Multiple Sclerosis Lesion Magnetic Susceptibility Activity

 描述(申请人提供)：该项目的长期目标是提高监测多发性硬化症(MS)炎症和神经变性过程的能力，以便有效地诊断和治疗。这项研究的具体目标是建立病变磁化率的时间进程，作为与炎症过程相关的脱髓鞘和铁含量的灵敏探针。目前，常规磁共振成像(MRI)中的Gd增强被广泛用于绘制MS病变形成过程中血脑屏障(BBB)破坏引起的炎症反应图。然而，在血脑屏障愈合后，大脑中仍然存在炎症，目前临床上还没有方法检测出血脑屏障背后的这种炎症。我们的初步数据表明，用定量磁化率图(QSM)测量的病变磁化率的时间进程可以检测到Gd增强后的病变活动性。因此，这项拟议的研究将试图通过三个具体目标来确定MS病变易感性的存在并对其时间过程有一个基本的了解：目的1：提高QSM扫描的稳健性和处理精度，以可靠地纵向测量易感性时间过程。我们假设QSM可以改进到高重复性和0.01ppm(百万分之几，敏感度单位)的精度。目的：通过前瞻性纵向研究各年龄段MS病变的磁化率，并结合常规MRI测量的Gd增强的时空相关性，确定MS病变的磁化率时程。我们假设病变易感性随着时间的推移而动态变化，即使在常规MRI测量的炎症活动消退之后也是如此。目的：利用MS患者和对照组的尸检脑组织标本，确定MS病变磁易感性的免疫组织化学相关性。我们假设MS病变的QSM信号部分与小胶质细胞/巨噬细胞的激活(即炎症活动)相关，完全脱髓鞘病变的QSM值由铁决定。

 DESCRIPTION (provided by applicant): The long term objective of this project is to improve the capability to monitor the inflammatory and neurodegenerative processes in Multiple Sclerosis (MS) for effective diagnosis and treatment. The specific goal of this research is to establish the time course of magnetic susceptibility of lesions as a sensitive probe of demyelination and iron content associated with inflammatory processes. Currently, gadolinium enhancement in conventional magnetic resonance imaging (MRI) is widely used to map inflammation caused by blood brain barrier (BBB) disruption during MS lesion formation. However, there is still inflammation in the brain after the BBB heals and currently there is no method in clinical practice to detect this inflammation behind the BBB. Our preliminary data demonstrates that the time course of lesion magnetic susceptibility as measured by quantitative susceptibility mapping (QSM) can detect lesion activity after the resolution of gadolinium enhancement. Accordingly, this proposed research will try to establish the existence of and gain a basic understanding of the time course of MS lesion susceptibility by carrying out three specific aims: Aim 1: Improve QSM scanning robustness and processing accuracy for reliable longitudinal measurement of susceptibility time course. We hypothesize that QSM can be improved to high reproducibility and accuracy of 0.01ppm (parts per million, susceptibility unit). Aim 2: Define the MS lesion magnetic susceptibility time course through prospective longitudinal study of the susceptibility of lesions at all ages, with spatiotemporal correlation of gadolinium enhancement measured by conventional MRI. We hypothesize that lesion susceptibility changes dynamically over time, even after inflammatory activity, as measured by conventional MRI, has subsided. Aim 3: Define the immunohistochemical correlates of MS lesion magnetic susceptibility using autopsied brain specimens from MS patients and controls. We hypothesize that the QSM signal of an MS lesion correlates in part with microglia/macrophages activation (i.e. inflammatory activity) and that the QSM value of a fully demyelinated lesion is determined by iron.