化为病变的解剖学患病率 坚持？多发性硬化（MS）患者的临床病程、预后和治疗反应 变化很大，很难预测复发缓解型（RR）和继发性进展型（PD）的临床亚型 (SP)分别被认为是MS病程的早期和晚期。然而，在这些发展中， 阶段和它们之间的转换可以在个体之间有很大差异，并且病理差异很小。 表征了我们假设持续的组织损伤是由解剖学上的区域病变发展引起的。 以及生理易感性，其中环境对正常修复过程具有限制性或抑制性（例如， 炎症消退、髓鞘再生）。我们将专门测试大脑中灌注良好的区域是否更有可能 从MS损伤中恢复，因此在疾病进展过程中导致更少的持续性病变。到 为此，我们将比较早期（RR）和晚期（SP）MS患者病变的空间分布， 这两组中的病变分布作为正常脑灌注的函数。将开展拟议的工作 根据临床亚型分层的MS患者大型队列的回顾性数据集（n = 1，607 RR，n = 495 SP）。这 该项目将提供有关白色病变的早期和晚期空间特异性的重要信息， MS的阶段以及这些分布如何与健康灌注的正常模式相关。

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.