Functional morphometry to estimate the alveolar surface area using a premature baboon model

Abstract

The main respiratory pathophysiological process following premature birth is the delayed or arrested alveolar development that translates to a smaller alveolar surface area (S_A). Histological morphometry is the gold standard method to measure the S_A but requires invasive tissue sampling or the removal of the whole organ for analysis. Alternatively, the S_A could be measured in living subjects by "functional morphometry" using Fick's first law of diffusion and noninvasive measurements of the ventilation to perfusion ratio (V̇a/Q̇). We herein aim to describe a novel functional morphometric method to measure S_A using a premature baboon model. We used both functional morphometry and postmortem histological morphometry to measure S_A in 11 premature baboons born at 135 days who received intensive care treatment for 14 days. For the calculation of the S_A by functional morphology, we measured the septal wall thickness using microscopy, the alveolar arterial oxygen gradient using concurrent measurements of arterial pressure of O₂ and CO₂, and pulmonary perfusion using echocardiography and integrated Doppler signals. The median [interquartile range (IQR)] S_A using functional morphometry was 3,100 (2,080-3,640) cm² and using histological morphometry was 1,034 (634-1,210) cm² (left lung only). The S_A measured by functional morphometry was not related to the S_A measured by histological morphometry. Following linear regression analysis, the V̇a/Q̇ significantly predicted the histologically measured S_A (R² = 0.659, P = 0.002). In conclusion, functional measurements of ventilation to perfusion ratio could be used to estimate the alveolar surface area in prematurely born baboons and the ventilation perfusion ratio was the main determinant of the alveolar surface area.NEW & NOTEWORTHY The main morphological characteristic of chronic respiratory disease in prematurely born infants is the impaired/arrested alveolar growth that corresponds to a smaller aggregated alveolar surface area (S_A). This decreased S_A might be the limiting factor later in life affecting exercise capacity and quality of life. There is paucity of sensitive, noninvasive biomarkers to monitor the evolution of neonatal respiratory disease. Our noninvasive functional morphometric S_A might help to bridge the gap between pathophysiology and clinical monitoring.

Keywords: Fick’s law; alveolar surface area; morphometry; prematurity; stereology.