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...

Between January 1993 and February 1996, we performed 150 bilateral lung volume reduction procedures for patients with severe emphysema. Patients were selected on the basis of severe dyspnea, increased lung capacity, and a pattern of emphysema that included regions of severe destruction, hyperinflation, and poor perfusion. Twenty percent to 30% of the volume of each lung was excised with the use of a linear stapler and bovine pericardial strips attached to buttress the staple line. Patients were between 36 and 77 years old, with an average 1-second forced expiratory volume of 25% of predicted, total lung capacity of 142% of predicted, and residual volume of 283% of predicted. Ninety-three percent of patients required supplemental oxygen, continuously or with exertion. All patients but one were extubated at the end of the procedure. The 90-day mortality was 4%. Hospital stay progressively decreased with experience, and for the last 50 patients the median hospital stay was 7 days. Prolonged air leakage was the major complication. Results at 6 months show a 51% increase in the 1-second forced expiratory volume and a 28% reduction in the residual volume. The Pao2 increased by an average of 8 mm Hg, and 70% of the patients who had previously required continuous supplemental oxygen no longer had this requirement. The improvements in measured pulmonary function were paralleled by a significant reduction in dyspnea and an improvement in the quality of life. Reevaluation at 1 year and 2 years after operation showed the benefit to be well maintained. We conclude that lung volume reduction offers benefits not achievable by any means other than lung transplantation for highly selected patients with severe emphysema.

No abstract

Lung volume reduction surgery produces significant functional improvement for selected patients with emphysema. For most of these patients, benefits appear to last at least 5 years.