The increasing occurrence of dementia within our ageing population is one of the pressing challenges facing society. Successful management of patients with dementia is significantly aided by early and accurate diagnosis. Imaging methods such as magnetic resonance imaging (MRI) and positron emission tomography (PET) are already used in the diagnostic process; we believe that there is substantial scope for both methods to be improved to provide more precise and sensitive diagnostic information, and to do so in a way that is easily tolerated by patients. If we are correct in this belief, then the methods we develop within this project will not only help in early diagnosis, but may also help in the discovery of new therapies and in the longer term with helping doctors select the best therapeutic strategies for patients with different forms of dementia. Imaging methods such as MRI and PET can tell us a lot more about brains than simply providing a picture of brain shape and size. We will focus on improving MRI and PET to be sensitive to two important microscopic aspects of dementia. Firstly, we will develop and validate new methods for measuring the loss of brain cells due to the condition; this loss is the cause of many of the symptoms of dementia, such as memory problems, and we hope to be able to detect these changes earlier than has previously been possible. Secondly we will develop and validate new methods for measuring changes in blood delivery to the brain and how this can affect oxygen delivery. These changes are thought to be part of one of the important processes involved in causing cell death and tissue loss, and are likely to be particularly relevant to vascular dementia. We will also spend considerable time checking that the measurements we develop are both accurate and practical for application in dementia patients in the future. We will optimise the way in which the scanning processes take place so that the time required for patients to lie in the scanner(s) is minimised. This will be important for future adoption of these methods in the clinical environment.

The term "dementia" is used to describe a syndrome that results, initially, in cognitive function impairment and in many cases, a descending staircase of psychological dysfunction, leading eventually to death. It is a major socio-economic challenge with care costs approaching 1% of global GDP. Several conditions that lead to serious loss of cognitive ability are grouped under this syndrome, including Alzheimer's disease (AD), Vascular Dementia (VaD), Frontotemporal Dementia, etc. A high publicity announcement was made in 2012, by the Prime Minister, emphasising the high priority that should be given to dementia-related research and that funding will more than double in the immediate future, to partially remedy the fact that the overwhelming impact of the syndrome has been over-looked (Guardian, 26/3/12). On Dec 2013, the G8 Summit hosted in London brought together G8 ministers, researchers, pharmaceutical companies, and charities to develop co-ordinated global action on dementia. Dementia has marked adverse effects on the quality of life of tens of millions of people (both patients and carers) and exerts tremendous pressure on healthcare systems, especially when clear trends towards an ageing population, changing environmental influences and contemporary lifestyle choices are considered. Ca. 35M people suffer from dementia worldwide, a figure to quadruple by 2050. Europe and North America share a disproportionally high burden: the effects of ageing are particularly stark for these regions, exacerbating the healthcare provision implications. The Clinical Relevance: Vascular Cognitive Impairment (VCI). VCI defines alterations in cognition attributable to cerebrovascular causes, ranging from subtle or fixed deficits to full-blown dementia. VCI is a wide and accepted term referring to the "syndrome with evidence of clinical stroke or subclinical vascular brain injury and cognitive impairment affecting at least one cognitive domain", with resulting VaD being its most severe form. VaD is responsible for at least 20% of dementias, second only to AD, with a prevalence doubling every 5. 3 years. Several trials examined cholinesterase inhibitors for the treatment of vascular dementia, but the benefits are very modest, except in the individuals with a combination of AD and VaD. Vascular changes result in white matter (WM) damage (leukoaraiosis), which profoundly affect the fidelity of the information transfer underlying brain function and cognitive health8. Cerebral Magnetic Resonance Imaging (MRI) of Diffusion and Perfusion. MRI is a medical imaging technique affording non-invasive investigation of anatomy and tissue function, which is particularly suited to studying cognitive disorders due to its sensitivity and reliability. Our main interest is to characterise vascular and non-vascular tissues using quantitative diffusion and perfusion MR. Our overall aim is to characterise and quantify early differential alterations in brain blood transport and subsequent microstructural tissue damage using one-stop-shop perfusion/diffusion MR GSI incorporating novel MR signal models and optimal MR sequence design based on new human brain histomorphometric data in health and disease.

The term "dementia" is used to describe a syndrome that results, initially, in cognitive function impairment and in many cases, a descending staircase of psychological dysfunction, leading eventually to death. It is a major socio-economic challenge with care costs approaching 1% of global GDP. Several conditions that lead to serious loss of cognitive ability are grouped under this syndrome, including Alzheimer's disease (AD), Vascular Dementia (VaD), Frontotemporal Dementia, etc. A high publicity announcement was made in 2012, by the Prime Minister, emphasising the high priority that should be given to dementia-related research and that funding will more than double in the immediate future, to partially remedy the fact that the overwhelming impact of the syndrome has been over-looked (Guardian, 26/3/12). On Dec 2013, the G8 Summit hosted in London brought together G8 ministers, researchers, pharmaceutical companies, and charities to develop co-ordinated global action on dementia. Dementia has marked adverse effects on the quality of life of tens of millions of people (both patients and carers) and exerts tremendous pressure on healthcare systems, especially when clear trends towards an ageing population, changing environmental influences and contemporary lifestyle choices are considered. Ca. 35M people suffer from dementia worldwide, a figure to quadruple by 2050. Europe and North America share a disproportionally high burden: the effects of ageing are particularly stark for these regions, exacerbating the healthcare provision implications. The Clinical Relevance: Vascular Cognitive Impairment (VCI). VCI defines alterations in cognition attributable to cerebrovascular causes, ranging from subtle or fixed deficits to full-blown dementia. VCI is a wide and accepted term referring to the "syndrome with evidence of clinical stroke or subclinical vascular brain injury and cognitive impairment affecting at least one cognitive domain", with resulting VaD being its most severe form. VaD is responsible for at least 20% of dementias, second only to AD, with a prevalence doubling every 5. 3 years. Several trials examined cholinesterase inhibitors for the treatment of vascular dementia, but the benefits are very modest, except in the individuals with a combination of AD and VaD. Vascular changes result in white matter (WM) damage (leukoaraiosis), which profoundly affect the fidelity of the information transfer underlying brain function and cognitive health8. Cerebral Magnetic Resonance Imaging (MRI) of Diffusion and Perfusion. MRI is a medical imaging technique affording non-invasive investigation of anatomy and tissue function, which is particularly suited to studying cognitive disorders due to its sensitivity and reliability. Our main interest is to characterise vascular and non-vascular tissues using quantitative diffusion and perfusion MR. Our overall aim is to characterise and quantify early differential alterations in brain blood transport and subsequent microstructural tissue damage using one-stop-shop perfusion/diffusion MR GSI incorporating novel MR signal models and optimal MR sequence design based on new human brain histomorphometric data in health and disease.

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.

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.