Pulmonary MRI and Cluster Analysis Help Identify Novel Asthma Phenotypes.

Abstract

Outside eosinophilia, current clinical asthma phenotypes do not show strong relationships with disease pathogenesis or treatment responses. While chest x-ray computed tomography (CT) phenotypes have previously been explored, functional MRI measurements provide complementary phenotypic information. To derive novel data-driven asthma phenotypic clusters using functional MRI airway biomarkers that better describe airway pathologies in patients. Retrospective. A total of 45 patients with asthma who underwent post-bronchodilator 129 Xe MRI, volume-matched CT, spirometry and plethysmography within a 90-minute visit. Three-dimensional gradient-recalled echo 129 Xe ventilation sequence at 3T. We measured MRI ventilation defect percent (VDP), CT airway wall-area percent (WA%), wall-thickness (WT, WT* [*normalized for age/sex/height]), lumen-area (LA), lumen-diameter (D, D*) and total airway count (TAC). Univariate relationships were utilized to select variables for k-means cluster analysis and phenotypic subgroup generation. Spirometry and plethysmography measurements were compared across imaging-based clusters. Spearman correlation (ρ), one-way analysis of variance (ANOVA) or Kruskal-Wallis tests with post hoc Bonferroni correction for multiple comparisons, significance level 0.05. Based on limited common variance (Kaiser-Meyer-Olkin-measure=0.44), four unique clusters were generated using MRI VDP, TAC, WT* and D* (52 ± 14 years, 27 female). Imaging measurements were significantly different across clusters as was the forced expiratory volume in 1-second (FEV1 %pred ), residual volume/total lung capacity and airways resistance. Asthma-control (P=0.9), quality-of-life scores (P=0.7) and the proportions of severe-asthma (P=0.4) were not significantly different. Cluster1 (n=15/8 female) reflected mildly abnormal CT airway measurements and FEV1 with moderately abnormal VDP. Cluster2 (n=12/12 female) reflected moderately abnormal TAC, WT and FEV1 . In Cluster3 and Cluster4 (n=14/6 female, n=4/1 female, respectively), there was severely reduced TAC, D and FEV1 , but Cluster4 also had significantly worse, severely abnormal VDP (7 ± 5% vs. 41 ± 12%). We generated four proof-of-concept MRI-derived clusters of asthma with distinct structure-function pathologies. Cluster analysis of asthma using 129 Xe MRI in combination with CT biomarkers is feasible and may challenge currently used paradigms for asthma phenotyping and treatment decisions. 3 TECHNICAL EFFICACY: Stage.