Robotically Assisted Sonic Therapy (RAST) for Noninvasive Hepatic Ablation in a Porcine Model: Mitigation of Body Wall Damage with a Modified Pulse Sequence

Abstract

Purpose: Robotically assisted sonic therapy (RAST) is a nonthermal, noninvasive ablation method based on histotripsy. Prior animal studies have demonstrated the ability to create hepatic ablation zones at the focal point of an ultrasound therapy transducer; however, these treatments resulted in thermal damage to the body wall within the path of ultrasound energy delivery. The purpose of this study was to evaluate the efficacy and safety of a pulse sequence intended to mitigate prefocal body wall injury.

Materials and methods: Healthy swine (n = 6) underwent hepatic RAST (VortxRx software version 1.0.1.3, HistoSonics, Ann Arbor MI) in the right hepatic lobe. A 3.0 cm spherical ablation zone was prescribed for each. Following treatment, animals underwent MRI which was utilized for ablation zone measurement, evaluation of prefocal injury, and assessment of complications. Each animal was euthanized, underwent necropsy, and the tissue was processed for histopathologic analysis of the ablation zone and any other sites concerning for injury.

Results: No prefocal injury was identified by MRI or necropsy in the body wall or tissues overlying the liver. Ablation zones demonstrated uniform cell destruction, were nearly spherical (sphericity index = 0.988), and corresponded closely to the prescribed size (3.0 × 3.1 × 3.4 cm, p = 0.70, 0.36, and 0.01, respectively). Ablation zones were associated with portal vein (n = 3, one occlusive) and hepatic vein thrombosis (n = 4, one occlusive); however, bile ducts remained patent within ablation zones (n = 2).

Conclusions: Hepatic RAST performed with a modified ultrasound pulse sequence in a porcine model can mitigate prefocal body wall injuries while maintaining treatment efficacy. Further study of hepatic RAST appears warranted, particularly in tumor models.

Keywords: Ablation; Histotripsy; Interventional oncology; RAST; Ultrasound.

Fig. 1. A

A Intra-procedural ultrasound image demonstrating the bubble cloud (arrow) within the right hepatic lobe. B Corresponding immediate post-procedure image shows the hypoechoic ablation zone (arrow). C Axial T1 pre-contrast images demonstrate a well-demarcated ablation zone (arrow) containing high-signal-intensity blood products. D Axial T1 post-contrast portal venous phase MRI image with no enhancement. E Axial STIR image demonstrates no evidence of body wall edema or injury. F Corresponding gross pathologic specimen of the liver with a well-demarcated ablation zone without damage to the surrounding liver. The thin area of light red tissue surrounding the ablation zone corresponds to the transition zone

Fig. 2. A

A Coronal 20-min delay MRI image demonstrating the close proximity of the ablation zone to the cranial aspect of the gallbladder. B Gross pathologic specimen demonstrates extension of the ablation zone to involve the gallbladder fossa. C Histology (× 100) demonstrates hemorrhage within the gallbladder wall with intact mucosa

Fig. 3. A

A Axial portal venous phase MRI demonstrates an occlusive portal vein thrombus (yellow arrow) distal to the ablation zone (red arrow). B Axial portal venous phase imaging of a different subject demonstrates nonocclusive proximal portal vein thrombus (yellow arrow) The gallbladder is also in view (green arrow). C Axial portal venous phase image of a third subject demonstrates nonocclusive hepatic vein thrombus (yellow arrow) adjacent to the ablation zone (red arrow)

Fig. 4. A

A Axial post-contrast 20 min delayed image demonstrates a patent bile duct containing Eovist within the ablation zone (blue arrow). B, C Histology (× 100) demonstrating the intact bile duct at the periphery of the ablation zone (green arrows)

Fig. 5. A

A Microscopic image (× 100) of the center of the ablation zone demonstrates a few small clusters of detached non-viable hepatocytes (H) and fibrinous debris (F) present. B Microscopic image (× 100) of the periphery of the ablation shows viable liver (L) liver with complete ablation effect (C) and a thin zone of transition (Z)