Early changes of lung function and structure in an elastase model of emphysema--a hyperpolarized 3He MRI study

Early changes of lung function and structure were studied in the presence of an elastase-induced model of emphysema in 35 Sprague-Dawley rats at mild (5 U/100 g) and moderate (10 U/100 g) severities. Lung ventilation was measured on a regional basis (at a planar resolution of 3.2 mm) by hyperpolarized 3He MRI at 5 and 10 wk after model induction. Subsequent to imaging, average alveolar diameter was measured from histological slices taken from the centers of each lobe. Changes of mean fractional ventilation, mean linear intercept, and intrasubject heterogeneity of ventilation were studied during disease progression. Mean fractional ventilation was significantly different between healthy controls (0.23 +/- 0.04) and emphysematous animals at both time points in the 10-unit group (0.06 +/- 0.02 and 0.12 +/- 0.05, respectively). Changes in average alveolar diameter were not statistically observable until the 10th wk between healthy (37 +/- 10 microm) and emphysematous rats (73 +/- 25 and 95 +/- 31 microm, for 5 and 10 units, respectively). Assessment of function-structure correlation suggested that the majority of the decline in fractional ventilation occurred in the first 5 wk, while enlargement of alveolar diameters appeared primarily between the 5th and 10th wk. A thresholding metric, based on the 20th percentile of fractional ventilation over the entire lung, was utilized to detect the onset of the disease with confidence, independent of whether the regional ventilation measurements were normalized with respect to the delivered tidal volume and estimated functional residual capacity of each individual rat.