The Developing Brain

Lead Research Organisation: King's College London
Department Name: Imaging & Biomedical Engineering

Abstract

The second half of pregnancy is a time of exuberant brain growth. We are exploring how brain structure develops and how its functional capabilities mature. We seek to study both normal and abnormal brain development by directly observing the fetus in the womb using advanced imaging techniques. Our studies straddle the birth process, enabling us to explore effects of premature birth and of brain damage caused by shortage of oxygen during birth at the right age. Our research aims to create novel imaging techniques and analysis methods to study the developing brain; to learn about both normal and abnormal brain development; and to develop and test novel cerebral rescue treatments for neonates that suffer brain damage from lack of oxygen or premature birth.
By combining imaging with genetic analysis and clinical follow-up we seek to learn about the brain and how it develops in this critical early period of life. The outcomes of our research include new imaging and analysis methods that we apply to study the developing brain but may prove useful in other applications as well, basic insights concerning brain development, clinical tools for characterizing and managing brain problems, and novel therapies for improving outcome.

Technical Summary

Our research programme uses a multi-disciplinary approach to study the developing brain, the damage it may suffer as a result of prematurity or birth trauma and to develop methods to improve the outcome of vulnerable infants by providing capabilities for more accurate and early diagnosis, and developing and testing novel therapies. Magnetic Resonance Imaging (MRI) is a core technology and we have pioneered its use both for studying the brain in utero and during the neonatal period. This has led to effective biomarkers of brain damage that have been used to test novel cerebral rescue therapies.
During the next 4 years we will aim to substantially further develop MR technology including motion tolerant functional imaging methods and patient specific multi-transmit RF techniques that will have wide application in perinatal research and clinical care as well as for use in high field imaging generally. These will be combined with novel analysis techniques to provide a detailed exploration of brain development in utero in both normal and compromised pregnancies and to link in utero findings to post natal studies to further explore effects of prematurity and support development of more effective neural rescue therapies. Key targets will be to characterize developing connectivity and brain function, to link imaging findings to underlying microstructural damage through study of tissue samples and post mortem imaging, and to integrate imaging and genetic methods to explore key childhood syndromes such as autism spectrum disorder and attention deficit hyperactivity disorder (ADHD).

Planned Impact

please see QQR Documentation (Jo Jenkinson)

Publications

10 25 50

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Ficial B (2017) A modified echocardiographic approach improves reliability of superior vena caval flow quantification. in Archives of disease in childhood. Fetal and neonatal edition

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Ficial B (2013) Validation study of the accuracy of echocardiographic measurements of systemic blood flow volume in newborn infants. in Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography

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Gale-Grant O (2020) Parental age effects on neonatal white matter development. in NeuroImage. Clinical

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Groppo M (2014) Development of the optic radiations and visual function after premature birth. in Cortex; a journal devoted to the study of the nervous system and behavior

 
Description Collaboration in science
Amount £4,000,000 (GBP)
Funding ID 201526/Z/16/Z 
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start  
 
Description ERC Synergy Grant
Amount € 14,900,000 (EUR)
Organisation European Commission 
Sector Public
Country European Union (EU)
Start 09/2013 
End 08/2019
 
Description European Society for Pediatric Research Consolidator Grant
Amount € 75,000 (EUR)
Organisation European Society Paediatric Research 
Sector Charity/Non Profit
Country Switzerland
Start 02/2018 
End 02/2019
 
Description Innovative Engineering for Health Award
Amount $3,000,000 (USD)
Funding ID 1U01HD087202-01 
Organisation National Institutes of Health (NIH) 
Department Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Sector Public
Country United States
Start 09/2016 
End 08/2019
 
Description MRC Clinical Training Fellowship
Amount £200,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 10/2013 
End 09/2016
 
Description PROJECT GRANT
Amount £174,035 (GBP)
Funding ID GN2630 
Organisation Action Medical Research 
Sector Charity/Non Profit
Country United Kingdom
Start 04/2018 
End 10/2020
 
Description Project Grant
Amount £1,000,000 (GBP)
Organisation Garfield Weston Foundation 
Sector Charity/Non Profit
Country United Kingdom
Start 10/2012 
End 09/2017
 
Description Project Grant
Amount £7,287,951 (GBP)
Organisation Medical Research Council (MRC) 
Department Medical Research Foundation
Sector Charity/Non Profit
Country United Kingdom
Start 07/2012 
End 06/2016
 
Description Senior Investigator Award
Amount £75,000 (GBP)
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom
Start 04/2012 
End 03/2017
 
Description Sparks Clinical Research Fellow
Amount £115,878 (GBP)
Organisation Sparks Charity 
Sector Charity/Non Profit
Country United Kingdom
Start 09/2012 
End 09/2015
 
Description Wellcome Centre
Amount £12,100,395 (GBP)
Funding ID 203148/Z/16/Z 
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 06/2017 
End 07/2022
 
Description Wellcome Trust/EPSRC Innovative Engineering for Health Award
Amount £8,717,267 (GBP)
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 03/2014 
End 03/2021
 
Title MRI methods research software 
Description Source code for MRI methods developed as part of research project 
Type Of Material Improvements to research infrastructure 
Year Produced 2016 
Provided To Others? Yes  
Impact Dissemination of research software that is being used by others in the field 
URL http://mriphysics.github.io/
 
Title NAAT 2010 reported_Research Infrastrucutre 
Description New dedicated MR scanning suite and clinical research facility for newborn infants 
Type Of Material Improvements to research infrastructure 
Year Produced 2013 
Provided To Others? Yes  
Impact Clinical Research Data not available otherwise is being collected 
 
Title Developing Human Connectome Project 
Description A large collection of brain images from newborn infants and foetuses which allow functional and structural connectivity to be defined, together with clinical and genetic data. Currently 550 subjects collected, target is around 1000. This is now funded by an ERC grant but the preliminary work was carried out by the linked project . 
Type Of Material Database/Collection of data 
Provided To Others? No  
Impact This will be an open source database for researchers to use. The first data release is in 2017 
URL http://www.developinghumanconnectome.org
 
Title ePRIME dataset 
Description A collection of 510 structural, diffusion and functional MR images of preterm infants at term, linked to genomic data and clinical outcomes 
Type Of Material Database/Collection of data 
Year Produced 2016 
Provided To Others? Yes  
Impact These data have provided the basis for a comprehensive assessment of the value of MR imaging for preterm infants, and for a series of studies developing machine learning and imaging genomic analysis to understand the nature of preterm brain injury. Multiple studies have now been published using these data, and 2 genes newly implicated in brain development and injury discovered. 
 
Description Bioinformatics 
Organisation Medical Research Council (MRC)
Department MRC Clinical Sciences Centre (CSC)
Country United Kingdom 
Sector Public 
PI Contribution Collaboration on MRC funded Clinical Research Fellowship with the Integrative Genomics group at the MRC Clinical Research Centre Hammersmith; Dr Enrico Pettretto
Collaborator Contribution Dr Petretto provides bioinformatics and genomics expertise and supervision- he has now moved to DUKE NUS graduate medical school.
Impact Krishnan et al, Nature Communications 2017; Krishnan et al PNAS 2017
Start Year 2013
 
Description Child Psychology 
Organisation King's College London
Department Social Psychiatry
Country United Kingdom 
Sector Academic/University 
PI Contribution Dr Chiara Nosarti has joined the research group half time. funded by KCL
Collaborator Contribution Expertise in child and adolescent psychology
Impact Grant applications and papers in progress
Start Year 2012
 
Description Department of Bioengineering, Imperial College London 
Organisation Imperial College London
Department Department of Bioengineering
Country United Kingdom 
Sector Academic/University 
PI Contribution We have a collaboration with Dr Etienne Burdet in the development of haptic devices for study and treatment of preterm infants, currently focusing on creation of somatosensory stimuli for fMRI studies
Collaborator Contribution Delivery of a device for somatosensory stimulation of preterm infants and collaborations on haptic devices
Impact 19854281 Multidisciplinary involving neonatal medicine, computational neuroscience, bioengineering, MRI
Start Year 2007
 
Description Department of Computing, Imperial College London 
Organisation Imperial College London
Department Department of Computing
Country United Kingdom 
Sector Academic/University 
PI Contribution We have a longstanding collaboration with Prof Daniel Rueckert and many joint projects and publications.
Collaborator Contribution Prof Rueckert has essential expertise in image analysis that underpins our MR imaging programme. We have been able to do research using grants on which he was PI funded by EPSRC.
Impact 18234511 18979782 17919930 17888685 17696128 17344066 17633705 18044561 16675269 20969966 20451627 20510375 20879376 20079440
 
Description Guy's and St Thomas' NHS Foundation Trust 
Organisation Evelina London Children's Hospital
Country United Kingdom 
Sector Hospitals 
PI Contribution Installation and use of a new neonatal MRI scanner in the Neonatal Intensive Care Unit of St Thomas' Hospital. We have moved our research group to this site and formed a new strategic alliance between our University (King's College London) and the Trust
Collaborator Contribution Infrastructure support
Impact New MR scanner and multidisciplinary group which uses this for research and clinical practice. This involves neonatal medicine, physics, computer science and neuroscience as well as cardiology and psychiatry
Start Year 2012
 
Description Imaging Genetics 
Organisation Duke-NUS Graduate Medical School
Country Singapore 
Sector Academic/University 
PI Contribution We have developed imaging genetics methods which combine the large MRI and genomic datasets to allow biologic inference from imaging datasets. Using this approach we have discovered new genes and biologic pathway involved in brain development and preterm brain injury. Our contributions have been to lead the project, define the medical problems, acquire and analyse the images, and to carry out the analysis
Collaborator Contribution We had no skills in genomics, and our partners have provided this to the programme.
Impact Multidisciplinary involving neuroscience, neonatology, imaging, genomics, statistics. Outputs include: Krishnan et al, Nature Communications 2017; Krishnan et al PNAS 2017
Start Year 2011
 
Description Imaging Genetics 
Organisation King's College London
Department Institute of Psychiatry, Psychology & Neuroscience
Country United Kingdom 
Sector Academic/University 
PI Contribution We have developed imaging genetics methods which combine the large MRI and genomic datasets to allow biologic inference from imaging datasets. Using this approach we have discovered new genes and biologic pathway involved in brain development and preterm brain injury. Our contributions have been to lead the project, define the medical problems, acquire and analyse the images, and to carry out the analysis
Collaborator Contribution We had no skills in genomics, and our partners have provided this to the programme.
Impact Multidisciplinary involving neuroscience, neonatology, imaging, genomics, statistics. Outputs include: Krishnan et al, Nature Communications 2017; Krishnan et al PNAS 2017
Start Year 2011
 
Description National Perinatal Epidemiology Unit 
Organisation University of Oxford
Department National Perinatal Epidemiology Unit Oxford
Country United Kingdom 
Sector Academic/University 
PI Contribution We have a longstanding collaboration with the NPEU, and this has led to substantial funded projects: these projects are initiated by our group and NPEU provides the expertise and facilites of a Clinical Trials Unit. 1. The MRC funded Total Body Hypothermia for Neonatal Encephalopathy Trial (TOBY), which was jointly led by our group (joint PI D Azzopardi) and the NPEU (Joint PI P Brocklehurst). This has now reported (Azzopardi et al N Engl J Med 2009) 2. The MRC funded TOBY childrens study, led by our group (PI Azzopardi), 6 year follow up of the TOBY subjects, in progress. 3. MRC funded study of Xenon as a neuroprotectant for neonatal encephalopathy, led from our group (PI Azzopardi). In progress 4. NIHR Applied Programme Grant: Evaluation of MR imaging for preterm infants (PI Edwards).
Collaborator Contribution NPEU provide clinical trials unit facilites and skills for a series of projects 1. The MRC funded Total Body Hypothermia for Neonatal Encephalopathy Trial (TOBY), which was jointly led by our group (joint PI D Azzopardi) and the NPEU (Joint PI P Brocklehurst). This has now reported (Azzopardi et al N Engl J Med 2009) 2. The MRC funded TOBY childrens study, led by our group (PI Azzopardi), 6 year follow up of the TOBY subjects, in progress. 3. MRC funded study of Xenon as a neuroprotectant for neonatal encephalopathy, led from our group (PI Azzopardi). In progress 4. NIHR Applied Programme Grant: Evaluation of MR imaging for preterm infants (PI Edwards).
Impact 19797281 19060009 17392043 16492950
 
Description Statistics of Networks 
Organisation King's College London
Department Division of Imaging Sciences and Biomedical Engineering
Country United Kingdom 
Sector Academic/University 
PI Contribution Collaboration on statistical analysis of networks
Collaborator Contribution mathematical expertise
Impact Publication Pandit et al, Cereb Cortex 2013 (multidisciplinary) ongoing collaborations
Start Year 2011
 
Description The Developing Human Connectome Project 
Organisation University of Oxford
Department Oxford Centre for Functional MRI of the Brain (FMRIB)
Country United Kingdom 
Sector Academic/University 
PI Contribution New collaboration leading to EU Synergy Grant
Collaborator Contribution fMRI technology and adult connectome experience
Impact EU Synergy Grant (€14.9m) multidisciplinary
Start Year 2013
 
Description Wellcome/EPSRC Centre for Medical Engineering, awarded 2019 
Organisation King's College London
Department Division of Imaging Sciences and Biomedical Engineering
Country United Kingdom 
Sector Academic/University 
PI Contribution Infrastructure funding for Medical Engineering, including the work from this grant
Collaborator Contribution Preliminary data for application; work theme within the Centre
Impact Collabrative work in progress
Start Year 2019
 
Description BBC Horizon: 10 things you need to know about the future 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Science programme about neonatal brain imaging and the analysis of MR scans to define the growth of connections in the infant brain.
Year(s) Of Engagement Activity 2017
 
Description Media engagement 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Interviews, Blogging, Tweets
Year(s) Of Engagement Activity 2015,2016,2017
URL http://www.ifindproject.org
 
Description School programme with the Westminster Academy 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Type Of Presentation Workshop Facilitator
Geographic Reach Local
Primary Audience Schools
Results and Impact We set up a programme for a local school, team members visiting the school and giving talks, and then inviting the children to the research MRI scanner. The teachers used this as a basis for science teaching.

very good feedback from the school, it will be continued next year
Year(s) Of Engagement Activity 2013
 
Description Television and radio interviews 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact We have given several media interviews and had filming on our unit with respect to our research outputs. This includes BBC News, Today Programme, Womens Hour

Difficult to ascertain
Year(s) Of Engagement Activity 2007,2008
 
Description Weston Programme of Patient-Oriented Research 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Type Of Presentation Workshop Facilitator
Geographic Reach Local
Primary Audience Schools
Results and Impact We are using new funding from the Weston Foundation to engage parents and schools in our research programme. This grant is £1,000,000 which will includes funding for patient involvement in research

First year of school programme run and a great success. First patient led research project in progress.
Year(s) Of Engagement Activity 2012