Association of Elbow Flexor MRI Fat Fraction With Loss of Hand-to-Mouth Movement in Patients With Duchenne Muscular Dystrophy.

Naarding, Karin J; van der Holst, Menno; van Zwet, Erik W; van de Velde, Nienke M; de Groot, Imelda J M; Verschuuren, Jan J G M; Kan, Hermien E; Niks, Erik H

OBJECTIVE To study the potential of quantitative MRI (qMRI) fat fraction (FF) as biomarker in non-ambulant Duchenne muscular dystrophy (DMD) patients, we assessed the additive predictive value of elbow flexor FF to age on loss of hand-to-mouth movement. METHODS Non-ambulant DMD patients (≥8 years) were included. 4-point Dixon MRI scans of the right upper arm were performed at baseline and at 12, 18 or 24 months follow-up. Elbow flexor FFs were determined from five central slices. Loss of hand-to-mouth movement was determined at study visits and by phone-calls every four months. FFs were fitted to a sigmoidal curve using a mixed model with random slope to predict individual trajectories. The added predictive value of elbow flexor FF to age on loss of hand-to-mouth movement was calculated from a Cox model with the predicted FF as a time varying covariate, yielding a hazard ratio. RESULTS Forty-eight MRIs of 20 DMD patients were included. The hazard ratio of a percent-point increase in elbow flexor FF for the time to loss of hand-to-mouth movement was 1.12 (95%-confidence interval 1.04-1.21; p=0.002). This corresponded to a 3.13-fold increase of the instantaneous risk of loss of hand-to-mouth movement in patients with a 10 percent-points higher elbow flexor FF at any age. CONCLUSION In this prospective study, elbow flexor FF predicted loss of hand-to-mouth movement independent of age. qMRI measured elbow flexor FF can be used as surrogate endpoint or stratification tool for clinical trials in non-ambulant DMD patients. CLASSIFICATION OF EVIDENCE This study provides Class II evidence that qMRI FF of elbow flexor muscles in patients with DMD predicts loss of hand-to-mouth movement independent of age.