MUSCLE IMAGING – MRI: P.166 Muscle MRI as biomarker of disease progression in Becker muscular dystrophy: a 2 year follow-up study

Abstract

Becker muscular dystrophy (BMD) is hallmarked by clinical variability and slow but unpredictable deterioration. Biomarkers are needed that correlate with function and reliably detect disease progression within the time of a trial. We explored the feasibility of quantitative muscle MRI (qMRI) in BMD as such a biomarker. In this 2 year follow up study, 24 BMD patients were included at baseline. 3-point Dixon 3T MRI scans (23 slices of 1 cm, 0.5cm gap) were acquired of the thigh and lower leg (LL). Weighted average fat fractions (wFF) of 12 thigh and 7 LL muscles and 5 muscle groups were determined over three central slices (3S) using landmarks, and over the whole muscle (WM). Functional assessment included 6-minute walk test (6MWT), North Star Ambulatory Assessment (NSAA) and maximal voluntary contraction of knee extension and flexion. Wilcoxon signed rank test and Spearman's correlation were used for statistics (significance p<0.05). Nineteen patients (median age 40.4 years, range 18.8-66.3) completed baseline and follow-up assessments. Baseline vastus lateralis and quadriceps wFF 3S and MW correlated highly to all functional parameters (rho>=0.720). At 2 years, wFF of 3S and WM increased in 11 of 19 muscles. The median FF increase was similar in 3S and WM for all muscles. High standardized response means (SRMs; >=0.8) were obtained in the thigh for all individual quadriceps WMs (SRMs 0.89-1.00) but not for 3S (SRMs 0.67-0.79). In the LL, only the SRM of gastrocnemius medialis WM was high (0.95). In muscle groups, highest SRMs were obtained for both 3S and WM in quadriceps and whole thigh (SRMs 0.91-1.21). Among function tests, only NSAA (-3.0, SD 4.0) and 10-meter run test velocity (-0.29m/s, SD 0.48) decreased, resulting in SRMs of -0.75 and -0.62. Knee flexion strength decreased by 2.1kg (SD 2.64, SRM -0.78). Due to high correlations with function and high SRMs, we propose qMRI as feasible biomarker in BMD. Composite WM thigh group SRMs were highest, potentially allowing for smaller sample sizes when used as outcome measure in trials.