Three-dimensional micro-CT analysis of vascular remodelling and vascular pruning in pulmonary arterial hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare, progressive pulmonary vascular disorder characterised by pulmonary arteriole remodelling leading to increased pulmonary vascular resistance (PVR). Key features of PAH are vascular pruning and plexiform lesion formation. While these features have been described histologically, a detailed quantitative analysis is lacking. In this study, we used micro-computed tomography (µCT) to provide three-dimensional quantification of pulmonary vascular alterations. METHODS: We performed µCT imaging on explanted lungs from seven patients with end-stage idiopathic (n=4) or heritable (n=3) PAH and five healthy controls. Arterial lumen diameter, the number of acinar vessels and plexiform lesion distribution were quantified and correlated with clinical and haemodynamic data. RESULTS: We observed a 50% reduction in the diameter of the acinar arterial lumen and a 61% decrease in the number of intra-acinar arterioles, confirming vascular pruning. Arterial narrowing correlated with PVR and mean pulmonary artery pressure. Heritable PAH showed a higher number of plexiform lesions than idiopathic PAH, with more distal, acinar-level localisation. CONCLUSIONS: This study provides quantitative evidence of arterial narrowing and objective loss of small intra-acinar arteries in end-stage PAH, supporting their central role in elevated PVR. Pulmonary vascular rarefaction may represent an initiating process of vascular remodelling rather than a secondary phenomenon. Heritable PAH was characterised by a higher number and more distal distribution of plexiform lesions than idiopathic PAH, which may contribute to its more severe phenotype.