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...

No abstract

Optical polarization of 3 He generates large nuclear spin magnetizations, allowing MR imaging of the gas spaces of human and animal lungs despite the low number density of spins in the gas. The atomic physics of optical pumping and spin exchange is explained; the hardware for polarizing, transporting, and imaging is detailed. Pulse sequences for optimum use of the nonrenewable magnetization require a different imaging strategy than traditional proton MRI. Examples are discussed for static lung images, diffusion images for characterization of the local alveolar structure, and high temporal resolution images.

The 3He longitudinal spin-relaxation rate T1-1 is crucial for production of highly polarized 3He by spin-exchange optical pumping. We show that T1-1 is increased by a factor of 2-20 solely by exposure of spin-exchange cells to a few-kG magnetic field. The original T1-1 can be restored by degaussing the cell. The effect is attributed to magnetic surface sites and has been observed in both Pyrex and aluminosilicate-glass cells. Our results both advance the understanding of wall relaxation and demonstrate the use of 3He as an extremely sensitive probe of surface magnetism.

No abstract