Correlation Between Quantitative MRI and Muscle Histopathology in Muscle Biopsies from Healthy Controls and Patients with IBM, FSHD and OPMD

Abstract

Background: Muscle MRI is increasingly used as a diagnostic and research tool in muscle disorders. However, the correlation between MRI abnormalities and histopathological severity is largely unknown. Objective: To investigate correlations between muscle MRI abnormalities and histopathological severity in healthy controls and patients with muscle disease. Methods: We performed quantitative MRI and histopathological analysis in 35 patients with inclusion body myositis, facioscapulohumeral muscular dystrophy or oculopharyngeal muscular dystrophy and 12 healthy controls. Participants contributed needle biopsies of the vastus lateralis and/or tibialis anterior, yielding 77 muscle biopsies with matched T1, T2 and TIRM MRI imaging. Muscle biopsies were evaluated with a semi-quantitative histopathology severity grading scale (range 0–12) and an inflammation severity grading scale (range 0–3). Results: In muscle disease, histopathology sum scores ranged from 0 to 11 and correlated significantly with fat percentage as measured on MRI (Spearman’s rho = 0.594, p < 0.001). Muscle edema on muscle MRI was associated with increased amounts of inflammation (p < 0.001). Mild abnormalities occured in 95% of control biopsies and were more pronounced in tibialis anterior (median sum score of 1±1 in vastus lateralis and 2±1 in tibialis anterior (p = 0.048)). Conclusion: In muscle disease, fatty infiltration on MRI correlates moderately with muscle histopathology. Histopathological abnormalities can occur prior to the onset of fatty infiltration. In middle-aged controls, almost all biopsies showed some histopathological abnormalities. The findings from this study may facilitate the choice for appropriate imaging sequences as outcome measures in therapeutic trials.

Long-Term Systemic Treatment of a Mouse Model Displaying Chronic FSHD-like Pathology with Antisense Therapeutics That Inhibit DUX4 Expression

“…In addition to muscle deterioration, excessive muscle fibrosis negatively affects muscle function and is an important hallmark of FSHD [ 44 ]. We therefore additionally examined the level of fibrosis in TA and DIA muscles using immunostaining for a commonly used marker of fibrosis, collagen VI [ 45 , 46 ] ( Figure 5 b,e,g).…”

Muscle magnetic resonance imaging in myotonic dystrophy type 1 (DM1): Refining muscle involvement and implications for clinical trials

“…This is also supported by a STIR‐T1 correspondence in the majority of muscles in the thigh and leg (Video 1 ). Evidence that STIR‐positive signal precedes the muscle degeneration has previously been reported in both acquired and genetic myopathies, such as idiopathic inflammatory myopathies and facioscapulohumeral muscular dystrophy [ 47 , 48 , 49 ] where STIR positivity corresponded to muscle edema and, more specifically, to inflammation [ 14 ]. To date, there is no evidence of an inflammatory process behind muscle degeneration in DM1 muscle biopsies.…”

“…Muscle magnetic resonance imaging (MRI) represents the gold standard technique for a muscle imaging study, providing useful information for diagnostic purposes through the detection of disease‐specific patterns of muscle involvement in various neuromuscular conditions [ 8 , 9 ]. Furthermore, muscle MRI has been considered a biomarker of disease progression [ 10 , 11 , 12 ], and also a potential non‐invasive tool to better understand the pathophysiology of specific muscle diseases [ 13 , 14 ].…”

Outcome Measures in Facioscapulohumeral Muscular Dystrophy Clinical Trials

“…The recent 48-week Losmapimod trial in 80 FSHD subjects also found a significant improvement in fat infiltration of some affected muscles with Losmapimod compared to placebo [ 27 ]. Notably, this study also utilized MRI STIR hyperintensity as a guide for muscle biopsy, as previous investigations have found that active inflammatory cell infiltration may be present in these areas [ 110 , 117 , 118 ].…”