Quantitative MRI of the Human Peripheral Nervous System In Vivo

体内人体周围神经系统的定量 MRI

• 批准号: 8300622
• 负责人: Richard Dortch
• 金额: $ 15万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 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/8300622
• 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

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). PUBLIC HEALTH RELEVANCE: The overall goal of this research is to develop and validate quantitative magnetic resonance imaging (MRI) techniques to assess diseases that affect the peripheral nervous system, or peripheral neuropathies. To date, no studies have applied quantitative MRI to study peripheral neuropathies in humans in vivo because of the technical challenges associated with imaging peripheral nerves. We propose to address these technical challenges with a program of innovative, technical developments that will provide a set of MRI parameters for characterizing peripheral nerves, which will in turn be evaluated as potential biomarkers of nerve pathology in neuropathy patients.

描述（由申请人提供）：提出的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，用于评估体内人类周围神经病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Expenential T2（主要对水室尺寸敏感）提供了有关组织微观结构和大脑病理变化的宝贵信息。但是，没有研究将这些方法应用于体内人类的周围神经病。这可以归因于与周围神经的MRI相关的技术挑战，包括需要更高的空间分辨率，缺乏对标准解剖图像的对比以及周围脂肪的影响。我们建议通过一项创新的技术发展计划来应对这些技术挑战，该计划将提供一组多个MRI参数，以表征外周神经，而外围神经又将被评估为神经病理学的潜在生物标志物。更具体地说，提出的研究将侧重于胫骨（从脚踝到膝盖）和坐骨神经（从膝盖到嘻哈）的鲁棒，可行，高分辨率，定量MRI方法（扩散，MT，MET2）的发展和验证访问某些神经病的长度依赖性。作为最初的应用，开发的方法将应用于Charcot-Marie-Tooth疾病的患者，这是一组具有明确定义的遗传原因的遗传性神经病组。在临床上，CMT根据神经传导研究（NCS）分为CMT1（具​​有继发轴突变性的一级脱髓鞘）和CMT2（初级轴突变性）。我们的最初研究将评估定量MRI检测和区分CMT亚型中病理的能力。为了进行验证，还将确定CMT患者中病理学（NCS，皮肤活检）报告（NCS，皮肤活检）和功能性（神经病障碍评分）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志物，以在临床试验和药物发现中使用。此外，所开发的方法可能对许多其他外周神经病（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（例如多发性硬化症）的疾病具有更大的影响。 公共卫生相关性：这项研究的总体目标是开发和验证定量磁共振成像（MRI）技术，以评估影响周围神经系统或周围神经病的疾病。迄今为止，由于与成像周围神经相关的技术挑战，还没有研究定量MRI来研究人体的周围神经病。我们建议通过一项创新的，技术发展的计划来应对这些技术挑战，该计划将提供一组MRI参数，以表征周围神经，而神经病患者中神经病理学的潜在生物标志物将被评估为神经病患者的潜在生物标志物。