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.
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).
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)
Organisations
- King's College London (Lead Research Organisation)
- UNIVERSITY OF OXFORD (Collaboration)
- Bill & Melinda Gates Foundation (Collaboration)
- Evelina London Children's Hospital (Collaboration)
- Medical Research Council (MRC) (Collaboration)
- IMPERIAL COLLEGE LONDON (Collaboration)
- UNIVERSITY OF CAMBRIDGE (Collaboration)
- KING'S COLLEGE LONDON (Collaboration)
Publications
Fenchel D
(2022)
Neonatal multi-modal cortical profiles predict 18-month developmental outcomes.
in Developmental cognitive neuroscience
Baburamani AA
(2019)
New approaches to studying early brain development in Down syndrome.
in Developmental medicine and child neurology
Nunes RG
(2014)
Highly accelerated Point-Spread Function mapping based on Finite Rate of Innovation for EPI distortion correction.
in EJNMMI physics
Wilson S
(2023)
Spatiotemporal tissue maturation of thalamocortical pathways in the human fetal brain.
in eLife
Story L
(2013)
Myo-inositol metabolism in appropriately grown and growth-restricted fetuses: a proton magnetic resonance spectroscopy study.
in European journal of obstetrics, gynecology, and reproductive biology
Martinez-Biarge M
(2012)
Feeding and communication impairments in infants with central grey matter lesions following perinatal hypoxic-ischaemic injury.
in European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society
Rastogi A
(2013)
Evaluating automated dynamic contrast enhanced wrist 3T MRI in healthy volunteers: one-year longitudinal observational study.
in European journal of radiology
Pecheva D
(2018)
Recent advances in diffusion neuroimaging: applications in the developing preterm brain.
in F1000Research
Description | House of Lords Select Committee on Preterm Birth |
Geographic Reach | National |
Policy Influence Type | Contribution to a national consultation/review |
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 | 08/2013 |
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 | 08/2016 |
End | 08/2019 |
Description | MRC Clinical Training Fellowship |
Amount | £200,000 (GBP) |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 09/2013 |
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 | 03/2018 |
End | 10/2020 |
Description | Project Grant |
Amount | £1,000,000 (GBP) |
Organisation | Garfield Weston Foundation |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 09/2012 |
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 | 06/2012 |
End | 06/2016 |
Description | Senior Investigator Award |
Amount | £75,000 (GBP) |
Organisation | National Institute for Health Research |
Sector | Public |
Country | United Kingdom |
Start | 03/2012 |
End | 03/2017 |
Description | Sparks Clinical Research Fellow |
Amount | £115,878 (GBP) |
Organisation | Sparks Charity |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 08/2012 |
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 | 05/2017 |
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 | Data for: Complex diffusion-weighted image estimation via matrix recovery under general noise models |
Description | Tools for complex DWI denoising using SVD shrinkage, adult and neonatal examples |
Type Of Material | Database/Collection of data |
Year Produced | 2019 |
Provided To Others? | Yes |
URL | https://data.mendeley.com/datasets/6b296z3dg3 |
Title | Data for: Complex diffusion-weighted image estimation via matrix recovery under general noise models |
Description | Tools for complex DWI denoising using SVD shrinkage, adult and neonatal examples |
Type Of Material | Database/Collection of data |
Year Produced | 2019 |
Provided To Others? | Yes |
URL | https://data.mendeley.com/datasets/6b296z3dg3/1 |
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 | A Brain Atlas for the Human Lifespan |
Organisation | University of Cambridge |
Department | Cambridge Neuroscience |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | We collaborated on the making of the first lifespan brain atlas- providing fetal and neonatal MRI data |
Collaborator Contribution | other groups provided data and the principal collaborators analysed the datasets |
Impact | Bethlehem et al. Brain charts for the human lifespan. Nature 2022 Apr;604(7906):525-533. doi: 10.1038/s41586-022-04554-y. Epub 2022 Apr 6. |
Start Year | 2021 |
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 | 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 | Ultralow Field MR imaging for newborn infants |
Organisation | Bill and Melinda Gates Foundation |
Country | United States |
Sector | Charity/Non Profit |
PI Contribution | new imaging methods for portable low-cost MRI brain imaging |
Collaborator Contribution | provided a novel 64mT MR scanner |
Impact | New methods for imaging newborn brain development and pathology- portable low-cost MRI |
Start Year | 2019 |
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 | Northwick Park invited Talk |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Professional Practitioners |
Results and Impact | talk to improve knowledge on perinatal MRI , enhance clinical practice |
Year(s) Of Engagement Activity | 2020 |
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 |
Description | addenbrookes |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Professional Practitioners |
Results and Impact | talk to improve knowledge and assist with clinical practice and encourage research participation |
Year(s) Of Engagement Activity | 2021 |
Description | birth defects talk |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Undergraduate students |
Results and Impact | talk designed to improve knowledge and encourage involvement in research |
Year(s) Of Engagement Activity | 2021 |
Description | invited talk UCL |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Professional Practitioners |
Results and Impact | improve clinical practice and assist with perinatal MR imaging |
Year(s) Of Engagement Activity | 2020 |
Description | perinatal seminars |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Professional Practitioners |
Results and Impact | series of seminars on perinatal imaging given weekly (n=7) |
Year(s) Of Engagement Activity | 2020 |