Acoustic radiation force impulse (push pulse)-induced lung hemorrhage: investigating the effect of ultrasound contrast agent in rabbits.

Purpose: Acoustic radiation force impulse (ARFI) elastography and contrast-enhanced ultrasonography (CEUS) are emerging techniques that are becoming common in ultrasound examinations. We previously reported that ARFI (push pulse) induced lung hemorrhage in rabbits, indicating that greater risks are associated with ARFI than with conventional ultrasound. In this study, we assessed the risk of lung hemorrhage under a combination of ARFI elastography and CEUS, considering potential exacerbation of ARFI-induced lung hemorrhage as a result of the ultrasound contrast agent (UCA) used in CEUS.

Methods: Twenty-three rabbits were divided into non-UCA and UCA groups. ARFI exposure parameters were set at six mechanical index (MI) levels (0.29, 0.45, 0.60, 0.88, 1.0, 1.39) in non-UCA groups and five MI levels (0.29, 0.66, 0.88, 0.97, 1.25) in UCA groups. Lung exposure was performed bilaterally through the intercostal space in each rabbit. Lung damage was assessed through macroscopic and microscopic observation post euthanasia.

Results: Lung hemorrhage was detected at MI_0.3 levels of 0.88 or higher. Logistic regression analyses showed that MI_0.3 was a statistically significant factor for occurrence of lung hemorrhage in both non-UCA and UCA groups, and the MI_0.3 threshold (ED₀₅) for inducing lung hemorrhage was 0.68 and 0.71, respectively. However, multivariate logistic regression and linear regression analyses across all samples indicated that UCA did not significantly affect the occurrence or area of lung hemorrhage.

Conclusion: This study demonstrates that UCA does not significantly worsen ARFI-induced lung hemorrhage in terms of occurrence or severity. However, risks and benefits of ARFI elastography on the lung should be considered, irrespective of UCA administration.