Magnetic Properties of Normal Appearing Brain White Matter in Multiple Sclerosis

磁共振成像（MRI）对我们了解多发性硬化症（MS）的脑部病理有重要贡献，然而传统的MRI往往不能解释患者的临床状况，这通常被称为临床-放射学悖论。一些组织学研究表明，其他正常的白质（NAWM）受到弥漫性炎症反应和小胶质细胞激活的影响。因此，人们对定量MRI技术寄予了极大的希望，如扩散张量成像或磁化转移成像。然而，事实证明，这些技术的敏感性和特异性不允许在个体水平上探测NAWM的这些变化。在本提案中，我们旨在利用定量敏感性制图（QSM）评估NAWM中MS相关的组织变化。QSM是近年来取得突破性进展的一种具有发展前景的MRI新技术。与仅提供基于松弛的图像对比度的传统MRI相比，QSM允许利用梯度回声MRI扫描的相位信息计算和绘制大脑的磁化率。有大量的证据表明，磁化率对MS的病理状况非常敏感，包括炎症、脱髓鞘和局灶性铁积累。我们希望NAWM中的QSM能够为MS病理提供更深入的了解，从而作为MS诊断和进展的新标志物。该国际合作项目将由格拉茨（奥地利）和耶拿（德国）合作开展。在三年的时间里，这两个中心将招募总共60名MS患者和60名健康对照者，并在基线和一年后使用完全相同的MR机器进行QSM。通过考虑结合池分数作为髓磷脂含量的标记，并通过确定磁化率的各向同性和各向异性成分，将对正常白质和NAWM的磁化率进行更详细的研究。在MS患者中，QSM的区域组织特征将与健康对照进行比较，并与临床和认知状况相关。我们期望格拉茨和耶拿在QSM、定量磁化转移和质谱研究方面提供的互补专业知识将有助于项目的成功。

Magnetic resonance imaging (MRI) has significantly contributed to our understanding of brain pathology in multiple sclerosis (MS), however conventional MRI often fails to explain the clinical condition of patients which is commonly known as the clinico-radiological paradox. Several histological studies have suggested that the otherwise normal appearing white matter (NAWM) is affected by a diffuse inflammatory response and microglial activation. Consequently, great hope had been put on quantitative MRI techniques such as diffusion tensor imaging or magnetization transfer imaging. However, it turned out that the sensitivity and specificity of these techniques do not allow to probe these changes in NAWM on an individual level.In this proposal, we aim at assessing MS related tissue changes in NAWM using quantitative susceptibility mapping (QSM). QSM is a new and promising MRI technique which has experienced a breakthrough in recent years. In contrast to conventional MRI, which provides relaxation based image contrast only, QSM allows to calculate and map the magnetic susceptibility of the brain utilizing the phase information from gradient echo MRI scans. There is a lot of evidence, that the magnetic susceptibility is highly sensitive to pathological conditions of MS including inflammation, demyelination, and focal accumulation of iron. We expect that QSM in NAWM could provide further insight into MS pathology and therefore could serve as a new marker for diagnosis and progression of MS.This international cooperation project will be conducted by Graz (Austria) and Jena (Germany) in a collaborative manner. Over a period of three years, both centers will recruit in total 60 MS patients and 60 healthy controls and will perform QSM at baseline and after one year using exactly the same MR machinery. The magnetic susceptibility in normal white matter and NAWM will be investigated in more detail by considering also the bound pool fraction as a marker of myelin content and by determining the isotropic and anisotropic components of the susceptibility. In the MS patients, regional tissue characterization by QSM will be compared to healthy controls and will be related to clinical and cognitive conditions. We expect that the complementary expertise that is provided by Graz and Jena with respect to QSM, quantitative magnetization transfer, and MS research will contribute to a successful project.