Macro-to-molecular correlative X-ray imaging of strain during spinal joint loading

Project Summary (Please complete the summary in the following format with headings present. Should be 4,000 characters Maximum):

1) Brief description of the context of the research including potential impact

Biological tissues operate in a dynamic mechanical environment. The body's response to these forces is mediated by a hierarchy of biophysical processes from the smallest (molecular) to the largest (organ) level. The mechanobiology of fibrillar composites is critical for physiological function, and their multiscale structural/ mechanical changes in disease or injury are often critical to loss of function. Treatment for these conditions imposes a huge healthcare burden. The bioengineering challenge is to determine the correlated 3D deformation and structural changes at the molecular-, fibrillar-, and cell-matrix length-scales under physiological load in intact tissue, and how these alter in ageing, injury and disease.

X-ray illumination of an organ can build up a 3D map of the collagen fibre bundles in the matrix (tomography or CT) with micron-level resolution. At a hundred times smaller size, these same X-rays can interact with the molecules making up the fibres via interference, building up a picture like a diffraction grating (small angle scattering or SAXS). When a brilliant X-ray beam (like the kind available at synchrotrons) is available, these methods can be used to study load-induced biophysical changes dynamically. If the information from these two techniques - CT and SAXS - could be combined, we would have an unprecedented molecular-to-macroscale visualisation of tissue biophysics.

This project aims to use phase-contrast CT with SAXS to image the multiscale biophysics of tissues to help understand the behaviour of organs like the intervertebral disc, which is crucially important for posture and preventing back pain.

2) Aims and Objectives

The overall aims is to gain new insights into multiscale biophysics of tissues to help understand the biomechanical behaviour of intervertebral disc. To achieve this the specific objects are to: 1. use phase contrast tomography and digital volume correlation on intact intervertebral discs to measure the fibre-structure. 2. To use in situ biomechanical loading coupled with imaging to develop and image injurious loading protocols which disrupt the native tissue matrix structure in physiologically relevant ways. 3. To analyse these injury-systems using digital volume correlation to predict the functional alterations in micromechanics in intact, injured joints, providing new insights into the function of the human body in health and disease.

3) Novelty of Research Methodology

This project will develop new injurious loading protocols which disrupt the native tissue matrix structure in physiologically relevant ways and image these dynamically.

4) Alignment to EPSRC's strategies and research areas

The project aligns with the EPSRC Engineering Grand Challenge Healthcare Technologies foci Optimising Treatment and Developing Future Therapies, via the Cross-cutting capabilities theme Novel imaging technologies. By taking a step-change in multiscale biophysical analysis of tissues, this project supports the Grand Challenge Understanding the Physics of Life. This research is aligned to EPSRC research areas Biophysics (Grow) and Musculoskeletal Biomechanics (Maintain).

5) Any companies or collaborators involved

This PhD is part of a collaboration between University College London (UCL), Queen Mary University of London (QMUL), Diamond Light Source (www.diamond.ac.uk), ESRF (www.esrf.eu), the University of Manchester and Oregon State University (USA).

The critical mass of scientists and engineers that i4health will produce will ensure the UK's continued standing as a world-leader in medical imaging and healthcare technology research. In addition to continued academic excellence, they will further support a future culture of industry and entrepreneurship in healthcare technologies driven by highly trained engineers with deep understanding of the key factors involved in delivering effective translatable and marketable technology. They will achieve this through high quality engineering and imaging science, a broad view of other relevant technological areas, the ability to pinpoint clinical gaps and needs, consideration of clinical user requirements, and patient considerations. Our graduates will provide the drive, determination and enthusiasm to build future UK industry in this vital area via start-ups and spin-outs adding to the burgeoning community of healthcare-related SMEs in London and the rest of the UK. The training in entrepreneurship, coupled with the vibrant environment we are developing for this topic via unique linkage of Engineering and Medicine at UCL, is specifically designed to foster such outcomes. These same innovative leaders will bolster the UK's presence in medical multinationals - pharmaceutical companies, scanner manufacturers, etc. - and ensure the UK's competitiveness as a location for future R&D and medical engineering. They will also provide an invaluable source of expertise for the future NHS and other healthcare-delivery services enabling rapid translation and uptake of the latest imaging and healthcare technologies at the clinical front line. The ultimate impact will be on people and patients, both in the UK and internationally, who will benefit from the increased knowledge of health and disease, as well as better treatment and healthcare management provided by the future technologies our trainees will produce.

In addition to impact in healthcare research, development, and capability, the CDT will have major impact on the students we will attract and train. We will provide our talented cohorts of students with the skills required to lead academic research in this area, to lead industrial development and to make a significant impact as advocates of the science and engineering of their discipline. The i4health CDT's combination of the highest academic standards of research with excellent in-depth training in core skills will mean that our cohorts of students will be in great demand placing them in a powerful position to sculpt their own careers, have major impact within our discipline, while influencing the international mindset and direction. Strong evidence demonstrates this in our existing cohorts of students through high levels of conference podium talks in the most prestigious venues in our field, conference prizes, high impact publications in both engineering, clinical, and general science journals, as well as post-PhD fellowships and career progression. The content and training innovations we propose in i4health will ensure this continues and expands over the next decade.