LUNG LESIONS INDUCED BY CONTINUOUS-WAVE AND PULSED-WAVE (DIAGNOSTIC) ULTRASOUND IN MICE, RABBITS, AND PIGS

These studies documented the presence or absence of macroscopic and mi croscopic intraparenchymal hemorrhage in individual lung lobes of mice , rabbits, and pigs exposed to continuous- and pulsed-wave (diagnostic ) ultrasound; we described the character of and lesions associated wit h the hemorrhage and compared differences in the lesions among species and exposure conditions to investigate the pathogenetic mechanisms an d species differences associated with ultrasound-induced lung hemorrha ge. In a series of three sequential interdependent studies, 312 mice, 91 rabbits, and 74 pigs were divided at random into experimental group s and exposed to continuous-wave ultrasound (3 kHz modulated at 120 Hz ) of acoustic pressure levels ranging from 0 to 490 kPa for 5, 10, or 20 minutes. In a fourth study, three mice, 43 rabbits, and six pigs we re divided at random into experimental groups and exposed to pulsed-wa ve ultrasound (3- and 6-MHz center frequency) of peak rarefactional ac oustic pressure levels ranging from 0 to 5.6 MPa for 5 minutes. Macros copic lesions induced by continuous- and pulsed-wave ultrasound consis ted of dark red to black areas of hemorrhage that extended from viscer al pleural surfaces into lung parenchyma. Hemorrhage appeared spatiall y related to the edges of lung lobes where pleura of dorsal and ventra l surfaces met, occurred in specific lung lobes in all three species, and appeared anatomically related to lung that was closest to and in c ontiguous alignment with the ultrasound transducer and thus the path o f the sound beam. Macroscopic lesions were similar in all species unde r all exposure conditions for both continuous- and pulsed-wave ultraso und; however, hemorrhage was not induced in pig lung exposed to pulsed -wave ultrasound at any peak rarefactional acoustic pressure level. Ei ghteen mice (145 kPa exposure pressure), 60 rabbits (145-460 kPa expos ure pressure), and 58 pigs (145-490 kPa exposure pressure) from study 3 were used for microscopic evaluation of lung exposed to continuous-w ave ultrasound; three mice (6 MHz; 2.9 and 5.4 MPa), 39 rabbits (3 and 6 MHz; 2.3-5.4 MPa), and six pigs (3 and 6 MHz; 3.3, 5.4, and 5.6 MPa ) from study 4 were used for microscopic evaluation of lung exposed to pulsed-wave ultrasound. Microscopic lesions and the character of hemo rrhage induced by continuous-wave ultrasound were different from those induced by pulsed-wave ultrasound. Lesions induced by continuous-wave ultrasound under all exposure conditions were similar in all three sp ecies. Lesions induced by pulsed-wave ultrasound under all exposure co nditions were similar in all three species. Microscopic lesions induce d by continuous-wave ultrasound affected alveoli and alveolar septa an d consisted of severe hemorrhage, accumulation of substantial volumes of protein-rich plasma admired with fewer numbers of cells, coagulated protein, and acute coagulative necrosis. Microscopic lesions induced by pulsed-wave ultrasound consisted of severe alveolar hemorrhage with out accumulation of substantial volumes of plasma, infrequent foci of coagulated plasma proteins, and absence of acute coagulative necrosis involving alveolar septa. Results of these studies suggest that 1) the principal target for the biologic effects of ultrasound in lung is th e microvasculature of alveolar septa, 2) differences in the character of the hemorrhage induced by the two wave forms may reflect fundamenta l distinctions in physical/biological interactions that the wave forms have with cellular junctions or membranes that ultimately lead to vas olytic events and hemorrhage, and 3) innate interspecies differences i n anatomy and physiology of lung may determine differences in species susceptibility to ultrasound-induced lung hemorrhage.