Radioactive microspheres could offer several advantages over gases in the investigation of pulmonary ventilation. Monodisperse microspheres of human serum albumin have been produced using a spinning-disc generator, and kits were prepared for subsequent labelling with technetium-99m. The average labeling efficiency was 88% and unlabeled Tc-99m was removed before aerosol delivery. A simple system was constructed to nebulize and deliver dry monodisperse microspheres. The ventilation images obtained were compared quantitatively with the corresponding krypton-81m images, subdividing the lung regions into inner, central, and peripheral zones. No significant difference was found in the proportions of the total counts for any lung region. There was good agreement between the distributions of microspheres obtained on separate days (r = 0.97, p less than 0.0001), An "aerosol penetration index" was defined as the ratio of the peripheral to the inner counts for the microspheres normalized by the corresponding ratio for krypton-81m. The mean value of this index for 16 normal subjects was 0.98 +/- 0.23 (s.d.), indicating that the microspheres had achieved penetration of the lung periphery. For patients with chronic obstructive lung disease, more localized defects were observed with the microspheres than with krypton-81m. The mean penetration index for this group was only 0.69 +/- 0.21 (s.d.). This was significantly different from the value for normal subjects (p less than 0.002).

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