Chest MRI to diagnose early diaphragmatic weakness in Pompe disease

Abstract

Background In Pompe disease, an inherited metabolic muscle disorder, severe diaphragmatic weakness often occurs. Enzyme replacement treatment is relatively ineffective for respiratory function, possibly because of irreversible damage to the diaphragm early in the disease course. Mildly impaired diaphragmatic function may not be recognized by spirometry, which is commonly used to study respiratory function. In this cross-sectional study, we aimed to identify early signs of diaphragmatic weakness in Pompe patients using chest MRI. Methods Pompe patients covering the spectrum of disease severity, and sex and age matched healthy controls were prospectively included and studied using spirometry-controlled sagittal MR images of both mid-hemidiaphragms during forced inspiration. The motions of the diaphragm and thoracic wall were evaluated by measuring thoracic cranial-caudal and anterior–posterior distance ratios between inspiration and expiration. The diaphragm shape was evaluated by measuring the height of the diaphragm curvature. We used multiple linear regression analysis to compare different groups. Results We included 22 Pompe patients with decreased spirometry results (forced vital capacity in supine position < 80% predicted); 13 Pompe patients with normal spirometry results (forced vital capacity in supine position ≥ 80% predicted) and 18 healthy controls. The mean cranial-caudal ratio was only 1.32 in patients with decreased spirometry results, 1.60 in patients with normal spirometry results and 1.72 in healthy controls (p < 0.001). Anterior–posterior ratios showed no significant differences. The mean height ratios of the diaphragm curvature were 1.41 in patients with decreased spirometry results, 1.08 in patients with normal spirometry results and 0.82 in healthy controls (p = 0.001), indicating an increased curvature of the diaphragm during inspiration in Pompe patients. Conclusions Even in early-stage Pompe disease, when spirometry results are still within normal range, the motion of the diaphragm is already reduced and the shape is more curved during inspiration. MRI can be used to detect early signs of diaphragmatic weakness in patients with Pompe disease, which might help to select patients for early intervention to prevent possible irreversible damage to the diaphragm.

Diaphragmatic dysfunction in neuromuscular disease, an MRI study

“…Patients were included consecutively between April 2017 and March 2019. We compared our findings to the results of 35 patients with a DNA-confirmed diagnosis of Pompe disease and 18 healthy controls matched for gender and age to the Pompe patients [11]. The protocol was approved by the Medical Ethical Committee of Erasmus MC University Medical Center (MEC-2007-103, amendment 7).…”

“…MRI images were conducted during a 20-25-minute protocol with a 3 Tesla Signa 750 MRI system (General Electric Healthcare, Milwaukee, Winconsin, USA) using the whole-body coil for radio-frequency excitation and a 32-channel torso coil for signal reception [11]. In the current study, we used three-dimensional (3D) static images acquired at end-inspiration and end-expiration and sagittal two-dimensional (2D) dynamic images at the level of the right mid-hemidiaphragm acquired during forced inspiration.…”

“…Breathing manoeuvres during MRI were spirometry-controlled to ensure the maximum performance and volume standardization for each patient. We did not include images of the left mid-hemidiaphragm since its segmentation is cumbersome due to the difficult delineation of heart and diaphragm contours [11]. Further, we had no indication for body side predominant involvement of respiratory muscle weakness in any of the patients who participated.…”

“…To remove any stray pixels, only the largest object in each segmented image was kept as the final result. The training data included manual segmentations of 18 healthy controls and 35 Pompe patients who also participated in the current study [11]. Data augmentation with elastic deformations was used to extend the training set [18].…”

“…Conversely, motion of the thoracic wall, expressed as function of the intercostal muscles, remained within the normal range [8][9][10]. We recently showed that MRI can be also used to investigate early impairment of the diaphragm in patients with Pompe disease [11]. It is unknown, however, whether these findings are specific for Pompe disease, or whether the diaphragm is affected in a similar way in other types of neuromuscular diseases.…”