Quantitativein vivoassessment of lung microstructure at the alveolar level with hyperpolarized³He diffusion MRI

Abstract

The study of lung emphysema dates back to the beginning of the 17th century. Nevertheless, a number of important questions remain unanswered because a quantitative localized characterization of emphysema requires knowledge of lung structure at the alveolar level in the intact living lung. This information is not available from traditional imaging modalities and pulmonary function tests. Herein, we report the first in vivo measurements of lung geometrical parameters at the alveolar level obtained with 3 He diffusion MRI in healthy human subjects and patients with severe emphysema. We also provide the first experimental data demonstrating that 3 He gas diffusivity in the acinus of human lung is highly anisotropic. A theory of anisotropic diffusion is presented. Our results clearly demonstrate substantial differences between healthy and emphysematous lung at the acinar level and may provide new insights into emphysema progression. The technique offers promise as a clinical tool for early diagnosis of emphysema.C hronic obstructive pulmonary disease in general and emphysema in particular are leading causes of death in industrialized countries and account for a substantial portion of health care spending (1). Several definitions of emphysema have been formulated by scientific bodies: according to ref. 2, emphysema is ''a condition of the lung characterized by abnormal, permanent enlargement of air spaces distal to the terminal bronchioles, accompanied by destruction of their walls, without fibrosis.'' This definition means that an accurate characterization of emphysema requires diagnostic methods that are noninvasive and sensitive to the regional lung microstructure at the alveolar level in the living lung. Diffusion MRI of 3 He gas, which has become available after recent advances in the physics of optical pumping and semiconductor diode lasers (see, for example, refs. 3-5), can provide this sensitivity. Previously, we and others have suggested (6-10) that measurement of 3 He gas diffusivity in the lung air spaces has potential for identifying changes in lung structure from emphysema at the alveolar level.In any medium, atoms or molecules diffuse; that is, atoms perform a Brownian-motion random walk. In time interval ⌬, in the absence of restricting walls or barriers, molecules will move a rms distance l 0 ϭ (2D 0 ⌬) 1/2 along any axis. The parameter D 0 is termed the free diffusion coefficient, which for 3 He in air at 37°C is D 0 ϭ 0.88 cm 2 ͞sec. Hence 3 He gas atoms can wander distances on the order of 1 mm in times as short as 1 ms. The alveolar walls, as well as the walls of bronchioles, alveolar ducts, sacs, and other branches of the airway tree, serve as obstacles to the path of diffusing 3 He atoms and reduce 3 He displacement. Indeed, the MR-measured average 3 He diffusion coefficient (the so-called apparent diffusion coefficient or ADC) in healthy human lungs is about 0.20 cm 2 ͞sec, more than a factor of four smaller than the free diffusion coefficient of 3 He in air (6, 7). In emphysema, the restriction...

Functional lung imaging using hyperpolarized gas MRI

“…[2]), is straightforward and provides regional information, it is now widely recognized that the signal decay due to diffusion in the lungs is multiexponential (51,94), most likely due to multiple scales of restricted diffusion within the lungs (92). Consequently, new directions in this very promising area incorporate multiple b-value measurements using Carr Purcell Meiboom Gill (CPMG) pulse sequences (95) and diffusion tensor imaging combined with modeling (92).…”

“…Consequently, new directions in this very promising area incorporate multiple b-value measurements using Carr Purcell Meiboom Gill (CPMG) pulse sequences (95) and diffusion tensor imaging combined with modeling (92). In the future, these techniques may be capable of estimating airway bore size in obstructive lung diseases such as asthma (92). Also, the lower diffusion constant of Xe-129 provides promise for probing smaller scale structures and thus may be more sensitive to disease than DW imaging using HP He-3.…”

q‐space analysis of lung morphometry in vivo with hyperpolarized3He spectroscopy

“…The attenuation parameter K is thus obtained by fitting the non-diffusion-weighted signals to Eq. [12]. Once K is determined, S DW (n) can be calculated by the following equation: …”

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

“…3 He apparent diffusion is described by two components: (i) a longitudinal diffusion coefficient (D L ), reflective of diffusion along the length of the alveolar duct, and (ii) a transverse diffusion coefficient (D T ), reflective of diffusion perpendicular to the duct. 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).…”

“…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)(5)(6) and animal models (3,(7)(8)(9).…”