Superthreshold behavior and threshold estimation of ultrasound-induced lung hemorrhage in adult mice and rats

Abstract

Threshold estimates and superthreshold behaviors for ultrasound-induced lung hemorrhage were investigated as a function of species (adult mice and rats) and ultrasound frequency (2.8 and 5.6 MHz). A total of 151 6-to-7-week-old female ICR mice and 160 10-to-11-week-old female Sprague-Dawley rats were randomly divided into two ultrasonic frequency groups, and further randomly divided into seven or eight ultrasonic peak rarefactional pressure groups. Each group consisted of about 10 animals. Animals were exposed to pulsed ultrasound at either 2.8-MHz center frequency (1-kHz PRF, 1.42-s pulse duration) or 5.6-MHz center frequency (1-kHz PRF, 1.17-s pulse duration) for a duration of 10 seconds. The in situ (at the pleural surface) peak rarefactional pressure levels ranged between 2.5 and 10.5 MPa for mice and between 2.3 and 11.3 MPa for rats. The mechanical index (MI) ranged between 1.4 and 6.3 at 2.8 MHz for mice and between 1.1 and 3.1 at 5.6 MHz for rats. The lesion surface area and depth were measured for each animal as well as the percentage of animals with lesions per group. The characteristics of the lesions produced in mice and rats were similar to those described in previous studies by our research group and others, suggesting a common pathogenesis in the initiation and propagation of the lesions at the gross and microscopic levels. The percentage of animals with lesions showed no statistical differences between species or between ultrasound frequencies. These findings suggest that mice and rats are similar in sensitivity to ultrasound-induced lung damage and that the occurrence of lung damage is independent of frequency. Lesion depth and surface area also showed no statistically significant differences between ultrasound frequencies for mice and rats. However, there was a significant difference between species for lesion area and a suggestive difference between species for lesion depth. The superthreshold behavior of lesion area and depth showed that rat lung had more damage than mouse lung, and the threshold estimates showed a weak, or lack of, frequency dependency, suggesting that the MI is not consistent with the observed findings.

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

“…Rats were selected as the experimental animal based on their use in our previous studies Zachary et al 2001aZachary et al ,2001bO'Brien et al 2002;Frizzell et al 2003;O'Brien et al 2003;Oelze et al 2003;O'Brien et al 2004). …”

“…The characteristics of these lesions were compared against lesions induced in lung by pulsed ultrasound. Lung lesions from previously published studies of ultrasound-induced lung hemorrhage in rats were pulled from the archives and served as the basis for comparison with laser-induced lung injury Zachary et al 2001aZachary et al ,2001b). …”

“…Ultrasound-induced lung lesions were similar in all species, under all exposure conditions. Ultrasound exposure conditions and transducer calibration procedures used in these studies were described previously (Sempsrott and O'Brien 1999;Sempsrott 2000;O'Brien et al 2001aO'Brien et al ,2001bZachary et al 2001aZachary et al ,2001b) and based on established standards (AIUM/NEMA 1998;ODS 1998).…”

“…Since 2000, we have published seven studies to evaluate whether inertial cavitation was responsible for ultrasound-induced lung hemorrhage Zachary et al 2001b;O'Brien et al 2002;Frizzell et al 2003;O'Brien et al 2003O'Brien et al ,2004, and each study has lacked support for the hypothesis that inertial cavitation is the mechanism. The results of these studies also suggested that ultrasound-induced lung hemorrhage was likely related to the transfer of acoustic energy into lung tissue because more injury occurred in lung under deflated conditions (O'Brien et al 2002;Oelze et al 2003).…”

Vascular lesions and s-thrombomodulin concentrations from auricular arteries of rabbits infused with microbubble contrast agent and exposed to pulsed ultrasound

“…US exposure conditions and transducer calibration procedures used in this study were described previously Zachary et al 2001aZachary et al ,2001b. In summary, a focused 19-mm diameter, lithium niobate ultrasonic transducer (Valpey Fisher, Hopkinton, MA, USA) was used to expose each auricular artery.…”