Muscle histology vs MRI in Duchenne muscular dystrophy

Abstract

Objective: There are currently no effective treatments to halt the muscle breakdown in Duchenne muscular dystrophy (DMD), although genetic-based clinical trials are being piloted. Most of these trials have as an endpoint the restoration of dystrophin in muscle fibers, hence requiring sufficiently well-preserved muscle of recruited patients. The choice of the muscles to be studied and the role of noninvasive methods to assess muscle preservation therefore require further evaluation.

Methods: We studied the degree of muscle involvement in the lower leg muscles of 34 patients with DMD >8 years, using muscle MRI. In a subgroup of 15 patients we correlated the muscle MRI findings with the histology of open extensor digitorum brevis (EDB) muscle biopsies. Muscle MRI involvement was assigned using a scale 0-4 (normal-severe).

Results: In all patients we documented a gradient of involvement of the lower leg muscles: the posterior compartment (gastrocnemius > soleus) was most severely affected; the anterior compartment (tibialis anterior/posterior, popliteus, extensor digitorum longus) least affected. Muscle MRI showed EDB involvement that correlated with the patient's age (p = 0.055). We show a correlation between the MRI and EDB histopathologic changes, with MRI 3-4 grades associated with a more severe fibro-adipose tissue replacement. The EDB was sufficiently preserved for bulk and signal intensity in 18/22 wheelchair users aged 10-16.6 years.

Conclusion: This study provides a detailed correlation between muscle histology and MRI changes in DMD and demonstrates the value of this imaging technique as a reliable tool for the selection of muscles in patients recruited into clinical trials.

Figure 1. Sagittal plane of the foot with the anatomic markings of the talus and the forepart of the upper and lateral surfaces of the calcaneus in a control subject

(A) Talus, (B) extensor digitorum brevis, (C) calcaneus.

Figure 2. Progressive involvement of the extensor digitorum brevis (EDB) muscle on MRI grading (patients from left to right)

Good correlation between the muscle MRI scoring of the EDB and tibialis anterior/posterior muscles. Grade 4 EDB was not obtained; see the table. H&E = hematoxylin-eosin.

Figure 3. Correlation between clinical, pathologic, and MRI findings

(A) Correlation between the patient's age at the time of the extensor digitorum brevis (EBD) biopsy and the EDB MRI score. (B) Correlation between the EDB MRI score and the EDB histology score. (C) Correlation between the EDB fat score and the EDB MRI score.