350P Multi-parametric MRI of lower leg muscle in patients with Becker muscular dystrophy

• Published in: Neuromuscular disorders : NMD Vol. 43; p. 104441
• Main Authors: Gerhalter, T., Schunk, V., Baudin, P., Rauh, S., Tkotz, K., Zaiss, M., Roemer, F., Dörfler, A., Uder, M., Gazzerro, E., Nagel, A.
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.10.2024
• DOI: 10.1016/j.nmd.2024.07.690
• ISSN: 0960-8966

Becker muscular dystrophy (BMD) is a hereditary neuromuscular disease caused by mutations in the dystrophin gene. It is associated with changes in energy metabolism and muscle fiber size, and inflammation, ultimately leading to the non-reversable replacement of muscle tissue with fatty and fibrotic tissue. Quantitative MRI has been used to describe the natural history of the disease and has been suggested as an outcome measure in clinical trials for BMD. Most of these studies evaluated the fat fraction (FF), which correlates highly with functional measures such as time-graded tests. However, the functionality of non-fat-replaced muscle tissue was found lower than in healthy control, highlighting the need of non-invasive measures reflecting changes in the muscle tissue itself. Here, we investigate the potential of diffusion tensor imaging (DTI), water T₂ relaxation times and chemical-exchange saturation transfer (CEST) parameters as early disease markers in ambulatory patients with BMD. MRI scans of the legs were performed on twelve BMD patients (age 41.9±13.3 years) and five controls (age 48.1±14.9 years) using a 3T MR system. Mean and standard deviation of the water T₂ was determined using a multi-slice-multi-echo sequence and a tri-exponential fitting procedure. FF was measured using a 6-point DIXON method. DTI parameters were calculated from diffusion-weighted spin-echo imaging and CEST effects were investigated at 3.5 ppm (amide-weighted), 2.5 ppm (phosphocreatine-weighted) and 2.0 ppm (total creatine-weighted) away from the water signal using a low-power saturation pulse approach. Region-of-interests were drawn on the gastrocnemius medialis and lateralis, soleus, peroneus, extensor digitorum longus, and tibialis anterior and posterior muscles. In addition, timed-graded tests were performed including 10mwt (10m walking test) and STS (supine-to-stand). Differences were tested with the Mann-Whitney U test. Patients exhibited slower performance in timed-graded tests (10mwt: BMD 1.2±0.1m/s, CTL 1.4±0.2m/s, p=0.0129; STS: BMD 5.9±4.2s, CTL 2.5±0.1s, p=0.045). FF were elevated in patients compared to healthy controls (BMD 0.15±0.19, CTL 0.06±0.04, p=0.025), especially in the gastrocnemius medialis and soleus muscles. Overall, dystrophic muscles showed a decreased mean diffusivity (BMD 1.3±0.2 ×0.001mm²/s CTL 1.5±0.1 ×0.001mm²/s, p=0.012) and increased water T₂ heterogeneity, reflected by higher standard deviations of water T₂ (BMD 12.2±5.5ms CTL 9.5±3.8ms, p=0.004), but no change in the mean water T₂ (BMD 31.0±5.3ms CTL 31.8±3.6ms, p=0.85) or fractional anisotropy (BMD 0.24±0.04 CTL 0.23±0.03, p=0.08). CEST effects were visible for amide-related (BMD 0.010±0.003 CTL 0.008±0.004, p<0.001), phosphocreatine-related (BMD 0.011±0.003 CTL 0.009±0.004, p<0.001), and total creatine-related (BMD 0.010±0.003 CTL 0.008±0.004, p=0.001) resonances. Changes in water T₂ heterogeneity and mean diffusivity in patients were found mainly in fat-replaced muscles (n=29, FF>0.1), but not in preserved muscles (n=48, FF<0.1). However, patients exhibited abnormally high CEST indices also in preserved muscles, indicating early metabolic disturbances in normal-appearing muscles of BMD that can be depicted non-invasively using ¹H MRI. We will further assess this observation as the study continues to enroll more participants in order to expand the study cohort. Additionally, we plan to conduct a follow-up investigation to establish correlations between the observed MR changes and clinical outcomes.