Quantitative assessment of lung microstructure in healthy mice using an MR-based ³He lung morphometry technique

Abstract

The recently developed technique of lung morphometry using hyperpolarized (3)He diffusion magnetic resonance (MR) (Yablonskiy DA, Sukstanskii AL, Woods JC, Gierada DS, Quirk JD, Hogg JC, Cooper JD, Conradi MS. J Appl Physiol 107: 1258-1265, 2009) permits in vivo study of lung microstructure at the alveolar level. Originally proposed for human lungs, it also has the potential to study small animals. The technique relies on theoretical developments in the area of gas diffusion in lungs linking the diffusion attenuated MR signal to the lung microstructure. To adapt this technique to small animals, certain modifications in MR protocol and data analysis are required, reflecting the smaller size of mouse alveoli and acinar airways. This is the subject of the present paper. Herein, we established empirical relationships relating diffusion measurements to geometrical parameters of lung acinar airways with dimensions typical for mice and rats by using simulations of diffusion in the airways. We have also adjusted the MR protocol to acquire data with much shorter diffusion times compared with humans to accommodate the substantially smaller acinar airway length. We apply this technique to study mouse lungs ex vivo. Our MR-based measurements yield mean values of lung surface-to-volume ratio of 670 cm(-1), alveolar density of 3,200 per mm(3), alveolar depth of 55 μm, and mean chord length of 62 μm, all consistent with published data obtained histologically in mice by unbiased methods. The proposed technique can be used for in vivo experiments, opening a door for longitudinal studies of lung morphometry in mice and other small animals.

Stem Cells and Cell Therapies in Lung Biology and Diseases: Conference Report

“…Hyperpolarized magnetic resonance imaging with 3He or 129Xe works by measuring the random atomic motion (diffusion) of the gas molecules (64,65). Because airway structures will limit the diffusion of gas, measurement of the atomic motion will provide information about the lung microstructure.…”

“…Because airway structures will limit the diffusion of gas, measurement of the atomic motion will provide information about the lung microstructure. Both gases have been used in humans, large animals, and, more recently, small animals in both healthy and diseased conditions and have provided important insights into the three-dimensional structure of the lungs (64)(65)(66)(67)(68)(69)(70)(71)(72)(73). The usefulness of this approach to treatment of human disease is obvious, with greater ability to determine the changes in lung microstructure as a function of disease and over time.…”

Mapping of 3He apparent diffusion coefficient anisotropy at sub‐millisecond diffusion times in an elastase‐instilled rat model of emphysema

“…D L measured at a diffusion time of 1.8 ms has been previously shown to be sensitive to emphysema in humans (6,19). Diffusion studies using the cylinder model have also been done using dogs and showed strong correlation to quantitative computed tomography (CT) lung density and volume measurements (13), and histology measurements in rats (9,20) and mice (21).…”

“…However, sub-millisecond diffusion times are typically not achievable in clinical MR imaging due to limitations in clinical gradient performance (i.e., gradient strength and slew rate). This is less of an issue for animal imaging, as higher performance gradients (21) are routinely available, making submillisecond diffusion times (<1 ms) possible. Whereas D L was predicted to be more sensitive to emphysema condition than D T at a diffusion time of 1.8 ms (6), in this study, we hypothesize that D T measured at submillisecond diffusion times in an elastase-instillation model of emphysema in rats will correlate with histology (i.e., mean linear intercept) and be more sensitive to elastase damage than D L and that of ADC alone.…”

Animal models of bronchopulmonary dysplasia. The preterm baboon models

“…Recent important advances in accurate, unbiased, stereological methods (53,56,82) combined with appropriate in vivo and/or ex vivo imaging techniques recently reported in rodents are needed and should prove extremely helpful in expanding our knowledge concerning the evolution and long-term outcomes of preterm lung injury following various therapeutic interventions (34,57,82).…”