Quantitative MR Imaging markers in Neuromuscular Diseases

神经肌肉疾病的定量 MR 成像标记

• 批准号: 446281479
• 负责人: Privatdozentin Dr. Lara Schlaffke
• 金额: --
• 依托单位: Neurologische Universitäts- und Poliklinik
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2020
• 资助国家: 德国
• 起止时间: 2019-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/446281479?language=en
• 关键词: Quantitative; MR; Imaging; markers; Neuromuscular

Worldwide incidence of inheritable muscle disease is about 1 in 2000 but diverse (> 800 variants for neuromuscular diseases) and manifest with symptoms such as muscle pain, muscle cramps, early fatigue and progressive weakness of the muscles. In severe cases, loss of ambulation, quadriplegia and a reduced life expectancy also occur. Due to microstructural changes in the muscle tissue, it is challenging to observe and quantify disease-depended changes with non-invasive methods. In the clinical routine different methods of which most of them are complimentary used to evaluate disease stage and progression. Muscle exercise testing for example is non-invasive, easily applicable, and repeatable. However, it is imprecise for subtle muscle changes and to some extent rater-dependent. Also very precise method in the clinical evaluation of muscular disease is histopathology. With this, you gain detailed information of muscle properties on a cellular level and e.g. observe the degree of sedimented glycogen. This however is invasive and mostly done in one specific region of one muscle and does not allow to compare different muscles or different properties within one muscle. Given the large variety in neuromuscular diseases, non-invasive and quantitative methods are needed, that allow for diagnosis, detailed monitoring of disease progression and evaluation of treatment strategies. Muscle imaging, with its various techniques allows on one hand for qualitative assessment and on the other hand also for quantitative assessment (qMRI). T2-mapping serves as a biomarker for inflammatory processes. It is very sensitive to even subtle changes in the muscle prior to severe oedma. mDixon is a very fast imaging technique, which allows not only the detection of fatty degeneration, but also the exact quantification of water / fat percentage. Using diffusion weighted imaging macro- and microscopic tissue state as well as inter- and intra- muscular differences can be assessed. In a previous study, we have evaluated a qMRI protocol in healthy volunteers, which is feasible for clinical usage and allows multicenter comparisons (which is of great benefit, since cohorts of rare muscular diseases are relatively small). In the proposed project, we will classify rare neuromuscular diseases (Limb-Girdle muscular dystrophy - LGMD, Inclusion Body myositis - IBM, muscular dystrophy type I - MDI, muscular dystrophy type II - MDII, glycogen storage disease type II - Pompe) as compared to the existing database of healthy volunteers. Together with the adjacent “Muskelzentrum Ruhrgebiet” we have access to a large number of patients with various disease types and will be able to recruit 10 patients for each of the above mentioned disease groups. By identifying and classifying qMRI parameters that go along with disease types and progression, we may be able to define biomarkers that allow for monitoring disease progression as well as treatment strategies in a non-invasive fashion.

遗传性肌肉疾病的全球发病率约为1/2000，但多种多样（神经肌肉疾病的变种超过800种），并表现出肌肉疼痛、肌肉痉挛、早期疲劳和进行性肌肉无力等症状。在严重的情况下，也会出现截肢、四肢瘫痪和预期寿命缩短。由于肌肉组织中的微结构变化，用非侵入性方法观察和量化疾病依赖性变化具有挑战性。在临床常规中，不同的方法，其中大多数是互补的，用于评估疾病的阶段和进展。例如，肌肉运动测试是非侵入性的，易于应用且可重复。然而，对于细微的肌肉变化，它是不精确的，并且在一定程度上依赖于心率。在肌肉疾病的临床评价中也非常精确的方法是组织病理学。通过这种方式，您可以在细胞水平上获得肌肉特性的详细信息，例如观察沉积糖原的程度。 然而，这是侵入性的，并且主要在一个肌肉的一个特定区域中进行，并且不允许比较不同的肌肉或一个肌肉内的不同特性。鉴于神经肌肉疾病的种类繁多，需要非侵入性和定量方法，以进行诊断，详细监测疾病进展和评估治疗策略。肌肉成像及其各种技术一方面可以进行定性评估，另一方面也可以进行定量评估（qMRI）。T2-映射作为炎症过程的生物标志物。它对严重水肿前肌肉的细微变化非常敏感。mDixon是一种非常快速的成像技术，不仅可以检测脂肪变性，还可以精确定量水/脂肪百分比。使用扩散加权成像，可以评估宏观和微观组织状态以及肌间和肌内差异。在之前的一项研究中，我们在健康志愿者中评估了qMRI方案，该方案适用于临床使用，并允许多中心比较（这是非常有益的，因为罕见肌肉疾病的队列相对较小）。在拟议的项目中，我们将与现有的健康志愿者数据库相比，对罕见的神经肌肉疾病（肢带型肌营养不良症- LGMD、包涵体肌炎- IBM、I型肌营养不良症- MDI、II型肌营养不良症- MDII、II型糖原累积病-庞贝氏症）进行分类。与邻近的“Muskelzentrum Ruhrgebiet”一起，我们可以接触到大量患有各种疾病类型的患者，并将能够为上述疾病组招募10名患者。通过识别和分类与疾病类型和进展沿着的qMRI参数，我们可以定义允许以非侵入性方式监测疾病进展以及治疗策略的生物标志物。