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

Abstract

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.

Muscle-MRI and Functional Levels for the Evaluation of Upper Limbs in Duchenne Muscular Dystrophy: A Critical Review of the Literature

“…After screening 72 articles by title and abstract, 10 studies met the inclusion criteria and were selected: five were prospective cross-sectional studies [ 14 , 15 , 16 , 17 , 18 ] and five were prospective longitudinal studies ( Table 1 ) [ 19 , 20 , 21 , 22 , 23 ]. These included information on a total of 296 DMD patients.…”

“…One hundred sixty-two DMD patients were ambulant and 140 were non-ambulant. In eight studies [ 14 , 16 , 17 , 18 , 19 , 21 , 22 , 23 ], patients were under steroid treatment. In two studies, the treatment was not specified [ 15 , 20 ].…”

“…Different MRI techniques were used for qualitative or quantitative assessment of fat degeneration in muscles. Only three studies, accounting for a total of 31 patients, used a semi-quantitative evaluation of fatty infiltration Turbo spin echo (TSE) T1 sequences evaluated by Mercuri score) [ 16 , 17 , 23 ], three studies [ 19 , 21 , 22 ] used quantitative fat-fraction analysis, and four studies [ 14 , 15 , 18 , 20 ] used both quantitative measurements and MRS.…”

“…Functional measures were available in nine of the ten studies [ 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 ] ( Table 1 ).…”

“…Different MRI qualitative (using standard T1 and T2 sequences) and quantitative (using Dixon sequences) techniques have been used to evaluate muscle involvement and the gradient of disease progression in DMD subjects by identifying fatty infiltration and muscle edema [ 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 ]. In addition, in the last few years, MRI spectroscopy has given important information on the metabolic composition of the muscular structure [ 7 , 8 , 14 , 15 , 18 , 20 ].…”