Quantifying disease activity in fatty-infiltrated skeletal muscle by IDEAL-CPMG in Duchenne muscular dystrophy

Abstract

Purpose To explore the use of iterative decomposition of water and fat with echo asymmetry and least-squares estimation Carr-Purcell-Meiboom-Gill (IDEAL-CPMG) to simultaneously measure skeletal muscle apparent fat fraction (AFF) and water T2 (T2,w) in patients with Duchenne muscular dystrophy (DMD). Materials and Methods In twenty healthy volunteer (HV) boys and thirteen subjects with DMD, thigh muscle AFF was measured by Dixon and IDEAL-CPMG, with the IDEAL-CPMG also providing T2,w as a measure of muscle inflammatory activity. A subset of subjects with DMD was followed up during a 48-week clinical study. The study was in compliance with the Patient Privacy Act and approved by the Institutional Review Board. Results AFF in the thigh muscles of subjects with DMD was significantly increased compared to HV boys (p < 0.001). Dixon and IDEAL-CPMG AFF strongly correlated (r = 0.92) and were in good agreement. Muscle T2,w measured by IDEAL-CPMG was independent of changes in AFF. Muscle T2,w was higher in the biceps femoris and vastus lateralis muscles of subjects with DMD (p < 0.05). There was a strong correlation (p < 0.004) between AFF in all thigh muscles and six-minute walk distance (6MWD) in subjects with DMD. Conclusions IDEAL-CPMG allowed independent and simultaneous quantification of skeletal muscle fatty degeneration and disease activity in DMD. IDEAL-CPMG AFF and T2,w may be useful as biomarkers in clinical trials of DMD as the technique disentangles two competing biological processes.

MRI biomarkers of proximal nerve injury in CIDP

“…Muscle PDFF values have been shown to relate to muscle strength in healthy subjects47 and to clinical parameters in patients with knee osteoarthritis48 and rotator cuff pathologies 35. Muscle PDFF mapping has recently been introduced as a noninvasive biomarker for disease progression in muscle dystrophies and myopathies 24, 25, 26, 27. One recent study also explored the utility of PDFF to assess neurogenic muscle atrophy in patients with Charcot‐Marie‐Tooth Type 1 and found significantly higher fat fractions in calf but not thigh muscles 49.…”

“…To explore changes in the muscle texture, we used a chemical shift encoding‐based water–fat separation technique to quantify the proton‐density fat fraction (PDFF) on a 0–100% scale. PDFF mapping has recently been introduced as a noninvasive biomarker for disease progression in different neuromuscular disorders including Charcot‐Marie‐Tooth (CMT) –Neuropathy 24, 25, 26, 27. We hypothesized that in CIDP, proximal nerve damage, and neurogenic muscle atrophy can be accurately visualized by these two techniques.…”

Skeletal muscle water T2 as a biomarker of disease status and exercise effects in patients with Duchenne muscular dystrophy

“…The healthy volunteer boys were recruited from the NIH Clinical Research Volunteer Program registry. Subject eligibility, inclusion and exclusion criteria have been described elsewhere [19]. All subjects were asked to avoid excessive physical activity beyond their normal levels for a week prior to the study visit.…”

Upper arm and cardiac magnetic resonance imaging in Duchenne muscular dystrophy

“…MRI biomarkers of muscle fat percentage are responsive to disease progression in the lower limb and forearm muscles of patients with DMD 4, 23, 24. Moreover, muscle fat percentage changes were detected in the lower limb muscles of younger patients who were functionally stable or showed improvement in the functional outcome measures over 1 year 23, 25. Imaging fatty replacement in the myocardium may be a noncontrast method of assessing the disease state of the myocardium in individuals with DMD.…”