Quantitative Muscle Ultrasound a Promising Noninvasive Biomarker for DMD

The results of a new study published in Muscle & Nerve suggest that quantitative muscle ultrasound (QMUS) could serve as a reliable, non-invasive biomarker for monitoring disease progression and functional status in patients with Duchenne muscular dystrophy (DMD).1 The research, conducted by investigators at the Samsung Medical Center, Seoul, addresses clinicians' growing need for practical biomarkers to evaluate DMD, particularly amid new therapeutic advances extending patient lifespans.

The authors reported robust correlations between composite mean greyscale values and key functional outcomes in DMD. | Image Credit: hafakot - stock.adobe.com

Current standard assessments of functional capacity in DMD, such as the six-minute walk test (6MWT), North Star Ambulatory Assessment (NSAA), Performance of Upper Limb (PUL) module, and timed function tests, are informative but limited, particularly in nonambulatory patients or those with cognitive and orthopedic comorbidities. As the authors point out, these methods often rely on patient cooperation, and "While these measurement tools provide valuable insights into motor function, they are less applicable for nonambulatory patients in the advanced stages of DMD."

In the study, investigators conducted a cross-sectional analysis of 23 patients with genetically confirmed DMD, aged 5 to 18 years, drawn from a larger longitudinal study. They evaluated muscle echogenicity using mean grayscale values (MGV) across multiple muscle groups, including the upper and lower limbs, head and neck, and diaphragm. Functional performance was assessed concurrently using the 6MWT, NSAA, PUL, timed function tests, quantitative muscle strength tests, and respiratory muscle strength tests.

The authors reported robust correlations between composite MGVs and key functional outcomes. In all patients, the rectus femoris and tibialis anterior muscles exhibited abnormal Heckmatt scores (grade ≥ 2), indicating that these were the most commonly affected muscles in the cohort. Both MGVleg and MGVarm exhibited strong negative correlations with 6MWT distance (correlation coefficients [CC], −0.74 and −0.68, respectively; P < .01). Similarly, moderate negative correlations were observed between composite MGVs and NSAA scores (CC, −0.44 to −0.53; P < .01), indicating that increased muscle echogenicity reliably reflects diminished ambulatory function.

Composite MGVs of the arms and legs also demonstrated strong to very strong positive correlations with timed function tests, including the rise-from-floor, 4-stair climb, and 10-meter walk/run tasks. Correlation coefficients ranged from 0.65 to 0.87 (P < .01). Notably, among individual muscles, the flexor carpi radialis was the only QMUS parameter to show a significant, albeit weaker, negative correlation with PUL scores (CC, −0.35; P = .02).

In addition, diaphragm muscle echogenicity failed to correlate significantly with any clinical functional tests, and neither quantitative muscle strength nor respiratory strength showed a relationship with the MGV of the corresponding muscles. The authors attribute this, in part, to the complex nature of strength generation and differences in the timing of muscle echogenicity changes versus strength or function loss, especially across wide pediatric age ranges.

Interestingly, while the age-related increase in MGVarm and MGVleg appeared to plateau after approximately 12 years of age, considerable variability in values persisted among individuals. These findings suggest that QMUS can continue to capture meaningful disease progression even when NSAA scores have bottomed out, highlighting its potential value for long-term monitoring of patients in advanced stages of DMD.

The study's authors argue, "This study provides evidence for the potential of QMUS as a clinically relevant imaging biomarker in DMD," particularly for its ability to detect muscle pathology even in patients who are nonambulatory, poorly compliant, or in whom traditional tests are impossible. Clinicians should note that the study was cross-sectional and limited by a small sample size, and that the absence of normative QMUS values in healthy controls means direct comparison to absolute values is not feasible at this time.

Up to a third of patients with DMD experience conditions such as intellectual disability or autism spectrum disorder, or have a fracture risk that can further restrict physical evaluation.2 Thus, a robust, non–cooperation-dependent biomarker applicable across all disease severities remains an unmet need in the clinic. The results of this study suggest that QMUS may become an increasingly useful tool for noninvasive assessment of disease severity and progression in DMD, filling an important gap in the management and research of this complex neuromuscular disorder.1

References

1. Im YJ, Choe Y, Lee J, Lee J, Do JG, Kwon JY. Quantitative muscle ultrasound: A non-invasive biomarker for monitoring Duchenne muscular dystrophy. Muscle Nerve. 2025:0:1–10. doi: 10.1002/mus.28469.

2. Vaillend C, Aoki Y, Mercuri E, et al. Duchenne muscular dystrophy: recent insights in brain related comorbidities. Nat Commun. 2025;16(1):1298. doi: 10.1038/s41467-025-56644-w