Grey Matter of Lesions and Neurodegeration in Multiple Sclerosis on 7-Telsa MRI

描述(申请人提供)：磁共振成像(MRI)是多发性硬化症(MS)患者护理中最重要的诊断和预后工具。然而，尽管技术有了许多进步，但目前的MRI技术并不能完全可视化导致MS患者残疾的所有病理因素。从尸检研究中早就知道，MS患者的大脑灰质受损，白质轴突退化，这两种情况都不能通过标准的MRI有效地成像。在这项提案中，候选人旨在证明使用7-特斯拉(7T)MRI的新成像技术能够对灰质病变和退行性白质病理进行成像，以这种方式量化病理疾病负担有助于解释MS的认知和身体残疾。7T MRI的磁强度增加使分辨率比传统MRI显著提高。分辨率的提高不仅提高了对微小结构的可视化能力，而且由于成像“噪声”的减少，还允许改进病理的定量测量。这种“噪音”可能会导致结构之间以及脑和脊髓液之间的边界不清，从而导致错误的测量。研究对象将在基线和每年两年的时间里接受7T磁共振成像和身体和认知残疾测试。灰质病变负荷将被量化，病变亚型将被识别。白质中轴突的完整性将通过一种新技术--扩散张量光谱学(DTS)来量化。然后将评估这些成像结果与认知和身体残疾以及临床病程的联系。假设皮质损害负担将与认知和身体功能障碍密切相关，在进展性MS患者中将是最大的；此外，软膜下皮质损害(一种皮质损害亚型)，在较低的视野强度下很难显示，被假设为易于显示，在进展性MS中将是最大的。最后，假设DTS对神经元N-乙酰天冬氨酸氨基转移酶的扩散特性进行量化将与残疾和进展性临床病程相关。应聘者期望 这项研究将建立DTS和高场强皮质损伤分析的临床相关性，这种技术可能被用于筛选当前和未来的药物，以了解它们预防灰质损伤和轴突退化的能力，从而防止困扰许多MS患者的认知和身体残疾。候选人的职业目标是继续进行这种性质的研究，提高神经成像显示皮质和神经退行性病变的能力，并推动治疗学的发展。在学习导师的监督和与学习团队的合作下，候选人将获得必要的技能，不仅完成这个项目，而且开始 独立调查员的职业生涯。

DESCRIPTION (provided by applicant): Magnetic resonance imaging (MRI) is the most important diagnostic and prognostic tool used in the care of patients with multiple sclerosis (MS). Despite many advances in technology, however, current MRI techniques are not able to fully visualize all elements of pathology contributing to disability in MS patients. It has long ben known from autopsy studies that the brains of MS patients have lesions in the grey matter and degradation of axons in the white matter, neither of which can be effectively imaged by standard MRI. In this proposal, the candidate aims to demonstrate that novel imaging techniques using 7-Tesla (7T) MRI are capable of imaging grey matter lesions and degenerative white matter pathology, and that quantification of pathologic disease burden in this manner helps to explain cognitive and physical disability in MS. The increased magnet strength of 7T MRI allows for remarkable improvements in resolution over conventional MRI. The increased resolution not only improves the ability to visualize small structures, but also allows for improvement in quantitative measurements of pathology due to the reduction in imaging "noise". Such "noise" can contribute to unclear boundaries between structures and between brain and spinal fluid, thus leading to false measurements. Study subjects will undergo 7T MRIs and physical and cognitive disability testing at baseline and yearly for two years. Grey matter lesion burden will b quantified and lesion subtypes will be identified. The integrity of axons in the white matter will e quantified by a new technology; diffusion tensor spectroscopy (DTS). These imaging findings will then be evaluated for their links with cognitive and physical disability and clinical disease course. It is hypothesized that cortical lesion burden will be strongly correlated with cognitive and physical disability, and will be greatest in patients with progressive MS. Also, subpial cortical lesions (a cortical lesion subtype), which are highly difficult to visualize at lower fiel strengths, are hypothesized to be readily visualized and will be greatest in progressive MS. Lastly, it is hypothesized that quantification of diffusion properties of neuronal n-acetyl aspartae by DTS will correlate with disability and a progressive clinical course. The candidate anticipates that the study will establish the clinical relevance of DTS and high field cortical lesion analysis Such techniques might potentially be used to screen current and future pharmaceutical agents for their ability to prevent grey matter lesions and degeneration of axons, and thus prevent the cognitive and physical disability that plagues many patients with MS. The candidate's career goal is to continue to perform studies of this nature, improving the ability of neuroimaging to visualize cortical and neurodegenerative pathology and drive forward developments in therapeutics. With the supervision of the study mentors and collaboration with the study team, the candidate will obtain the skills necessary to not only complete this project, but also to begin a career as an independent investigator.