Quantitative MRI of the Human Peripheral Nervous System In Vivo

体内人体周围神经系统的定量 MRI

基本信息

批准号：
8459416
负责人：
Richard Dortch
金额：
$ 15万
依托单位：
VANDERBILT UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-05-01 至 2017-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8459416
关键词：
Address Affect Amyotrophic Lateral Sclerosis Ankle Axon Biological Markers Biopsy Brain Charcot-Marie-Tooth Disease Chronic Inflammatory Demyelinating Polyneuropathy Clinical Clinical Trials Demyelinations Dependence Development Diabetic Neuropathies Diffusion Diffusion Magnetic Resonance Imaging Disease Distal Echo-Planar Imaging Fatty acid glycerol esters Genetic Goals Gold Hip region structure Human Image Imaging Techniques Impairment Knee Leg Length Magnetic Resonance Imaging Measurement Measures Methods Metric Multiple Sclerosis Muscular Atrophy Myelin Nature Nerve Neural Conduction Neuraxis Neuropathy Pathology Patients Peripheral Nerves Peripheral Nervous System Peripheral Nervous System Diseases Protocols documentation Protons Recovery Relative (related person)Reporting Reproducibility Research Resolution Sensory Skin Specificity Structure Structure of tibial nerve Time Tissues Validation Water axonal degeneration base disability disorder subtype drug discovery follow-up hereditary neuropathy imaging modality in vivo innovation meetings novel peroneal nerve programs sciatic nerve treatment response validation studies water diffusion

项目摘要

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).

描述（由申请人提供）：所提议研究的总体目标是开发和验证一套定量、多参数磁共振成像（MRI）技术，用于评估体内人类周围神经病变伴随的病理和功能变化。扩散的定量 MRI 指标（主要对轴突敏感）结构）、磁化转移（主要对髓磷脂敏感）和多指数 T2（主要对水室大小敏感）提供了有关大脑组织微观结构和病理变化的宝贵信息。然而，还没有研究应用这些方法来研究人类体内周围神经病变。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。我们建议通过一项创新技术开发计划来解决这些技术挑战，该计划将提供一组用于表征周围神经的多个 MRI 参数，这些参数反过来将被评估为神经病理学的潜在生物标志物。更具体地说，拟议的研究将侧重于开发和验证胫骨神经（从脚踝到膝盖）和坐骨神经（从膝盖到臀部）的稳健、临床可行、高分辨率、定量 MRI 方法（扩散、MT、MET2），以了解某些神经病的长度依赖性。作为初步应用，开发的方法将应用于腓骨肌萎缩症患者，这是一种进展缓慢的遗传性神经病，具有明确的遗传原因。临床上，CMT根据神经传导研究（NCS）分为CMT1（原发性脱髓鞘伴继发性轴突变性）和CMT2（原发性轴突变性）。我们的初步研究将评估定量 MRI 检测和区分 CMT 亚型之间病理的能力。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）变化的临床测量之间的相关性。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志物，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病（例如糖尿病神经病）以及影响中枢神经系统内髓磷脂和/或轴突的疾病（例如多发性硬化症）具有更广泛的影响。