Imaging to inform models of whole organ behaviour in health and disease

1) Brief description of the context of the research including potential impact
UCL researchers have recently developed a method for using high-energy X-rays to create images of whole human organs at high resolution (ca. 1 um) and in three dimensions, called HiP-CT. The 3D (and 3D plus time) images from this method will be used to simulate biophysical processes in the human body from blood and air flow to joint movement; allowing investigations into dynamics processes with real human organ geometries with a resolution up to 100 times greater than prior studies.

The images are generated using the European Synchrotron Radiation facility (ESRF) in Grenoble. This X-ray source offers the brightest and most coherent high energy beam in the world, allowing imaging of entire human organs (including lung, heart, brain) with 25um resolution, and then zoom in on cellular structures at ~1.2um resolution without cutting the tissue. EPRSC researchers have imaged human organs in health and disease (Covid-19 victims, see https://mecheng.ucl.ac.uk/HiP-CT).

The HiP-CT research team of scientists, X-ray physicists and medics has recently received a Chan Zuckerberg Initiative grant to further develop this technique and apply it to whole human organs.

This PhD project will develop ML segmentation techniques and then use the segmented synchrotron data as input for models of blood flow prediction, air flow prediction, and other transport processes (for example delivery of therapeutics). Models of joint motion are also possible, coupled to DVC measurement of nano-strains during mechanical loading, depending on the researcher's interests. The models will be used as a tool to infer insights about physiology and pathophysiology from the structural data sets.

2) Aims and Objectives
The specific objectives are to: use segmented synchrotron data from a variety of organs as inputs computational models of: blood flow prediction, air flow prediction, drug delivery. Using these models, functional information will be predicted from segmented structural information, providing new insights into the function of the human body in health and disease (including Covid-19).

3) Novelty of Research Methodology
The HiP-CT imaging method enables imaging of human organ geometries with a resolution up to 100 times greater than prior studies. Using these high resolution geometries in models of blood flow prediction, air flow prediction and drug delivery could provide insights into organ behaviour in health and disease.

4) Alignment to EPSRC's strategies and research areas
The project aligns with the priorities of the EPSRC Healthcare Technologies Theme, specifically around Developing New Therapies and Optimising Disease Prediction, Diagnosis and Intervention. The PhD project brings together state-of-the-art imaging, computational modelling methodologies to gain insight into organ pathophysiology, disease progression and response to therapy. The technologies will be shared through open science initiatives for take up by the broader communities active in related areas.

5) Any companies or collaborators involved
Chan Zuckerberg Initiative

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.