Numerous chronic diseases, such as cancer and early heart disease, are often symptomless. Consequently, these diseases are often diagnosed at a late stage which reduces the treatment options that are available to the patient. We are creating new ways of seeing inside the body to identify the processes that go wrong with these devastating diseases using a process called 'molecular imaging'. These innovative scans require the administration of radioactive drugs into the blood stream. The drugs home to the site of the disease, or identify a particular feature related to the disease that will help medical professionals provide the correct treatments for the specific patient. The radioactivity is needed so advanced medical scanners can identify the disease location in the body. Instead of taking a picture of the outside, these scanners can see deep within the body and locate regions of disease that are just millimetres in size. The type and amount of radioactivity used are not harmful but provide the 'beacon' so these diseases can visualised by the scanner. At King's College London we have pioneered the discovery of new molecular imaging applications for the past fifteen+ years. We have built a critical mass and extensive research infrastructure to make pioneering discoveries in molecular imaging research with the ultimate goal of improving human health. This exciting area of research is now on the cusp of new discoveries to not only see but treat disease. By changing the nature of the radioactivity attached to the drug we can deliver a targeted therapeutic payload to the site of disease, resulting in its elimination. Known as 'radionuclides therapies', they have already shown improvements over normal chemotherapy in prostate cancer patients with a lower number of side effects. At King's College London we have the facilities, know-how and ambition to make a significant contribution to this emerging field of research. To fully exploit our critical mass in molecular imaging and radionuclide research we require new scanners to detect both imaging and therapeutic radioactivity. Here, we have requested funds to purchase miniaturised clinical scanners for research using animal models of human diseases. Replacing our >12-year-old equipment they possess advanced features that enable researchers to develop and optimise these imaging tools before their use in humans. Specifically, we will be able to track the movement of these radioactivity-based treatments throughout the body in real time. The improved resolution of the scans will also allow us to identify microstructures in the body or track just a few thousand therapeutic cells that are injected to fight cancer. Working with researchers across the UK will use these scanners to improve our understanding of a host of different diseases including cancer, neurodegenerative disorders, heart disease, pregnancy, inflammatory disorders, and arthritis. Finally, by partnering with pharmaceutical and biotech companies we aim to commercialise these discoveries to deliver maximum benefit to a wide range of patients both in the UK and world-wide.

For the last half-century doctors have routinely used radioactive drugs - radiopharmaceuticals - to detect and diagnose disease in patients and to treat cancer. This speciality is known as nuclear medicine. Modern imaging with radiopharmaceuticals is known as molecular imaging, and treating cancer with them is known as radionuclide therapy. Currently there are economic and geographical barriers, both in the UK and overseas, for patients accessing these scans and treatments. Our programme will develop technologies to perform both molecular imaging and radionuclide therapy more cost-effectively, benefitting more patients and greatly enhancing quality of information, depth of understanding of the disease, and therapeutic benefit. We will use new chemistry to make synthesis of the radiopharmaceuticals faster, more cost-effective and usable in more locations, and hence more accessible for patients. It will improve healthcare by producing and clinically translating new radioactive probes for positron emission tomography (PET), single photon emission computed tomography (SPECT) and radionuclide therapy, to harness the potential of emerging new scanners and therapeutic radionuclides, and provide a diagnostic foundation for emerging advanced therapies. Advanced medicines such as cell-based and immune therapies, targeted drug delivery and radionuclide therapy pose new imaging challenges such as personalised profiling to optimise benefit to patients and minimise risk, and tracking the fate of drug/radionuclide carriers and therapeutic cells in the body. New alpha-emitting radionuclides for cancer therapy are impressing in early trials. New understanding of cancer heterogeneity shows that imaging a single molecular process in a tumour cannot predict treatment outcome. New generation scanners such as combined PET-MR are finding clinical utility, creating niche applications for combined modality tracers; new gamma camera designs and world-wide investment in production of technetium-99m, the staple raw material for gamma camera imaging, demand a new generation of technetium-99m tracers; and "total body PET" will emerge soon, enhancing the potential of long-lived radionuclides for cell and nanomedicine tracking. Demand for new tracers is thus greater than ever, but their short half-life (minutes/hours) means that many of them must be synthesised at the time and place of use. Except for outdated technetium-99m probes, current on-site syntheses are complex and costly, limiting availability, patient access and market size, particularly for modern biomolecule-based probes. Therefore, to grasp opportunities to improve healthcare afforded by the aforementioned advances in therapies and scanners, they must be matched by new chemistry for tracer synthesis. This Programme will dramatically enhance patient access to molecular imaging and radionuclide therapy in both developed and low/middle-income countries, by developing and biologically evaluating faster, simpler, more efficient, kit-based biomolecule labelling with radioactive isotopes for imaging and therapy, streamlining production and reducing need for costly and complex automated synthesisers. In addition, it will maximise future impacts of total body PET, SPECT, PET-MR by evaluating and developing the potential of multiplexed PET to harness the full potential of total body PET: combined imaging of multiple molecular targets, not just one, using fast chemistry for several very short half-live tracers in tandem in a single session to offer a new level of personalised medicine. The programme will also enable the tracking of nanomedicines and cells within the body using long half-life radionuclides - an area where total body PET and PET-MR will be transformative). Finally, we will secure additional funding of selected probes into clinical use in heart disease, cancer, inflammation and neurodegenerative disease.

A vital challenge for modern engineering is the modelling of the multiscale complex particle-liquid flows at the heart of numerous industrial and physiological processes. Industries dependent on such flows include food, chemicals, consumer goods, pharmaceuticals, oil, mining, river engineering, construction, power generation, biotechnology and medicine. Despite this large range of application areas, industrial practice and processes and clinical practice are neither efficient nor optimal because of a lack of fundamental understanding of the complex, multiscale phenomena involved. Flows may be turbulent or viscous and the carrier fluid may exhibit complex non-Newtonian rheology. Particles have various shapes, sizes, densities, bulk and surface properties. The ability to understand multiscale particle-liquid flows and predict them reliably would offer tremendous economic, scientific and societal benefits to the UK. Our fundamental understanding has so far been restricted by huge practical difficulties in imaging such flows and measuring their local properties. Mixtures of practical interest are often concentrated and opaque so that optical flow visualisation is impossible. We propose to overcome this problem using the technique of positron emission particle tracking (PEPT) which relies on radiation that penetrates opaque materials. We will advance the fundamental physics of multiscale particle-liquid flows in engineering and physiology through an exceptional experimental and theoretical effort, delivering a step change in our ability to image, model, analyse, and predict these flows. We will develop: (i) unique transformative Lagrangian PEPT diagnostic methodology for engineering and physiological flows; and (ii) innovative Lagrangian theories for the analysis of the phenomena uncovered by our measurements. The University of Birmingham Positron Imaging Centre, where the PEPT technique was invented, is unique in the world in its use of positron-emitting radioactive tracers to study engineering processes. In PEPT, a single radiolabelled particle is used as a flow follower and tracked through positron detection. Thus, each component in a multiphase particle-liquid flow can be labelled and its behaviour observed. Compared with leading optical laser techniques (e.g. LDV, PIV), PEPT has the enormous and unique advantage that it can image opaque fluids, and fluids inside opaque apparatus and the human body. To make the most of this and image fast, complex multiphase and multiscale flows in aqueous systems, improved tracking sensitivity and accuracy, dedicated new radiotracers and simultaneous tracking of multiple tracers must be developed, and new theoretical frameworks must be devised to analyse and interpret the data. By delivering this, we will enable multiscale complex particle-liquid flows to be studied with unprecedented detail and resolution in regimes and configurations hitherto inaccessible to any available technique. The benefits will be far-reaching since the range of applications of PEPT in engineering and medicine is extremely wide. This multidisciplinary Programme harnesses the synergy between world-leading centres at Birmingham (chemical engineering, physics), Edinburgh (applied maths) and King's College London (PET chemistry, biomedical engineering) to develop unique PEPT diagnostic tools, and to study experimentally and theoretically outstanding multiscale multiphase flow problems which can only be tackled by these tools. The advances of the Programme include: a novel microPEPT device designed to image microscale flows, and a novel medical PEPT validated in small animals for translation to humans. The investigators' combined strengths and the accompanying wide-ranging industrial collaborations, will ensure that this Programme leads to a paradigm-shift in complex multiphase flow research.

Medical imaging has made major contributions to healthcare, by providing noninvasive diagnostics, guidance, and unparalleled monitoring of treatment and understanding of disease. A suite of multimodal imaging modalities is nowadays available, and scanner hardware technology continues to advance, with high-field, hybrid, real-time and hand-held imaging further pushing on technological boundaries; furthermore, new developments of contrast agents and radioactive tracers open exciting new avenues in designing more targeted molecular imaging probes. Conventionally, the individual imaging components of probes and contrast mechanisms, acquisition and reconstruction, and analysis and interpretation are addressed separately. This however, is creating unnecessary silos between otherwise highly synergistic disciplines, which our current EPSRC CDT in Medical Imaging at King's College London and Imperial College London has already started to successfully challenge. Our new CDT will push this even further by bridging the different imaging disciplines and clinical applications, with the interdisciplinary research based on complementary collaborations and new research directions that would not have been possible five years ago. Through a comprehensive, integrated training programme in Smart Medical Imaging we will train the next generation of medical imaging researchers that is needed to reach the full potential of medical imaging through so-called "smart" imaging technologies. To achieve this ambitious goal we have developed four new Scientific Themes which are synergistically interlinked: AI-enabled Imaging, Smart Imaging Probes, Emerging Imaging and Affordable Imaging. This is complemented by a dedicated 1+3 training programme, with a new MRes in Healthcare Technologies at King's as the foundation year, strong industry links in form of industry placements, careers mentoring and workshops, entrepreneurship training, and opportunities in engaging with international training programmes and academic labs to become part of a wider cohort. Cohort building, Responsible Research & Innovation, Equality, Diversity & Inclusion, and Public Engagement will be firmly embedded in this programme. Students graduating from this CDT will have acquired a broad set of scientific and transferable skills that will enable them to work across the different medical imaging sub-disciplines, gaining a high employability over wider sectors.