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

Abstract

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.

Figure 1. Longitudinal Clinical and FF_EF Data

(A) Example of a region of interest drawn on the elbow flexor muscles (line) is shown on a water image (left) and corresponding fat image (right). (B) Longitudinal performance of the upper limb (PUL) 2.0 total scores (maximum 42 points) are plotted vs age. PUL total scores decrease with age, but there is a large variation in scores between patients with Duchenne muscular dystrophy of similar ages. (C) Elbow flexor fat fraction (FF_EF) results that were acquired are plotted vs age, as well as FF_EF results that were predicted with a logit transformation, linear (mixed) model, and logistic transformation. Patients with higher FF_EF results at younger ages or faster FF_EF increases had steeper predicted FF_EF slopes. (D) Predicted FF_EF results are plotted vs age, and predicted FF_EF at age at loss of hand-to-mouth movement is shown with a cross. Colors used in panels B–D are unique for each participant.

Figure 2. Elbow Flexor Fat Fraction and Preserved Hand-to-Mouth Movement vs Age

In (A) we generated an FFEF growth chart with a 3rd, 10th, 25th, 50th, 75th, 90th and 97th percentile curve from the predicted FFEF data. (B) Using the resulting hazard ratio, we transformed the predicted FFEF growth curves to a 3rd, 10th, 25th, 50th, 75th, 90th and 97th percentile survival curve for preserved hand-to-mouth movement. A patient on the 3rd percentile in the FFEF growth chart is also on the 3rd percentile in the survival chart.