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Published on: September 21, 2021
An ex vivo study of the correlation between acoustic emission and microvascular damage
Stanley Samuel1, Michol A Cooper, Joseph L Bull
1Department of Radiology, University of Michigan Medical Center, University of Michigan, Ann Arbor, 48109, USA. ssamuel@umich.edu
Abstract:
The objective of this study was to conduct an ex vivo examination of correlation between acoustic emission and tissue damage. Intravital microscopy was employed in conjunction with ultrasound exposure in cremaster muscle of male Wistar rats. Definity microbubbles were administered intravenously through the tail vein (80microL.kg(-1).min(-1)infusion rate) with the aid of a syringe pump. For the pulse repetition frequency (PRF) study, exposures were performed at four locations of the cremaster at a PRF of 1000, 500, 100 and 10Hz (one location per PRF per rat). The 100-pulse exposures were implemented at a peak rarefactional pressure (P(r)) of 2MPa, frequency of 2.25MHz with 46 cycle pulses. For the pressure amplitude threshold study, 100-pulse exposures (46 cycle pulses) were conducted at various peak rarefactional pressures from 0.5MPa to 2MPa at a frequency of 2.25MHz and PRF of 100Hz. Photomicrographs were captured before and 2-min postexposure. On a pulse-to-pulse basis, the 10Hz acoustic emission was considerably higher and more sustained than those at other PRFs (1000, 500, and 100Hz) (p<0.05). Damage, measured as area of extravasation of red blood cells (RBCs), was also significantly higher at 10Hz PRF than at 1000, 500 and 100Hz (p<0.01). The correlation of acoustic emission to tissue damage showed a trend of increasing damage with increasing cumulative function of the relative integrated power spectrum (CRIPS; R(2)=0.75). No visible damage was present at P(r)< or =0.85MPa. Damage, however, was observed at P(r)> or =1.0MPa and it increased with increasing acoustic pressure.
Insights
Lower pulse repetition frequency (PRF) ultrasound (10Hz) significantly increases acoustic emission and tissue damage, correlating strongly with microbubble-mediated extravasation. This highlights PRF as a critical factor in ultrasound-induced biological effects.
Area of Science:
- Biomedical Engineering
- Acoustics
- Microscopy
Background:
- Ultrasound (US) technology is widely used in medical diagnostics and therapeutics.
- Understanding the bioeffects of US, particularly related to microbubble contrast agents, is crucial for safety and efficacy.
- Acoustic emission and tissue damage are key indicators of US-induced bioeffects.
Purpose of the Study:
- To investigate the correlation between acoustic emission and tissue damage during ex vivo ultrasound exposure.
- To evaluate the impact of pulse repetition frequency (PRF) and acoustic pressure on microbubble-mediated tissue effects.
- To establish a relationship between acoustic emission metrics and the extent of red blood cell extravasation.
Main Methods:
- Ex vivo intravital microscopy of rat cremaster muscle exposed to ultrasound.
- Intravenous administration of Definity microbubbles at a controlled infusion rate.
- Ultrasound exposures at varying PRFs (10, 100, 500, 1000 Hz) and peak rarefactional pressures (0.5–2 MPa).
- Quantification of tissue damage via red blood cell (RBC) extravasation and measurement of acoustic emission.
Main Results:
- Acoustic emission was significantly higher and more sustained at 10 Hz PRF compared to higher PRFs (p<0.05).
- Tissue damage, measured by RBC extravasation, was significantly greater at 10 Hz PRF (p<0.01).
- A strong positive correlation was observed between acoustic emission (CRIPS) and tissue damage (R(2)=0.75).
- Visible tissue damage occurred at peak rarefactional pressures ≥1.0 MPa, increasing with pressure.
Conclusions:
- Lower PRF (10 Hz) significantly enhances acoustic emission and microbubble-induced tissue damage.
- Acoustic emission metrics can serve as reliable indicators of ultrasound-induced tissue injury.
- PRF is a critical parameter influencing the bioeffects of microbubble-enhanced ultrasound therapies.

