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

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.

To investigate MRI as a non-invasive imaging modality to assess diaphragm impairment in DMD, we proposed MRI measurements of diaphragm structure and function. Patients with a defined diagnosis of DMD, ranging in age from 6 to 32 years, were consecutively enrolled in the study between September 2016 and September 2017. Exclusion criteria were: claustrophobia, cognitive deficits, all-day dependence on non-invasive mechanical ventilation, inability to stay still in the scanner and perform a 10-seconds breath-hold. Age-matched healthy male controls were recruited among relatives of the researchers and students of the laboratory who volunteered to take part to the study. The following measures were analyzed:

Spirometry was performed in DMD patients on the same day of MR imaging, including forced-expiratory volume in 1 second (FEV1), forced vital capacity (FVC), forced expiratory flow at 25-75% of FVC (FEF 25-75), forced expiratory flow at 50% of FVC (FEF 50) and peak expiratory flow (PEF).

Opto-electronic plethysmography (OEP-System; BTS, Milan, Italy) was performed to assess the breathing pattern, both in patients and in controls on the same day of MR imaging. Total and compartmental volumes were measured during five minutes of quiet breathing and inspiratory capacity maneuver (IC). Measures included: tidal volume (VT), respiratory rate (RR), minute ventilation, rapid and shallow breathing index (RSBi; calculated as RR/VT), ribcage and abdominal tidal volumes (ΔVRC and ΔVAB), maximal inspiratory total volume (ICcw), ribcage and abdominal volumes during the IC (ΔVRC_IC and ΔVAB_IC).

MRI was acquired in breath-hold at full-expiration (EXP) and full-inspiration (INSP) with a 3-point gradient echo Dixon sequence at 3T. INSP and EXP lung volumes were segmented and the diaphragm surface was reconstructed as the bottom surface of the left and the right lung, by identifying the most inferior voxels of the segmented lungs, which were characterized by a negative curvature of the lower lung contours on coronal and sagittal slices. The inspiratory and the expiratory diaphragm surfaces were aligned by a non-rigid iterative closest point algorithm. On MRI we measured: 1) cranio-caudal diaphragmatic excursion, as the vertical component of the deformation field; 2) diaphragm fatty infiltration in 3D ROIs manually traced over the costal and crural parts of the diaphragm by using the three-point Dixon technique.