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

1)研究背景的简要描述，包括潜在的影响英国有6000多人正在等待器官移植。同时，由于供体心脏保存时间短，器官移植的利用率不高（约60%的供体心脏未被利用）。低温储存器官（冷冻保存）有可能促进增加可用性。然而，临床使用的冷冻保存体积小于3 mL，因为当使用标准水浴浸泡时，甚至使用先进的磁性纳米颗粒和微波方法时，在复温大体积组织时存在困难。器官冷冻保存的关键在于找到一种合适的方法来均匀、快速地复温组织，超声加热是一种潜在的大体积组织复温方法。当超声波穿过组织时，能量以热量的形式沉积。通过控制超声波传播，可以沉积能量用于快速和均匀的加热。为了最佳地输送超声能量，需要了解低温下组织的物理特性。这个博士研究的目的是开发用于绘制低温下组织的声学特性的方法，这将加速超声复温的发展。2）目的和目的是验证生物材料在低温下的声学特性，以告知低温保存后生物组织的超声复温的发展。这将有助于确定最佳的超声参数的升温，并有助于超声在冷冻组织中的传播模型的发展。发展和验证低温下生物材料声学特性的实验方法。3）研究方法的新奇表征固体材料的声学材料特性具有挑战性，在低温下更是如此，样品和测量设备的热环境必须严格控制。在文献中关于生物材料在零度以下的声学特性的信息有限，因此这项研究将产生新的方法和知识，这对这项研究和学术界都很重要。这些技术将扩展到空间分辨映射或成像的声学特性。4)与EPSRC的战略和研究领域保持一致该项目是多学科工作计划的一部分，并专注于未来的临床翻译。这项研究有可能在移植手术，再生医学和组织工程中产生广泛的影响。超声复温的发展将支持组织工程（与生物材料和组织工程研究领域相一致）和细胞治疗产品的开发和临床转化，并支持移植供体组织的长期保存，以及实现细胞和组织低温生物学的基础科学研究。该研究与UKRI的“技术触及生命”优先领域保持一致，并与当前EPSRC战略中再生医学的进展保持一致。具体而言，EPSRC医疗保健技术的重大挑战包括“开发未来疗法”和“物理干预前沿”，通过再生医学的创新技术可能产生影响。5）参与该项目的任何公司或合作者工作计划的合作者包括UCL/皇家自由伦敦的学者，UCL/皇家自由伦敦的科学家，国家物理实验室的科学家和精密声学有限公司

1) Brief description of the context of the research including potential impactOver 6000 people in the UK are waiting for organ transplants. Simultaneously, theutilization 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 ObjectivesThe 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 MethodologyThe 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 areasThis 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 involvedCollaborators 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