Lung fibrosis has specific computed tomography (CT) findings and represents a common finding in advanced COVID-19 pneumonia whose reversibility has been poorly investigated. The aim of this study was to quantify the extension of collagen deposition and aeration in postmortem cryobiopsies of critically ill COVID-19 patients and to describe the correlations with qualitative and quantitative analyses of lung CT. Postmortem transbronchial cryobiopsy samples were obtained, formalin fixed, paraffin embedded and stained with Sirius red to quantify collagen deposition, defining fibrotic samples as those with collagen deposition above 10%. Lung CT images were analyzed qualitatively with a radiographic score and quantitatively with computer-based analysis at the lobe level. Thirty samples from 10 patients with COVID-19 pneumonia deceased during invasive mechanical ventilation were included in this study. The median [interquartile range] percent collagen extension was 6.8% (4.6–16.2%). In fibrotic compared to nonfibrotic samples, the qualitative score was higher (260 (250–290) vs. 190 (120–270), p = 0.036) while the gas fraction was lower (0.46 (0.32–0.47) vs. 0.59 (0.37–0.68), p = 0.047). A radiographic score above 230 had 100% sensitivity (95% confidence interval, CI: 66.4% to 100%) and 66.7% specificity (95% CI: 41.0% to 92.3%) to detect fibrotic samples, while a gas fraction below 0.57 had 100% sensitivity (95% CI: 66.4% to 100%) and 57.1% specificity (95% CI: 26.3% to 88.0%). In COVID-19 pneumonia, qualitative and quantitative analyses of lung CT images have high sensitivity but moderate to low specificity to detect histopathological fibrosis. Pseudofibrotic CT findings do not always correspond to increased collagen deposition.

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BackgroundIdentification of lung parenchyma on computer tomographic (CT) scans in the research setting is done semi-automatically and requires cumbersome manual correction. This is especially true in pathological conditions, hindering the clinical application of aeration compartment (AC) analysis. Deep learning based algorithms have lately been shown to be reliable and time-efficient in segmenting pathologic lungs. In this contribution, we thus propose a novel 3D transfer learning based approach to quantify lung volumes, aeration compartments and lung recruitability.MethodsTwo convolutional neural networks developed for biomedical image segmentation (uNet), with different resolutions and fields of view, were implemented using Matlab. Training and evaluation was done on 180 scans of 18 pigs in experimental ARDS (u2NetPig) and on a clinical data set of 150 scans from 58 ICU patients with lung conditions varying from healthy, to COPD, to ARDS and COVID-19 (u2NetHuman). One manual segmentations (MS) was available for each scan, being a consensus by two experts. Transfer learning was then applied to train u2NetPig on the clinical data set generating u2NetTransfer. General segmentation quality was quantified using the Jaccard index (JI) and the Boundary Function score (BF). The slope between JI or BF and relative volume of non-aerated compartment (SJI and SBF, respectively) was calculated over data sets to assess robustness toward non-aerated lung regions. Additionally, the relative volume of ACs and lung volumes (LV) were compared between automatic and MS.ResultsOn the experimental data set, u2NetPig resulted in JI = 0.892 [0.88 : 091] (median [inter-quartile range]), BF = 0.995 [0.98 : 1.0] and slopes SJI = −0.2 {95% conf. int. −0.23 : −0.16} and SBF = −0.1 {−0.5 : −0.06}. u2NetHuman showed similar performance compared to u2NetPig in JI, BF but with reduced robustness SJI = −0.29 {−0.36 : −0.22} and SBF = −0.43 {−0.54 : −0.31}. Transfer learning improved overall JI = 0.92 [0.88 : 0.94], P < 0.001, but reduced robustness SJI = −0.46 {−0.52 : −0.40}, and affected neither BF = 0.96 [0.91 : 0.98] nor SBF = −0.48 {−0.59 : −0.36}. u2NetTransfer improved JI compared to u2NetHuman in segmenting healthy (P = 0.008), ARDS (P < 0.001) and COPD (P = 0.004) patients but not in COVID-19 patients (P = 0.298). ACs and LV determined using u2NetTransfer segmentations exhibited < 5% volume difference compared to MS.ConclusionCompared to manual segmentations, automatic uNet based 3D lung segmentation provides acceptable quality for both clinical and scientific purposes in the quantification of lung volumes, aeration compartments, and recruitability.