Diaphragm Involvement in Duchenne Muscular Dystrophy (DMD): An MRI Study

Abstract

Background Duchenne muscular dystrophy (DMD) is characterized by progressive weakness and wasting of skeletal, cardiac, and respiratory muscles, with consequent cardiopulmonary failure as the main cause of death. Reliable outcome measures able to demonstrate specific trends over disease progression are essential. Purpose To investigate MRI as a noninvasive imaging modality to assess diaphragm impairment in DMD. In particular, we sought to correlate MRI measurement of diaphragm structure and function with pulmonary function tests and with the abdominal volumes (VAB) measured by optoelectronic plethysmography, being an index of the action of the diaphragm. Study Type Cross‐sectional study. Population Twenty‐six DMD patients (17.9 ± 6.2 years) and 12 age‐matched controls (17.8 ± 5.9 years). Field Strength/Sequence 3‐Point gradient echo Dixon sequence at 3T. Assessment Images were acquired in breath‐hold at full‐expiration (EXP) and full‐inspiration (INSP). INSP and EXP lung volumes were segmented and the diaphragm surface was reconstructed as the bottom surface of the left and the right lung. The inspiratory and the expiratory diaphragm surfaces were aligned by a nonrigid iterative closest point algorithm. On MRI we measured: 1) craniocaudal diaphragmatic excursion; 2) diaphragm fatty infiltration. Statistical Tests Three‐parameter sigmoid regression, one‐way analysis of variance (ANOVA), Spearman's correlation. Results In patients, diaphragm excursion decreased with age (r2 = 0.68, P < 0.0001) and fat fraction increased (r2 = 0.51, P = 0.0002). In healthy subjects, diaphragm excursion and fat fraction had no relationship with age. Diaphragm excursion decreased with decreasing FEV1 %pred (r = 0.78, P < 0.0001) and FVC %pred (r = 0.76, P < 0.0001) and correlated with VAB (r = 0.60, P = 0.0002). Fatty infiltration increased with decreasing FEV1 %pred (r = –0.88, P < 0.0001) and FVC %pred (r = –0.88, P < 0.0001). Data Conclusion The progressive structural and functional diaphragm impairment is highly related to pulmonary function tests and to VAB. The results suggest that MRI might represent a new and noninvasive tool for the functional and structural assessment of the diaphragm. Level of Evidence: 2 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2020;51:461–471.

Muscle Twitch Kinetics Are Dependent on Muscle Group, Disease State, and Age in Duchenne Muscular Dystrophy Mouse Models

“…The symptoms of Duchenne muscular dystrophy typically onset in young males between the ages of 3 and 5 years, with initial symptoms including delay in motor function, abnormal stride, difficulty standing from a sitting position and maintaining balance ( Darras et al, 2015 ). As the disease worsens, it affects all striated muscles, including weakening of the diaphragm ( Khirani et al, 2014 ; Gudmundson et al, 2019 ; Pennati et al, 2019 ) and limb muscles ( McDonald et al, 1995 ; Wallace and McNally, 2009 ), and in later stages, the disease also affects the heart ( Buddhe et al, 2018 ; Mavrogeni et al, 2018 ; Meyers and Townsend, 2019 ).…”

Thoracoabdominal asynchrony and paradoxical motion in Duchenne muscular dystrophy and healthy subjects during cough: A case control study

“…13,35 Thus, the diaphragm becomes weaker compared to the other inspiratory muscles. Pennati et al 37 previously suggested in DMD that during quiet breathing the ribcage muscles partially compensate the increased fat fraction of the diaphragm, quantified by MRI, by increasing ribcage volume variation, quantified by OEP, to retain tidal volume.…”

Donnan dominated ion homeostasis and the longevity of ischemic Na+-loaded dystrophic skeletal muscle

“…Cell and molecular therapies are emerging for DMD (e.g. Datta et al 2020), concurrent with improved non-invasive monitoring of patients' ion homeostatic indicators (Mankodi et al 2017;Bishop et al 2018;Gerhalter et al 2019;Ropars et al 2020;Meng et al 2020;Pennati et al 2020). Whether Na +overload in DMD patients indicates fiber swelling that "is likely osmotically relevant" and thus "may contribute to the progressive muscle degeneration" (Weber et al 2011(Weber et al ,2012 has been unclear.…”