title: Parametric Response Mapping as an Imaging Biomarker in Lung Transplant Recipients.
abstract: The predominant cause of chronic lung allograft failure is small airway obstruction arising from bronchiolitis obliterans. However, clinical methodologies for evaluating presence and degree of small airway disease are lacking.
  
  
  
  To determine if parametric response mapping (PRM), a novel computed tomography voxel-wise methodology, can offer insight into chronic allograft failure phenotypes and provide prognostic information following spirometric decline.
  
  
  
  PRM-based computed tomography metrics quantifying functional small airways disease (PRMfSAD) and parenchymal disease (PRMPD) were compared between bilateral lung transplant recipients with irreversible spirometric decline and control subjects matched by time post-transplant (n = 22). PRMfSADat spirometric decline was evaluated as a prognostic marker for mortality in a cohort study via multivariable restricted mean models (n = 52).
  
  
  
  Patients presenting with an isolated decline in FEV1(FEV1First) had significantly higher PRMfSADthan control subjects (28% vs. 15%; P = 0.005), whereas patients with concurrent decline in FEV1and FVC had significantly higher PRMPDthan control subjects (39% vs. 20%; P = 0.02). Over 8.3 years of follow-up, FEV1First patients with PRMfSADgreater than or equal to 30% at spirometric decline lived on average 2.6 years less than those with PRMfSADless than 30% (P = 0.004). In this group, PRMfSADgreater than or equal to 30% was the strongest predictor of survival in a multivariable model including bronchiolitis obliterans syndrome grade and baseline FEV1%predicted (P = 0.04).
  
  
  
  PRM is a novel imaging tool for lung transplant recipients presenting with spirometric decline. Quantifying underlying small airway obstruction via PRMfSADhelps further stratify the risk of death in patients with diverse spirometric decline patterns.
authors: 1 Division of Pulmonary and Critical Care Medicine.
authors: Elizabeth A
authors: EA
authors: Belloli
authors: 2 Department of Biostatistics, and.
authors: Irina
authors: I
authors: Degtiar
authors: 2 Department of Biostatistics, and.
authors: Xin
authors: X
authors: Wang
authors: 3 Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, Michigan; and.
authors: Gregory A
authors: GA
authors: Yanik
authors: 4 Department of Pharmacy, and.
authors: Linda J
authors: LJ
authors: Stuckey
authors: 5 Lung Transplant Unit, Department of Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium.
authors: Stijn E
authors: SE
authors: Verleden
authors: 6 Department of Radiology, University of Michigan Health System, Ann Arbor, Michigan.
authors: Ella A
authors: EA
authors: Kazerooni
authors: 6 Department of Radiology, University of Michigan Health System, Ann Arbor, Michigan.
authors: Brian D
authors: BD
authors: Ross
authors: 2 Department of Biostatistics, and.
authors: Susan
authors: S
authors: Murray
authors: 6 Department of Radiology, University of Michigan Health System, Ann Arbor, Michigan.
authors: Craig J
authors: CJ
authors: Galbán
authors: 1 Division of Pulmonary and Critical Care Medicine.
authors: Vibha N
authors: VN
authors: Lama
mesh_terms: D000328:Adult; D000402:Airway Obstruction / Q000000981:diagnostic imaging* / Q000503:physiopathology; D015415:Biomarkers; D015331:Cohort Studies; D005260:Female; D005541:Forced Expiratory Volume; D006084:Graft Rejection / Q000000981:diagnostic imaging* / Q000503:physiopathology; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D008168:Lung / Q000000981:diagnostic imaging* / Q000503:physiopathology; D016040:Lung Transplantation; D008297:Male; D008875:Middle Aged; D015203:Reproducibility of Results; D014057:Tomography, X-Ray Computed / Q000379:methods*; D066027:Transplant Recipients
chemical_list: D015415:Biomarkers
keywords: bronchiolitis obliterans syndrome; chronic lung allograft dysfunction; computed tomography of the chest; parametric response mapping; prognosis