![]() ![]() Possible applications of BH include the ablation of solid tumours, local drug delivery, and cavity formation for direct intrahepatic cell delivery for cell therapy. The interplay between these parameters has been studied by many groups and extensively reported. The efficacy of mechanical fractionation, the ablation rate, and the reliability of boiling histotripsy depend on the correct choice of ultrasound frequency, focal peak pressure levels, pulse duration, the pulse duty cycle, and the number of BH pulses. The interaction of incident shocks with the boiling bubble causes tissue disruption and liquefaction without significant thermal injury to adjacent tissue. High-amplitude shocks cause rapid and transient tissue heating, resulting in the nucleation of a boiling bubble. The nonlinear propagation of ultrasound waves results in the formation of shockwaves at the beam focus. The one employed in this study is referred to as boiling histotripsy (BH), where a series of millisecond-long ultrasound pulses are delivered to the treatment site. Different ultrasound pulsing protocols can be used to cause mechanical tissue damage. Ultrasound histotripsy is a non-invasive procedure used to mechanically fractionate and liquefy soft tissue without causing thermal damage. The 3D reconstruction of two histotripsy sites was successful and confirmed the feasibility of this approach to investigate the effects of histotripsy on tissue in detail. The core of the typical lesion consisted of eosinophilic material associated with reticulin loss, collagen damage including loss of birefringence to fibrous septa, and perilesional portal tracts, including large portal vein branches, but intact peri-lesional hepatic plates. Additionally, two lesion sites were used for 3D reconstruction. Sections were stained with Haematoxylin and Eosin and picro-Sirius red, and they were also stained for reticulin. Fifteen lesional sites were formalin-fixed and paraffin-embedded. Whilst under perfusion, histotripsy was performed to randomly selected sites on the live. Five whole porcine livers were retrieved fresh from the abattoir using human transplant retrieval and cold static preservation techniques and were then perfused using an organ preservation circuit. Here, we present the histological analysis, including 3D reconstruction of histotripsy sites. The histotripsy nidus was created with a 2 MHz single-element focused US transducer, producing 50 pulses of 10 ms duration, with peak positive and negative pressure values of P+ = 77.7 MPa and Pā = ā13.7 MPaat focus, respectively, and a duty cycle of 1%. We have performed US histotripsy in viable perfused ex vivo porcine livers as a step in the development of a novel approach to hepatocyte cell transplantation. Non-invasive therapeutic-focused ultrasound (US) can be used for the mechanical dissociation of tissue and is described as histotripsy. ![]()
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