Imaging of the brain- a major investment into diseases of the brain

Paul M. Matthews, MD, DPhil, FMedSci Edmond and Lily Safra Chair, Head, Division of Brain Sciences and Associate Director, UK Dementia Research

Institute at Imperial College London

http://aerospaceengineeringblog.com/big-data-in-aerospace/; http://scienceblogs.com/insolence/2016/06/17/the-mend-protocol-for-alzheimers-disease-functional-medicine-on-steroids/ accessed 16 May 2017

We need to understand how environment and lifestyle -- “exposome”– influence the brain through life

We need to understand how diseases of the brain start- decades before they appear

Lifestyle and environment interact with underlying genetic susceptibilities to influence the risks of brain disease

G.J. Biessels, and L.J. Kappelle Biochm. Soc. Trans. 2005;33:1041-1044

We need to undertand how conditions and diseases affecting the body influence brain diseases

We also need to see risks of disease in their full context Clinical expression of brain disease itself also is influenced - and, in turn, influences- by the way people interact at home and in work

The UK Biobank Imaging Enhancement • UK Biobank enhancement evaluation for 100,000 of the 500,000 subjects

was initiated pilot phase from in 2014 and entered its full phase in 2017 • Providing a comprehensive, quantitative imaging phenotype f (brain,

cardiac, whole body MRI, 3D Carotid US, DEXA)

Imaging in UK Biobank provides different views of the brain- and links them all to an immensely rich range of other measures and outcomes

James Fallon, UCSD

Details of brain structure

A “wiring diagram” for individual brains

Maps of how different regions of the brain work together

Structural brain imaging provides a window on changes in the abundance and integrity of neurons in the brain

N. Ryan, N.Fox, Ann NY Acad Sci 1180 (2009) 20

Functional and connectional brain imaging provide insights into patterns of gene expression and how different regions interact across the brain

J. Richiardi et al. Science 249 (2015) 6240

Brain regions with similar gene expression patterns (and, by inference, related cell populations) have highest functional connectivity- this can be

tested more directly by mapping the “wiring diagram”

What can we use these data for?

JH Cole et al Mol Psych 2017

Assessing brain health

Influences of lifestyle and environment on brain structures

K. Miller et al. Nat Neurosci 19 (2016) 1523

Influences of lifestyle and environment on how the brain is functioning

r2 0.0059- 0.032

K Miller et al. Nat Neurosci 19 (2016) 1523-1536

How different regions of the brain are working together at “rest”

Influences of lifestyle and environment on how the brain is functioning

K. Miller et al. Nat Neurosci 19 (2016) 1523

How different regions of the brain are working together when we need to make perceptual decisions

Brain images from Miller et al. Nature Neurosci 2016; body fat images courtesy of Prof. J. Bell, Univ of Westminster

A unique opportunity to understand how changes in the body influence the brain

Seeing how risk factors for disease affect the brain: effects of hypertension in the aging brain

SR Cox et al. Nat Comm 7. 13629 (2016)

H. Suzuki et al, submitted for publication

Enhancing the value of UK Biobank for studies of disease by integrating it with studies of other cohorts: Dementia Platforms UK

UK Biobank and the Imaging Enhancement are huge team efforts: acknowledging the Imaging Working Group and…

Musculoskeletal Advisory Group Chair: Prof Cyrus Cooper (MRC Lifecourse Epidemiology Unit; Southampton) Co-chair: Prof Nick Harvey (MRC Lifecourse Epidemiology Unit; Southampton) Prof Juliet Compston (Bone Medicine; Cambridge) Prof Richard Eastell (Mellanby Centre for Bone Research; Sheffield) Prof Roger Francis (Bone Clinic; Newcastle) Prof Stuart Ralston (Rheumatic Disease Unit; Edinburgh) Prof David Reid (Institute of Medical Sciences; Aberdeen) Prof Alan Silman (Botnar Research Centre; Oxford) Prof Jon Tobias (Academic Rheumatology; Bristol)

Body MRI Advisory Group Chair: Prof Jimmy Bell (University of Westminster; London) Co-chair: Dr Tony Goldstone (MRC Clinical Sciences Centre; London) Prof Fiona Gilbert (Biomedical Imaging Centre; Aberdeen) Prof Paul Matthews (Imperial College London; London) Prof Robert Ross (School of Kinesiology and Health Studies; Canada) Prof Wei Shen (Columbia University Obesity Research Center; USA) Dr Lidia Szczepaniak (Cedars Sinai Medical Center; USA) Dr Garry Tan (Diabetes and Endocrinology Department; Nottingham) Dr Louise Thomas (University of Westminster; London) Dr Andoni Toms (Musculosketal Radiology; Norwich) Prof N Jon Shah (Juelich-Aachen Brain Research Alliance; Germany) Prof Henry Volzke (German National Cohort; Germany) Prof John Waterton (Translational Imaging; Manchester) Dr Rajarshi Banerjee (Radcliffe Dept. of Medicine; Oxford) Prof Matthew Robson (Radcliffe Dept. of Medicine; Oxford)

Carotid Ultrasound Advisory Group Chair: Dr Paul Leeson (Oxford Cardiovascular Clinical Research Facility; Oxford) Ram Bedi, Rudi Meijer Takenori Fukomoto (Panasonic) Kadoorie Biobank Dr Aaron Fenster (Robarts Imaging Research Laboratories; Canada) Prof Valentin Fuster (Mount Sinai Cardiovacular Institute; USA) Prof Henrik Sillesen (Department of Vascular Surgery; Denmark) Prof David Spence (Stroke Prevention & Atherosclerosis Research Centre; Canada)

Cardiovascular MR image analysis consortium Prof Sebastian Ourselin (UCL London) Dr Stefan Piechnik (Oxford) Prof Alison Noble (Oxford) Prof Stefan Neubauer (Oxford) Prof James Duncan (Yale) Nicholas Ayache (INRIA) Herve Delingette (INRIA) Prof Daniel Rueckert (Imperial College) Prof Wiro Nissen (Erasmus MC) Prof Alistair Young (University of Auckland) Dr A Gooya (University of Sheffield) Prof Alex Frangi (University of Sheffield) Prof Steffen Petersen (QMUL)

Brain MRI Advisory Group Chair: Prof Steve Williams (Centre for Neuroimaging Sciences; London) Prof John Ashburner (WT Centre for Neuroimaging; London) Prof Nick Fox (Dementia Research Centre; London) Prof Paul Matthews (Division of Brain Sciences, London) Dr Karla Miller (Oxford Centre for Functional MRI of the Brain; Oxford) Prof Tom Nichols (Institute for Digital Healthcare; Warwick) Prof Stephen Smith (Oxford Centre for Functional MRI of the Brain; Oxford) Prof David Van Essen (NIH Human Connectome Project; Washington, USA) Prof Meike Vernooij (Rotterdam Study; Holland) Prof Henry Volzke (German National Cohort; Germany) Prof Nikolaus Weiskopf (WT Centre for Neuroimaging; London)