Hyperpolarized (3) He gas can provide detailed anatomical maps of the macroscopic airways in the lungs (i.e., ventilation) as well as insight into the lung microstructure through the apparent diffusion coefficient. In particular, the apparent diffusion coefficient of (3) He in the lung exhibits anisotropic effects that depend on diffusion time (δ), and it has been shown to be extraordinarily sensitive to enlargement in terminal airways and alveoli associated with emphysema. In this study, the anisotropic nature of the (3) He apparent diffusion coefficient is studied in a rat model of emphysema, based on elastase instillation, specifically for δ values less than one millisecond. Longitudinal (D(L) ) and transverse (D(T) ) diffusion coefficients were mapped at δ = 360 μs and δ = 800 μs based on a cylinder model of lung structure and correlated with histological measurement of alveolar damage based on mean linear intercept (L(m) ). Whole-lung mean D(T) measured at δ = 360 μs in the elastase-instilled rat lungs (0.14 ± 0.09 cm(2) /s) demonstrated the most significant increase (p = 0.00195) compared to the sham-instilled cohort (0.06 ± 0.06 cm(2) /s) and had a strong linear correlation with L(m) (Pearson's correlation coefficient of 0.9). These results suggest that measurement of (3) He apparent diffusion coefficient anisotropy, specifically D(T) , can provide a sensitive indicator of emphysema, particularly at very short diffusion times (δ = 360 μs).
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