Jacob RE, Minard KR, Laicher G, Timchalk C. 3D3 He diffusion MRI as a local in vivo morphometric tool to evaluate emphysematous rat lungs. J Appl Physiol 105: 1291-1300, 2008. First published August 21, 2008 doi:10.1152/japplphysiol.90375.2008In this work, we investigate 3 He magnetic resonance imaging as a noninvasive morphometric tool to assess emphysematous disease state on a local level. Emphysema was induced intratracheally in rats with 25 U/100 g body wt of porcine pancreatic elastase dissolved in 200 l saline. Rats were then paired with saline-dosed controls. Nine threedimensional (3D) 3 He diffusion-weighted images were acquired at 1, 2, or 3 wk postdose, after which the lungs were harvested and prepared for histological analysis. Recently introduced indexes sensitive to the heterogeneity of the air space size distribution were calculated. These indexes, D1 and D2, were derived from the moments of the mean equivalent airway diameters. Averaged over the entire lung, it is shown that the average 3 He diffusivity (Dave) correlates well with histology (R ϭ 0.85, P Ͻ 0.0001). By matching small (0.046 cm 2 ) regions in 3 He images with corresponding regions in histological slices, Dave correlates significantly with both D1 and D2 (R ϭ 0.88 and R ϭ 0.90, respectively, with P Ͻ 0.0001). It is concluded that 3 He MRI is a viable noninvasive morphometric tool for localized in vivo emphysema assessment. hyperpolarized gas; elastase; lung histology; diffusion anisotropy EMPHYSEMA is a chronic obstructive pulmonary disease (COPD) typified by tissue destruction and airway expansion (40). Emphysema, particularly the early stages, may be characterized by a heterogeneous distribution of air space sizes (13). Indeed, McLaughlin and Tueller (23) showed that in apparently normal lungs of smokers harvested at autopsy (none of the deaths were attributed to COPD), numerous localized regions of tissue destruction were surrounded by normal tissue. Because early detection of COPD can play a significant role in managing the disease and improving patient outcomes (2, 20), a locally specific and sensitive method of detection may prove beneficial. Hyperpolarized (HP) 3 He and 129 Xe gas have been exploited in clinical and preclinical magnetic resonance imaging (MRI) studies to evaluate lung tissue structure (5,6,8,18,22,33), although perfluorinated gases have also been used (14). In several studies, 3 He MRI has been demonstrated to be sensitive to mild or early emphysema (10,28,34,38). Gas-phase MRI is well suited for detecting emphysema because the diffusivity (Brownian motion) of gas is strongly affected by restrictive barriers, such as alveolar walls. Additionally, the gas contained in larger air spaces contributes proportionally more to the MRI signal in each voxel, making the signal within each voxel a volume-weighted average sensitive to the presence of enlarged air spaces or blebs. Therefore, MRI provides noninvasive, localized information about lung structure while allowing for frequent assessment of disease state wit...