UNRAVELING THE LUNG VASCULAR REMODELING IN PULMONARY HYPERTENSION USING A QUANTITATIVE DIGITAL PATHOLOGY SOFTWARE

Abstract

Pulmonary arterial hypertension (PAH) is a rare chronic life-threatening disorder, characterized by the elevation of the mean pulmonary arterial pressure above 20 mmHg at rest. Histologically, PAH induces lung vascular remodeling, with the thickening of vessel wall. The conventional histological analysis commonly used in non-clinical models to assess lung vascular remodeling relies on manual measurements of representative lung vessels and is time-consuming. We have developed a fully automated reader-independent software (MorphoQuant-Lung) to both specifically detect vessels and measure vascular wall components from a-SMA rat lung sections. Analysis was performed on monocrotaline-and Sugen/hypoxia-induced PH rat models, treated or not with Sildenafil. The software requires 3-5 minutes to detect up to 1500 vessels per section, classify them per size, quantify intima, media and wall thicknesses, and calculate their level of occlusion. A comparison of our digital analysis results with those of the pathologists conventional visual analysis was performed for wall thickness and lumen radius showing a strong correlation between the two techniques (r: 0.80 and r: 0.88) regardless of the rat model. In addition, the occlusion estimated by automated analysis also strongly correlated with the mean pulmonary arterial pressure and the pulmonary vascular resistance (r ranging from 0.71 to 0.83) in both rat models. The added value of the present digital analysis paves the way for a more in-depth understanding of the PAH physiopathology in preclinical research and provides a robust and reliable tool for efficient therapeutic drug development.