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

Abstract

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 (d), 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 d values less than one millisecond. Hyperpolarized helium 3 ( 3 He) MR imaging can provide both anatomical and functional information that may be important for diagnosing lung diseases. One of the most interesting implementations of 3 He imaging is diffusionweighted MR imaging, taking advantage of the much larger apparent diffusion coefficient (ADC) of 3 He compared to 1.1 Â 10 À5 cm 2 /s for hydrogen ( 1 H). 3 He diffusion in the lungs is restricted by airway and alveolar walls and therefore is highly dependent on lung microstructure. Diffusion measurements are sensitive to lung morphological information such as airway sizes and surface to volume ratio, by measuring the ADC that is largely dependent on lung geometry (1). This enables the tracking of disease progression, such as human chronic obstructive pulmonary disease (1,2) and asthma in mouse models (3). 3 He ADC has been shown to be sensitive to changes in terminal airway anatomy, specifically alveolar damage due to emphysema in both humans (1,4-6) and animal models (3,7-9).The lungs branch off from the trachea to bronchi, bronchioles, and eventually terminate at the alveolar sacs after approximately 25 divisions. The radii of alveoli range from approximately 0.12 to 0.18 mm (10,11) in humans to approximately 0.05 mm alveolar radius in rats (12). The duct size in humans range from 0.22 to 0.60 mm, depending on the generation (10), up to three times the size of an alveoli radius. In this geometry, diffusion is highly restricted for 3 He nuclei as the diffusion lengthis about 0.6 mm given a diffusion time (d) of 1.8 ms, which is typical of diffusion-weighted MR imaging. D 0 in Eq. 1 is the free diffusion coefficient and is equal to 1.91 Â 10 À4 m 2 /s (11) for pure 3 He at room temperature and 0.88 cm 2 /s when diluted in air. It has been shown that 3 He ADC obtained at millisecond diffusion times can distinguish normal from emphysematous tissue and correlates with mean linear intercept histology, an accepted measure of alveolar damage (12,13). 3 He ADC values obtained at sub-millisecond diffusion times (14) are expected to be even more sensitive to emphysema, especially in small animals. At longer diffusion times on the order of seconds, 3 He ADC is expected to reflect changes in lung anatomy over much larger length scales on the order of centimetres. Recent work has demonstrated ADC sensitivity to collateral pathway changes...

Commentary on “The influence of lung airways branching structure and diffusion time on measurements and models of short-range 3He gas MR diffusion”

“…While diffusion in each airway is anisotropic, it is almost isotropic on a macroscopic scale since each imaging voxel contains a multitude of acinar airways with a nearly isotropic distribution of directions. This fundamental property of gas diffusion in lung acinar airways was confirmed by experimental MRI measurements in humans (2,4,6), canines (15), mice (8,9) and rats (10,16) using hyperpolarized 3 He gas. It was also recently confirmed in humans (17) and rats (18) using hyperpolarized 129 Xe gas.…”

“…For 3 He gas this restricts the diffusion time Δ in human lungs to about 2 ms (4,5) and for 129 Xe, with its smaller free diffusivity, to about 15 ms (7). In small animal lungs, where the alveolar ducts and sacs are shorter, the diffusion time Δ should be much shorter, a fraction of a millisecond (7-10). This constraint recognizes acinar airways as the elementary geometrical units contributing to the gas diffusion MR signal.…”

Magnetic resonance imaging with hyperpolarized agents: methods and applications

“…These studies have served a useful role in optimizing 129 Xe DWI [216, 217] via comparison with the more mature 3 He DWI. Similar studies have explored the anisotropy and dependence on delay time of dimensional measures derived from DWI for both 3 He [218] and 129 Xe [219]. …”

Measurement of 129Xe gas apparent diffusion coefficient anisotropy in an elastase‐instilled rat model of emphysema

“…An increase in 3 He ADC is observable in chronic obstructive lung disease (4, 10–12) due to airway tissue expansion and alveolar destruction (i.e., emphysema), and correlates well with histological measurements, such as mean linear intercept; an indication of alveolar size (11, 13). Furthermore, 3 He ADC can be anisotropic in the lung (14), and depends on the duration of observation during which the nuclei diffuse in the restricted environment (i.e., the diffusion time) (15).…”