A thriving nuclear industry is crucial to the UKs energy security and to clean up the legacy of over 50 years of nuclear power. The research performed in the ICO (Imperial Cambridge Open universities, pronounced ECO!) CDT will enable current reactors to be used longer, enable new reactors to be built and operated more safely, support the clean up and decommissioning of the UKs contaminated nuclear sites and place the UK at the forefront of international programmes for future reactors for civil and marine power. It will also provide a highly skilled and trained cohort of nuclear PhDs with a global vision and international outlook entirely appropriate for the UK nuclear industry, academia, regulators and government. Key areas where ICO CDT will significantly improve our current understanding include in civil, structural, mechanical and chemical engineering as well as earth science and materials science. Specifically, in metallurgy we will perform world-leading research into steels in reactor and storage applications, Zr alloy cladding, welding, creep/fatigue and surface treatments for enhanced integrity. Other materials topics to be covered include developing improved and more durable ceramic, glass, glass composite and cement wasteforms; reactor life extension and structural integrity; and corrosion of metallic waste containers during storage and disposal. In engineering we will provide step change understanding of modelling of a number of areas including in: Reactor Physics (radionuclide transport, neutron transport in reactor systems, simulating radiation-fluid-solid interactions in reactors and finite element methods for transient kinetics of severe accident scenarios); Reactor Thermal Hydraulics (assessment of critical heat flux for reactors, buoyancy-driven natural circulation coolant flows for nuclear safety, simulated dynamics and heat transfer characteristics of severe accidents in nuclear reactors); and Materials and Structural Integrity (residual stress prediction, fuel performance, combined crystal plasticity and discrete dislocation modelling of failure in Zr cladding alloys, sensor materials and wasteforms). In earth science and engineering we will extend modelling of severe accidents to enable events arising from accidents such as those at Chernobyl and Fukushima to be predicted; and examine near field (waste and in repository materials) and far field (geology of rocks surrounding the repository) issues including radionuclide sorption and transport of relevance to the UKs geological repository (especially in geomechanics and rock fracture). In addition, we will make key advances in development of next generation fission reactors such as examining flow behaviour of molten salts, new fuel materials, ultra high temperature non-oxide and MAX phase ceramics for fuels and cladding, thoria fuels and materials issues including disposal of wastes from Small Modular Reactors. We will examine areas of symbiosis in research for next generation fission and fusion reactors. A key aspect of the ICO CDT will be the global outlook given to the students and the training in dealing with the media, a key issue in a sensitive topic such as nuclear where a sensible and science-based debate is crucial.

Micromegas detectors are used in a variety of physics projects including in low-energy nuclear physics and neutron-beam related detectors. With this proposal we intend to develop a “transparent” orthogonal strip Micromegas neutron detector with unprecedented position and time resolving data acquisition capabilities, for use at the major neutron time-of-flight facilities. Typical usages are neutron flux and reaction cross section measurements, and neutron beam imaging. A very thin detector with both a segmented anode and segmented mesh, coupled to the dedicated VMM3 chip developed for Micromegas detectors, will lead to an innovative detection device. The new detector will also be used as a time-projection chamber (TPC) to investigate angular distribution measurements of reaction particles of interest for nuclear reaction studies and nuclear data. The TPC mode will be tested in the neutron beam of GELINA with light charged particles and fission fragments.

Electronic properties of metal oxides such as superconductivity and colossal magnetoresistance are important both for fundamental science and for applications. We aim to discover new materials with notable properties by preparing new or ill-characterised perovskites at high temperatures (1000 C) and pressures (5-20 GPa) - perovskites are dense phases and so are favoured under such conditions. Target materials include cubic and layered Cr4+ perovskites, new Bi materials with multiferroic properties, and new magnetic cuprate superconductors. A press and a Walker multianvil module are requested for synthesis. The materials will be characterised by X-ray and neutron diffraction and electron microscopy, and conducting, magnetic and ferroelectric properties will be measured. The project will benefit from collaborations with other UK groups for measurements and with leading European high pressure synthesis laboratories (through an EU COST network).

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.

Heart Failure (HF) is defined by the heart's reduced ability to pump blood due to a drop in cellular contractility, enlarged anatomy and increased coronary micro-vascular resistance. This loss of pump function accounts for a significant increase in both mortality and morbidity in western society. With the U.K.'s elderly population expanding, HF is rapidly becoming an epidemic. There is currently a 1 in 5 life-time risk of HF and costs associated with acute and long term hospital treatments are accelerating. The significance of the disease has motivated the application of state of the art clinical imaging techniques to aid diagnosis and clinical planning. Measurements of cardiac wall motion, chamber flow patterns and coronary perfusion currently provide high resolution data sets for characterising HF patients. However, the clinical practice of using population-based metrics derived from separate image sets often indicates contradictory treatments plans due to inter-individual variability in pathophysiology. Thus, despite imaging advances, determining optimal treatment strategies for HF patients remains problematic. To exploit the full value of imaging technologies, and the combined information content they produce, requires the ability to integrate multiple types of functional data into a consistent framework. This in turn will support a paradigm shift away from predefined clinical indices determining treatment options and a move towards true personalisation of care based on an individual's physiology.An exciting and highly promising strategy for underpinning this shift is the assimilation of multiple image sets into personalised and biophysically consistent mathematical models. The development of such models provides the ability to capture the multi-factorial cause and effect relationships which link the underlying pathophysiological mechanisms. Furthermore, using a biophysical basis presents unique opportunities to assist with treatment decisions through the derivation of quantities that cannot be imaged but are likely to play a key mechanistic role in HF e.g. tissue stress and pump efficiency.In parallel with imaging advances the approach is also underpinned by the ongoing development of complementary technologies, including improved numerical methods and increased performance per unit cost of computing. This computational progress has accelerated the addition of multi-physics functionality to a range of organ models which have recently been organized into international initiatives such as the IUPS sponsored Physiome and VPH projects. Within these programmes the heart is arguably the most advanced current exemplar of an integrated organ model. As such it represents a promising first candidate with which to focus on an important human disease.My goal during this fellowship will be to focus on personalising and applying these models in clinical and industrial settings for treating HF patients. Model simulations will be focused on quantifying diagnosis, aiding patient selection and guiding interventional planning for specific treatments carried out by leading clinicians based in the cardio-vascular imaging group at Kings College London (KCL). In addition to this direct clinical application of the model, the research will also be focused on the tuning of Left Ventricular Assist Devices (LVADs) which are often connected to the heart in HF to reduce mechanical load by pumping blood from the left ventricle directly into the aorta. Through these applications my aim is to both improve our understanding of this significant cardiovascular disease and demonstrate the potential of biophysical models for improving human healthcare.