Threshold estimation of ultrasound-induced lung hemorrhage in adult rabbits and comparison of thresholds in mice, rats, rabbits and pigs

Abstract

The objective of this study was to assess the threshold and superthreshold behavior of ultrasound (US)-induced lung hemorrhage in adult rabbits to gain greater understanding about species dependency. A total of 99 76 ± 7.6-d-old 2.4 ± 0.14-kg New Zealand White rabbits were used. Exposure conditions were 5.6-MHz, 10-s exposure duration, 1-kHz PRF and 1.1-μs pulse duration. The in situ (at the pleural surface) peak rarefactional pressure, p r(in situ) , ranged between 1.5 and 8.4 MPa, with nine acoustic US exposure groups plus a sham exposure group. Rabbits were assigned randomly to the 10 groups, each with 10 rabbits, except for one group that had nine rabbits. Rabbits were exposed bilaterally with the order of exposure (left then right lung, or right then left lung) and acoustic pressure both randomized. Individuals involved in animal handling, exposure and lesion scoring were blinded to the exposure condition. Probit regression analysis was used to examine the dependence of the lesion occurrence on in situ peak rarefactional pressure and order of exposure (first vs. second). Likewise, lesion depth and lesion root surface area were analyzed using Gaussian tobit regression analysis. Neither probability of a lesion nor lesion size measurements was found to be statistically dependent on the order of exposure after the effect of p r(in situ) was considered. Also, a significant correlation was not detected between the two exposed lung sides on the same rabbit in either lesion occurrence or size measures. The p r(in situ) threshold estimates (in MPa) were similar to each other across occurrence (3.54 ± 0.78), depth (3.36 ± 0.73 and surface area (3.43 ± 0.77) of lesions. Using the same experimental techniques and statistical approach, great consistency of thresholds was demonstrated across three species (mouse, rat and rabbit). Further, there were no differences in the biologic mechanism of injury induced by US and US-induced lesions were similar in morphology in all species and age groups studied. The extent of US-induced lung damage and the ability of the lung to heal led to the conclusion that, although US can produce lung damage at clinical levels, the degree of damage does not appear to be a significant medical problem.

Lesions of ultrasound-induced lung hemorrhage are not consistent with thermal injury

“…Thus, the mechanical mechanism(s) capable of causing such damage are likely related to the stress that focused ultrasound imposes directly on the lung's air-blood barrier such as radiation forces (Chu and Apfel 1982;Elrod et al 1989). We have shown that the histopathologic characteristics of the gross and microscopic lesions of pulsed ultrasound-induced lung hemorrhage are identical in four species (mice, rats, rabbits and pigs) (O'Brien et al 2006) and that hemorrhage in these species occurs at exposure conditions similar to those used for scanning in human beings. Thus, these findings suggested a common pathogenesis in the initiation and propagation of the lesions at the gross and microscopic levels; however, the exact mechanism of injury remained elusive.…”

Pulmonary Capillary Hemorrhage Induced by Fixed-Beam Pulsed Ultrasound

“…The variation in PCH observed with various limited parameter sets have been reviewed by AIUM (2000) and Church et al (2008). Different species have been used in the research, including mice, rats, rabbits, pigs, monkeys and humans (AIUM, 2000; O’Brien et al 2006; Church et al 2008). In addition, biological conditions are important, including age (Dalecki et al 1997; O’Brien et al 2003) and the specific anesthesia techniques (Miller et al 2014a; Miller et al 2015b).…”

On the safety of diagnostic ultrasound in pregnancy: Have we handled the available data correctly?

“…[11] More importantly, the threshold of all UILH was within the range of diagnostic ultrasound and the mechanism of injury appeared to be specie and age independent; which increases the transposability of these findings to human fetuses. The possibility of a substantial temperature rise in the brain of fetuses when insonated in utero with diagnostic pulsed ultrasound have been demonstrated in guinea pigs, sheep, and human fetuses, [12] thus, again, demonstrating specie independent bioeffect.…”