Respiratory magnetic resonance imaging biomarkers in Duchenne muscular dystrophy

Abstract

ObjectiveTo examine the diaphragm and chest wall dynamics with cine breathing magnetic resonance imaging (MRI) in ambulatory boys with Duchenne muscular dystrophy (DMD) without respiratory symptoms and controls.MethodsIn 11 DMD boys and 15 controls, cine MRI of maximal breathing was recorded for 10 sec. The lung segmentations were done by an automated pipeline based on a Holistically‐Nested Network model (HNN method). Lung areas, diaphragm, and chest wall motion were measured throughout the breathing cycle.ResultsThe HNN method reliably identified the contours of the lung and the diaphragm in every frame of each dataset (~180 frames) within seconds. The lung areas at maximal inspiration and expiration were reduced in DMD patients relative to controls (P = 0.02 and <0.01, respectively). The change in the lung area between inspiration and expiration correlated with percent predicted forced vital capacity (FVC) in patients (r s = 0.75, P = 0.03) and was not significantly different between groups. The diaphragm position, length, contractility, and motion were not significantly different between groups. Chest wall motion was reduced in patients compared to controls (P < 0.01).InterpretationCine breathing MRI allows independent and reliable assessment of the diaphragm and chest wall dynamics during the breathing cycle in DMD patients and controls. The MRI data indicate that ambulatory DMD patients breathe at lower lung volumes than controls when their FVC is in the normal range. The diaphragm moves normally, whereas chest wall motion is reduced in these boys with DMD.

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

“…One 3D MRI study in Pompe disease reported by Mogalle et al measures differences in craniocaudal, anteroposterior, and left–right lung diameters after manual lung segmentation . Recently, cine‐MRI has been applied in DMD to study the dynamic motion of the chest wall and of the diaphragm on sagittal images in patients younger than 15 years old . Nevertheless, the temporal resolution required for a dynamic acquisition leads to low spatial resolution and challenging image analysis .…”

Non-Invasive Respiratory Assessment in Duchenne Muscular Dystrophy: From Clinical Research to Outcome Measures

“…On dynamic MRI, lung cross sectional area was reported smaller in patients than in controls at both tidal and maximal inspiration and expiration [63][64][65]. These results were also confirmed when lung cross sectional area was normalized to height, to account for shorter stature resulting from long-term steroid treatment [63].…”

“…Reconstructing the 3D shape of the diaphragm as the bottom surfaces of the segmented left and right lungs, the inspiratory-expiratory diaphragm excursion can be investigated in 3D [59,62]. Using dynamic MRI, these parameters can be measured in each frame of the cine-MRI dataset, during free-and deep-breathing conditions, and their temporal profile can be obtained [62][63][64][65]. Free-breathing acquisitions have the advantage of being performable also in patients who have difficulties holding their breath.…”

“…Intercostal muscles appear to have limited fatty infiltration, even in patients with nearly complete fatty replacement of other muscles surrounding the ribcage [63]. Such structural damage induced by the dystrophy results in an impaired function, because of the loss of contracting units, with reduced diaphragm excursion and ventrodorsal lung expansion [59,63,64]. Additionally, in severe advanced stage, paradoxical motion of the diaphragm has been reported during maximal expirations [59,63].…”

Dynamic respiratory muscle function in late-onset Pompe disease

“…Static MRI images of the thorax at total lung capacity and residual volume indicate that lung volumes and diaphragm descent are reduced in LOPD, and these appear to correlate with clinical pulmonary function tests such as forced vital capacity 3,5,7 . Dynamic mode (cinematic) thoracic MRI has also been employed to quantify rate of change of diaphragm descent and disease severity in pulmonary disease, scoliosis, and Duchenne muscular dystrophy 17–20 . Dynamic scans are advantageous because they do not require static breath-holds at fixed volumes to calculate respiratory muscle excursions, and multiple repeated breaths can be acquired and averaged over a short duration.…”