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

BACKGROUND AND

OBJECTIVES

To study the potential of quantitative MRI (qMRI) fat fraction (FF) as a biomarker in nonambulant patients with Duchenne muscular dystrophy (DMD), we assessed the additive predictive value of elbow flexor FF to age at loss of hand-to-mouth movement.

METHODS

Nonambulant patients with DMD (age ≥8 years) were included. Four-point Dixon MRI scans of the right upper arm were performed at baseline and at the 12-, 18-, or 24-month follow-up. Elbow flexor FFs were determined from 5 central slices. Loss of hand-to-mouth movement was determined at study visits and by phone calls every 4 months. FFs were fitted to a sigmoidal curve by use of a mixed model with random slope to predict individual trajectories. The added predictive value of elbow flexor FF to age at 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 patients with DMD 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 in the instantaneous risk of loss of hand-to-mouth movement in patients with a 10-percent points higher elbow flexor FF at any age.

DISCUSSION: In this prospective study, elbow flexor FF predicted loss of hand-to-mouth movement independently of age. qMRI-measured elbow flexor FF can be used as a surrogate endpoint or stratification tool for clinical trials in nonambulant patients with DMD.

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 independently of age.