Implementation of a benchtop energy-dispersive X-ray diffraction computed tomography system for in vitro tissue characterisation

The project will develop novel geometries for Energy-Dispersive X-ray Diffraction Computed Tomography (EDXRDCT) for the characterisation of biological tissue, with specific focus on breast tissue. It will be carried out in collaboration with the School of Materials of the University of Manchester, the Cellular Pathology Department at Royal Surrey County Hospital, the National Coordinating Centre for Physics in Mammography and the Breast Screening Unit at Barts and The London NHS Trust and with the support of industrial collaborators (Morpho Detection, Inc. and South East Health Technology Alliance).X-ray diffraction allows identification of low-contrast lesions and their characterisation, including cancer identification and staging. Due to the intrinsic non-uniformity of biological tissue, characterisation of typical specimens based on X-ray diffraction requires the use of Computed Tomography (CT). However, work so far in the field of diffraction CT using polychromatic sources was limited to the first generation CT geometry, requiring overall acquisition times incompatible with clinical requirements.The present work will be based around the development and optimisation of two novel geometries that will reduce the acquisition times to a few minutes/slice. A system based on the combination of the two geometries could be used in the future for fast biopsy or characterisation of post-operatory specimens with a short enough timescale to guarantee minimum disruption to the clinical routine. This will allow fast and effective diagnosis of cancer, targeted treatment and reduction of unnecessary operations, thus contributing to an optimised use of resources in the Healthcare Service and to the general welfare of the population.The two geometries proposed will rely on a combination of cutting-edge technology and advanced data processing algorithms.Custom test objects will be designed and built to simulate the diffraction and geometrical properties of breast lesions. The two geometries proposed will be evaluated initially on these objects, and then, in the final stages of the project, on formalin-fixed breast tissue samples provided form the Cellular Pathology Department at Royal Surrey County Hospital. Tests on tissue samples will assess the repeatability of results from the same specimen using different geometries, and the repeatability of diffraction patterns from tissue regions from different specimens with the same histological properties.Results from these lab-based systems will be compared to those obtained using synchrotron radiation in collaborative experiments with the School of Materials at the University of Manchester, and to histological assessment using conventional methods.

In the medium term (~ 5 years), the main beneficiary of the research will be the Healthcare Service. The project will develop a prototype for a system allowing fast and accurate characterisation of tissue specimens both in a histopathology environment and in the operating theatre. This will reduce the rate of unnecessary operations and allow an optimised use of the healthcare resources. For this reason, the research has a potential impact not only on the patients that will be directly diagnosed through the technique proposed, but also on all healthcare users. Moreover, a more accurate diagnosis in the operating theatre will allow targeted treatment, avoiding both undertreatment and overtreatment. This will mean longer life expectancy and better life quality, as well as a better use of resources of the social care services. In the more immediate future, the project will foster the development of a range of interdisciplinary skills (awareness of medical requirements, ethical implications of the work with tissue, use of different detector technologies) that the junior staff involved (post-doctoral research assistant, PhD student) will be able to exploit in their future careers, whether in Academia, Hospitals or Industry. Existing collaborations (School of Materials at Manchester and National Coordinating Centre for Physics in Mammography) will be strengthened, and new synergies will be created with Hospitals, both at the local and the regional level. This will allow the development of the career of the Principal Investigator as a leading interdisciplinary scientist. The results and their impact will be disseminated at the specialist level through publications on scientific journals, conference presentations and seminars at Academic and Medical collaborating Institutions, whether directly involved in the project or collaborators of the Physics Department at Surrey (e.g., SEPNET consortium). Dissemination of results to the general population, as the end-beneficiary of the research, will be done through School Outreach events, University Open Days and advertisement in the University and Departmental website. Resources are in place at the University of Surrey that will facilitate dissemination, such as the Faculty and the University Outreach and Marketing teams. Commercial exploitation of the research and protection of intellectual property rights will be addressed through the Research and Enterprise Support Team and the Technology Transfer Office, and through mechanisms in place for the Surrey/National Physics Laboratories Knowledge Transfer Account (KTA). Further applications of the research and of its primary (the diffraction CT system) and secondary outcomes (data correction and reconstruction algorithms, test objects) will be identified together with the industrial collaborators at Morpho Detection. Other potential partners for future exploitation of the research outcomes will be identified through the Surrey/NPL KTA and through collaboration with the South East Health Technologies Alliance (SEHTA).