Plexiform lesions in human explant lungs with end-stage pulmonary arterial hypertension: µCT analysis

Plexiform lesions (PLs) are a histopathological hallmark of pulmonary arterial hypertension (PAH). PLs are intricate vascular formations thought to arise from abnormal cell proliferation and pulmonary vascular remodeling. Current study methods do not allow for quantification of the number of PLs or analysis of their spatial distribution. The aim of this pilot study is to demonstrate the possibility to quantitatively and spatially assess PLs using micro-computed tomography (µCT). We included one explant lung from a 30-year-old female with a heterozygous BMPR2 mutation who was diagnosed with PAH. The explant lung was frozen while inflated at total lung capacity, and sectioned into 2 cm thick slices. One tissue cylinder (ø=1.4cm) was selected per slice and scanned using µCT. The number of PLs/mL of lung volume was calculated and the distribution was determined based on anatomical occurrence. We found an average of 3.5 PLs/mL of lung volume. PLs occurred in different anatomical regions, with notable occurrences observed on arterioles adjacent to alveoli (55%), respiratory (29%) and terminal bronchioles (6%) and at unexpected abrupt ends of the arterioles (10%). In summary, we were able to quantify PLs using µCT in lungs from a PAH patient. Interestingly, PLs were mostly observed at the precapillary level close to alveoli.