Quantification of vascular and neuronal pathology in dementia using PET and MRI

Lead Research Organisation: University of Manchester
Department Name: School of Health Sciences

Abstract

The increasing occurrence of dementia within our ageing population is one of the pressing challenges facing society. Successful management of patients with dementia is significantly aided by early and accurate diagnosis. Imaging methods such as magnetic resonance imaging (MRI) and positron emission tomography (PET) are already used in the diagnostic process; we believe that there is substantial scope for both methods to be improved to provide more precise and sensitive diagnostic information, and to do so in a way that is easily tolerated by patients. If we are correct in this belief, then the methods we develop within this project will not only help in early diagnosis, but may also help in the discovery of new therapies and in the longer term with helping doctors select the best therapeutic strategies for patients with different forms of dementia.

Imaging methods such as MRI and PET can tell us a lot more about brains than simply providing a picture of brain shape and size. We will focus on improving MRI and PET to be sensitive to two important microscopic aspects of dementia. Firstly, we will develop and validate new methods for measuring the loss of brain cells due to the condition; this loss is the cause of many of the symptoms of dementia, such as memory problems, and we hope to be able to detect these changes earlier than has previously been possible. Secondly we will develop and validate new methods for measuring changes in blood delivery to the brain and how this can affect oxygen delivery. These changes are thought to be part of one of the important processes involved in causing cell death and tissue loss, and are likely to be particularly relevant to vascular dementia.

We will also spend considerable time checking that the measurements we develop are both accurate and practical for application in dementia patients in the future. We will optimise the way in which the scanning processes take place so that the time required for patients to lie in the scanner(s) is minimised. This will be important for future adoption of these methods in the clinical environment.

Planned Impact

The outputs of this research will benefit a range clinical and industrial sectors. The obvious clinical benefit is for neurology and gerontology, where the methods provided by this work will add to the toolkit available to clinicians to aid diagnosis and patient monitoring. Industrial beneficiaries are likely to include scanner manufacturers, such as Philips, Siemens (see letters of support) and GE, who are the major manufacturers of both PET and MRI scanners; more efficient and informative imaging methods are likely to increase demand for imaging equipment. The emerging field of PET+MRI hybrid systems is also likely to benefit from our work, which explicitly aims to maximise the combined information obtainable when these two modalities are used closely together. Imaging contract research, equipment and software companies also stand to benefit indirectly from our research (see letters of support from SMEs Icometrix and Bioxydyn), as we expect better imaging techniques to lead to more clinical trials of new therapies for dementia. The pharmaceutical industry will be the main industrial beneficiary of those trials; it will exploit better imaging methods to shorten trials and/or to run trials with fewer patients, as the effects of new drugs will be more readily apparent with more specific and sensitive imaging tools.

Ultimately the highest benefit of our proposed work will be felt by dementia patients and society at large. The pressing need for action on dementia within our ageing population highlights the need for earlier and more precise diagnosis. In time, patients will be provided with more appropriate treatments for their condition due to better diagnosis, and that treatment will start earlier; both factors are likely to have a significant impact on wellbeing by slowing disease progression. Healthcare systems will benefit from substantial cost savings by being able to treat earlier and more precisely, as the more severe (and costly to manage) symptoms of dementia are delayed and reduced due to better clinical decision making enabled by better diagnosis.

Publications

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Abid KA (2018) Assessing Inflammation in Acute Intracerebral Hemorrhage with PK11195 PET and Dynamic Contrast-Enhanced MRI. in Journal of neuroimaging : official journal of the American Society of Neuroimaging

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Al-Bachari S (2017) Structural and physiological neurovascular changes in idiopathic Parkinson's disease and its clinical phenotypes. in Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism

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Chaney A (2018) In vivo molecular imaging of neuroinflammation in Alzheimer's disease in Journal of Neurochemistry

 
Description Water exchange across the blood brain barrier is altered in a model of early Alzheimer's disease.
Exploitation Route Improved early diagnosis of Alzheimer's disease.
Sectors Pharmaceuticals and Medical Biotechnology

 
Description Institutional Strategic Support Fund
Amount £12,000 (GBP)
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 10/2016 
End 04/2017
 
Description MRC confidence in concept
Amount £97,000 (GBP)
Organisation University of Manchester 
Sector Academic/University
Country United Kingdom
Start 11/2018 
End 01/2020
 
Description MRC/UoM Momentum award for dementia research
Amount £750,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 07/2017 
End 01/2019
 
Description Strategic Support Fund for Public Engagement
Amount £2,400 (GBP)
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 04/2016 
End 10/2016
 
Description Collaboration on phantoms for diffusion and perfusion MRI 
Organisation Cardiff University
Department Brain Research Imaging Centre (CUBRIC)
Country United Kingdom 
Sector Academic/University 
PI Contribution Production of electrospun phantoms for diffusion and perfusion MRI
Collaborator Contribution Development of models of DWI signal in the presence of diffusion and perfusion; histological validation.
Impact Multidisciplinary: physics, computer science, materials science, neuroscience, radiology, cancer biology
Start Year 2015
 
Description Collaboration on phantoms for diffusion and perfusion MRI 
Organisation Hvidovre Hospital
Country Denmark 
Sector Hospitals 
PI Contribution Production of electrospun phantoms for diffusion and perfusion MRI
Collaborator Contribution Development of models of DWI signal in the presence of diffusion and perfusion; histological validation.
Impact Multidisciplinary: physics, computer science, materials science, neuroscience, radiology, cancer biology
Start Year 2015
 
Description Collaboration on phantoms for diffusion and perfusion MRI 
Organisation University College London
Country United Kingdom 
Sector Academic/University 
PI Contribution Production of electrospun phantoms for diffusion and perfusion MRI
Collaborator Contribution Development of models of DWI signal in the presence of diffusion and perfusion; histological validation.
Impact Multidisciplinary: physics, computer science, materials science, neuroscience, radiology, cancer biology
Start Year 2015
 
Description Collaboration on phantoms for diffusion and perfusion MRI 
Organisation University of Sheffield
Country United Kingdom 
Sector Academic/University 
PI Contribution Production of electrospun phantoms for diffusion and perfusion MRI
Collaborator Contribution Development of models of DWI signal in the presence of diffusion and perfusion; histological validation.
Impact Multidisciplinary: physics, computer science, materials science, neuroscience, radiology, cancer biology
Start Year 2015
 
Description DPUK Imaging Network 
Organisation Cardiff University
Country United Kingdom 
Sector Academic/University 
PI Contribution I am MRI lead for Manchester for the Dementia Platform UK Initiative and take part in regular teleconference calls with the rest of the network My team and I provide MRI protocol advice and implementation for dementia imaging studies at the University of Manchester and work to harmonise protocols across the network.
Collaborator Contribution Members from the partner organisations have been very helpful in discussions on best practice regarding MRI protocols to ensure we are implementing the most appropriate techniques for each study.
Impact This collaboration is multi-disciplinary involving physicists, engineers, mathematicians and radiologists. One output is a research grant from Alzheimer's Research UK to harmonise MRI protocols between the sites. I am a collaborator on this grant which is led by Dr. David Thomas, UCL.
Start Year 2016
 
Description DPUK Imaging Network 
Organisation Imperial College London
Country United Kingdom 
Sector Academic/University 
PI Contribution I am MRI lead for Manchester for the Dementia Platform UK Initiative and take part in regular teleconference calls with the rest of the network My team and I provide MRI protocol advice and implementation for dementia imaging studies at the University of Manchester and work to harmonise protocols across the network.
Collaborator Contribution Members from the partner organisations have been very helpful in discussions on best practice regarding MRI protocols to ensure we are implementing the most appropriate techniques for each study.
Impact This collaboration is multi-disciplinary involving physicists, engineers, mathematicians and radiologists. One output is a research grant from Alzheimer's Research UK to harmonise MRI protocols between the sites. I am a collaborator on this grant which is led by Dr. David Thomas, UCL.
Start Year 2016
 
Description DPUK Imaging Network 
Organisation King's College London
Country United Kingdom 
Sector Academic/University 
PI Contribution I am MRI lead for Manchester for the Dementia Platform UK Initiative and take part in regular teleconference calls with the rest of the network My team and I provide MRI protocol advice and implementation for dementia imaging studies at the University of Manchester and work to harmonise protocols across the network.
Collaborator Contribution Members from the partner organisations have been very helpful in discussions on best practice regarding MRI protocols to ensure we are implementing the most appropriate techniques for each study.
Impact This collaboration is multi-disciplinary involving physicists, engineers, mathematicians and radiologists. One output is a research grant from Alzheimer's Research UK to harmonise MRI protocols between the sites. I am a collaborator on this grant which is led by Dr. David Thomas, UCL.
Start Year 2016
 
Description DPUK Imaging Network 
Organisation University College London
Country United Kingdom 
Sector Academic/University 
PI Contribution I am MRI lead for Manchester for the Dementia Platform UK Initiative and take part in regular teleconference calls with the rest of the network My team and I provide MRI protocol advice and implementation for dementia imaging studies at the University of Manchester and work to harmonise protocols across the network.
Collaborator Contribution Members from the partner organisations have been very helpful in discussions on best practice regarding MRI protocols to ensure we are implementing the most appropriate techniques for each study.
Impact This collaboration is multi-disciplinary involving physicists, engineers, mathematicians and radiologists. One output is a research grant from Alzheimer's Research UK to harmonise MRI protocols between the sites. I am a collaborator on this grant which is led by Dr. David Thomas, UCL.
Start Year 2016
 
Description DPUK Imaging Network 
Organisation University of Cambridge
Country United Kingdom 
Sector Academic/University 
PI Contribution I am MRI lead for Manchester for the Dementia Platform UK Initiative and take part in regular teleconference calls with the rest of the network My team and I provide MRI protocol advice and implementation for dementia imaging studies at the University of Manchester and work to harmonise protocols across the network.
Collaborator Contribution Members from the partner organisations have been very helpful in discussions on best practice regarding MRI protocols to ensure we are implementing the most appropriate techniques for each study.
Impact This collaboration is multi-disciplinary involving physicists, engineers, mathematicians and radiologists. One output is a research grant from Alzheimer's Research UK to harmonise MRI protocols between the sites. I am a collaborator on this grant which is led by Dr. David Thomas, UCL.
Start Year 2016
 
Description DPUK Imaging Network 
Organisation University of Edinburgh
Country United Kingdom 
Sector Academic/University 
PI Contribution I am MRI lead for Manchester for the Dementia Platform UK Initiative and take part in regular teleconference calls with the rest of the network My team and I provide MRI protocol advice and implementation for dementia imaging studies at the University of Manchester and work to harmonise protocols across the network.
Collaborator Contribution Members from the partner organisations have been very helpful in discussions on best practice regarding MRI protocols to ensure we are implementing the most appropriate techniques for each study.
Impact This collaboration is multi-disciplinary involving physicists, engineers, mathematicians and radiologists. One output is a research grant from Alzheimer's Research UK to harmonise MRI protocols between the sites. I am a collaborator on this grant which is led by Dr. David Thomas, UCL.
Start Year 2016
 
Description DPUK Imaging Network 
Organisation University of Newcastle
Country Australia 
Sector Academic/University 
PI Contribution I am MRI lead for Manchester for the Dementia Platform UK Initiative and take part in regular teleconference calls with the rest of the network My team and I provide MRI protocol advice and implementation for dementia imaging studies at the University of Manchester and work to harmonise protocols across the network.
Collaborator Contribution Members from the partner organisations have been very helpful in discussions on best practice regarding MRI protocols to ensure we are implementing the most appropriate techniques for each study.
Impact This collaboration is multi-disciplinary involving physicists, engineers, mathematicians and radiologists. One output is a research grant from Alzheimer's Research UK to harmonise MRI protocols between the sites. I am a collaborator on this grant which is led by Dr. David Thomas, UCL.
Start Year 2016
 
Description DPUK Imaging Network 
Organisation University of Oxford
Country United Kingdom 
Sector Academic/University 
PI Contribution I am MRI lead for Manchester for the Dementia Platform UK Initiative and take part in regular teleconference calls with the rest of the network My team and I provide MRI protocol advice and implementation for dementia imaging studies at the University of Manchester and work to harmonise protocols across the network.
Collaborator Contribution Members from the partner organisations have been very helpful in discussions on best practice regarding MRI protocols to ensure we are implementing the most appropriate techniques for each study.
Impact This collaboration is multi-disciplinary involving physicists, engineers, mathematicians and radiologists. One output is a research grant from Alzheimer's Research UK to harmonise MRI protocols between the sites. I am a collaborator on this grant which is led by Dr. David Thomas, UCL.
Start Year 2016
 
Description Development of MR-PET methods 
Organisation GE Healthcare Limited
Country United Kingdom 
Sector Private 
PI Contribution New MRI and PET methods
Collaborator Contribution Implementation on GE MR-PET systems
Impact None to date
Start Year 2015
 
Description Development of MRI methods 
Organisation Philips Healthcare
Country Netherlands 
Sector Private 
PI Contribution New MRI methods
Collaborator Contribution Implementation of the methods on Philips scanners
Impact Conference proceedings and journal publications
 
Description Preston 
Organisation Royal Preston Hospital
Department Neurology Department
Country United Kingdom 
Sector Hospitals 
PI Contribution I have jointly supervised medical students and clinical fellows on dissertation projects and PhDs, providing advice on implementation and analysis of imaging measurements.
Collaborator Contribution Joint supervision of medical students and clinical fellows on dissertation projects and PhDs, providing advice on clinical mechanisms and impact.
Impact This long-term research partnership with neurologist Prof. Emsley has resulted in many publications: Al-Bachari S, Vidyasagar R, Emsley HCA, Parkes LM, 'Structural and Physiological Neurovascular Changes in Idiopathic Parkinson's Disease and its Clinical Phenotypes' Journal of Cerebral Blood Flow and Metabolism, in press [2017]. Hanby MF, Al-Bachari S, Makin F, Vidyasagar R, Parkes LM, Emsley HCA, 'Structural and physiological MRI correlates of occult cerebrovascular disease in late-onset epilepsy.' Neuroimage Clinical 9:128-133, Sept [2015]. DOI: 10.1016/j.nicl.2015.07.016 Al-Bachari S, Parkes LM, Vidyasagar R, Hanby MF, Tharaken V, Leroi I, Emsley H, 'Arterial Spin Labeling Reveals Prolonged Arterial Arrival Time in Idiopathic Parkinson's Disease.' Neuroimage Clinical 6:1-8 [2014]. DOI: 10.1016/j.nicl.2014.07.014 Gibson LM, Hanby M, Al-bachari S, Parkes LM, Allan SM, Emsley HCA, 'Late Onset Epilepsy and Occult Cerebrovascular Disease' JCBFM 34(4):564-570 April [2014]. DOI: 10.1038/jcbfm.2014.25 Maxwell H, Hanby M, Parkes LM, Gibson L, Coutinho C, Emsley HCA, 'Prevalence and subtypes of radiological cerebrovascular disease in late-onset isolated seizures and epilepsy' Clin Neurol and Neurosurgery 115(5): 591-596 May [2013]. DOI: 10.1016/j.clineuro.2012.07.009 Mohtasib RS, Lumley G, Goodwin JA, Emsley HCA, Sluming V, Parkes LM 'Calibrated fMRI during a cognitive Stroop task reveals reduced metabolic response with increasing age' Neuroimage 59:2 1143-1151 Jan [2012]. DOI: 10.1016/j.neuroimage.2011.07.092 Gibson LM, Allan SM, Parkes LM, Emsley HC 'Occult cerebrovascular disease and late onset epilepsy: could loss of neurovascular unit integrity be a viable model?' Cardiovascular Psychiatry and Neurology 2011:130406. Epub Mar [2011]. DOI: 10.1155/2011/130406 And a number of research grants: 2012 - 2016 Cerebrovascular Mechanisms of Idiopathic Parkinson's Disease; Correlations with Clinical Phenotypes and Features. Biomedical Imaging Institute Studentship. Grant Holders: Laura Parkes (PI), Hedley Emsley (£70k). 2012 -2013 Investigating comorbid cerebrovascular disease in idiopathic Parkinson's disease. Manchester Mental Health and Social Care Trust and the Neuroscience Research Institute, University of Manchester. Grant holders: Laura Parkes (PI), Hedley Emsley and Ira Leroi. (£32k).
Start Year 2006
 
Description Water exchange measurements in multiple sclerosis 
Organisation University College London
Country United Kingdom 
Sector Academic/University 
PI Contribution Contribution of methodological expertise on water exchange measurements based on those developed within the grant.
Collaborator Contribution Funding and supervision for PhD studentship.
Impact Collaboration is multidisciplinary, with physics and neurology input.
Start Year 2019
 
Description Big Brain 2017 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact A 'hands-on' 2 day event for local school children aged 13 - 14. I led a theme on brain imaging with the aim of highlighting the need for physics and maths in brain imaging not just biology. Children were engaged and asked many questions. They enjoyed the day.
Year(s) Of Engagement Activity 2017
 
Description Brainbox 2016 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact The Brainbox event was held in Manchester town hall on 'Manchester day' and attracted over 5000 members of the public.
My team ran one of 8 themes on neuroimaging. Our exhibit explain how imaging techniques work (eg MRI, EEG, PET), the importance of physical scientists in this work, and the impact of imaging technologies on neuroscience research and healthcare.
Year(s) Of Engagement Activity 2016
URL https://mcrbrainbox.wordpress.com/legacy/
 
Description British Science Week 2017 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact This was a week long event attracting hundreds of local school children (secondary and primary) to tour the exhibition. I led a theme on neuroimaging in action.
Year(s) Of Engagement Activity 2017
 
Description Keynote speaker at Christie medical physics evening 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact 140 'A' level school children attended.
Year(s) Of Engagement Activity 2019
 
Description Presentation at the National Student Conference of the Academy of Medical Sciences 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Undergraduate students
Results and Impact Presented on 'Imaging in neurology and neuroscience' to a group of medical students to enthuse them on the role of imaging in medical research.
Year(s) Of Engagement Activity Pre-2006,2017
 
Description ScienceGrrl event at MOSI 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact I was one of a team of female scientists at the Museum of Science and Industry. We roamed the Museum carrying gadgets and engaged children in our work and explained what we do and what the gadget is for. Specifically aimed at changing people's perception of 'what a scientist looks like' and engaging young girls in science.
Year(s) Of Engagement Activity 2015
 
Description Talk to U3A Stockport 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Presentation of Research findings to the U3A group, some of whom had participated in the research.
Year(s) Of Engagement Activity 2015