A Novel Sonoablation of Liver Tissue Based on Acoustic Droplet Vaporization: A Feasibility Study
Hui Li1, Jiabei Yin2, Xiaoxiao Dong1
1Department of Ultrasound, Army Medical University Xinqiao Hospital, Chongqing 400037, China (H.L., J.Y., X.D., Z.L.).
Rationale And Objectives:
Histotripsy uses a large array and high peak negative pressure (PNP) for mechanical tissue ablation. Our prior study shows that manual injection of exogenous cavitation nuclei-perfluoropentane (PFP) droplets, substantially lowers the needed PNP. Combined with low-frequency (300-600 kHz) and low-PNP (1-5 MPa) focused ultrasound (FUS), this approach effectively induces mechanical liver tissue damage. However, the high fluidity of PFP droplets leads to bubble cloud dispersion beyond the target zone, potentially causing non-target tissue damage during sustained FUS exposure. To address this issue, we developed an innovative sonoablation strategy utilizing an acoustic droplet vaporization acoustically responsive scaffold (ARS) designed to spatially confine PFP droplets, thereby generating localized bubble clouds strictly within the intended ablation zone.
Materials And Methods:
15 healthy New Zealand rabbits were divided into three groups based on different transducers: CK960, PRO2.1, and PRO4.1. ARS is composed of a mixture of fibrinogen solution, DMEM, phase-change perfluoropentane microparticles, and thrombin. ARS were injected into the liver mid-lobe under ultrasound (US), then treated with FUS.
Results:
We discovered that the optimal fibrinogen concentration for achieving the best limited high-concentration bubble cloud and mechanical ablation effect with ADV in the target area was 1.47 mg/mL. Conventional US 2D images revealed that ARS effectively restricted the flow of PFP droplets, resulting in localized high-concentration bubble clouds in the target region. Gross observation indicated cavitation necrosis in the liver tissue target area. HE staining showed grade 3 pathological damage across all groups. The damaged areas in the liver target were 6.86±2.62mm2, 13.72±6.08mm2, and 11.68±9.43mm2 for the CK960, PRO2.1, and PRO4.1 groups, respectively. White cavity structures of varying sizes were observed in all groups. Masson staining revealed significant fibrosis surrounding the white cavity structure in the liver tissue target area in all groups.
Conclusion:
ARS vaporization under FUS in the study produced concentrated bubble clouds in the targeted area, causing targeted liver damage without affecting surrounding tissue.
