Disease staging from amnestic mild cognitive impairment to probable Alzheimer's disease via MRI and[18F]flutemetamol PET
Lead Research Organisation:
University of Oxford
Department Name: Biomedical Imaging CDT
Abstract
Key project deliverables include determination of the degree of association between region-specific amyloid burden as measured by [18-F] Flutemetamol PET brain imaging and the rate of conversion from amnestic Mild Cognitive Impairment (aMCI) to probable Alzheimer's Disease (pAD); furthermore, will involve the identification of structural (multi-modal) MR imaging biomarkers strongly correlated with cognitive decline, and utilising these cross-sectional PET-MR derived imaging measures to drive the development of a predictive analytic software product. An automated quantitative PET-MR neuro-imaging processing and analysis pipeline will also be developed as part of this project to process imaging data readily available from a 2009 multi-centre cohort clinical study during which 232 subjects presenting aMCI underwent a [18-F] PET brain scan along with a T1, T2 and/or T2-FLAIR MRI brain scan at baseline, and their psychometric score and conversion status reviewed periodically over three years. The developed predictive analytic tool will be applied to pathologically confirmed patient data - via direct tau measurements obtained from CSF, alternatively via PET tau measures and psychometric data; and its predictive strength evaluated with respect to the extent of neuronal disruption. The project will, therefore, serve to deepen insight into patients' disease trajectory. It is anticipated that the output of the research project will facilitate earlier and more effective diagnosis, better guiding clinical intervention strategies - patient monitoring and care planning, moreover, it will potentially provide a foundation on which clinicians can effectively assess patient suitability / eligibility for emerging clinical trials and thus advancing medical research within the treatment domain. The project is a collaborative effort between the Wellcome Institute for Integrative Neuroimaging (WINN), University of Oxford and the Imaging Technology Group of General Electric (GE) Healthcare Life Sciences; with Dr Mark Jenkinson and Dr Christopher Buckley leading the DPhil research project in the role of academic and industrial supervisors, respectively. In light of the above, the research project corresponds to priorities 1, 3, 6 and 7 of the EPSRC's Medical Imaging / Medical Image and Vision Computing Research Area.
Planned Impact
The UK has made a significant research impact in the area of biomedical imaging, especially given the size of its research volume. This impact was highlighted in the 2012 EPSRC/MRC Report on Medical Imaging Technologies, that placed the UK first for relative world impact in the neuroimaging field, and third in the world for research in radiology, nuclear medicine and medical imaging (see Appendix 1 of that report). However, the UK does not have a good track record in translating its medical imaging technologies into commercial enterprises. Indeed, most of the major medical imaging technology companies are based outside the UK.
Based on this excellence of biomedical imaging research expertise, however, an opportunity does exist to promote enterprise in the UK, which ultimately may lead to the growth of smaller specialist companies, particularly in the area of supporting drug discovery and assessment of pharmaceutical efficacy. For the pharmaceutical industry the ideal situation is to partner with academically strong medical centres via specialist contract research organizations (of the type represented by one of our industry partners P1Vital) who have imaging experts to guide the complex trials work that is required. In order to prevent emerging markets, with their increasingly competitive academic centres, from being first choice options for hosting such industries, the UK must train a larger pool of entrepreneurially minded imaging scientists.
The other major beneficiary of biomedical imaging science is in the healthcare sector, where NHS delivery costs are rising dramatically, and more focused and quantitative characterization of patients and their treatment progression will be needed. This is true across all scales of imaging, from better tissue characterization at the cellular level (from biopsies and via endoscopic procedures), all the way to human-organ and whole-body imaging methods. The opportunities for cost savings for a more personalized medicine delivery are enormous, but only provided that carefully targeted imaging procedures can be generated and used in combination with personalized genetic information. If successful, imaging could help greatly reduce healthcare costs by better stratifying patients for specific treatments, and by ensuring via longitudinal follow up that those treatments are being effective.
Clearly the biggest impact of the CDT, however, will be the work that the projected 75+ students perform once they complete their studies. This injection of highly trained and inter-connected imaging scientist experts will maintain UK academia's prominence in this field and will greatly strengthen UK industry and the UK healthcare sector. Based on past experience we would expect approximately 60% will move straight into academic research and 20% into industrial research. The remaining students will go into a variety of careers including the healthcare sector and other professional careers. Given the industrial involvement and stimulation in this CDT we would also expect several of our students to be attracted towards an entrepreneurial pathway and to form their own startup companies (e.g. the existing DTCs at the maths/physical/biomedicine interface in Oxford have resulted in 12 such startups). This demonstrates the likely impact of the career development opportunities provided by the ONBI CDT programme, and the resulting excellent employment prospects. Academically we would expect, based on previous and existing similar programmes, that each student will publish 2-3 journal papers arising from their doctoral work, including many in high impact journals, and likely some will file patents. It should finally be noted that all students will be required to participate in public and schools outreach activities in the later years of their training, with the hope and expectation that this will be an activity that they continue beyond their training, thus with a lasting impact.
Based on this excellence of biomedical imaging research expertise, however, an opportunity does exist to promote enterprise in the UK, which ultimately may lead to the growth of smaller specialist companies, particularly in the area of supporting drug discovery and assessment of pharmaceutical efficacy. For the pharmaceutical industry the ideal situation is to partner with academically strong medical centres via specialist contract research organizations (of the type represented by one of our industry partners P1Vital) who have imaging experts to guide the complex trials work that is required. In order to prevent emerging markets, with their increasingly competitive academic centres, from being first choice options for hosting such industries, the UK must train a larger pool of entrepreneurially minded imaging scientists.
The other major beneficiary of biomedical imaging science is in the healthcare sector, where NHS delivery costs are rising dramatically, and more focused and quantitative characterization of patients and their treatment progression will be needed. This is true across all scales of imaging, from better tissue characterization at the cellular level (from biopsies and via endoscopic procedures), all the way to human-organ and whole-body imaging methods. The opportunities for cost savings for a more personalized medicine delivery are enormous, but only provided that carefully targeted imaging procedures can be generated and used in combination with personalized genetic information. If successful, imaging could help greatly reduce healthcare costs by better stratifying patients for specific treatments, and by ensuring via longitudinal follow up that those treatments are being effective.
Clearly the biggest impact of the CDT, however, will be the work that the projected 75+ students perform once they complete their studies. This injection of highly trained and inter-connected imaging scientist experts will maintain UK academia's prominence in this field and will greatly strengthen UK industry and the UK healthcare sector. Based on past experience we would expect approximately 60% will move straight into academic research and 20% into industrial research. The remaining students will go into a variety of careers including the healthcare sector and other professional careers. Given the industrial involvement and stimulation in this CDT we would also expect several of our students to be attracted towards an entrepreneurial pathway and to form their own startup companies (e.g. the existing DTCs at the maths/physical/biomedicine interface in Oxford have resulted in 12 such startups). This demonstrates the likely impact of the career development opportunities provided by the ONBI CDT programme, and the resulting excellent employment prospects. Academically we would expect, based on previous and existing similar programmes, that each student will publish 2-3 journal papers arising from their doctoral work, including many in high impact journals, and likely some will file patents. It should finally be noted that all students will be required to participate in public and schools outreach activities in the later years of their training, with the hope and expectation that this will be an activity that they continue beyond their training, thus with a lasting impact.