Multiphase micro-CT (µCT) as a surrogate for longitudinal pulmonary function quantification in a lung fibrosis model

µCT strongly complements end-stage histomorphometry in preclinical models of lung disease. We aim to derive respiratory dynamics from µCT in a Bleomycin (BLM)-induced model of lung fibrosis, to quantify disease progression and antifibrotic effect of Nintedanib (NTD). Pulmonary fibrosis was BLM-induced in 42 mice. Animals were treated daily from day 7 to 21, either with vehicle or NTD. µCT was performed on days 7 and 21 with a 4-minute scanning protocol, allowing the retrospective reconstruction of ~30 phases per breath cycle. Lung volumes were segmented and gas volume was calculated in each phase to estimate 1) the gas volume curve 2) the gas-flow curve (first derivative of gas volume curve) 3) the flow-volume loop. On day 7, minute ventilation (MV) was lower in BLM compared to saline (~20 ml/min vs 30 ml/min, p=0.005), due to lower inspiratory duty cycle and reduced expiratory flow (p<0.01). On day 21, MV was still reduced in BLM and NINT (~20 ml/min), due to lower volumes and flows. Corresponding flow-volume loops are shown in Figure 1. Results highlight an obstructive pattern on day 7, due to the BLM-induced inflammatory reaction, and a restrictive pattern on day 21, due to fibrotic tissue formation. NINT showed milder restriction. Multiphase-µCT closely resembles PFTs conducted by spirometry, thus represents a novel tool for longitudinal lung function assessment in preclinical drug discovery. <fig><object-id>erj;64/suppl_68/PA3387/F1</object-id><object-id>F1</object-id><object-id>F1</object-id><graphic></graphic></fig>