This project aims to build a research group to drive a transformation in the use of x-rays in science and society by replacing the mechanism upon which this has been based for over a century, x-ray absorption. X-rays are electromagnetic waves, and are therefore characterized not only by their amplitude, which is changed by absorption, but also by their phase. Pioneering experiments carried out in the nineties at large and expensive facilities called synchrotrons showed that phase effects can solve the main problem of x-ray imaging, low image contrast due to small absorption differences. This both enhances the visibility of all details in an image, and allows the detection of features invisible to conventional x-ray methods. The benefits this could bring to fields as diverse as medicine, biology, material science, etc were immediately understood, but an effective translation into real-world applications failed because it looked like using a synchrotron was necessary to obtain significant image enhancements.Recently, the PI developed a technique (coded-aperture phase contrast imaging) which showed that this is not true. This technique allows achieving advantages comparable to those obtained at synchrotrons with conventional x-ray sources. This makes the above transformation a concrete possibility for the first time.Although a complete transformation will take longer than the five years of the project, we will seed it by running a series of pilot experiments which will:1) explore the potential of the proposed approach and adapt it to applications in a variety of important fields;2) develop new scientific instruments allowing studies which until now were only possible at synchrotrons to be carried out in conventional labs;3) develop new x-ray methods which will allow the investigation of new scientific fields currently inaccessible.The technique invented by the PI will be applied in new areas of medicine, security, material science, and others. In medicine, we will tackle problems such as imaging blood vessels without contrast agents, enabling earlier detection of breast and other cancers and of osteoporosis, and developing new contrast agents to allow physiological studies with x-rays. We will develop strategies to substantially reduce x-ray dose, which would make radiology safer and allow the expansion of screening campaigns. In security, we will improve threat detection and material recognition. In material science, we will develop tools to detect defects in new materials (e.g. composites, the basis of future aerospace and transport industry, currently posing a challenge to existing test tools) and to allow earlier detection of cracks and corrosion in metals and defects in plastics.Phase-based x-ray scanners will be developed to enable microscopic studies of cells and detection of plaques and metal concentration in tissues in a conventional laboratory setting. X-ray phase methods will be combined with other, functional imaging modalities to develop a new generation of small-animal scanners which will be used in biology and drug development.At synchrotrons, we will combine the increased phase sensitivity of the method developed by the PI with other, cutting-edge methods to push the sensitivity of phase techniques further. These methods will be used to study important scientific areas currently inaccessible, e.g. the mechanisms of tumour invasion.The group will disseminate the obtained results both to specialized audiences (through scientific publications and conference presentations) and to the general public (through public engagement activities). We will collaborate with industry to ensure that the outcome of the applied elements of the research programme are taken to the exploitation stage, and therefore that its full impact is realized. The group will become a world-leading team and produce a step change in x-ray science and its application, to the benefit of society as a whole and UK plc in particular.

We propose to create the EPSRC Centre for Doctoral Training (CDT) in intelligent integrated imaging in healthcare (i4health) at University College London (UCL). Our aim is to nurture the UK's future leaders in next-generation medical imaging research, development and enterprise, equipping them to produce future disruptive healthcare innovations either focused on or including imaging. Building on the success of our current CDT in Medical Imaging, the new CDT will focus on an exciting new vision: to unlock the full potential of medical imaging by harnessing new associated transformative technologies enabling us to consider medical imaging as a component within integrated healthcare systems. We retain a focus on medical imaging technology - from basic imaging technologies (devices and hardware, imaging physics, acquisition and reconstruction), through image computing (image analysis and computational modeling), to integrated image-based systems (diagnostic and interventional systems) - topics we have developed world-leading capability and expertise on over the last decade. Beyond this, the new initiative in i4health is to capitalise on UCL's unique combination of strengths in four complementary areas: 1) machine learning and AI; 2) data science and health informatics; 3) robotics and sensing; 4) human-computer interaction (HCI). Furthermore, we frame this research training and development in a range of clinical areas including areas in which UCL is internationally leading, as well as areas where we have up-and-coming capability that the i4health CDT can help bring to fruition: cancer imaging, cardiovascular imaging, imaging infection and inflammation, neuroimaging, ophthalmology imaging, pediatric and perinatal imaging. This unique combination of engineering and clinical skills and context will provide trainees with the essential capabilities for realizing future image-based technologies. That will rely on joint modelling of imaging and non-imaging data to integrate diverse sources of information, understanding of hardware the produces or uses images, consideration of user interaction with image-based information, and a deep understanding of clinical and biomedical aims and requirements, as well as an ability to consider research and development from the perspective of responsible innovation. Building on our proven track record, we will attract the very best aspiring young minds, equipping them with essential training in imaging and computational sciences as well as clinical context and entrepreneurship. We will provide a world-class research environment and mentorship producing a critical mass of future scientists and engineers poised to develop and translate cutting-edge engineering solutions to the most pressing healthcare challenges.

Medical imaging has transformed clinical medicine in the last 40 years. Diagnostic imaging provides the means to probe the structure and function of the human body without having to cut open the body to see disease or injury. Imaging is sensitive to changes associated with the early stages of cancer allowing detection of disease at a sufficient early stage to have a major impact on long-term survival. Combining imaging with therapy delivery and surgery enables 3D imaging to be used for guidance, i.e. minimising harm to surrounding tissue and increasing the likelihood of a successful outcome. The UK has consistently been at the forefront of many of these developments. Despite these advances we still do not know the most basic mechanisms and aetiology of many of the most disabling and dangerous diseases. Cancer survival remains stubbornly low for many of the most common cancers such as lung, head and neck, liver, pancreas. Some of the most distressing neurological disorders such as the dementias, multiple sclerosis, epilepsy and some of the more common brain cancers, still have woefully poor long term cure rates. Imaging is the primary means of diagnosis and for studying disease progression and response to treatment. To fully achieve its potential imaging needs to be coupled with computational modelling of biological function and its relationship to tissue structure at multiple scales. The advent of powerful computing has opened up exciting opportunities to better understand disease initiation and progression and to guide and assess the effectiveness of therapies. Meanwhile novel imaging methods, such as photoacoustics, and combinations of technologies such as simultaneous PET and MRI, have created entirely new ways of looking at healthy function and disturbances to normal function associated with early and late disease progression. It is becoming increasingly clear that a multi-parameter, multi-scale and multi-sensor approach combining advanced sensor design with advanced computational methods in image formation and biological systems modelling is the way forward. The EPSRC Centre for Doctoral Training in Medical Imaging will provide comprehensive and integrative doctoral training in imaging sciences and methods. The programme has a strong focus on new image acquisition technologies, novel data analysis methods and integration with computational modelling. This will be a 4-year PhD programme designed to prepare students for successful careers in academia, industry and the healthcare sector. It comprises an MRes year in which the student will gain core competencies in this rapidly developing field, plus the skills to innovate both with imaging devices and with computational methods. During the PhD (years 2 to 4) the student will undertake an in-depth study of an aspect of medical imaging and its application to healthcare and will seek innovative solutions to challenging problems. Most projects will be strongly multi-disciplinary with a principle supervisor being a computer scientist, physicist, mathematician or engineer, a second supervisor from a clinical or life science background, and an industrial supervisor when required. Each project will lie in the EPSRC's remit. The Centre will comprise 72 students at its peak after 4 years and will be obtaining dedicated space and facilities. The participating departments are strongly supportive of this initiative and will encourage new academic appointees to actively participate in its delivery. The Centre will fill a significant skills gap that has been identified and our graduates will have a major impact in academic research in his area, industrial developments including attracting inward investment and driving forward start-ups, and in advocacy of this important and expanding area of medical engineering.