High intensity focused ultrasound (HIFU) is gaining rapid clinical acceptance as a treatment modality enabling non-invasive tissue heating and ablation for numerous applications. HIFU treatments are usually carried out in a single session, often as a day case procedure, with the patient either fully conscious, lightly sedated or under light general anaesthesia. A major advantage of HIFU over other thermal ablation techniques is that there is no necessity for the transcutaneous insertion of probes into the target tissue. The high powered focused beams employed are generated from sources placed either outside the body (for treatment of tumours of the liver, kidney, breast, uterus, pancreas and bone) or in the rectum (for treatment of the prostate), and are designed to enable rapid heating of a target tissue volume, while leaving tissue in the ultrasound propagation path relatively unaffected. Given the wide-ranging applicability of HIFU, numerous extra-corporeal, transrectal and interstitial devices have been designed to optimise application-specific treatment delivery. Their principle of operation is described here, alongside an overview of the physical mechanisms governing HIFU propagation and HIFU-induced heating. Present methods of characterising HIFU fields and of quantifying HIFU exposure and its associated effects are also addressed.

Biomedical acoustics is rapidly evolving from a diagnostic modality into a therapeutic tool, and acoustic cavitation is often the common denominator in a wide range of new therapeutic applications. High-intensity focused ultrasound (HIFU) waves generated outside the body can be used to deposit heat deep within the body. Through a quantitative analysis of heat deposition by ultrasound, it is shown that inertial cavitation can help address some of the major challenges of HIFU therapy by providing a means of enhancing and monitoring treatment noninvasively. In the context of drug delivery, both inertial and stable cavitation play roles in enhancing drug activity and uptake. In particular, shape oscillations arising during stable cavitation provide an effective micropumping mechanism for enhanced mass transport across inaccessible interfaces.

The number of donor organs suitable for liver transplantation is restricted by cold preservation and ischemia–reperfusion injury. We present the first patients transplanted using a normothermic machine perfusion (NMP) device that transports and stores an organ in a fully functioning state at 37°C. In this Phase 1 trial, organs were retrieved using standard techniques, attached to the perfusion device at the donor hospital, and transported to the implanting center in a functioning state. NMP livers were matched 1:2 to cold‐stored livers. Twenty patients underwent liver transplantation after NMP. Median NMP time was 9.3 (3.5–18.5) h versus median cold ischaemia time of 8.9 (4.2–11.4) h. Thirty‐day graft survival was similar (100% NMP vs. 97.5% control, p = 1.00). Median peak aspartate aminotransferase in the first 7 days was significantly lower in the NMP group (417 IU [84–4681]) versus (902 IU [218–8786], p = 0.03). This first report of liver transplantation using NMP‐preserved livers demonstrates the safety and feasibility of using this technology from retrieval to transplantation, including transportation. NMP may be valuable in increasing the number of donor livers and improving the function of transplantable organs.

Acoustic cavitation has been shown to play a key role in a wide array of novel therapeutic ultrasound applications. This paper presents a brief discussion of the physics of thermally relevant acoustic cavitation in the context of high-intensity focussed ultrasound (HIFU). Models for how different types of cavitation activity can serve to accelerate tissue heating are presented, and results suggest that the bulk of the enhanced heating effect can be attributed to the absorption of broadband acoustic emissions generated by inertial cavitation. Such emissions can be readily monitored using a passive cavitation detection (PCD) scheme and could provide a means for real-time treatment monitoring. It is also shown that the appearance of hyperechoic regions (or bright-ups) on B-mode ultrasound images constitutes neither a necessary nor a sufficient condition for inertial cavitation activity to have occurred during HIFU exposure. Once instigated at relatively large HIFU excitation amplitudes, bubble activity tends to grow unstable and to migrate toward the source transducer, causing potentially undesirable pre-focal damage. Potential means of controlling inertial cavitation activity using pulsed excitation so as to confine it to the focal region are presented, with the intention of harnessing cavitation-enhanced heating for optimal HIFU treatment delivery. The role of temperature elevation in mitigating bubble-enhanced heating effects is also discussed, along with other bubble-field effects such as multiple scattering and shielding.

Transplantation of organs retrieved after cardiac arrest could increase the donor organ supply. However, the combination of warm ischemia and cold preservation is highly detrimental to the reperfused organ. Our objective was to maintain physiological temperature and organ function during preservation and thereby alleviate this injury and allow successful transplantation. We have developed a liver perfusion device that maintains physiological temperature with provision of oxygen and nutrition. Reperfusion experiments suggested that this allows recovery of ischemic damage. In a pig liver transplant model, we compared the outcome following either conventional cold preservation or warm preservation. Preservation periods of 5 and 20 hours and durations of warm ischemia of 40 and 60 minutes were tested. After 20 hours preservation without warm ischemia, post-transplant survival was improved (27%-86%, P = 0.026), with corresponding differences in transaminase levels and histological analysis. With the addition of 40 minutes warm ischemia, the differences were even more marked (cold vs. warm groups 0% vs. 83%, P = 0.001). However, with 60 minutes warm ischemia and 20 hours preservation, there were no survivors. Analysis of hemodynamic and liver function data during perfusion showed several factors to be predictive of posttransplant survival, including bile production, base excess, portal vein flow, and hepatocellular enzymes. Organ preservation by warm perfusion, maintaining physiological pressure and flow parameters, has enabled prolonged preservation and successful transplantation of both normal livers and those with substantial ischemic damage. This technique has the potential to address the shortage of organs for transplantation.