Magnetisation transfer as a biomarker for chronic airway fibrosis in a mouse lung transplantation model

Abstract

BackgroundChronic airway fibrosis (CAF) is the most prevalent complication in human lung transplant recipients. The aim of the study is to evaluate magnetisation transfer (MT) as a biomarker of developing CAF of lung transplants in a mouse model.MethodsLung transplantation was performed in 48 mice, applying major or minor histocompatibility mismatches between strains for the induction of CAF. MT measurements were performed in vivo with systematic variation of off-resonance frequencies and flip angle of the MT prepulse. MT ratios (MTRs) were compared for lungs showing CAF and without CAF.ResultsSeven out of 24 animals (29%) showed a pattern of CAF at histology. All mice developing CAF also showed signs of acute rejection, whereas none of the lungs showed signs of other post-transplant complications. After lung transplantation, pulmonary infiltration was a frequent finding (14 out of 24) exhibiting a higher MTR (24.8% ± 4.5%) compared to well-ventilated lungs (12.3% ± 6.9%, p = 0.001) at 8000 Hz off-resonance frequency, 3000° flip angle. In infiltrated lung tissue exhibiting CAF, lower MTR values (21.8% ± 5.7%) were found compared to infiltrated lungs showing signs of acute rejection alone (26.5% ± 2.9%, p = 0.028), at 8000 Hz, 3000° flip angle. The highest MTR values were observed at 3000° flip angle, using a 1000 Hz off-resonance frequency.ConclusionMTR might serve as a tool for the detection of CAF in infiltrated lung tissue.