Quantitative muscle MRI as an assessment tool for monitoring disease progression in LGMD2I: a multicentre longitudinal study

Abstract

Background: Outcome measures for clinical trials in neuromuscular diseases are typically based on physical assessments which are dependent on patient effort, combine the effort of different muscle groups, and may not be sensitive to progression over short trial periods in slow-progressing diseases. We hypothesised that quantitative fat imaging by MRI (Dixon technique) could provide more discriminating quantitative, patient-independent measurements of the progress of muscle fat replacement within individual muscle groups.

Objective: To determine whether quantitative fat imaging could measure disease progression in a cohort of limb-girdle muscular dystrophy 2I (LGMD2I) patients over a 12 month period.

Methods: 32 adult patients (17 male;15 female) from 4 European tertiary referral centres with the homozygous c.826C>A mutation in the fukutin-related protein gene (FKRP) completed baseline and follow up measurements 12 months later. Quantitative fat imaging was performed and muscle fat fraction change was compared with (i) muscle strength and function assessed using standardized physical tests and (ii) standard T1-weighted MRI graded on a 6 point scale.

Results: There was a significant increase in muscle fat fraction in 9 of the 14 muscles analyzed using the quantitative MRI technique from baseline to 12 months follow up. Changes were not seen in the conventional longitudinal physical assessments or in qualitative scoring of the T₁w images.

Conclusions: Quantitative muscle MRI, using the Dixon technique, could be used as an important longitudinal outcome measure to assess muscle pathology and monitor therapeutic efficacy in patients with LGMD2I.

Conflict of interest statement

Competing Interests: Professor Vissing has given lectures for and received travel expenses from Genzyme. Professor Straub serves on the advisory boards of Genzyme and Acceleron, on the Joint Imaging Committee of Prosensa for which he receives research support, and has presented lectures for Genzyme. All other authors report no disclosures. This does not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials.

Figures

Figure 1. Quantitative fat fraction images of the thigh in LGMD2I patients showing the wide range of severity in fat replacement at baseline, from minimal involvement (a) to sparing of only gracilis and sartorius (e).

Figure 2. Quantitative fat fraction differences from baseline to 12 month follow-up.

The box indicates the lower and upper quartiles, with the median change with time represented as the bar within the box. The bars enclose the outliers.

Figure 3. Quantitative fat fraction images at baseline in an individual patient (a – mid lower leg level, c – mid thigh level) and at 12 months follow-up (b – mid lower leg level, d – mid thigh level).

Analysis reveals an increase in fat fraction of the medial and lateral gastrocnemius, peroneus longus, vastus lateralis and medialis, semimembranosus, semitendinosus, sartorius and gracilis.

Figure 4. Quantitative fat fraction images at baseline in an individual patient (a – mid lower leg level, c – mid thigh level) and at 12 months follow-up (b – mid lower leg level, d – mid thigh level).

Analysis reveals an increase in fat fraction of the lateral and medial gastrocnemius, sartorius, gracilis, semitendinosus, rectus femoris and vastus lateralis.