A new collaborative ultra-high field MRI facility for dementia and neuroscience research

Magnetic Resonance Imaging (MRI) has revolutionised the study of the brain and brain diseases like dementia over the last 20 years. Conventional MRI scanners have their limitations however. We will therefore build an "ultrahigh-field" MRI, which offers a major step forward in how clearly one can study the brain's structure, function and chemistry. This new scanner will be dedicated to the challenge of dementia, supported by scientific work to understand the normal brain and advanced analysis. It will be a major contributor to the UK Dementia Platform, a unique and radical approach to join up medical research across the country's specialist centres and drug company partners in the fight against dementia.
The new "7T" scanner will be built on the Cambridge Biomedical Campus, next to Addenbrookes Hospital. It is a collaboration between Cambridge University and the Medical Research Council's Cognition and Brain Sciences Unit (CBSU), working closely with the NHS. We will use the new scanner to detect and characterise over time the major brain diseases like Alzheimer's, Stroke and Parkinson's Disease.
With our ageing population, the number of people suffering from dementia is likely to increase from the current level of 800,000. The need is urgent to identify people in the earliest stages of such diseases, or even before symptoms, in order to test treatments that combat dementia. Cambridge is ideally suited for this research, because of i) its existing expertise in dementia and MRI brain scanning, ii) its key role in national initiatives to understand dementia and the healthy ageing process, iii) its collaborations with major pharmaceutical companies to develop new treatments, and iv) the existence of large cohort studies that track normal ageing over decades, and groups of research volunteers who, because of genetics or lifestyle, are at-risk of dementia.
MRI is a very versatile technology. MRI scanners can be "tuned" to measure the grey matter (home to most of the brain cells), white matter (the wiring of the brain), the major chemicals in the brain and microscopic effects of dementia. MRI can also measure brain function, allowing researchers to map the brain areas needed for attention, memory or language. The new scanner gives much greater detail across the entire brain, allowing researchers to understand how the brain works as a whole while still seeing detail at a sub-millimetre scale. This detail is important for diseases like Alzheimer's and Parkinson's, for which small and deep parts of the brainstem are critical but difficult to see with conventional MRI.
Moreover, the increased detail offered by ultrahigh field MRI opens the window on an important level of organisation in the brain: the thin layers of the surface of the brain, which have until recently only been studied with invasive recordings. With the new scanner, we can safely study this fundamental level of brain organisation in humans. This will accelerate our scientific understanding of the basic workings of the brain. This draws on the very large community of brain researchers in Cambridge, to investigate, for example, the i) brain changes that put some people at risk of addiction, ii) brain networks linked to obesity, iii) how the brain normally ages, and why some people are resilient as they get older, and iv) how the brain matures through teenage years, when major mental illness like schizophrenia normally begin. Other medical researchers will use the scanner to understand i) recovery of the brain after head injury, ii) the brain systems implicated in pain, and iii) stroke and other disorders associated with impairments in the brain's blood supply.
The depth and breadth of brain research is why the University of Cambridge and partners are planning to join together with the Medical Research Council to invest in this breakthrough technology. The ultrahigh-field MRI will advance both basic and medical research, to improve the health of the nation.

The resolution of 7T MRI will be used to study the pathogenesis of dementia, mechanisms of resilience, and response to therapy in terms of structure (volumetric and diffusion weighted), function (BOLD) and spectroscopy. Sensitivity to iron deposition by quantitative susceptibility mapping is especially relevant to Alzheimer's disease, while structural and functional changes in vasculature will be examined as markers and targets in stoke, dementia and Huntington's disease. We will delineate the aetiological role of small but critical subcortical structures (eg hypothalamus, brainstem nuclei, hippocampal subfields). Columnar and laminar resolution of 7T fMRI will be used to understand the neuronal code, testing the predicted functional dissociations between cortical layers for hierarchical information processing. The cross linking of neurochemistry (MRS) with functional and structural data will reveal mechanisms of individual differences, in health and disorders, and potential stratification of therapeutic strategies. The new facility is part of the UK7T network, to promote knowledge transfer, data sharing, training, and coordinated of magnet supply. WBIC and CBSU have Master Research Agreements with Siemens and costs follow a Siemens 7T review, but tendering is open to all manufacturers. We require a minimum of 70mT/m gradients, 8 channel parallel transmission, 32 channel receiver, multinuclear spectroscopy and high order shimming. WBIC is controlled through a Clinical Radiology Information system to collect and monitor data, research protocols and scheduled transfer to PACS for long term secure storage, and secure access control. The proposed high performance informatics hub (data management plan) proposes to increase UoC data analysis capacity from 256 to 1024x16 Gb cores, fast user access to data and efficient parallel processing (using GRIDengine). A new informatics hub enhances integration with NHS systems and high volume data sharing with multisites (eg UKDP).

Through the scientific program and investigators in the Case for Support, the new 7T facility in Cambridge will achieve Academic and Clinical Impacts on the major disorders of the brain: dementia, stroke, mental health and cognitive decline with ageing. In addition, we anticipate breakthroughs in understanding the normal human brain, its neuronal codes and network organisation.
Early Academic impacts include (i) the establishment of state of the art ultra-high imaging facility that will be widely used, ensuring that the Cambridge Biomedical Campus remains internationally competitive as a leading neuroscience centre; (ii) through our membership of the UK 7T network and the UK Dementias Platform, this facility will ensure the UK as a whole is seen as a global academic leader in MR imaging, especially relevant as MRI was discovered here; (iii) we will enhance the UK's competitive research advantage in biomedical imaging and maximize the impact of the MRC's investment across several areas of neuroscience, healthy ageing and dementia. The novel interdisciplinary programmes will advance knowledge globally, together with development and application of innovative methodologies to increase the UK knowledge economy. The evident long running impact of the MRCs intramural Cognition and Brain Sciences Unit, a key partner in this facility, will be amplified through access to cutting edge technologies with 7T MRI.
Early clinical scientific impact: we recognise that full clinical and health economic impact can take several years to fulfil, but we anticipate early clinical impacts in several areas. For example, greater sensitivity to plasticity underpins interventional studies for healthier cognitive ageing, in population derived cohorts. Early translation of basic discoveries to clinical disorders - with new therapeutic targets - is made possible, for example in the ability to test the vascular hypothesis in Huntington's disease, iron dysregulation in addiction, or CNS disorders in obesity.
Longer term health and economic impact come from better understanding, diagnosis and management of dementia, and thereby improved health, wellbeing and the UK economy. The 7T system will be a focus for training the next generation of researchers, both those involved in the study of the clinical disorders being examined, and methodologists to advance technological developments. The Facility coalesces a critical mass for exceptional teaching and learning, working closely with key academic groups locally (in the Schools of Medicine and Biological Sciences and the MRC Cognition and Brain Sciences Unit) and internationally.
Our longer term impact (~5 years) is not only to be measured through the high impact publications, major new grant awards, or even the training of a new cohort of students, researchers and future academic leaders. Our close integration with NHS services at local, regional and national level will ensure that advances are rapidly translated and disseminated for maximum early patient benefit. The imaging facility will catalyse inward commercial investment, including our partners in global pharmaceutical companies, with excellent prospects that innovations will lead to successful commercialisation.
Through our strong links with national bodies and guideline groups (e.g. NICE, MHRA, EFNS) we can ensure that academic advances at 7T imaging diffuse quickly to inform wider evidence based policy making and commissioning, directly and by guiding the translation to widely available systems and novel interventions. With increasing public interest and awareness of imaging and brain disorders such as dementia, the outward facing side of the Facility will increase public engagement with research in general, and with research in imaging and dementia in particular. This will be facilitated through our PPI programme and our links with local and national patient groups and other third sector organisations, most especially patient charities.