Lesion resolution following exposure of rat lung to pulsed ultrasound

Ultrasound has an exceptional safety record, but concerns have been raised by reports of clinical-level ultrasound-induced lung haemorrhage in mice, rats, rabbits, monkeys, and pigs. This study characterized the temporal reparative (healing) responses in lung following the induction of lesions by pulsed ultrasound (3.14 MHz, 1700-Hz PRF, 1.4-μs pulse duration, 60-s exposure duration, in situ [at the pleural surface] peak rarefactional pressure of 17 MPa, and in situ peak compressional pressure of 39.7 MPa). Following exposure, lung lesions were evaluated at 0, 1, 2, 5, 7, 9, 12, 14, and 16 days post exposure (dpe). Lungs were scored for the presence of lesions, recorded digitally, and fixed in 10% formalin. After fixation, the dimensions of each lesion at the visceral pleural surface were measured. The lesions were bisected and the depth measured. The temporal changes were indicative of degradation of erythrocytes through processing and removal of hemoglobin and iron pigments. Microscopic lesions paralleled the gross lesions and reparative responses resulted in minimal alteration of lung structure. The reparative response in lung was analogous to reparative responses in soft tissues associated with bruising, but also had a proliferative phase characterized by focal hyperplasia of spindloid cells whose phenotypes need to be determined