From the Novartis Institutes for Biomedical Research (D.L., P.H., R.R., D.A.P.), Basel, Switzerland; BioTel Research (J.R.), Rochester, NY; Neuroradiological Academic Unit (C.D.J.S., T.A.Y., J.S.T.), UCL Institute of Neurology, London, United Kingdom; Isomics Inc. (A.N., S.P.), Cambridge, MA; Department of Medical Physics and Informatics (A.N.), University of Szeged, Hungary; Lysholm Department of Neuroradiology (T.A.Y.), National Hospital for Neurology and Neurosurgery; Department of Neuromuscular Diseases (M.G.H., P.M.M.), UCL Queen Square Institute of Neurology, University College London; and Centre for Rheumatology (P.M.M.), Department of Inflammation, Division of Medicine, University College London, United Kingdom.
Neurology. 2022 Aug 30;99(9):e865-e876. doi: 10.1212/WNL.0000000000200776. Epub 2022 Jun 3.
Limited data suggest that quantitative MRI (qMRI) measures have potential to be used as trial outcome measures in sporadic inclusion body myositis (sIBM) and as a noninvasive assessment tool to study sIBM muscle pathologic processes. Our aim was to evaluate changes in muscle structure and composition using a comprehensive multiparameter set of qMRI measures and to assess construct validity and responsiveness of qMRI measures in people with sIBM.
This was a prospective observational cohort study with assessments at baseline (n = 30) and 1 year (n = 26). qMRI assessments include thigh muscle volume (TMV), inter/intramuscular adipose tissue (IMAT), muscle fat fraction (FF), muscle inflammation (T2 relaxation time), IMAT from T2* relaxation (T2*-IMAT), intermuscular connective tissue from T2* relaxation (T2*-IMCT), and muscle macromolecular structure from the magnetization transfer ratio (MTR). Physical performance assessments include sIBM Physical Functioning Assessment (sIFA), 6-minute walk distance, and quantitative muscle testing of the quadriceps. Correlations were assessed using the Spearman correlation coefficient. Responsiveness was assessed using the standardized response mean (SRM).
After 1 year, we observed a reduction in TMV (6.8%, < 0.001) and muscle T2 (6.7%, = 0.035), an increase in IMAT (9.7%, < 0.001), FF (11.2%, = 0.030), connective tissue (22%, = 0.995), and T*-IMAT (24%, < 0.001), and alteration in muscle macromolecular structure (ΔMTR = -26%, = 0.002). A decrease in muscle T2 correlated with an increase in T2*-IMAT ( = -0.47, = 0.008). Deposition of connective tissue and IMAT correlated with deterioration in sIFA ( = 0.38, = 0.032; = 0.34, = 0.048; respectively), whereas a decrease in TMV correlated with a decrease in quantitative muscle testing ( = 0.36, = 0.035). The most responsive qMRI measures were T2*-IMAT (SRM = 1.50), TMV (SRM = -1.23), IMAT (SRM = 1.20), MTR (SRM = -0.83), and T2 relaxation time (SRM = -0.65).
Progressive deterioration in muscle quality measured by qMRI is associated with a decline in physical performance. Inflammation may play a role in triggering fat infiltration into muscle. qMRI provides valid and responsive measures that might prove valuable in sIBM experimental trials and assessment of muscle pathologic processes.
This study provides Class I evidence that qMRI outcome measures are associated with physical performance measures in patients with sIBM.
有限的数据表明，定量磁共振成像（qMRI）测量具有作为散发性包涵体肌炎（sIBM）临床试验结果指标的潜力，并作为一种无创评估工具来研究 sIBM 肌肉病理过程。我们的目的是使用全面的 qMRI 指标评估肌肉结构和组成的变化，并评估 sIBM 患者的 qMRI 指标的结构有效性和反应性。
这是一项前瞻性观察队列研究，基线（n=30）和 1 年（n=26）时进行评估。qMRI 评估包括大腿肌肉体积（TMV）、肌内/肌间脂肪组织（IMAT）、肌肉脂肪分数（FF）、肌肉炎症（T2 弛豫时间）、来自 T2弛豫的 IMAT（T2-IMAT）、来自 T2弛豫的肌间结缔组织（T2-IMCT）和来自磁化转移比的肌肉大分子结构（MTR）。体能评估包括 sIBM 功能评估（sIFA）、6 分钟步行距离和股四头肌定量肌肉测试。使用 Spearman 相关系数评估相关性。使用标准化反应均值（SRM）评估反应性。
1 年后，我们观察到 TMV（6.8%，<0.001）和肌肉 T2（6.7%，=0.035）减少，IMAT（9.7%，<0.001）、FF（11.2%，=0.030）、结缔组织（22%，=0.995）和 T*-IMAT（24%，<0.001）增加，以及肌肉大分子结构改变（ΔMTR=-26%，=0.002）。肌肉 T2 的减少与 T2*-IMAT 的增加相关（=0.47，=0.008）。结缔组织和 IMAT 的沉积与 sIFA 的恶化相关（=0.38，=0.032；=0.34，=0.048；分别），而 TMV 的减少与定量肌肉测试的减少相关（=0.36，=0.035）。最敏感的 qMRI 指标是 T2*-IMAT（SRM=1.50）、TMV（SRM=-1.23）、IMAT（SRM=1.20）、MTR（SRM=-0.83）和 T2 弛豫时间（SRM=-0.65）。
qMRI 测量的肌肉质量进行性恶化与体能下降有关。炎症可能在触发脂肪浸润肌肉中起作用。qMRI 提供了有效的、敏感的指标，在 sIBM 实验性试验和肌肉病理过程的评估中可能具有价值。
本研究提供了 I 级证据，表明 qMRI 结局指标与 sIBM 患者的体能指标相关。
