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: 8099655
• 负责人: BRUCE M. DAMON
• 金额: $ 33.31万
• 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/8099655
• 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; Health; 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; 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）、多发性肌炎（PM）和包涵体肌炎（IBM），是导致肌肉炎症、无力和疼痛的自身免疫性疾病。通常会进行实验室和影像 (MRI) 研究，但并不总是与疾病严重程度有很好的相关性；患者管理必须基于主观临床发现。因此，本研究的总体目标是开发和阐明一系列 MRI 测试的病理学基础，这些测试将客观、定量地跟踪 IIM 的具体方面。这些测试将包括典型的结构图像；使用 Dixon 成像进行肌内脂肪定量；使用扩散张量 MRI 评估肌肉质量和结构；使用短 tau 反转恢复评估炎症；使用动态对比增强 MRI 对灌注进行量化；使用血氧水平依赖性 MRI 和 31P MR 波谱进行运动期间的代谢评估。在目标 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) 对照 C57/Bl6 小鼠； 2）小鼠过表达aquaporin-4，以增加膜通透性； 3)小鼠注射λ-角叉菜胶，引起水肿； 4) 两个条件。然后，我们将随着时间的推移研究经过转基因诱导的 PM 形式的治疗和未治疗小鼠。先进的多维图像分析方法将用于将 MRI 结果的全部或子集与肌肉损伤的定量组织学测量相关联。在目标 2 中，MRI 测试将应用于 1) 遭受受控肌肉损伤的人类和 2) DM、PM 和 IBM 患者以及年龄和性别匹配的对照受试者。将采用多维图像分析方法，以便将成像结果与患者自我报告的疾病严重程度和临床结果相关联。总的来说，我们期望这些研究将为 IIM 中肌肉结构和功能的定量表征提供新的工具和方法。这些工具将允许改善个体患者的临床管理，并允许在小组研究中描述对拟议治疗的反应。此外，这些研究将为更广泛地评估神经肌肉疾病的肌肉功能提供新工具。公共卫生相关性：肌肉炎症性疾病会导致疼痛、肿胀、虚弱和生活质量下降。然而，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，我们希望开发基于非侵入性成像方法的新工具，使临床医生能够以更具体和定量的方式描述炎症性肌肉疾病引起的肌肉损伤。