Multiparametric Classification of Muscle Damage in Inflammatory Myopathy

炎症性肌病肌肉损伤的多参数分类

• 批准号: 7908746
• 负责人: BRUCE M. DAMON
• 金额: $ 34.51万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-05 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7908746
• 关键词: 3-Dimensional; Activities of Daily Living; Adipose tissue; Age; Aldehyde-Lyases; Animal Model; Architecture; Atrophic; Autoimmune Diseases; Cell Membrane Permeability; Chronic; Chronic Disease; Classification; Clinical; Clinical Management; Cohort Studies; Complex; Control Animal; Controlled Study; Creatine Kinase; Deglutition; Deglutition Disorders; Dermatomyositis; Development; Diagnostic; Diffusion; Disease; Edema; Exercise; Fatty acid glycerol esters; Gender; Histology; Human; Idiopathic Inflammatory Myopathies; Image; Image Analysis; Inclusion Body Myositis; Individual; Infiltration; Inflammation; Intramuscular; Judgment; Laboratories; Laboratory Finding; Lactate Dehydrogenase; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Measures; Metabolic; Methods; Microscopic; Mus; Muscle; Muscle Fibers; Muscle function; Myopathy; Myositis; Neuromuscular Diseases; Pain; Pathologic Processes; Pathology; Patient Self-Report; Patients; Perfusion; Pharmaceutical Preparations; Physicians; Physiological; Polymyositis; Property; Quality of life; Recovery; Rehabilitation therapy; Research; Research Personnel; Serum; Severities; Severity of illness; Skeletal Muscle; Swelling; Techniques; Testing; Time; Translating; Variant; aquaporin 4; base; blood oxygen level dependent; experience; falls; human subject; imaging modality; improved; mouse model; muscle form; muscular structure; overexpression; public health relevance; reconstruction; response; tau Proteins; tool

DESCRIPTION (provided by applicant): The idiopathic inflammatory myopathies (IIM), including dermatomyositis (DM), polymyositis (PM), and inclusion body myositis (IBM), are autoimmune diseases resulting in muscle inflammation, weakness, and pain. Laboratory and imaging (MRI) studies are typically performed, but are not always well correlated with disease severity; patient management must be based on subjective clinical findings. Therefore, the overall objective of this study is to develop and elucidate the pathological basis of a battery of MRI tests that will objectively and quantitatively track specific aspects of IIM. These tests will include typical structural images; intramuscular adipose quantification using Dixon imaging; assessment of muscle quality and architecture using diffusion-tensor MRI; assessment of inflammation using short-tau inversion recovery; quantification of perfusion using dynamic-contrast enhanced MRI; metabolic assessments during exercise using blood oxygenation-level dependent MRI and 31P MR spectroscopy. In Aim 1, these tests will be applied to increasingly complex mouse models of IIM. First, we will study 1) control C57/Bl6 mice; 2) mice overexpressing aquaporin-4, to increase membrane permeability; 3) mice injected with lambda-carageenan, to cause edema; and 4) both conditions. Then, we will study treated and untreated mice with a transgenically induced form of PM, over time. Advanced, multi-dimensional image analysis approaches will be used to correlate all of or a subset of the MRI findings with quantitative histological measures of muscle damage. In Aim 2, the MRI tests will be applied to 1) humans undergoing controlled muscle damage and 2) DM, PM, and IBM patients and age- and gender- matched control subjects. Multidimensional image analysis approaches will be employed in order to correlate imaging findings with patient self-report of disease severity and clinical findings. Overall, we expect that these studies will provide new tools and approaches for quantitative characterization of muscle structure and function in IIM. These tools will allow for improved clinical management of individual patients and allow for characterization of responses to proposed treatments in group studies. Moreover, these studies will provide new tools for assessing muscle function i neuromuscular disorders more generally. PUBLIC HEALTH RELEVANCE: Inflammatory diseases of muscle cause pain, swelling, weakness, and reduced quality of life. Typical clinical tests do not always correspond to disease severity, however. In this study, we would like to develop new tools, based on non-invasive imaging methods, that will allow clinicians to describe muscle damage brought about inflammatory muscle disease in a more specific and quantitative fashion.

描述（由申请人提供）：特发性炎症性肌病（IIM），包括皮肌炎（DM），多聚肌炎（PM）和纳入体内肌炎（IBM），是自身免疫性疾病，导致肌肉炎症，弱点和疼痛。通常进行实验室和成像（MRI）研究，但并不总是与疾病严重程度相关。患者管理必须基于主观临床发现。因此，这项研究的总体目的是开发和阐明一系列MRI测试的病理基础，这些MRI测试将客观地和定量地跟踪IIM的特定方面。这些测试将包括典型的结构图像。使用Dixon成像肌内脂肪定量；使用扩散张量MRI评估肌肉质量和建筑；使用短TAU反演恢复评估炎症；使用动态对比度增强MRI来定量灌注；使用血液氧化级依赖性MRI和31p MR光谱法进行运动过程中的代谢评估。在AIM 1中，这些测试将应用于日益复杂的IIM小鼠模型。首先，我们将研究1）控制C57/BL6小鼠； 2）过表达水通道蛋白4的小鼠，以增加膜渗透性； 3）注射兰巴达 - 卡拉制嫩的小鼠引起水肿； 4）这两个条件。然后，随着时间的流逝，我们将以传递转基因诱导的PM形式研究和未经处理的小鼠。先进的多维图像分析方法将使用将MRI发现的全部或子集与肌肉损伤的定量组织学测量相关联。在AIM 2中，MRI测试将应用于1）受控肌肉损害的人和2）DM，PM和IBM患者以及年龄和性别匹配的对照组受试者。将采用多维图像分析方法，以将成像发现与疾病严重程度和临床发现的患者自我报告相关联。总体而言，我们预计这些研究将为IIM中肌肉结构和功能定量表征提供新的工具和方法。这些工具将允许改善各个患者的临床管理，并可以表征小组研究中对拟议治疗的反应。此外，这些研究将为评估肌肉功能I神经肌肉疾病提供新的工具。公共卫生相关性：肌肉的炎症性疾病会导致疼痛，肿胀，虚弱和生活质量降低。但是，典型的临床测试并不总是与疾病的严重程度相对应。在这项研究中，我们想以非侵入性成像方法开发新工具，这将使临床医生以更具体和定量的方式描述肌肉损害。