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Ultrasonic Histotripsy for Cell Therapy

Pahk, KJ; (2016) Ultrasonic Histotripsy for Cell Therapy. Doctoral thesis , UCL (University College London). Green open access

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Abstract

Liver transplantation is the mainstay of the treatment for end stage liver diseases including metabolic and congenital liver diseases. The number of suitable donor organs is, however, limited. Intra-portal hepatocytes transplantation has been considered as a bridging therapy to liver transplantation but has shown a mixed clinical outcome with limited success including low level of engraftment of transplanted hepatocytes. To enhance the level of cell engraftment, this thesis introduces an alternative and novel approach to traditional intra-portal cell therapy mediated by High Intensity Focused Ultrasound (HIFU) histotripsy. The proposed novel strategy is to create damage to the recipient liver by producing a number of cavities inside the liver parenchyma through histotripsy and then delivering donor hepatocytes into the cavities. The aim of histotripsy is to mechanically fractionate soft tissue as an alternative to thermal ablation for therapeutic applications. While a number of studies have demonstrated the efficacy of histotripsy for fractionating solid tumours, the exact mechanisms underpinning this phenomenon are poorly understood. The main objectives of this thesis are to (a) investigate the major mechanisms involved in histotripsy and (b) demonstrate the feasibility of the proposed new cell therapy. A high-speed camera with a passive cavitation detection (PCD) system were used to observe the dynamics of bubbles produced in optically transparent tissue phantoms exposed to HIFU fields. Numerical studies on the bubble dynamics and both ex- and in vivo liver experiments were conducted with histological and serological analyses. Boiling bubbles were generated in a localised super-heated region and cavitation clouds were subsequently induced ahead of the expanding bubble. This process was repeated with HIFU pulses and eventually resulted in a tadpole shaped lesion. The in vivo experimental results together with histological observations showed that direct injection of cells inside the cavity facilitated successful uptake, proliferation and integration of the transplanted hepatocytes in the recipient liver. A week after the transplantation, the plasma albumin level was partially restored to 50% of the normal level in Nagase analbuminemic rats (serum albumin level was initially nil) by cell therapy after HIFU histotripsy. This novel method of intra-hepatic hepatocyte transplantation might be an invaluable tool for cell therapy in the future.

Type: Thesis (Doctoral)
Title: Ultrasonic Histotripsy for Cell Therapy
Event: UCL (University College London)
Open access status: An open access version is available from UCL Discovery
Language: English
Keywords: High Intensity Focused Ultrasound, Histotripsy, Cell therapy, Hepatocyte transplantation, Cavitation activity, Bubble dynamics
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Mechanical Engineering
URI: https://discovery.ucl.ac.uk/id/eprint/1508315
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