Pulmonary Capillary Hemorrhage Induced by Fixed-Beam Pulsed Ultrasound

Abstract

The induction of pulmonary capillary hemorrhage (PCH) by pulsed ultrasound was discovered 25 yr ago but early research utilized fixed-beam systems rather than actual diagnostic ultrasound machines. In this study, fixed-beam focused ultrasound exposures for 5 min at 1.5 MHz and 7.5 MHz were performed in rats for comparison to recent research with diagnostic ultrasound. One exposure condition at each frequency used 10 µs pulses delivered at 25 ms intervals. Three conditions involved Gaussian modulation of the pulse amplitudes at 25 ms intervals to simulate diagnostic scanning: 7.5 MHz with 0.3 µs and 1.5 µs pulses at 100 µs and 500 µs pulse repetition periods, respectively, and 1.5 MHz with 1.7 µs pulses at 500 µs repetition periods. Four groups were tested for each condition to assess PCH areas at different exposure levels and to determine occurrence thresholds. The conditions with identical pulse timing showed smaller PCH areas for the smaller 7.5 MHz beam, but both had thresholds of 0.69–0.75 MPa in situ peak rarefactional pressure amplitude (PRPA). The Gaussian modulation conditions for 7.5 MHz with 0.3 µs pulses and 1.5 MHz with 1.7 µs pulses both had thresholds of 1.12–1.20 MPa PRPA, although the relatively long 1.5 µs pulses at 7.5 MHz gave a threshold of 0.75 MPa. The fixed-beam pulsed ultrasound exposures produced lower thresholds than diagnostic ultrasound. There was no clear tendency for thresholds to increase with increasing ultrasonic frequency when pulse timing conditions were similar.

Influence of Scan Duration on Pulmonary Capillary Hemorrhage Induced by Diagnostic Ultrasound

“…Most early studies were performed using laboratory pulsed ultrasound systems configured for relevance to diagnostic ultrasound. The results of a comparison between PCH from diagnostic and laboratory systems indicated that the diagnostic scanning results were comparable with the earlier findings, which provides a large and reasonably consistent data base (Miller et al 2015b). The diagnostic ultrasound frequency does not strongly influence the threshold for PCH (Miller et al 2015c), which questions the use of the on-screen Mechanical Index as a safety index for gauging the likelihood of PCH.…”

“…In addition to the dose-response trends for ultrasonic output parameters, the exposure duration appears to be a key dosage parameter (Miller et al 2015b). For example, a 2.0 MPa threshold for 2.8 MHz, 11.6 µs pulses, 1 ms interval and 10 s exposure duration (O’Brien et al 2003) was substantially higher than our 0.75 MPa threshold at 1.5 MHz for 10 µs pulses, 25 ms interval and 300 s exposure duration, even though the numbers of pulses delivered and total on-time were similar.…”

Mechanisms for Induction of Pulmonary Capillary Hemorrhage by Diagnostic Ultrasound: Review and Consideration of Acoustical Radiation Surface Pressure

“…That is, for apparently identical exposure conditions near the thresholds, the result for two different animals can be PCH or not (hit-or-miss), which complicates the interpretation of results. However, the threshold determinations appear to be reproducible and confirmable by different laboratories (Church and O’Brien, 2007; Miller et al 2015b). …”

“…There was little dependence of PCH thresholds on frequency as shown in Fig. 4 for rats (Miller et al 2015a, 2015b, 2015c). This lack of significant frequency dependence for the thresholds in rats reduces the expectation that cavitation or resonance phenomena are important for induction of PCH.…”

“…For focused ultrasound, either in laboratory pulsed ultrasound systems or diagnostic ultrasound, the beam width typically decreases with frequency. The magnitude of effects depend on beam width, but the threshold apparently does not (O’Brien et al 2001; Miller et al 2015b). Indeed, the threshold was found to be about the same for focused or unfocused ultrasound (Child et al 1990).…”