Lung Morphometry with HP Gas Diffusion MRI: From Theoretical Models to Experimental Measurements

Diffusion magnetic resonance imaging (MRI) is a unique tool that allows studying tissue structure at a scale that is much smaller than experimentally achievable voxel resolution. Diffusion methods based on conventional proton ¹H MRI have been used in different parts of the body to obtain information on healthy and disease tissue structure at the cellular level. In this review we describe recent developments in diffusion lung MRI with hyperpolarized gases. We show that a combination of modeling results of gas diffusion in lung airspaces and diffusion measurements with variable diffusion-sensitizing gradients allows extracting quantitative information on the structure of lung acinar airways (alveolar sacs and ducts) and alveoli. This approach, called in vivo lung morphometry, allows from a short 10-s MRI scan, providing quantitative values and spatial distributions of the same physiological parameters as are measured by means of "standard" invasive stereology (mean linear intercept, surface-to-volume ratio, density of alveoli), as well as some advanced Weibel parameters characterizing lung microstructure-average radii of alveolar sacs and ducts, as well as the depth of their alveolar sleeves. Such measurements, never before available from in vivo studies, are of great importance and interest to a broad range of physiologists and clinicians studying lung microstructure in health and disease. We also discuss new type of experiments that are based on the in vivo lung morphometry technique combined with Gradient Echo MRI measurements of hyperpolarized gas transverse relaxation in the lung airspaces. Such experiments provide additional information on blood vessel volume fraction, specific gas volume, the length of acinar airways, and allows evaluation of lung parenchymal and nonparenchymal tissue. Both advanced (in vivo lung morphometry) and traditional (based on apparent diffusion coefficient measurements) methods are discussed in this review.