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 micros; 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 x 4 factorial design study (PRF: 50, 170, 500, and 1700 Hz; PD: 1.3, 4.4, 8.2, and 11.6 mus) 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 x 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 x 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.