Over 3 million people in the UK suffer from cardiovascular disease causing over 150,000 premature deaths in people under the age of 75. Restriction of blood flow and blockage of blood vessels surrounding the heart leads to interruption of the blood supply to the heart muscle causing heart cells to die. The oxygen shortage, if left untreated can cause damage or death of the heart muscle resulting in heart attack or complete heart failure. Narrowing of the blood vessels in the legs can lead to blockage, amputation and limb loss if left untreated. Patients requiring amputation face a diminished quality of life and severe disability. The primary goal is to restore at least one straight line of blood flow by using a stent depending on the degree of obstruction. The application of stenting is carried out using a minimally invasive approach. A stent is a small mesh tube that is inserted using a catheter, and is deployed at the same time as a balloon is inflated across the diseased vessel wall. The stent acts as a scaffold to hold open the artery to restore blood flow. However, severe healthcare concerns have been raised with current stents, which release drugs through localised allergic reactions, chronic swelling (inflammation) and repeat episodes of thrombosis (or blood clotting), which requires a lifetime prescription of anti-platelet and blood thinning medication causing unwanted side effects followed by repeat surgery. To overcome the current problems with stenting, we plan to build upon our knowledge and expertise to deliver a new generation of stents by developing two products: 1) a novel surface coating with tiny particles embedded in a polymer or plastic coating called nanocomposite polymers, and 2) inclusion of capture antibodies (present on the surface of cells) in to the coating layer to capture stem cells from the circulating blood and converting it to endothelial cells from shear flow, the endothelial is type cells cover entire our cardiovascular system , to protect from blood thrombosis. The nanocomposite polymers have already undergone extensive testing in the laboratory, and in animals demonstrating that the polymer can be potentially used safely in humans. For example, we developed a range of surgical implants using nanocomposite polymers with a number of successful outcomes, such as the world's first synthetic wind pipe over 2.5 years ago and the patient is doing very well, 6 tubes that drain the tears (lacrimal duct) have been carried out in patients to date, and coronary artery bypass graft using same materials has started at Heart Hospital, heart valves at the preclinical. We have already optimised the polymer coating for stents, and in this study our plan is to carry out a final assessment of coated stents and compare them with currently used stents (as product 1). Pre-clinical animal studies will be used to evaluate their effectiveness application in humans. The development of product 2 is at the proof-of-principle stage. Here, we carry out preliminary tests using antibodies (raised against circulatory stem cells in the blood) incorporated in to the polymer coating for capturing stem cells from the blood, and perform tests to obtain sufficient data to apply for funding towards pre-clinical studies. This proposal will enable us to test polymer coated stents in preparation for first-in-man studies after consultation with the MHRA (UK regulatory agencies) and FDA. We will then be in a strong position to apply for funding towards clinical trials, which can be implanted in humans. The development of a new generation of nanocomposite polymer coated stents, which prevent thrombosis along with the inclusion of stem cell capture technology to enhance endothelisationcells would have a significant impact on the global economy, as individuals affected will be active in the workforce for longer, enjoy a greater quality of life and reduce the strain on vital healthcare resources.

A patient's health is in great danger when there is a prolonged lack of oxygen delivery to meet the metabolic demand of the tissue. This will eventually lead to cell death and organ failure. Therefore, it is very important for clinicians to monitor oxygenation in the body especially in critically ill patients or those undergoing major surgery. For example a measure of the oxygen levels in the venous system (venous oxygen saturation) has been shown to be very useful in reducing the death rate of patients with severe symptoms of whole body infection (sepsis). Also, measurements of venous oxygen saturation have been shown to be a good predictor of post-operative complications. Currently, clinical monitoring of venous oxygen saturation involves inserting an invasive catheter into a vein near the neck to perform measurements directly on the blood. However, the invasive procedures required to make these measurements demand considerable surgical skill and are associated with risk such as infection and bleeding. These procedures are only carried out in patients deemed sick enough to justify the risk, e.g. patients in the intensive care unit. These practicalities preclude many patients who can potentially benefit from the diagnostic value of the venous oxygen saturation measurement. The main objective of this work is to develop a new clinical monitor which can measure venous oxygen saturation non-invasively by combining optical and ultrasound technologies. The new clinical monitor has a probe containing both optical and ultrasound components which can be placed on the skin surface over the measurement site and target a localised region beneath. For example, it can be placed over the chest and measure the venous oxygen saturation in the pulmonary artery which contains the blood that has circulated through the whole body. This non-invasive venous oxygen saturation measurement can replace its invasive catheter based counterpart for clinical monitoring. The new monitor can also be used to target a vein draining the blood from the brain (jugular vein) so that the condition of the brain can be monitored. Other applications include the monitoring of limbs with poor circulation, recovery after surgery and the functioning of transplanted organs. Apart from venous oxygen saturation, the new monitor can also be used to measure blood flow and oxygen consumption, which indicates oxygen delivery to the tissue and the amount of oxygen used up by the tissue respectively. The principle of the new monitor is based on the phenomenon that ultrasound waves can cause periodic movement within a specific tissue region changing the way light travels through it. When light passes through this region, the intensity of the light will be altered and can be detected by a surface mounted optical detector. In other words, the light is tagged by the ultrasound waves which are the strongest in the target region. The detected tagged light is known as the acousto-optic signal and can be used to derive localized oxygenation, blood flow and oxygen consumption.In this work, different ways of combining the optical and ultrasound techniques will be systematically investigated, including the enhancement of the acousto-optic signals using short bursts of high energy ultrasound and microbubbles (an ultrasound contrast agent often used in modern ultrasound scan to improve image quality). The investigation will be conducted by both laboratory based and human experiments. For a thorough understanding, computer models will also be developed to explain the different mechanisms that generate the acousto-optic signals. These investigations will allow the design of a reliable hybrid monitor optimized for clinical use in a range of different settings.

The research will produce a new imaging paradigm called active imaging . Traditional imaging techniques are designed by physicists; medical or biological researchers use them if they provide useful contrast between different types of material or correlate with interesting effects. Recent trends in medical imaging are towards quantitative imaging techniques that combine biophysical models of tissue with traditional imaging techniques to provide more specific information relevant to particular applications. Active imaging extends this idea to exploit biophysical models more completely to design the imaging techniques themselves. More specifically, the technique uses optimization algorithms to search for combinations of images that provide the most information about the biophysical model and the best estimates of biologically relevant quantities.For example, Alzheimer's diseaseattacks and destroys brain cells. It leaves holes in brain tissue and deposits of unusual proteins. Brain tissue from Alzheimer's patients looks very different to normal tissue under a microscope, but the differences are not apparent on images from standard techniques like magnetic resonance imaging (MRI). Even techniques like diffusion-tensor MRI, which has acute sensitivity to tissue microstructure, show only moderate contrast. A broader class of technique, called diffusion MRI, measures the scattering of water molecules in tissue. The tissue microstructure controls the scatter pattern and so diffusion MRI provides information about the microstructure. Diffusion-tensor MRI provides only particular features of the scatter pattern that happen to be insensitive to the microstructural changes in Alzheimer's. However, we can tune the sensitivity of diffusion MRI in an almost infinite number of other ways. Active imaging will use a model of the microstructural changes in Alzheimer's to find the precise combination of diffusion MRI measurements that is most sensitive to those changes and discriminates them most successfully from normal tissue or other diseases.The project considers three diseases: Alzheimer's, multiple sclerosis and focal cortical dyplasia (a common cause of epilepsy). Each has characteristic abnormalities in brain tissue microstructure that current imaging techniques do not reveal reliably. The project will construct biophysical models of the abnormalities and use active imaging to devise diffusion MRI techniques that reveal them. The project will also use active imaging to tune diffusion MRI to reveal specific microstructural features of normal brain tissue, such as size and density of axons in white matter. No current technique can image these features in live subjects, but the information would provide fundamental new information about the structure and function of the brain. The active-imaging paradigm extends to almost any other imaging technique including other MRI techniques, X-ray or optical tomography or positron-emission tomography (PET). Although the project focusses on active imaging for diffusion MRI, it also aims to initiate follow-on projects to explore applications to other diseases (such as cancers) and other imaging techniques.

Cancer is one of the most prevalent diseases in the UK. Each year it accounts for nearly 1 in 3 of all deaths. For patients with late-stage cancer, the cancer cells often spread to other parts of the body. This process is called metastasis, and the secondary tumours that form are called metastases. One of the most common sites for metastases to develop is bones. Around 2 in 3 patients with late-stage breast and prostate cancer, and 1 in 3 with late-stage lung, thyroid, and kidney cancer will develop bone metastases. This can cause debilitating pain, which has a significant impact on patients' quality of life. The most common treatment for reducing pain from bone metastases is external beam radiation therapy. This is aimed at relieving symptoms and controlling the growth of the cancer to improve quality of life, rather than trying to cure the patient (this is known as palliative care). However, as many as 1 in 3 patients treated with radiation therapy do not experience adequate pain relief, and the treatment cannot be repeated due to the toxicity of radiation to healthy tissue inside the body. A very promising alternative therapy for pain palliation is focused ultrasound surgery, also known as high-intensity focused ultrasound or HIFU. This technique works by sending a tightly focused beam of ultrasound into the tissue. At the focus, the ultrasound energy is sufficient to heat the tissue and cause cell death in a very localised region, while the surrounding tissue is not harmed. This is akin to focusing sunlight through a magnifying glass, where only in the focus is the energy high enough to singe an object. Focused ultrasound surgery can be used to alleviate the pain from bone metastases by treating the layer of nerves and connective tissue that surrounds the bone. The major challenge is to ensure the focus is accurately placed at the desired target within the body. This is difficult because bones and other organs can significantly distort the path of the ultrasound beam. The aim of this fellowship is to develop, validate, and apply new computer models to simulate how sound waves travel inside the human body. These models will be based on innovative advances in theoretical acoustics and numerical methods, and will use state-of-the-art computing facilities that have only recently become available. The computer models will allow the position of the focus and the heating of bones during focused ultrasound surgery to be accurately predicted for the first time. This will allow physicians to carefully plan and optimise the treatment parameters to eliminate the pain arising from bone metastases. This is expected to increase the effectiveness of focused ultrasound surgery, reduce the time it takes to treat patients, and extend the range and location of cancers that are eligible for treatment. As part of the fellowship, the models will be rigorously validated using patient data from previous clinical treatments, along with carefully planned laboratory experiments using phantom materials designed to mimic human tissue.

Health, quality of life and wellbeing have become the number one priority areas for individuals, communities and governments worldwide and directly impact policy making across much of the developed world. A significant body of evidence and numerous policy directives acknowledge the important role culture and access to heritage plays in active citizenship, community engagement, improving wellbeing and life satisfaction. The heritage sector has the opportunity to more closely engage with this broad agenda and in return benefit from its strength as a priority with funders and partners. Museums and galleries already have an effect on wellbeing through their learning, access and outreach programmes and have done throughout much of their history. The challenge, as with learning, is measuring the distinctive but potentially significant contribution museums and galleries make to individual and community wellbeing, and articulately advocating for further work to potential partners and funders. It is therefore vital we establish a robust, repeatable, measure for assessing the value to health and wellbeing that this interaction affords. Furthermore, such engagement requires strong theoretical and empirical evidence, and a conceptual language, in order to clearly articulate the value of the heritage sector's contribution to health and wellbeing. Previous AHRC-funded research has demonstrated that heritage-focused activities in hospitals and other healthcare settings have shown significant improvements in wellbeing as measured by scales commonly used in clinical practice. Analysis of interviews showed that patients are distracted from their clinical surroundings and feel happier and healthier as a result of heritage-focused activities such as handling and discussing museum objects. The effects of arts-focused interventions in healthcare contexts are also well-documented and reviewed. Studies have found that arts-focused activities can lead to reduced drug consumption, decreased hospital stay, improvements in mental wellbeing and social inclusion, and increased empathy in healthcare professionals with mental health patients. There are many other examples of good practice from UK museums and galleries whose community access programmes have revealed a significant impact on enhancing social wellbeing; a few highlights include the Dulwich Picture Gallery's 'Good Times - Prescription for Art' programme, the Museum of East Anglian Life's social inclusion programme, Colchester and Ipswich Museum's work with mental health service users and the arts-for-health programme run across Manchester Museums. To date the above 'wellbeing' programmes and others like them have used a range of techniques to assess the value and impact of their work, including 'social return on investment' models, mental health wellbeing scales and quality of life measures. The sector however, lacks a defined approach for assessing the impact of its work on health and wellbeing. In the last ten years, many museums and galleries have used a set of measures called the Generic Learning Outcomes (GLOs) to assess the impact of their work on learning. Subsequently, the Generic Social Outcomes (GSOs) were devised to measure the social benefits resulting from a museum or heritage visit such as the level of interaction between visitors as a result of engagement with an object or historic site. The goal of this project is to move beyond the GLOs and GSOs to develop a heritage focused wellbeing measure and create a new conceptual and methodological framework (or Generic Wellbeing Outcome, GWO), for evaluating the heritage sectors contribution to health and wellbeing. Through testing and validating the GWO across a variety of museums and galleries, the project will assess and promote the benefits to health, wellbeing and quality of life of heritage-focused activities.