Indexed on: 02 May '19Published on: 01 May '19Published in: Annals of the American Thoracic Society
Lymphangioleiomyomatosis (LAM) is a rare disease associated with cystic destruction of the pulmonary parenchyma and chronic respiratory failure, and there are trials underway to determine if early intervention can prevent disease progression. An imaging technique that is sensitive to early regional disease would therefore be valuable for patient care and clinical trials. We postulated that hyperpolarized Xe MRI would be sensitive to ventilation abnormalities and alveolar-airspace dilation in patients with mild LAM disease and normal pulmonary function and that Xe MRI would reveal important features of cyst ventilation. Xe ventilation and diffusion-weighted MR images were acquired in 22 LAM patients during two breath-holds of hyperpolarized Xe. Xe ventilation defect percentage (VDP; percentage of voxels <60% of the mean whole-lung Xe MRI signal) and apparent-diffusion coefficient (ADC), a measure of alveolar-airspace size, were quantified and compared to pulmonary-function test (PFT) parameters with Spearman statistics. Sixteen of the LAM patients had a recent, clinical chest CT scan available, and cyst ventilation was assessed by thresholding cysts on the CT images and registration to the Xe ventilation images. Ventilation deficits were observed in all LAM patients including those with normal pulmonary function and few cysts, and the mean VDP was 19.2% (95% CI 14.8%-23.5%). Xe VDP was strongly correlated with FEV/FVC ratio (r = -0.51, p= 0.02) and DLCO (r = -0.60, p = 0.009), but not with FEV (r = -0.33, p = 0.13), likely due to the sensitivity of Xe MRI to mild LAM disease in patients with normal FEV. The mean ADC was 0.048 cm/s (95% CI 0.042-0.053 cm/s), and in many cases, ADC was elevated relative values previously reported in adults, and ADC was correlated with the three PFT parameters (p ≤ 0.02). Co-registered Xe MRI and CT revealed considerable ventilation heterogeneity within individual LAM patients and across LAM patients with similarly-sized cysts. Xe MRI is sensitive to early ventilation abnormalities and airspace dilation in LAM patients with mild disease, and ventilation within the LAM cysts is heterogeneous. Xe MRI provides a means to assess the complex regional ventilation and alveolar-airspace size changes of LAM, and the sensitivity of Xe MRI to early LAM disease changes is appealing as a future tool for screening and managing patients and for measuring treatment efficacy.