Development of MRI scan methods to image inhaled fluorocarbon gases as biomarkers of lung structure and function.

The aim of this project is to develop new magnetic resonance imaging (MRI) methods to measure lung functional and structural properties. We will image the distribution within the lung of perfluoropropane - an inert, inhalable gas that can be visualised with 19F-MRI: an MRI scan that detects the fluorine nuclei within inhaled perfluoropropane gas. We will implement and test new MRI scanner hardware and scan acquisition methods to improve the image quality of lung scans made with this method, and use accelerate scan methods to improve scan tolerability for patients with respiratory disorders.
Whilst there are methods to assess lung structural and functional properties in current clinical practice, these either lack spatial information (and so don't detect subtle localised changes associated with early respiratory disease) or use ionising radiation that carries a risk to the patient. MRI offers a safely repeatable and radiation-free imaging method and our approach to lung imaging permits quantitative measurement of lung ventilation properties than is sensitive to respiratory disease.
The novel healthcare technologies developed in this project will underpin the downstream use of lung 19F-MRI clinical research and clinical practice.

Project objectives
The key objectives of this study are to measure the impact of MRI acceleration methods on 19F-MRI measures of lung ventilation properties, and to employ accelerated 19F-MRI methods in the development of lung functional and structural measurements than can ultimately be applied in clinical research and clinical practice. We hypothesise that a combination of advanced acceleration techniques can deliver a marked improvement in scan resolution and reduced scan duration, which in turn can improve ability to quantify ventilation defects in patients with respiratory disease and deliver better and more patient-friendly scan methods (such as free-breathing rather than breath-held scanning).

MRI scan acceleration methods are well established for conventional clinical MRI scanning. Acceleration methods such as parallel imaging and compressed sensing are available as products from all major MRI scanner manufacturers, however their use in multinuclear MRI (such as 19F-MRI of inhaled perfluoropropane) is not widespread or easily implemented on a standard clinical scanner. We recognise that existing lung 19F-MRI methods have not yet fully exploited the capabilities provided by scan acceleration methods, and we see scope for significant improvement of image quality for lung 19F-MRI beyond the current state of the art.

Our studies will use lung-mimicking test objects and studies of healthy volunteers to test new MRI scanner sensor (RF coil) hardware and scanner software (MRI pulse sequences). We will combine parallel imaging and compresses sensing to produce more detailed (higher resolution) 3D images of lung ventilation properties and advance from static lung images to dynamic (movie) 3D images that show the wash-in and wash-out of our tracer gases throughout the lungs. The new imaging technologies developed in this project will then be positioned for immediate use in clinical research studies that assess the progression of respiratory diseases, and that assess the effects of therapeutic strategies (e.g. novel drug treatments) on lung function, and the imaging methods have potential for development towards the ultimate goal of use in clinical practice for respiratory disease diagnosis and monitoring.

The CDT has five primary beneficiaries:
The CDT cohort
Our students will receive an innovative training experience making them highly employable and equipping them with the necessary knowledge and skillset in science and enterprise to become future innovators and leaders. The potential for careers in the field is substantial and students graduating from the CDT will be sought after by employers. The Life Sciences Industrial strategy states that nearly half of businesses cite a shortage of graduates as an issue in their ability to recruit talent. Collectively, the industrial partners directly involved in the co-creation of the proposal have identified recruitment needs over the next decade that already significantly exceed the output of the CDT cohort.
Life science industries
The cohort will make a vital contribution to the UK life sciences industry, filling the skills gap in this vital part of the economy and providing a talented workforce, able to instantly focus on industry relevant challenges. Through co-creation, industrial partners have shaped the training of future employees. Additional experience in management and entrepreneurship, as well as peer-to-peer activities and the beginning of a professional network provided by the cohort programme will enable graduates to become future leaders. Through direct involvement in the CDT and an ongoing programme of dissemination, stakeholders will benefit from the research and continue to contribute to its evolution. Instrument manufacturers will gain new applications for their technologies, pharmaceutical and biotech companies will gain new opportunities for drug discovery projects through new insight into disease and new methods and techniques.
Health and Society
Research outputs will ultimately benefit healthcare providers and patients in relevant areas, such as cancer, ageing and infection. Pathways to such impact are provided by involvement of industrial partners specialising in translational research and enabling networks such as the Northern Health Science Alliance, the First for Pharma group and the NHS, who will all be partners. Moreover, graduates of the CDT will provide future healthcare solutions throughout their careers in pharmaceuticals, biotechnology, contract research industries and academia.
UK economy
The cohort will contribute to growth in the life sciences industry, providing innovations that will be the vehicle for economic growth. Nationally, the Life Sciences Industrial Strategy Health Advanced Research Programme seeks to create two entirely new industries in the field over the next ten years. Regionally, medicines research is a central tenet of the Northern Powerhouse Strategy. The CDT will create new opportunities for the local life sciences sector, Inspiration for these new industries will come from researchers with an insight into both molecular and life sciences as evidenced by notable successes in the recent past. For example, the advent of Antibody Drug Conjugates and Proteolysis Targeting Chimeras arose from interdisciplinary research in this area, predominantly in the USA and have led to significant wealth and job creation. Providing a cohort of insightful, innovative and entrepreneurial scientists will help to ensure the UK remains at the forefront of future developments, in line with the aim of the Industrial Strategy of building a country confident, outward looking and fit for the future.
Institutions
Both host institutions will benefit hugely from hosting the CDT. The enhancement to the research culture provided by the presence of a diverse and international cohort of talented students will be beneficial to all researchers allied to the theme areas of the programme, who will also benefit from attending many of the scientific and networking events. The programme will further strengthen the existing scientific and cultural links between Newcastle and Durham and will provide a vehicle for new collaborative research.