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

描述（由申请人提供）：磁共振成像（MRI）是最重要的诊断和预后工具，用于治疗多发性硬化症（MS）患者。然而，尽管技术取得了许多进步，目前的MRI技术还不能完全可视化导致MS患者残疾的所有病理因素。从尸检研究中我们早就知道，多发性硬化症患者的大脑在灰质中有损伤，在白质中有轴突的退化，这两者都不能通过标准的MRI有效地成像。在该提案中，候选人旨在证明使用7-特斯拉（7T） MRI的新型成像技术能够成像灰质病变和退行性白质病理，并且以这种方式量化病理性疾病负担有助于解释ms的认知和身体残疾。7T MRI的磁铁强度增加使得分辨率比传统MRI有显着提高。增加的分辨率不仅提高了小结构可视化的能力，而且由于减少了成像“噪音”，也允许在病理定量测量的改进。这种“噪音”可能导致结构之间以及脑和脊髓液之间的界限不清，从而导致错误的测量。研究对象将在基线和每年接受7T核磁共振成像和身体和认知障碍测试，为期两年。将对灰质病变负荷进行量化，并确定病变亚型。一种新技术将量化脑白质中轴突的完整性；扩散张量光谱（DTS）。然后将评估这些影像学结果与认知和身体残疾以及临床病程的联系。假设皮质损伤负荷与认知和身体残疾密切相关，且在进展性ms患者中最大。此外，在较低场强下很难观察到的枕下皮质损伤（一种皮质损伤亚型）在进展性ms中更容易被观察到，且最大。假设DTS对神经元n-乙酰天冬氨酸扩散特性的量化与残疾和进展的临床过程有关。候选人预期

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.