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Superthreshold Behavior of Ultrasound-Induced Lung Hemorrhage in Adult Rats

Role of Pulse Repetition Frequency and Exposure Duration Revisited

Bioacoustics Research Laboratory, Department of Electrical and Computer Engineering, University of Illinois, Urbana, Illinois USA (W.D.O., L.A.F.); Department of Statistics, University of Illinois, Champaign, Illinois USA (D.G.S.); and Department of Veterinary Pathobiology (J.F.Z.), University of Illinois, Urbana, Illinois USA.

Address correspondence and reprint requests to William D. O’Brien, Jr, PhD, Bioacoustics Research Laboratory, Department of Electrical and Computer Engineering, University of Illinois, 405 N Mathews, Urbana, IL 61801 USA. E-mail: wdo{at}uiuc.edu

Objective. The purpose of this study was to augment and reevaluate the ultrasound-induced lung hemorrhage findings of a previous 5 x 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 x 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 x 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 x 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.

Key Words: exposure duration • lung hemorrhage • pulsed ultrasound • pulse repetition frequency • rat lung • ultrasound bioeffects

Abbreviations: ED, exposure duration • MI, mechanical index • p_c, peak compressional pressure • PRF, pulse repetition frequency • p_r, peak rarefactional pressure

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