Nerve fibre bundles in the newborn brain captured by Magnetic Resonance Imaging

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2 Nerve fibre bundles in the newborn brain captured by Magnetic Resonance Imaging

3 Contents Aim 2 Academic Staff 4 Funding 6 Research 8 Beyond the Laboratory 12 Neonatal Intensive Care

4 Aim Our goal is to reduce the number of children who suffer brain damage due to problems around the time of birth. We work to understand the causes of brain injury, to improve diagnosis and develop effective new treatments. MRI of the newborn brain: surface map showing regions with most connections in blue.

5 The Centre for the Developing Brain, established with strategic funding from the Medical Research Council in King s College London, has stateof-the-art clinical research, imaging and laboratory facilities at St Thomas Hospital, London. The unique neonatal Magnetic Resonance Imaging (MRI) Clinical Research Facility is based within the Neonatal Intensive Care Unit of the Evelina Children s Hospital at St Thomas, and researchers work in close collaboration with the Guy s and St Thomas Hospitals NHS Trust, particularly the staff, parents and patients on the Neonatal Unit. Researchers are deeply embedded in the National Health Service, notably King s Health Partners, and the National Institute for Health Research, through the Biomedical Research Centre, the Medicines for Children Research Network and Comprehensive Local Research Networks. The Centre has sustained collaborations and joint appointments with a number of major institutions. There are longstanding links to Imperial College London, and a joint laboratory with the University of Gothenburg and the Inserm Centre at Hôpital Robert- Debre in Paris. Collaborative research programmes have been established with The University of Oxford, the Donders Institute, University College London and St George s, University of London One of the family

6 Academic Staff David Edwards Director Professor of Paediatrics and Neonatal Medicine, King s College London. Professor, Department of Bioengineering, Imperial College London. Consultant Neonatologist, Evelina Children s Hospital Denis Azzopardi Head of Clinical Studies Professor of Neonatal Medicine, King s College and Imperial College London Consultant Neonatologist, Evelina Children s and Queen Charlotte s Hospitals Serena Counsell Head of Advanced Neuroimaging Professor of Perinatal Imaging, King s College London Pierre Gressens Co-head of Neurobiology Professor of Fetal and Neonatal Neurology, King s College London Director, UMR 676 Inserm-Paris 7 University, Hôpital Robert-Debre, Paris Henrik Hagberg Co-head of Neurobiology Professor of Fetal Medicine, King s College London Professor and Consultant, Department of Obstetrics and Gynaecology, Sahlgrenska Academy, University of Gothenburg

7 Alan Groves Head of Cardiovascular Imaging Senior Lecturer in Neonatology, King s College London Consultant Neonatologist, Evelina Children s Hospital Jo Hajnal Head of Imaging Physics Professor of Imaging Physics, King s College London Chiara Nosarti Head of Psychology and Outcome Studies Senior Lecturer in Mental Health Studies and Neuroimaging, King s College London Daniel Rueckert Head of Image Analysis Professor of Visual Information Processing, Imperial College London Mary Rutherford Head of Perinatal Imaging Professor of Perinatal Imaging, King s College London

8 Research Funding Medical Research Council Strategic Funding for the Centre for the Developing Brain Total Body Hypothermia for Neonatal Encephalopathy: Children s Study MRC Clinician Scientist Fellowship: Cardiac MRI in preterm infants Experimental Medicine Grant: Melatonin as a novel neuroprotectant Experimental Medicine Grant: Xenon as a neuroprotectant in infants treated with hypothermia after birth asphyxia Special Post-doctoral Fellowship in Biomedical Informatics National Institute for Health Research Applied Programme Grant: Evaluation of Imaging in Preterm Infants (eprime) Senior Investigator Award Academic Clinical Lecturers Academic Clinical Fellows Clinical research support from the Biomedical Research Centres, Medicines for Children Research Network and Local Research Networks European Research Council Synergy Grant with Imperial College London and University of Oxford: The Developing Human Connectome Project Marie Curie Fellowship: Flexible Application of Uncertainty for Scanning and Tracking Engineering and Physical Sciences Research Council Healthcare Partnership with Action Medical Research: Computer-aided diagnosis of neurological damage to improve care for infants born prematurely Programme Grant: Intelligent Imaging: Motion, Form and Function Across Scale

9 Wellcome Trust Programme Grant: Mitochondria-targeted protective strategies for limiting injury in the developing brain Clinical Training Fellowship: Functional and structural thalamocortical connectivity after preterm birth and its relation to later cognitive abilities Leducq Foundation International Research Network and Project Grant Garfield Weston Foundation Family Centred Research Programme Action Medical Research Project Grant: Magnetic resonance imaging (MRI) as a biomarker in early childhood problems: Volumetric approaches Project Grant: Death receptor signalling in oligodendrocyte and neuronal cell death following hypoxia-ischaemia in the developing brain British Heart Foundation Clinical Research Fellowship: Quantitative assessment and functional correlates of cardiac mechanics in preterm infants Sparks Clinical Research Fellowship: Construction of a biventricular functional atlas of the human preterm heart using 3.0T cardiac MRI The Belvedere Trust The Eva Bursary Scheme

10 Research The Centre for the Developing Brain brings together specialists in fundamental and systems neuroscience, Magnetic Resonance Imaging (MRI) and clinical research, to create an integrated scientific programme. The Neurobiology Laboratory is run by Henrik Hagberg and Pierre Gressens as a forward-looking tripartite collaboration with their groups in Paris and Gothenburg, and experiments are co-ordinated and shared between the sites. This highly efficient and effective approach led to major programme grants from the Wellcome Trust and the Leducq Foundation. The research focuses on the mechanisms of cell death, mitochondrial function and inflammation in the newborn brain. They have discovered important new treatments with specific neonatal neuroprotective effects, including melatonin and a novel Caspase-2 inhibitor. 1. The Developing Human Connectome Project Modern brain imaging and computer science makes it possible to map the brain in hitherto unimagined detail. The Centre for the Developing Brain is leading a 15 million project funded by the European Research Council to chart the growth of connections in the human brain before and after birth. With colleagues from Imperial College London and the University of Oxford we will define normal development and determine how this is affected by problems like premature birth, and conditions such as autism. The Neonatal MRI Scanner in action.

11 MRI is a core research activity. Jo Hajnal and Daniel Rueckert have developed and implemented novel imaging methods for studying brain development and damage (Box 1). Their technical advances underpin programmes for imaging: the fetal brain, led by Mary Rutherford (Box 2); the preterm infant, led by Serena Counsell; and the newborn heart, led by Alan Groves. MRI is an invaluable tool for clinical trials of new treatments led by Denis Azzopardi, and studies of childhood cognitive and behavioural outcomes, led by Chiara Nosarti. 2. Fetal Imaging Magnetic Resonance Imaging of the human fetus has been challenging because conventional imaging methods are severely disrupted by normal fetal movements. Researchers at the Centre for the Developing Brain have developed methods to counter the effects of motion that now create full three-dimensional images of the fetal brain, allowing more accurate diagnosis of brain abnormalities before delivery, and advanced research into the development of brain structure and function. Fetal MRI: the human brain before birth.

12 Growth and development of the human brain before the normal age of birth The Centre for the Developing Brain has a new Neonatal Clinical Research Facility including a state-of-the-art 3.0 T MRI scanner situated within the Evelina Children s Hospital Neonatal Intensive Care Unit. This unique facility allows study of even the smallest and sickest newborn babies, as well as older children and adults. To make the research environment suitable for patients of all ages innovative lighting has been designed which allows it to change from a clinical area to a child s fantasy playground at the touch of a button. Nerve fibre bundles in a newborn infant s brain 3. Evaluation of Preterm Imaging (eprime) The eprime programme, funded by the National Institute for Health Research, is a randomized controlled trial of the effect of brain imaging on the care of children. High-resolution MRI is compared to the commonly used lowresolution ultrasound method. The trial is not about how accurate the methods are (although it will find this out), it is about how the information from the tests affects parents and families, and whether it helps them care for their child.

13 Clinical trials are central to improving treatment and the Centre is leading several major trials, for example: testing the value of different brain imaging methods (Box 3); whether melatonin improves brain development following preterm birth; and whether xenon gas prevents brain damage after birth asphyxia. The Centre works to implement successful therapies: having developed the first successful treatment for birth asphyxia the researchers supported and monitored roll-out across the NHS (Box 4) Primary neurons in culture showing the cell nucleus in purple and mitochondria in yellow. Newborn brain activity detected by MRI 4. A success story: Hypothermic Brain Rescue Birth asphyxia is one of the commonest causes of neonatal death and severe disability worldwide. The Centre for the Developing Brain, together with colleagues around the world, has carried out a sustained campaign of research over 20 years to find a treatment to prevent brain damage in infants who are starved of oxygen at birth. Early work showed that after oxygen starvation it is some hours before brain cells die, and that moderate cooling during this period reduces brain damage. A programme of experiments, pilot studies and clinical trials, funded by the Medical Research Council, the Wellcome Trust and others, showed that this doubles the chance of normal survival. This treatment is now in use across the world.

14 Beyond the Laboratory Science and medicine are too important, and too interesting, to be left to scientists and doctors alone. The Centre for the Developing Brain enjoys the opportunity to engage with patients, families, students, schools and other healthcare professionals to enrich the research process. Funding from the Garfield Weston Foundation has established the Weston Programme for Family Centered Research, which engages parents and families in deciding what research is important and needs to be done, and provides research funds to start these projects, establishing a Citizen Science programme unique in neonatal research. The Centre for the Developing Brain has formed alliances with local secondary schools and academies, giving school students the opportunity to come and enjoy the excitement of brain science and understand the value of medical research. Close engagement with the school s teachers ensures that this experience adds value to the normal school curriculum. With funding from the Belvedere Trust we have established Bursaries to fund research projects designed and carried out by medical students and nurses with the full support of senior staff within the Centre for the Developing Brain. Together with our programme of training Clinical Research Fellows and PhD students this programme underlines the commitment to train the next generation of neonatal researchers

15 Installing the MRI scanner, 2012

16 The Neonatal MRI Scanner