Superthreshold behavior of ultrasound-induced lung hemorrhage in adult rats: Role of pulse repetition frequency and exposure duration revisited

Objective. The purpose of this study was to augment and reevaluate the ultrasound-induced lung hemorrhage findings of a previous 5 × 3 factorial design study (Ultrasound Med Biol 2001; 27:267-277) that evaluated the role of pulse repetition frequency (PRF: 25, 50, 100, 250, and 500 Hz) and exposure duration (ED; 5, 10, and 20 s) on ultrasound-induced lung hemorrhage at an in situ (at the pleural surface) peak rarefactional pressure [p _{r(in situ)}] of 12.3 MPa; only PRF was found to be significant. However, saturation (response plateau) due to the high p_{r(in situ)} might have skewed the results. In this follow-up 3 × 3 factorial design study, a wider range of PRFs and EDs were used at a lower p _{r(in situ)}. Methods. Sprague Dawley rats (n = 198) were divided into 18 ultrasonically exposed groups (10 rats per group) and 6 sham groups (3 per group). The 3 × 3 factorial design study (PRF: 17, 170, and 1700 Hz; ED: 5, 31.6, and 200 s) was conducted at 2 frequencies (2.8 and 5.6 MHz). The p _{r(in situ)} was 6.1 MPa. Logistic regression analysis evaluated lesion occurrence, and Gaussian tobit analysis evaluated lesion depth and surface area. Results. Frequency did not have a significant effect, so the analysis combined results for the 2 frequencies. For lesion occurrence and sizes, the main effects for PRF and ED were not significant. The interaction term was highly significant, indicating a strong dependence of lesion occurrence and size on the total number of pulses (PRF × ED). Conclusions. The results of both studies are consistent with the hypothesis that the total number of pulses is an important factor in the genesis of ultrasound-induced lung hemorrhage.