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Biomedical Imaging and Instrumentation

Biomedical Imaging and Instrumentation - Poster Session C & D

V5 - Histotripsy for Non-invasive Tissue Selective Liver Decellularization: A Parameter Study

Friday, October 10, 2025
10:00 AM - 11:00 AM PDT
Location: Exhibit Hall F, G & H

Introduction: : Liver disease causes 2 million global deaths annually [1]. For end-stage conditions like cirrhosis or hepatocarcinoma, transplantation remains the only effective treatment. Tissue engineering offers a promising alternative via hepatocyte transplantation, which requires a suitable engraftment medium. Decellularized extracellular matrix (dECM)-based scaffolds preserve native structure and vasculature, providing hepatocytes with an optimal niche for engraftment. Current decellularization methods rely on chemical or enzymatic agents, but these can cause structural damage, introduce toxicity, and compromise vascular preservation—limiting clinical translation [2]. Histotripsy, a non-invasive, non-thermal, non-ionizing focused ultrasound modality, was recently FDA-approved for liver tumor treatment. It has demonstrated the ability to selectively ablate soft tissue while sparing surrounding vasculature, bile ducts, and nerves [3]. This ex vivo study aims to evaluate histotripsy’s tissue selectivity for preserving fine structures, connective tissue, and ECM in the liver.

Materials and

Methods: : Healthy, fresh porcine livers were acquired from Virginia Tech’s Meat Center or local slaughterhouses and treated within 72 hours. Liver samples were embedded in a 1% agarose gel phantom. A 500 kHz or a 3 MHz, single cycle histotripsy transducer was used to treat a cubic volume at varying pulse rate frequencies (number of pulses delivered per second, PRF) and dosage levels (quantified as pulses per point, ppp). Dosage levels ranged from 25 ppp to 500 ppp, with each level delivered at three different PRFs: 100 Hz, 500 Hz, and 1000 Hz. The applied pressure was kept at ~ 42 MPa for 500 kHz and ~ 32 MPa for 3 MHz to ensure consistent cavitation, and all tests were guided using an ultrasound imaging probe. Extent of decellularization was assessed through histological analysis via Trichrome staining.

Results, Conclusions, and Discussions:: For both center frequencies, increased damage was observed of both cells and collagenous structures with increasing dose. For 500 kHz, complete ablation of both tissue components was observed at or after 500 pulses. At this frequency, there were no cases of complete cellular ablation with remaining intact collagen networks. For 3 MHz exposures, cellular damage increased with dose for all PRFs, with complete cellular ablation as low as 50 pulses for a PRF of 1000 Hz. Effective decellularization was observed in multiple instances at 3MHz, with higher PRF requiring less dose to achieve complete cellular ablation while preserving the collagenous networks. Higher frequency demonstrated greater potential for tissue selective ablation, aligning with our hypothesis that reduced bubble expansion imposes less strain, sparing structures of higher mechanical strength (matrix) while ablating weaker components (hepatocytes). Interestingly, higher PRF also appeared to improve tissue selectivity and decellularization. Ongoing studies will further advance treatment parameters for decellularization and explore recellularization efficacy for “ablate and replace” histotripsy treatment approaches.

Acknowledgements and/or References (Optional): : [1] Asrani et al., J Hepatology, 2019, v. 70, 151-171.
[2] Zhang et al., Bioact. Mater., 2022, v. 10, 15-31.
[3] Vlaisavljevich et al., Phys. Med. Biol., 2013, v. 59, 253.