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

Objective. The purpose of this study was to enhance the findings of an earlier ultrasound-induced lung hemorrhage study (Ultrasound Med Biol 2003; 29:1625-1634) that estimated pressure thresholds as a function of pulse duration (PD: 1.3, 4.4, 8.2, and 11.6 μs; 2.8 MHz; 10-s exposure duration [ED]; 1-kHz pulse repetition frequency [PRF]). In this study, the roles of PRF and PD were evaluated at 5.9 MPa, the peak rarefactional pressure threshold near that of the ED₅₀ estimate previously determined. Methods. A 4 × 4 factorial design study (PRF: 50, 170, 500, and 1700 Hz; PD: 1.3, 4.4, 8.2, and 11.6 μs) was conducted (2.8 MHz; 10-s ED). Sprague Dawley rats (n = 175) were divided into 16 exposure groups (10 rats per group) and 1 sham group (15 rats); no lesions were produced in the sham group. Logistic regression analysis evaluated significance of effects for lesion occurrence, and Gaussian tobit analysis evaluated significance for lesion depth and surface area. Results. For lesion occurrence and sizes, the main effect of PRF was not significant. The interaction term, PRF × PD, was highly significant, indicating a strong positive dependence of lesion occurrence on the duty factor. The main effect of PD was almost significant (P = .052) and thus was included in the analysis model for a better fit. Conclusions. Compared with the findings from a PRF × ED factorial study (J Ultrasound Med 2005; 24:339-348), a function that considers PRF, PD, and ED might yield a sensitive indicator for consideration of a modified mechanical index, at least for the lung.