Longitudinal Changes in MRI Muscle Morphometry and Composition in People With Inclusion Body Myositis
Didier Laurent, Jon Riek, Christopher D. J. Sinclair, P Houston, Ronenn Roubenoff, Dimitris A. Papanicolaou, Attila Nagy, Steve Pieper, Tarek Yousry, Michael G. Hanna, John S. Thornton, Pedro Machado
Abstract
<h3>Background and Objectives</h3> 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. <h3>Methods</h3> 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). <h3>Results</h3> After 1 year, we observed a reduction in TMV (6.8%, <i>p</i> < 0.001) and muscle T2 (6.7%, <i>p</i> = 0.035), an increase in IMAT (9.7%, <i>p</i> < 0.001), FF (11.2%, <i>p</i> = 0.030), connective tissue (22%, <i>p</i> = 0.995), and T<sub>2</sub>*-IMAT (24%, <i>p</i> < 0.001), and alteration in muscle macromolecular structure (ΔMTR = −26%, <i>p</i> = 0.002). A decrease in muscle T2 correlated with an increase in T2*-IMAT (<i>r</i> = −0.47, <i>p</i> = 0.008). Deposition of connective tissue and IMAT correlated with deterioration in sIFA (<i>r</i> = 0.38, <i>p</i> = 0.032; <i>r</i> = 0.34, <i>p</i> = 0.048; respectively), whereas a decrease in TMV correlated with a decrease in quantitative muscle testing (<i>r</i> = 0.36, <i>p</i> = 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). <h3>Discussion</h3> 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. <h3>Classification of Evidence</h3> This study provides Class I evidence that qMRI outcome measures are associated with physical performance measures in patients with sIBM.