Cyst Ventilation Heterogeneity and Alveolar Airspace Dilation as Early Disease Markers in Lymphangioleiomyomatosis

Abstract

Rationale: 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.Objectives: We postulated that hyperpolarized ¹²⁹Xe MRI would be sensitive to ventilation abnormalities and alveolar airspace dilation in patients with mild LAM disease and normal pulmonary function and that ¹²⁹Xe MRI would reveal important features of cyst ventilation.Methods:¹²⁹Xe ventilation and diffusion-weighted MR images were acquired in 22 patients with LAM during two breath-holds of hyperpolarized ¹²⁹Xe. ¹²⁹Xe ventilation defect percentage (VDP; percentage of voxels <60% of the mean whole-lung ¹²⁹Xe MRI signal) and apparent diffusion coefficient (ADC), a measure of alveolar airspace size, were quantified and compared with pulmonary function test parameters with Spearman statistics. Sixteen patients with LAM had a recent, clinical chest computed tomography (CT) scan available, and cyst ventilation was assessed by thresholding cysts on the CT images and registration to the ¹²⁹Xe ventilation images.Results: Ventilation deficits were observed in all patients with LAM, including those with normal pulmonary function and few cysts, and the mean VDP was 19.2% (95% confidence interval [CI], 14.8-23.5%). ¹²⁹Xe VDP was strongly correlated with forced expiratory volume in 1 second (FEV₁)/forced vital capacity (FVC) ratio (r = -0.51, P = 0.02) and diffusing capacity of the lung for carbon monoxide (Dl_CO) (r = -0.60, P = 0.009) but not with FEV₁ (r = -0.33, P = 0.13), likely because of the sensitivity of ¹²⁹Xe MRI to mild LAM disease in patients with normal FEV₁. The mean ADC was 0.048 cm²/s (95% CI, 0.042-0.053 cm²/s). In many cases, ADC was elevated relative to previously reported values in adults, and ADC was correlated with FEV₁, FEV₁/FVC ratio, and Dl_CO (P ≤ 0.02 for all). Co-registered ¹²⁹Xe MRI and CT imaging revealed considerable ventilation heterogeneity within individual patients with LAM and across patients with similarly sized cysts.Conclusions:¹²⁹Xe MRI provides a means to assess the complex regional ventilation and alveolar airspace size changes of LAM with high sensitivity and may be a clinically useful future tool for screening, managing patients, and measuring treatment efficacy.

Keywords: cyst; hyperpolarized xenon; magnetic resonance imaging; ventilation.