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: 8506978
• 负责人: BRUCE M. DAMON
• 金额: $ 31.68万
• 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 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8506978
• 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.

描述(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、虚弱和疼痛的自身免疫性疾病。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很好地相关；患者管理必须基于主观的临床结果。因此，这项研究的总体目标是开发和阐明一系列MRI测试的病理基础，这些测试将客观和定量地追踪IIM的特定方面。这些测试将包括典型的结构图像；使用Dixon成像量化肌肉内脂肪；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量化灌注；使用血氧水平依赖的MRI和31P磁共振波谱评估运动期间的代谢。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)对照组C57/BL6小鼠；2)过度表达水通道蛋白-4的小鼠，以增加膜通透性；3)小鼠注射Lambda-carageenan，引起水肿；以及4)两种情况下。然后，随着时间的推移，我们将用转基因诱导的PM形式来研究治疗和未治疗的小鼠。先进的多维图像分析方法将用于将所有MRI发现或部分MRI发现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)接受受控肌肉损伤的人类，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，以便将成像结果与患者对疾病严重程度的自我报告和临床结果相关联。总体而言，我们期望这些研究将为定量描述IIM的肌肉结构和功能提供新的工具和方法。这些工具将允许改进对个别患者的临床管理，并允许在群体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的工具。

项目成果

Quantitative effects of inclusion of fat on muscle diffusion tensor MRI measurements.

• DOI: 10.1002/jmri.24045
• 发表时间: 2013-11
• 期刊: JOURNAL OF MAGNETIC RESONANCE IMAGING
• 影响因子: 4.4
• 作者: Williams, Sarah E.;Heemskerk, Anneriet M.;Welch, E. Brian;Li, Ke;Damon, Bruce M.;Park, Jane H.
• 通讯作者: Park, Jane H.