Quantitative CT Correlates with Local Inflammation in Lung of Patients with Subtypes of Chronic Lung Allograft Dysfunction
Sundaresh Ram,
Stijn E. Verleden,
Alexander J. Bell,
Benjamin A. Hoff,
Wassim W. Labaki,
Susan Murray,
Bart M. Vanaudenaerde,
Robin Vos,
Geert M. Verleden,
Ella A. Kazerooni,
Stefanie Galbán,
Charles R. Hatt,
Meilan K. Han,
Vibha N. Lama,
Craig J. Galbán
Affiliations
Sundaresh Ram
Department of Radiology, University of Michigan, Ann Arbor, MI 48109, USA
Stijn E. Verleden
Antwerp Surgical Training, Anatomy and Research Centre (ASTARC), Faculty of Medicine and Health Sciences, University of Antwerp, Wilrijk, 2610 Antwerp, Belgium
Alexander J. Bell
Department of Radiology, University of Michigan, Ann Arbor, MI 48109, USA
Benjamin A. Hoff
Department of Radiology, University of Michigan, Ann Arbor, MI 48109, USA
Wassim W. Labaki
Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, MI 48109, USA
Susan Murray
Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI 48109, USA
Bart M. Vanaudenaerde
Department of Chronic Diseases and Metabolism (CHROMETA), Katholieke Universiteit Leuven, 3000 Leuven, Belgium
Robin Vos
Department of Chronic Diseases and Metabolism (CHROMETA), Katholieke Universiteit Leuven, 3000 Leuven, Belgium
Geert M. Verleden
Department of Chronic Diseases and Metabolism (CHROMETA), Katholieke Universiteit Leuven, 3000 Leuven, Belgium
Ella A. Kazerooni
Department of Radiology, University of Michigan, Ann Arbor, MI 48109, USA
Stefanie Galbán
Department of Radiology, University of Michigan, Ann Arbor, MI 48109, USA
Charles R. Hatt
Imbio, LLC, Minneapolis, MN 55405, USA
Meilan K. Han
Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, MI 48109, USA
Vibha N. Lama
Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, MI 48109, USA
Craig J. Galbán
Department of Radiology, University of Michigan, Ann Arbor, MI 48109, USA
Chronic rejection of lung allografts has two major subtypes, bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS), which present radiologically either as air trapping with small airways disease or with persistent pleuroparenchymal opacities. Parametric response mapping (PRM), a computed tomography (CT) methodology, has been demonstrated as an objective readout of BOS and RAS and bears prognostic importance, but has yet to be correlated to biological measures. Using a topological technique, we evaluate the distribution and arrangement of PRM-derived classifications of pulmonary abnormalities from lung transplant recipients undergoing redo-transplantation for end-stage BOS (N = 6) or RAS (N = 6). Topological metrics were determined from each PRM classification and compared to structural and biological markers determined from microCT and histopathology of lung core samples. Whole-lung measurements of PRM-defined functional small airways disease (fSAD), which serves as a readout of BOS, were significantly elevated in BOS versus RAS patients (p = 0.01). At the core-level, PRM-defined parenchymal disease, a potential readout of RAS, was found to correlate to neutrophil and collagen I levels (p < 0.05). We demonstrate the relationship of structural and biological markers to the CT-based distribution and arrangement of PRM-derived readouts of BOS and RAS.
