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1 Medicine and Physiology and Biophysics, University of Washington, Seattle, Washington, United States
* To whom correspondence should be addressed. E-mail: tomrobt{at}u.washington.edu.
Systematically mapped samples cut from lungs previously labeled with intravascular and aerosol microspheres can be used to create high-resolution maps of regional perfusion and regional ventilation. With multiple radioactive or fluorescent microsphere labels available, this methodology can compare regional flow responses to different interventions without partial volume effects or registration errors that complicate interpretation of in vivo imaging measurements. Microsphere blood flow maps examined at different levels of spatial resolution have revealed that regional flow heterogeneity increases progressively down to an acinar level of scale. This pattern of scale-dependent heterogeneity is characteristic of a fractal distribution network, and suggests that the anatomic configuration of the pulmonary vascular tree is the primary determinant of high-resolution regional flow heterogeneity. At a 1-cm3 resolution, the large-scale gravitational gradients of blood flow per unit weight of alveolar tissue account for less than 5% of the overall flow heterogeneity. Furthermore, regional blood flow per gram of alveolar tissue remains relatively constant with different body positions, gravitational stresses and exercise. Regional alveolar ventilation is accurately represented by the deposition of inhaled 1.0-µm FMS aerosols, at least down to the 1-cm3 level of scale. Analysis of these ventilation maps has revealed the same scale-dependent property of regional ventilation heterogeneity, with a strong correlation between ventilation and blood flow maintained at all levels of scale. The VA/Q distributions obtained from microsphere flow maps of normal animals agree well with simultaneously acquired multiple inert gas elimination technique VA/Q distributions, but underestimate gas exchange impairment in diffuse lung injury.
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