Quantitative MRI of the Human Peripheral Nervous System In Vivo

描述(申请人提供)：这项研究的总体目标是开发和验证一套定量的、多参数的磁共振成像(MRI)技术，用于评估活体内伴随人类周围神经病变的病理和功能变化。弥散的定量MRI指标(主要对轴突敏感 磁化传递(主要对髓鞘敏感)和多指数T2(主要对水室大小敏感)提供了有关脑组织微结构和病理变化的宝贵信息。然而，还没有研究将这些方法应用于人体周围神经疾病的活体研究。这可以归因于与周围神经MRI相关的技术挑战，包括需要更高的空间分辨率，标准解剖图像缺乏对比度，以及周围脂肪的影响。我们建议通过一个创新的技术开发计划来解决这些技术挑战，该计划将提供一套多个MRI参数来表征周围神经，这些参数将被评估为神经病理的潜在生物标记物。更具体地说，拟议的研究将侧重于开发和验证胫骨(从脚踝到膝盖)和坐骨神经(从膝盖到髋关节)的健壮、临床可行、高分辨率、定量MRI方法(弥散、MT、MET2)，以了解某些神经疾病的长度依赖性质。作为初步应用，开发的方法将应用于Charcot-Marie-Tooth病患者，这是一组进展缓慢的遗传性神经疾病，具有明确的遗传原因。临床上根据神经传导研究(NCS)将CMT分为CMT1(原发性脱髓鞘伴继发性轴索变性)和CMT2(原发性轴索变性)。我们的初步研究将评估定量MRI检测和区分CMT亚型及其之间的病理的能力。为了验证，还将确定MRI指标与报告CMT患者病理(NCS、皮肤活检)和功能(神经病变残疾评分)变化的临床指标之间的相关性。如果成功，这些研究可能会产生治疗反应和组织状态的生物标记物，用于临床试验和药物发现。此外，所开发的方法可能对许多其他周围神经疾病(例如，糖尿病神经病变)以及影响中枢神经系统内的髓鞘和/或轴突的疾病(例如，多发性硬化症)具有更广泛的影响。

DESCRIPTION (provided by applicant): The overall goal of the research proposed is to develop and validate a quantitative, multi-parametric set of magnetic resonance imaging (MRI) techniques for the assessment of pathological and functional changes accompanying human peripheral neuropathy in vivo. Quantitative MRI metrics of diffusion (primarily sensitive to axonal structure), magnetization transfer (primarily sensitive to myelin), and multiexponential T2 (primarily sensitive to water compartment sizes) have provided valuable information on tissue microstructure and pathological changes in the brain. However, no studies have applied these methods to study peripheral neuropathies in humans in vivo. This can be attributed to the technical challenges associated with MRI of peripheral nerves, including the need for higher spatial resolution, a lack of contrast on standard anatomical images, and the influence of surrounding fat. We propose to address these technical challenges with a program of innovative, technical developments that will provide a set of multiple MRI parameters for characterizing peripheral nerves that in turn will be evaluated as potential biomarkers of nerve pathology. More specifically, the research proposed would focus on development and validation of robust, clinically feasible, high-resolution, quantitative MRI methods (diffusion, MT, MET2) of tibial (from ankle to knee) and sciatic nerves (from knee to hip) to access the length dependent nature of certain neuropathies. As an initial application, the developed methods will be applied in patients with Charcot-Marie-Tooth disease, a slowly progressing group of inherited neuropathies with well-defined genetic causes. Clinically, CMT is divided on the basis of nerve conduction studies (NCS) into CMT1 (primary demyelination with secondary axonal degeneration) and CMT2 (primary axonal degeneration). Our initial studies will assess the ability of quantitative MRI to detect and distinguish pathology in and between CMT subtypes. For validation, correlations between MRI metrics and clinical measures that report of pathological (NCS, skin biopsy) and functional (neuropathy disability score) changes in CMT patients will also be determined. If successful, these studies may yield biomarkers of treatment responses and tissue status for use in clinical trials and drug discovery. Additionally, the developed methods may have broader implications in a number of other peripheral neuropathies (e.g., diabetic neuropathy) as well as in diseases that affect myelin and/or axons within the central nervous system (e.g., multiple sclerosis).