PICUP - Point-of-Care Fracture Prediction

Lead Research Organisation: Cranfield University
Department Name: Cranfield Defence and Security


A significant and escalating worldwide health burden is the ageing population and its demand for accurate medical diagnostics. Of particular concern are osteo diseases such as osteoporosis (OP) as this results in a very high healthcare burden, particularly in elderly populations. More than 1000 people die every month in the UK from OP related hip fractures and the NHS costs associated with OP hip fracture are >£2.0b per annum.

This proposal concerns the development of a new clinical instrument to predict osteoporotic fractures within an individual and thus improve quality of life and reduce this health burden. The proposal, for the first time, will combine two recently developed technologies within a new, point-of-care clinical instrument. This proposal has been developed from a recently completed EPSRC research programme, "Point-of-Care High Accuracy Fracture Risk Prediction" (EP/K020196/1). This took the first research steps towards providing the underpinning science and engineering proof of principle for a new approach to fracture prediction. It was premised upon the thesis that bone is a complex engineering material where composition is critical to performance, i.e. osteoporotic compromise of fracture strength is related to changes in architecture, mass and material chemistry. The work also attempted to secure proof of principle for a new measurement technique (focal construct technology, FCT) that could derive critical chemistry features based upon X-ray scattering.

The research was a great success in that a new set of biomarkers, sensitive to osteoporosis, was discovered, and the novel data acquisition approach was demonstrated to provide the quantified parameters within the required precision. Other, smaller (short term) development research grants (IAA) awarded within the previous 18 months have also enabled us to explore options for alternative geometries and the use of other optical elements within the measurement space. Further, a current, joint STFC research programme (ST/N006526/1) is exploring the combined use of our FCT approach with a novel pixelated detector, Hexitec, albeit within a different application sector.

At this stage, the technological risks remain high, the demand for such research is tangible, and the potential societal and financial benefits are very large.

Planned Impact

The programme will ultimately deliver a novel and accurate, non-invasive clinical instrument to assess bone quality and provide an individualised fracture risk prediction. Therefore, the ultimate beneficiary of this programme will be the aging general population who present with an increasing risk of fragility fracture. Currently, without the successful conclusion of this research, the management of osteoporosis sufferers is compromised by limited intelligence. Thus whether an individual needs "safeguarding" measures to minimise the risk of a fracture cannot be reliably determined. Equally importantly, the enhanced medical diagnostics afforded by this research will also prevent over safeguarding for those presenting with osteoporotic changed (as revealed by DXA) but mechanically robust bone.
The research programme is the second step (the first being the research that recognised new diagnostic markers) towards the development of the novel technology. The solution builds upon cutting edge science coupled with highly innovative state-of-the-art engineering. The application of the technology will enable patients to be accurately diagnosed within community environments. Our approach has the potential for wide spread impact in patient care, N.H.S. cost savings, U.K. industrial development and wealth generation. In particular the work will have impact for:

> Elderly populations, as individuals will be significantly less likely to suffer from factures (or even death following fracture) and thus have enhanced quality of life. The reduced times to receive any diagnosis will also relieve associated psychological stress.

> Patients receiving therapy for bone disease as this group will have improved care through faster and more accurate diagnostic testing.

> The N.H.S. as >£20 billion per annum is currently spent on treating hip fractures and this would be significantly reduced if accurate fracture assessment were possible. Further, rapid and more accurate diagnosis within the community would produce efficiency savings both for GP's and hospital clinicians.

> U.K. industry that will assume a world lead in this growing medical technology. This will underpin significant potential global R&D investment ultimately contributing to the U.K.'s economic growth. The clinical technology development will form part of what is planned to be a significant commercial commitment from Halo X-ray Technology Ltd (HXT) to this application area and thus will directly create new jobs and industrial activity. They intend to leverage the successful award of this grant to raise additional InnovateUK and private venture funding, which will be used to develop HXT presence and technology in the medical field. The development of new HXT products and the expansion into new markets will lead to greater support of local and national businesses. All HXT production is outsourced; increased sales will therefore boost all aspects of the company supply chain, including improved employment prospects within these companies. The export opportunity for new products based on this development will be significant and add substantially to the UK economy. In a similar commercial development, the work will significantly enhance the ability of the Science and Technology Funding Council to create licence agreements for its detector systems and thus offset the taxpayers contributions to scientific research within the U.K.

> The young scientists employed for the duration of the programme will benefit from training within an exciting and growing applied research field providing a springboard for future careers in academia and or industry.

> The Universities involved in the programme will benefit directly through an expanded research base, new collaborations and networks.


10 25 50
Description We have developed the design specifications for the novel imaging platform as promised by the proposal.
We have built and commissioned the pre-protype platform to be used in assessing the imaging technology.
We have produced the first data sets measured by our 'sparse sampling' approach and have refined the data collection protocols.
We have been able to show the relationships between CT imaging features and bone strength.
Exploitation Route The development about is currently being used to fabricate the platform and these designs could be exploited by other groups wishing to explore this new imaging modality.
Sectors Healthcare,Culture, Heritage, Museums and Collections,Security and Diplomacy

URL http://www.picup-diagnostics.com
Description Duke Diagnostic Imaging 
Organisation Duke University
Country United States 
Sector Academic/University 
PI Contribution Duke University have a research team that is developing a new imaging modality for rapid examination of tissue specimens, including bone. Duke approached the Cranfield team to discuss how Cranfield's expertise in interpretation of X-ray scatter data from bone may be used for diagnostics. Thus Cranfield provides the data interpretation component of this collaboration.
Collaborator Contribution Duke University have been using a novel imaging approach by exploiting coded apertures to provide rapid, high resolution, depth resolved imaging based upon transmission X-ray imaging and orthogonal scattering data (e.g. James R. Spencer, Joshua E. Carter, Crystal K. Leung, Shannon J. McCall, Joel A. Greenberg, and Anuj J. Kapadia "Coded aperture coherent scatter spectral imaging for assessment of breast cancers: an ex-vivo demonstration", Proc. SPIE 10132, Medical Imaging 2017: Physics of Medical Imaging, 101324K (9 March 2017); https://doi.org/10.1117/12.2253975). This recently resulted in the first prototype that has been placed (Feb 2020) within a clinical Pathology Department for a full evaluation.
Impact The collaboration is a little early to have produced any definitive outputs. However, in collaboration, an NIH grant was submitted (Feb 2020) to support the work through its next stages. This is a multi-disciplinary collaboration with contributions from the physics community (understanding the optical features of the instrument), medical physics (providing an interface to the clinical community), crystallography (signal interpretation) and medicine (providing tissue specimens and clinical direction).
Start Year 2019
Description Halo exploitation 
Organisation HALO X-ray Technologies Ltd
Country United Kingdom 
Sector Private 
PI Contribution We are providing the underpinning scientific expertise and skills required for commercialisation
Collaborator Contribution Halo X-ray are translating the research ideas that arise in response to outcomes from the EPSRC grant from ourselves to a practical and commercial space.
Impact CA
Start Year 2016
Description Longitudinal imaging of bone tissue remodeling: a novel platform for probing skeletal adaptation 
Organisation University of Saskatchewan
Department Department of Anatomy and Cell Biology
Country Canada 
Sector Academic/University 
PI Contribution The goal of this interdisciplinary research is to advance understanding of the spatio-temporal regulation of cortical bone remodeling. Stated simply, we seek to understand how a BMU plots its course through bone and what factors affect its progression both in terms of its resorptive and formative phases. Our role in the project would be to utilize image data to target post-mortem assessment of ultrastructural properties adjacent to BMUs in both the rabbit and the human bones. The culmination of our partnership will be the development of new computational models that allow integration of complex regulatory mechanisms governing the path and progression of BMUs through existing micro- and ultrastructure.
Collaborator Contribution This collaborative programme resulted in a major applicatio to the presidigeous Human Frontiers Science Programme involving a number of International collaborators. The Partners contributions were to realise the following objectives : 1. Establish a novel in vivo imaging protocol for longitudinal 3D observation of BMUs in the rabbit 2. Perform comparative 3D ex vivo imaging on human materials 3. Incorporate image data within multilevel computational models of BMU regulation for both humans and rabbits.
Impact We have yet to be successful in our efforts to fund this proposal. Further actions will be undertaken over the next 24 months.
Start Year 2016
Description NISTA Diagnostics 
Organisation Nista Diagnostics
Country United States 
Sector Private 
PI Contribution Our team is providing a component of the technical support to enable proper interpretation of data.
Collaborator Contribution This is a new collaboration that started in Oct 2019. This new US medical diagnostics company Nista Diagnostics Inc, are attempting to augment the pathological assessment of biological tissues through the use of X-ray scattering to examine a wide range of conditions. Nista made an approach to the Cranfield team as they were aware of the work we had been undertaking on osteoporosis and disease in other tissues. Nista have requested that the Cranfield team undertake all the essential 'up-front' work to commence a small clinical trial within the UK at two Centres and then manage the trials. The networks formed as a component of the EPSRC grant have enabled this to be undertaken quickly and we hope to be starting the trials within 2020.
Impact This is a commercial, multidisciplinary collaboration that is within early gestation stages, hence there are no definitive outputs as yet.
Start Year 2019
Description Clinical engegment group 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Industry/Business
Results and Impact We have generated a new clinical focus group who have agreed to review the project outcomes as the project progresses and also provide access to patient focus groups to enable input to the future prototype design stages
Year(s) Of Engagement Activity 2018