The Neuromod+ network will represent UK research, industry, clinical and patient communities, working together to address the challenge of minimally invasive treatments for brain disorders. Increasingly, people suffer from debilitating and intractable neurological conditions, including neurodegenerative diseases and mental health disorders. Neurotechnology is playing an increasingly important part in solving these problems, leading to recent bioelectronic treatments for depression and dementia. However, the invasiveness of existing approaches limits their overall impact. Neuromod+ will bring together neurotechnology stakeholders to focus on the co-creation of next generation, minimally invasive brain stimulation technologies. The network will focus on transformative research, new collaborations, and facilitating responsible innovation, partnering with bioethicists and policy makers. As broadening the accessibility of brain modification technology my lead to unintended consequences, considering the ethical and societal implications of these technological development is of the utmost importance, and thus we will build in bioethics research as a core network activity. The activities of NEUROMOD+ will have global impact, consolidating the growing role of UK neurotechnology sector.

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.

A major part of the diagnosis of any disease but particularly various forms of cancer, is obtained though a biopsy. This involves removing a small sample of tissue, or a few cells, from the patient. These samples, either tissue or cells are then examined by a pathologist looking down an optical microscope. In most cases the sample is stained with a combination of dyes to help gain some contrast. In most cases, based upon visual inspection of the sample a diagnosis is made. This process if far from ideal since it relies on the expertise of the clinician concerned as is subject to intra in inter observer error. Recently a number of proof of concept studies have shown that molecular spectroscopic techniques such as infrared and Raman are capable of distinguishing diseased from non diseased cells and tissue based upon the inherent chemistry contained within the cells. The UK is at the forefront of these developments but there are many hurdles that need to be overcome if this technology is to move from the proof of concept stage through the translational stage and into the clinical setting. It is the belief of the academic community that we are much more likely to overcome these hurdles if we pool our resources, bring in both industrial and clinical partners and work on these generic problems together. This application is for funding to support such a network of partners for the next three years.

Incremental Sheet Forming (ISF) is a flexible, cost effective, energy and resource efficient process. It only requires a simple tool to deform the sheet material incrementally by moving the tool along a predefined tool path created directly from the CAD model of a product. Without using moulds, dies or heavy-duty forming machines, it is flexible to manufacture small-batch or customised sheet products with complex geometries. However, existing ISF processes cannot manufacture hard-to-form materials, such as high strength aluminium, magnesium and titanium alloys, because these materials have limited ductility at room temperature. This EPSRC follow-on project aims to build on the initial success of an EPSRC Adventurous Manufacturing grant (EP/T005254/1) in developing a rotational vibration assisted incremental sheet forming (RV-ISF) process to manufacture hard-to-form materials for industrial applications. The RV-ISF process is centred on a novel ISF tooling to generate low frequency and high amplitude vibration in ISF processing, which produces localised heating and material softening therefore improve the material ductility without the need of additional heating or extra energy input. By developing and implementing the novel tooling, RV-ISF experimental testing of a well-known hard-to-form material has demonstrated a 300% increase in forming depth, more than 70% reduction of average grain size through microstructure refinement, 20% improvement in average hardness and up to 37% reduction of average surface roughness. To capitalise the promising findings from the EPSRC Adventurous Manufacturing grant (EP/T005254/1), this follow-on project assembles a multidisciplinary team with expertise in flexible sheet forming, material science and plasticity, advanced manufacturing technologies, novel tooling and bespoke machine systems. The aim is to develop an in-depth understanding of the material deformation mechanisms under RV-ISF processing conditions and to use this new knowledge to expand the material types and products that can be successfully manufactured using this innovative process. In working with the project partners, the follow-on project aims to deliver a range of demonstrable products and to engage in dissemination activities for a swift translation of the developed flexible, cost effective and sustainable forming process into UK's medical, automotive, aerospace and nuclear industries.

Modern cancer treatment is largely a combination of 3 techniques: surgery, chemotherapy and radiotherapy. Radiotherapy uses beams of X-rays to irradiate the tumour from many different directions. The effect is to kill the cancer by depositing as much radiation dose in the tumour as possible, whilst minimising the dose to the surrounding area to spare healthy tissue. Proton therapy is a more precise form of radiotherapy that provides significant benefits over conventional X-ray radiotherapy. Protons lose energy - and therefore deposit their dose - in a much smaller region within the body, making the treatment much more precise: this leads to a more effective cancer treatment with a smaller chance of the cancer recurring. This is particularly important in the treatment of deep-lying tumours in the head, neck and central nervous system, particularly for children whose bodies are still developing and are particularly vulnerable to long-term radiation damage. The advantages of proton therapy, coupled to the reduced cost of the equipment, has led to a surge in interest in proton therapy treatment worldwide: there are now over 70 centres, with this number currently doubling every 3 years. In the UK, the NHS has funded 2 full-sized proton therapy centres - at University College Hospital in London and The Christie in Manchester - to operate alongside the eye treatment facility at the Clatterbridge Cancer Centre. These will provide treatment for a much wider range of cancers, allowing more patients to be treated closer to home. Treating these cancers requires machinery that is significantly more complex than a conventional radiotherapy system. Protons are accelerated to the right energy for treatment by a particle accelerator: once the beam leaves the accelerator, it then has to be transported to the treatment rooms many metres away by a series of steering and focussing magnets. When the proton beam reaches the treatment room, it has to be delivered through a gantry to the correct place. Proton therapy gantries are enormous - more than 3 storeys tall and weighing more than a hundred tonnes - and have to rotate around the patient to deliver the beam from any angle with millimetre precision. In order to ensure that treatment with such complex machinery is carried out safely, a range of quality assurance (QA) procedures are carried out each day before treatment starts. A significant fraction of this time is spent verifying that the proton beam travels the correct depth and is carried out for several different energies: protons are counted at different depths in a material, like ware, that mimics human tissue. These QA measurements of the proton range take significant time to set up and adjust for different energies: the full procedure can take over an hour. The focus of this project is to develop a detector that can make faster and more accurate measurements of the proton range than existing systems. The detector is built from layers of plastic scintillator that has the same density as water and resembles a sliced loaf of broad. Protons passing through this scintillator stack deposit energy in each layer which is converted into light: by recording the light from each layer, the amount of energy the protons deposit along their path can be measured. Such a system provides a direct measurement of the range of protons in tissue, since the absorption of the plastic is virtually identical to human tissue. As such, a measurement of the proton range for multiple energies would allow the complete morning energy QA procedure to be carried out in a few minutes, with an accuracy of less than a millimetre. At the two new NHS centres, this would translate into being able to treat an extra 12-18 patients every single day. A prototype detector is being assembled and tested at UCL with the intention to develop a full commercial system that can make range QA measurements with the necessary speed and accuracy.