Magnetic resonance imaging of human post-mortem tissues with a clinical diagnosis of multiple sclerosis using inhomogeneous magnetization transfer

项目总结/摘要 国家多发性硬化症（MS）协会估计，在美国有100万人患有MS。 States.磁共振成像在神经系统脱髓鞘病变诊断中的价值 根据McDonald标准指南，MS疾病是明显的。然而，MRI在MS诊断中的应用是 对来自中枢神经系统的图像的定性和分析通常是主观的。本申请是 致力于开发一种强大的定量MRI技术，称为非均匀 磁化转移（ihMT），用于将来在MS诊断中使用。ihMT MRI技术显示， 髓鞘敏感性，由于其部分依赖于偶极顺序，这是特别突出的独特的 构成髓磷脂的脂质双层结构。髓鞘的丢失是MS进展所固有的，并且许多 其他神经系统疾病。证明ihMT对MS中髓鞘变化的敏感性和特异性 不仅在检测方面，而且在监测进展和检测方面都将提供巨大的益处， 非侵入性治疗。事实上，ihMT MRI的初步研究表明， EDSS，残疾的衡量标准。然而，MS是一种复杂的疾病，不仅涉及脱髓鞘， 其他过程，如炎症，可能会混淆最先进的MRI技术。 我们相信定量的ihMT MRI，它可以提供多个定量参数的洞察力， 与大脑和脊髓的微观结构相关，将能够提供有关 以非侵入性方式研究潜在的MS病理学。确认MS提供的信息 定量ihMT需要与组织学进行比较，组织学仍然是金标准。我们的目标是提供 这种通过在有和没有临床病理检查的死后组织中应用定量ihMT的比较， 该研究将用于确定ihMT中的定量参数， 在MS存在下的变化，组织学将证实这些变化如何与微结构相关。 中枢神经系统组织为了证明定量ihMT MRI相对于其他MRI的益处， 方法，我们还计划将定量ihMT与其他最先进的MRI技术进行比较， 为了允许更高分辨率的MRI和更有信息量的比较， 组织学，大部分MRI实验将在高场扫描仪上进行。我们将确认， 通过验证在较高场强下收集的信息是否适用于临床3 T场强， 在两种场强下，ihMT定量参数的变化都是可证实的。 这项关于定量ihMT与 组织学将是非常宝贵的未来应用的定量ihMT MRI的非侵入性 评估患者的MS，以及指导其在其他神经系统疾病中的使用。

PROJECT SUMMARY/ABSTRACT The National Multiple Sclerosis (MS) Society estimates that 1 million people are living with MS in the United States. The importance of magnetic resonance imaging (MRI) in diagnosis of the demyelinating neurological disease MS is evident from the McDonald Criteria guidelines. However the use of MRI in diagnosis of MS is often qualitative and analysis of images from the central nervous system is subjective. This application is dedicated to development of a robust, quantitative MRI technique, known as inhomogeneous magnetization transfer (ihMT), for future use in MS diagnosis. The ihMT MRI technique demonstrates myelin sensitivity due to its partial dependency on dipolar order, which is particularly prominent in the unique lipid bilayer structure that makes up myelin. Loss of myelin is inherent to the progression of MS, and many other neurological disorders. Demonstration of ihMT's sensitivity and specificity to myelin changes in MS would provide untold benefit not only in detection, but also for monitoring progression and testing therapies non-invasively. Indeed, preliminary study of ihMT MRI demonstrates a significant correlation with EDSS, a measure of disability. However MS is a complex disease that not only involves demyelination, but other processes like inflammation, that may confound state-of-the-art MRI techniques. We believe quantitative ihMT MRI, which can provide insight into multiple quantitative parameters associated with the microstructure of the brain and spinal cord, will be able to provide information on the underlying MS pathology in a non-invasive manner. Confirmation of the information on MS provided by quantitative ihMT requires comparison with histology, which still represents a gold standard. We aim to provide such a comparison by application of quantitative ihMT in post-mortem tissues with and without a clinical diagnosis of MS. This proposed study would serve to determine the quantitative parameters in ihMT that change in the presence of MS, and histology would confirm how those changes relate to the microstructure of central nervous system tissue. In order to demonstrate the benefit of quantitative ihMT MRI over other methods, we also plan to compare quantitative ihMT with other state-of-the-art MRI techniques that have been applied in prior studies of MS. To allow higher resolution MRI and a more informative comparison with histology, the bulk of MRI experiments will be conducted on a high field scanner. We will confirm that the information collected at the higher field strength is applicable at clinical 3T field strength by verifying any changes in quantitative ihMT parameters are demonstrable at both field strengths. The information provided by this proposed study on the relationship between quantitative ihMT and histology would be invaluable to future application of quantitative ihMT MRI for non-invasive assessment of MS in patients, as well as guiding its use in other neurological disorders.