Discovery of Functionally Relevant Imaging Biomarkers in Multiple Sclerosis

描述（由申请人提供）：该提案侧重于磁共振成像（MRI）在多发性硬化症（MS）中的应用，多发性硬化症是一种中枢神经系统慢性疾病，是年轻人非创伤性神经功能障碍的最常见原因，并导致MRI扫描的显着异常。为了研究MS的进展，我将使用新的MRI技术，特别是弥散张量成像，来研究临床功能障碍-特别是视觉系统-与成像异常之间的联系。我的假设是，定量和功能相关的措施将大大提高我们随着时间的推移监测多发性硬化症的能力，因此将直接适用于常规患者护理，并作为新的多发性硬化症治疗临床试验的基于成像的生物标志物。要证明这一假设，需要从大量多发性硬化症患者中仔细获取一系列MRI和临床数据，同时开发新的成像序列，并对其结果进行创新分析。我将在约翰·霍普金斯大学（Johns Hopkins University）完成该奖项的指导部分，该大学为这项研究提供了一个特别丰富的环境。此外，我的背景使我非常适合执行这个建议：我在神经病学、诊断放射学和神经放射学方面的七年联合住院医师实习期即将结束；我完成了实验和定量系统神经生理学（包括动物实验）的博士学位；我的本科专业是数学和物理。结合临床、实验室和定量技能，我将开发新的成像方法，并将其完善为强大的工具，为在患者床边工作的临床医生提供关键信息。

DESCRIPTION (provided by applicant): This proposal focuses on magnetic resonance imaging (MRI) in multiple sclerosis (MS), a chronic disease of the central nervous system that is the most common cause of non-traumatic neurologic disability in young adults and that causes dramatic abnormalities on MRI scans. To study the progression of MS, I will use new MRI techniques, particularly diffusion tensor imaging, to study the links between clinical dysfunction - especially in the visual system - and imaging abnormalities. My hypothesis is that quantitative and functionally relevant measures will substantially improve our ability to monitor MS over time and will therefore be directly applicable to routine patient care and as imaging-based biomarkers for clinical trials of new MS therapies. Proving this hypothesis will require careful acquisition of serial MRI and clinical data from a large cohort of MS patients, together with development of new imaging sequences and innovative analysis of their results. Johns Hopkins University, where I will carry out the mentored portion of the award, offers a particularly rich environment for this research. In addition, my background ideally positions me to carry out this proposal: I am near the end of a seven-year combined residency-fellowship in neurology, diagnostic radiology, and neuroradiology; I completed a Ph.D. in experimental and quantitative systems neurophysiology (including animal experimentation); and I received my undergraduate education in mathematics and physics. With this combination of clinical, laboratory, and quantitative skills, I will develop new imaging methods and refine them into powerful tools to provide crucial information for clinicians working at the patient's bedside. Public Health Relevance: There is both an urgent need and a promising opportunity to develop automated, quantitative methods that are functionally relevant, that are straightforward to use in routine clinical practice, and that can sensitively assess disease progression in multiple sclerosis as well as response to therapy. The proposed research is directed toward this goal, investigating the links between imaging abnormalities and clinical disability, especially in the visual system, and identifying markers for use in clinical care and future drug trials.