Robotically Assisted Sonic Therapy as a Noninvasive Nonthermal Ablation Modality: Proof of Concept in a Porcine Liver Model

Abstract

Purpose To determine the feasibility of creating a clinically relevant hepatic ablation (ie, an ablation zone capable of treating a 2-cm liver tumor) by using robotically assisted sonic therapy (RAST), a noninvasive and nonthermal focused ultrasound therapy based on histotripsy. Materials and Methods This study was approved by the institutional animal use and care committee. Ten female pigs were treated with RAST in a single session with a prescribed 3-cm spherical treatment region and immediately underwent abdominal magnetic resonance (MR) imaging. Three pigs (acute group) were sacrificed immediately following MR imaging. Seven pigs (chronic group) were survived for approximately 4 weeks and were reimaged with MR imaging immediately before sacrifice. Animals underwent necropsy and harvesting of the liver for histologic evaluation of the ablation zone. RAST ablations were performed with a 700-kHz therapy transducer. Student t tests were performed to compare prescribed versus achieved ablation diameter, difference of sphericity from 1, and change in ablation zone volume from acute to chronic imaging. Results Ablation zones had a sphericity index of 0.99 ± 0.01 (standard deviation) (P < .001 vs sphericity index of 1). Anteroposterior and transverse dimensions were not significantly different from prescribed (3.4 ± 0.7; P = .08 and 3.2 ± 0.8; P = .29, respectively). The craniocaudal dimension was significantly larger than prescribed (3.8 ± 1.1; P = .04), likely because of respiratory motion. The central ablation zone demonstrated complete cell destruction and a zone of partial necrosis. A fibrous capsule surrounded the ablation zone by 4 weeks. On 4-week follow-up images, ablation zone volumes decreased by 64% (P < .001). Conclusion RAST is capable of producing clinically relevant ablation zones in a noninvasive manner in a porcine model. RSNA, 2018.

Review on Acoustic Droplet Vaporization in Ultrasound Diagnostics and Therapeutics

“…The frequencies used in current clinically approved applications are typically below 1 MHz to further enhance the cavitation, which is inversely proportional to the frequency [97]. Although this technique has shown great potential for treating pathologies such as kidney stones [98] and liver cancer [99], its efficacy is limited to situations in which a single target can be accurately visualized and linearized prior to treatment [100]. Combined with the difficulty to image the region of interest, there is a risk of unwanted bioeffects in surrounding healthy tissue due to the high pressures (>28 MPa) required for successful procedure.…”

Robotically-Assisted Sonic Therapy for Renal Ablation in a Live Porcine Model: Initial Preclinical Results

“…Previous studies with this technology have demonstrated tissue-selective properties, suggesting that large vessels and collecting system structures may be spared, while tumors and normal parenchyma are lysed (6,7). This promising early work has led to robotic integration and development of a clinical system, resulting in Robotically Assisted Sonic Therapy (RAST) (8).…”

“…The nonthermal nature of histotripsy is distinct from high-intensity focused ultrasound, which uses longer ultrasound pulses to create focal heating of targeted tissue (12). To date, histotripsy has been applied in a variety of large and small animal preclinical models in different organs (8,10,13,14).…”

“…Experience with histotripsy in kidneys has been limited to small animal models or the creation of small ablation zones in larger animals (13–17). Recently, a RAST prototype system being developed for use in humans became available (8). Given the tissue-selective nature noted in these previous studies and the availability of a clinical prototype system, a feasibility study of performing histotripsy in a human-scale model is warranted.…”

For Whom the Bubble Grows: Physical Principles of Bubble Nucleation and Dynamics in Histotripsy Ultrasound Therapy

“…In addition to diagnostic ultrasound modalities, histotripsy-induced liquefaction zones have been visualized with MRI at field strengths between 7 and 9 T (Allen et al 2014(Allen et al , 2015Khokhlova et al 2009;Vlaisavljevich et al 2016c). Changes in the structure of media have been clearly delineated with T2-, T1-and diffusion-weighted and contrast-enhanced sequences in vitro and in vivo (Allen et al 2017;Smolock et al 2018). Lesion appearance varies based on tissue viability (in vivo vs. ex vivo) and the time at which the image is acquired relative to the histotripsy therapy.…”