Mapping the acoustic properties of tissues at low temperatures for ultrasound rewarming

1) Brief description of the context of the research including potential impact
Over 6000 people in the UK are waiting for organ transplants. Simultaneously, the
utilization rate of organ transplantation is not high (approximately 60% of donor hearts are not used), limited by the short time they can be preserved. Storage organs at low temperature (cryopreservation) has the potential to facilitate the increased availability. However, the volume of cryopreservation in clinical use is less than 3 mL, since there are difficulties in rewarming the large-volume tissues, when using standard water bath immersion, and even with advanced magnetic nanoparticle and microwave methods. The key solution for organ cryopreservation lies in finding a suitable method to rewarm the tissue uniformly and quickly.
Ultrasound heating is a potential tool for rewarming large-volume tissues. Energy is deposited as heat as ultrasound passes through the tissues. By controlling ultrasound propagation, energy can be deposited for rapid and uniform warming. To deliver the ultrasound energy optimally, knowledge of the physical properties of tissues at low temperatures is needed. This Ph.D. research aims to develop methods for mapping the acoustic properties of tissues at low temperatures, which will accelerate the development of ultrasound rewarming.

2) Aims and Objectives
The aim is to characterise the acoustic properties of biological materials at low temperatures to inform the development of ultrasonic rewarming of biological tissues after cryopreservation. This will help identify the optimal ultrasonic parameters for warming and contribute to development of models of ultrasound propagation in frozen tissues.
The specific objectives are:
1. To develop and validate experimental methods for mapping the acoustic properties of biological materials at low temperatures,
2. To characterise the acoustic and thermal properties of a range of biological materials at low temperatures.

3) Novelty of Research Methodology
The characterisation of acoustic material properties of solid materials is challenging and more so at low temperatures, where the thermal environment of both the sample and the measurement equipment must be tightly controlled. There is limited information in the literature on the acoustic properties of biological materials at temperatures below zero so the research will generate new methods and knowledge which will be significant for this research and for the academic community. These techniques will be extended to spatially resolved mapping or imaging of the acoustic properties.

4) Alignment to EPSRC's strategies and research areas
This project forms part of a programme of work that is strongly multidisciplinary and focused on future clinical translation. This research has the potential for broad impact in transplant surgery, regenerative medicine, and tissue engineering. The development of ultrasonic rewarming will support the development and clinical translation of tissue-engineered (which aligns with the Biomaterials and tissue engineering research area) and cell therapy products and support the long-term preservation of donor tissues for transplant, as well as enable basic scientific studies of the cryobiology of cells and tissues. The research is aligned with the UKRI 'Technology touching life' priority area, and with advances in regenerative medicine within the current EPSRC strategy. Specifically, the EPSRC Healthcare technologies grand challenges include 'Developing Future Therapies' and 'Frontiers of Physical Intervention', with possible impacts achieved through innovative technologies for regenerative medicine.

5) Any companies or collaborators involved
Collaborators on the programme of work with which this project is aligned include academics from UCL/Royal Free London, scientists from the UCL/Royal Free London, scientist from the National Physical Laboratory, and Precision Acoustics Ltd

The critical mass of scientists and engineers that i4health will produce will ensure the UK's continued standing as a world-leader in medical imaging and healthcare technology research. In addition to continued academic excellence, they will further support a future culture of industry and entrepreneurship in healthcare technologies driven by highly trained engineers with deep understanding of the key factors involved in delivering effective translatable and marketable technology. They will achieve this through high quality engineering and imaging science, a broad view of other relevant technological areas, the ability to pinpoint clinical gaps and needs, consideration of clinical user requirements, and patient considerations. Our graduates will provide the drive, determination and enthusiasm to build future UK industry in this vital area via start-ups and spin-outs adding to the burgeoning community of healthcare-related SMEs in London and the rest of the UK. The training in entrepreneurship, coupled with the vibrant environment we are developing for this topic via unique linkage of Engineering and Medicine at UCL, is specifically designed to foster such outcomes. These same innovative leaders will bolster the UK's presence in medical multinationals - pharmaceutical companies, scanner manufacturers, etc. - and ensure the UK's competitiveness as a location for future R&D and medical engineering. They will also provide an invaluable source of expertise for the future NHS and other healthcare-delivery services enabling rapid translation and uptake of the latest imaging and healthcare technologies at the clinical front line. The ultimate impact will be on people and patients, both in the UK and internationally, who will benefit from the increased knowledge of health and disease, as well as better treatment and healthcare management provided by the future technologies our trainees will produce.

In addition to impact in healthcare research, development, and capability, the CDT will have major impact on the students we will attract and train. We will provide our talented cohorts of students with the skills required to lead academic research in this area, to lead industrial development and to make a significant impact as advocates of the science and engineering of their discipline. The i4health CDT's combination of the highest academic standards of research with excellent in-depth training in core skills will mean that our cohorts of students will be in great demand placing them in a powerful position to sculpt their own careers, have major impact within our discipline, while influencing the international mindset and direction. Strong evidence demonstrates this in our existing cohorts of students through high levels of conference podium talks in the most prestigious venues in our field, conference prizes, high impact publications in both engineering, clinical, and general science journals, as well as post-PhD fellowships and career progression. The content and training innovations we propose in i4health will ensure this continues and expands over the next decade.