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

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 ((V) over dotA/(Q) over dot). 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 septa! wall thickness using microscopy, the alveolar arterial oxygen gradient using concurrent measurements of arterial pressure of O-2 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) cm(2) and using histological morphometry was 1,034 (634-1,210) cm(2) (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 (V) over dotA/(Q) over dot significantly predicted the histologically measured S-A (R-2 = 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.