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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...

The structure and integrity of pulmonary acinar airways and their changes in different diseases are of great importance and interest to a broad range of physiologists and clinicians. The introduction of hyperpolarized gases has opened a door to in vivo studies of lungs with MRI. In this study we demonstrate that MRI-based measurements of hyperpolarized (3)He diffusivity in human lungs yield quantitative information on the value and spatial distribution of lung parenchyma surface-to-volume ratio, number of alveoli per unit lung volume, mean linear intercept, and acinar airway radii-parameters that have been used by lung physiologists for decades and are accepted as gold standards for quantifying emphysema. We validated our MRI-based method in six human lung specimens with different levels of emphysema against direct unbiased stereological measurements. We demonstrate for the first time MRI images of these lung microgeometric parameters in healthy lungs and lungs with different levels of emphysema (mild, moderate, and severe). Our data suggest that decreases in lung surface area per volume at the initial stages of emphysema are due to dramatic decreases in the depth of the alveolar sleeves covering the alveolar ducts and sacs, implying dramatic decreases in the lung's gas exchange capacity. Our novel methods are sufficiently sensitive to allow early detection and diagnosis of emphysema, providing an opportunity to improve patient treatment outcomes, and have the potential to provide safe and noninvasive in vivo biomarkers for monitoring drug efficacy in clinical trials.

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1 H, 7 Li, and 11 B NMR measurements were used to understand atomic translational motions in both the lowand high-temperature phases (LT, HT) of LiBH 4 . In the HT phase 7 Li spectra, spin-echo T 2 , and T 1 all indicate very rapid lithium ion diffusion. Just above the phase transition, the hydrogen resonance is broad, about 22 kHz fwhm (full width at half of maximum), showing that H translations remain slow. From 120 to 170°C, a rapidly decreasing T 1D (relaxation time of dipolar spin-order) shows that the hydrogens diffuse increasingly rapidly. This motion eventually results in marked hydrogen line-narrowing centered near 190°C; the hydrogen diffusion is likely relevant to the kinetics of dehydriding. The extent of 11 B line-narrowing demonstrates that the boron atoms also diffuse rapidly at temperatures above 200°C. In the LT phase, the hydrogen T 1D decreases rapidly with increasing temperature, here due to 7 Li diffusion which is too slow for line-narrowing.