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）是治疗多发性硬化症（MS）患者最重要的诊断和预后工具。尽管在技术上取得了许多进步，但是，目前的MRI技术不能完全可视化导致MS患者残疾的所有病理因素。从尸检研究中早已知道，MS患者的大脑在灰质中有病变，在白色物质中有轴突退化，这两者都不能通过标准MRI有效成像。 在本提案中，候选人旨在证明使用7特斯拉（7 T）MRI的新型成像技术能够对灰质病变和退行性白色病变进行成像，并且以这种方式量化病理疾病负担有助于解释MS中的认知和身体残疾。7 T MRI的磁强度增加使得分辨率优于传统MRI。提高的分辨率不仅提高了可视化小结构的能力，而且由于成像“噪声”的减少，还允许改善病理学的定量测量。这种“噪声”可能导致结构之间以及脑和脊髓液之间的边界不清晰，从而导致错误的测量。 研究受试者将在基线时和每年接受7 T MRI和身体和认知障碍测试，持续两年。将对灰质病变负荷进行B量化，并确定病变亚型。白色物质中轴突的完整性将通过一种新技术进行量化;扩散张量光谱（diffusion tensor spectroscopy，简称MRS）。然后将评估这些成像结果与认知和身体残疾以及临床疾病进程的联系。假设皮质损伤负荷与认知和身体残疾密切相关，并且在进行性MS患者中最大。（皮质病变亚型），其在较低场强度下非常难以可视化，被假设为容易可视化并且在进行性MS中最大。最后，假设通过ELISA定量神经元N-乙酰基辅酶A的扩散性质将与残疾和进行性临床过程相关。 候选人预计， 该研究将建立MRI和高场皮质病变分析的临床相关性。这些技术可能潜在地用于筛选当前和未来的药剂，以确定其预防灰质病变和轴突变性的能力，从而预防困扰许多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，提高神经成像的能力，使皮质和神经退行性病变可视化，并推动治疗学的发展。在研究导师的监督和与研究团队的合作下，候选人将获得不仅完成本项目，而且开始所需的技能 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.