Magnetic Properties of Normal Appearing Brain White Matter in Multiple Sclerosis

磁共振成像(MRI)有助于我们了解多发性硬化症(MS)的脑病理，但常规MRI往往不能解释患者的临床情况，这就是通常所说的临床-放射学悖论。一些组织学研究表明，正常外观的白质(NAWM)受到弥漫性炎症反应和小胶质细胞激活的影响。因此，弥散张量成像或磁化传递成像等定量磁共振成像技术被寄予厚望。然而，这些技术的敏感性和特异性不允许在个体水平上探索NAWM的这些变化。在这项建议中，我们旨在使用定量易感图谱(QSM)来评估NAWM中与MS相关的组织变化。QSM是近年来取得突破性进展的一种新的、有发展前途的磁共振成像技术。与仅提供基于松弛的图像对比度的传统MRI不同，QSM允许利用来自梯度回波MRI扫描的相位信息来计算和绘制大脑的磁化率。有很多证据表明，磁化率对MS的病理条件高度敏感，包括炎症、脱髓鞘和铁局灶性堆积。我们期待NAWM中的QSM能够进一步深入了解MS的病理，从而成为MS诊断和进展的新标记物。这一国际合作项目将由奥地利的Graz和德国的耶拿共同开展。在三年的时间里，两个中心将招募总共60名多发性硬化症患者和60名健康对照，并将在基线和一年后使用完全相同的MR机器进行QSM。正常白质和NAWM的磁化率将通过考虑结合池分数作为髓鞘含量的标志，并通过确定磁化率的各向同性和各向异性分量来更详细地研究。在MS患者中，QSM的区域组织特征将与健康对照组进行比较，并将与临床和认知状况有关。我们期待Graz和Jena在QSM、定量磁化转移和MS研究方面提供的互补专业知识将有助于一个成功的项目。

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.