Perinatal Imaging

Lead Research Organisation: MRC London Institute of Medical Sciences

Abstract

Our group uses magnetic resonance imaging techniques to investigate the developing brain, integrating data from fetal, early postnatal and postmortem scanning. We are developing fetal imaging and spectroscopy acquisition and post-acquisition processing methods to produce high resolution, high signal to noise datasets of the developing brain from 17 weeks - 40 weeks gestation. The aim is to overcome major obstacles such as fetal motion to produce images that are of similar quality to those obtained postnatally. In parallel with these projects we are optimising computational software to allow objective quantification of neural pathways in the developing brain. This will allow unprecedented insights into brain development in vivo providing a unique template against which disorders of brain development, both genetic and acquired can be objectively measured. Optimisation of postmortem scanning techniques including diffusion tensor imaging allows superb resolution of brain tissue. We wish to establish imaging correlates for normal and abnormal histological processes in the brain, in particular the sites of resident and activated microglia in the normal brain, in the brains of preterm infants and following an injurious process.

Technical Summary

With recent improvements in obstetric and neonatal care, survival of the compromised fetus and neonate is now assured. However this survival is frequently accompanied by significant neurological morbidity. Current techniques for assessing the immature brain are limited and recent advances in neuroimaging need to be developed and exploited to study this high-risk group. Detailed understanding of developmental brain processes in vivo will improve the early detection of abnormalities, allow basic questions on the effect of gender, nutrition, prematurity and adverse events to be explored and answered. This will lead to targeted interventions with imaging serving as a biomarker for their effect in addition to providing very early surrogate outcome measures.||The aim of this programme is to develop and optimise both fetal and post-mortem magnetic resonance imaging (MRI) to produce comparable datasets to those acquired in vivo postnatally.||This programme of work seeks to answer the following research questions:||- What is the relationship between thalamo-cortical innervation, subplate evolution and cortical synapse formation in the normally developing brain in vivo?|- Do fetuses with intrauterine growth restriction demonstrate altered brain development that is responsible for later neurocognitive impairments?|- Can optimised diffusion tensor imaging detect significant abnormalities in the developing fetal brain following an adverse event?|- Can MR imaging reliably detect the sites of resident microglia within the developing brain?|- Is diffuse white matter abnormality of prematurity associated with increased activation of microglia and alteration of the extracellular matrix?||The in vivo programme involves serial MR scanning antenatally (1.5 Tesla) and postnatally (3 Tesla) and neurodevelopmental follow-up into school age. Imaging examinations currently involve conventional T2-weighted single shot approaches, magnetic resonance spectroscopy and a new dynamic single shot approach which oversamples the brain providing data rich acquisitions that can be registered into 3-D volumetric datasets, reformattable into any plane and suitable for objective quantification by optimised computer programmes. Our postmortem imaging combines detailed MRI with histology findings from conventional autopsy, the application of different staining techniques allowing us to detect imaging signatures for specific cellular processes in the brain.||The programme enjoys close collaboration with other MRC groups - the BIC, Imaging Physics and Engineering, and Neonatal Medicine as well as collaborations within Imperial College; The Centre for Fetal Care and the Hammersmith Hospital Trust; and the Departments of Perinatal Pathology and Radiology. In addition we have an ongoing collaboration on microglial research with INSERM, Paris and are currently setting up similar collaborations on subplate research with the cerebral cortical development group in Oxford.

Publications

10 25 50
publication icon
Alansary A (2017) PVR: Patch-to-Volume Reconstruction for Large Area Motion Correction of Fetal MRI. in IEEE transactions on medical imaging

publication icon
Aljabar P (2010) Combining morphological information in a manifold learning framework: application to neonatal MRI. in Medical image computing and computer-assisted intervention : MICCAI ... International Conference on Medical Image Computing and Computer-Assisted Intervention

publication icon
Astrea G (2009) Muscle MRI in FHL1-linked reducing body myopathy. in Neuromuscular disorders : NMD

publication icon
Atkinson J (2008) Cortical vision, MRI and developmental outcome in preterm infants. in Archives of disease in childhood. Fetal and neonatal edition

publication icon
Baburamani AA (2015) Does Caspase-6 Have a Role in Perinatal Brain Injury? in Developmental neuroscience

publication icon
Ball G (2013) Development of cortical microstructure in the preterm human brain. in Proceedings of the National Academy of Sciences of the United States of America

 
Title best beginnings cines 
Description cine films with voice overs of fetal MR videos for best beginnings charity 
Type Of Art Image 
Year Produced 2018 
Impact increased views on charity app 
 
Description 16770663; 20109974 ; 20432000 pubmed
Geographic Reach Multiple continents/international 
Policy Influence Type Citation in clinical reviews
Impact increased usage of MR imaging as a clinical and reearch tool in neonatal neurology
URL http://europepmc.org/abstract/MED/16770663
 
Description 18383541,19996870;20413207 pubmed
Geographic Reach Multiple continents/international 
Policy Influence Type Citation in clinical reviews
Impact Incresaed use of fetal MR techniques for assessment of the brain
URL http://europepmc.org/abstract/MED/18383541
 
Description SUDI
Geographic Reach National 
Policy Influence Type Participation in a national consultation
Impact . Guidelines for investigation of infants with sudden death perinatally have now been distributed to all neonatal units nationally. no impact figures available yet
 
Description training
Geographic Reach Multiple continents/international 
Policy Influence Type Influenced training of practitioners or researchers
Impact steady imporvement in image acquisition across the UK . Incresaed use of MR as a clinical tool in neonatal neurology and fetal medicine
 
Description Action Medical Research, Project Grant
Amount £170,000 (GBP)
Organisation Action Medical Research 
Sector Charity/Non Profit
Country United Kingdom
Start  
 
Description Action Medical Research, Project Grant
Amount £199,000 (GBP)
Organisation Action Medical Research 
Sector Charity/Non Profit
Country United Kingdom
Start  
 
Description Biomedical Research Centre
Amount £132,050 (GBP)
Organisation National Institute for Health Research 
Department NIHR Imperial Biomedical Research Centre
Sector Academic/University
Country United Kingdom
Start  
 
Description Bloomsbury Colleges Studentship
Amount £65,000 (GBP)
Organisation Birkbeck, University of London 
Sector Academic/University
Country United Kingdom
Start 09/2018 
End 08/2021
 
Description ELA Project Grant
Amount £150,000 (GBP)
Organisation European Leukodystrophy Association (ELA) 
Sector Charity/Non Profit
Country European Union (EU)
Start  
 
Description EPSRC Project Grant EP/F011830/1 Computational Morphometry of the Developing Cortex - shared with J Hajnal
Amount £286,543 (GBP)
Funding ID EP/F011830/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Academic/University
Country United Kingdom
Start  
 
Description EPSRC healthcare partnership EP/I000445/1 Computer aided diagnosis of neurological damage to improve care for infants born prematurely - shared with J Hajnal
Amount £511,738 (GBP)
Funding ID EP/I000445/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Academic/University
Country United Kingdom
Start  
 
Description MRC Project Grant
Amount £409,326 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start  
 
Description NIHR CLRN
Amount £27,957 (GBP)
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom
Start  
 
Description The Moonbeam Trust Project Grant
Amount £300,000 (GBP)
Organisation The Moonbeam Trust 
Sector Charity/Non Profit
Country United Kingdom
Start  
 
Description project
Amount £2,000,000 (GBP)
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom
Start  
 
Title SNAPIR 
Description Development of T1 weighted image acquisition for mobile fetus 
Type Of Material Biological samples 
Year Produced 2010 
Provided To Others? Yes  
Impact Publication 
 
Title SVR 
Description Methodology for image acquisition of mobile fetus 
Type Of Material Biological samples 
Year Produced 2010 
Provided To Others? Yes  
Impact Publications. Currently used as part of standard clinical examination for fetal and neonatal brain imaging 
 
Title placental imaging database 
Description red Cap database for placental imaging project 
Type Of Material Database/Collection of data 
Year Produced 2018 
Provided To Others? No  
Impact allows for analysis of data from multiple techniques by numerous researchers. 
 
Description Brain development in Downs syndrome 
Organisation Birkbeck, University of London
Country United Kingdom 
Sector Academic/University 
PI Contribution Perofm MRI scans on fetuses and neonates with Downs syndrome. We refer patients to Birkbeck for developmental follow up.
Collaborator Contribution Birkbeck :Developmental assessments of our patients Kings: provision of clinical information St Georges : Provision of clinical information
Impact nil as yet workshop in February 2014
Start Year 2013
 
Description Brain development in Downs syndrome 
Organisation King's College Hospital
Country United Kingdom 
Sector Hospitals 
PI Contribution Perofm MRI scans on fetuses and neonates with Downs syndrome. We refer patients to Birkbeck for developmental follow up.
Collaborator Contribution Birkbeck :Developmental assessments of our patients Kings: provision of clinical information St Georges : Provision of clinical information
Impact nil as yet workshop in February 2014
Start Year 2013
 
Description Brain development in Downs syndrome 
Organisation St George's University of London
Country United Kingdom 
Sector Academic/University 
PI Contribution Perofm MRI scans on fetuses and neonates with Downs syndrome. We refer patients to Birkbeck for developmental follow up.
Collaborator Contribution Birkbeck :Developmental assessments of our patients Kings: provision of clinical information St Georges : Provision of clinical information
Impact nil as yet workshop in February 2014
Start Year 2013
 
Description Declan Murphy 
Organisation King's College London
Country United Kingdom 
Sector Academic/University 
PI Contribution autism research . provision of fetal MRI . joint supervision of a PhD student
Collaborator Contribution Provision of high risk cohort
Impact not available yet
Start Year 2012
 
Description Downs mouse model 
Organisation Francis Crick Institute
Country United Kingdom 
Sector Charity/Non Profit 
PI Contribution Sharing of data on T21 mouse brain and heart findings
Collaborator Contribution development of mouse model.
Impact Further funding GOSH/SPARKS
Start Year 2017
 
Description Downs mouse model brain study 
Organisation University College London
Department Institute of Epidemiology and Health Care
Country United Kingdom 
Sector Academic/University 
PI Contribution We are histologically phenotyping the brain a mouse model of Downs syndrome
Collaborator Contribution They have provided mouse pups of the model at different gestational ages.
Impact Multidisciplinary. Further joint funding being sought. Further funding achieved from two sources.. LeJeune foundation and GOSH/SPARKS
Start Year 2016
 
Description Histological brain findings 
Organisation University of Miami
Country United States 
Sector Academic/University 
PI Contribution Working with Dr Regina Vontell on histological findings in mouse and human brain tissue
Collaborator Contribution Regina is giong to stain our tissue for dendritic morpholgies in the first instance
Impact Nil as yet
Start Year 2018
 
Description Histological brain findings in mouse and human T21 tissue 
Organisation Boston University
Country United States 
Sector Academic/University 
PI Contribution ew will be providing human and mouse tissue and doing complimentary analysis on white matter at similar gestationl ages.
Collaborator Contribution Dr Tarik Haydar will be looking at white matter development in our human and mouse tissue
Impact nil as yet
Start Year 2019
 
Description MRI in Congenital cardiac disorders 
Organisation King’s Health Partners
Country United Kingdom 
Sector Academic/University 
PI Contribution Collaboration with fetal and neonatal cardiologists to assess the role of MRI to image the heart in fetuses with congenital cardiac disease. In addition to assess brain development . We perform MR exmainations and analyiss of image data. We will perform developmental follow up assessments
Collaborator Contribution Referral of patients. Sharing of clinical data Assisting in optimising fetal cardiac sequences
Impact Non as yet
Start Year 2014
 
Description Studies of the fetus and placenta in complications of pregnancy 
Organisation National Institute for Health Research
Department NIHR Biomedical Research Centre (Guy's, St Thomas' and KCL)
Country United Kingdom 
Sector Hospitals 
PI Contribution Grant writing. Imaging studies. Student supervision
Collaborator Contribution Staff provision. Patient recruitment . US imaging. Biomarker analysis
Impact multidisciplinary. Joint studentships MD. Applied for joint PhD student.
Start Year 2016
 
Description Twins 
Organisation St George's University of London
Country United Kingdom 
Sector Academic/University 
PI Contribution This has just started . The collaborators will refer pregnant women with monochorioinc twin pregnancies. We will perform fetal and enonatal brain MRI
Collaborator Contribution Identification of patients. provision of clinical and ultrasound data.
Impact None as yet
Start Year 2014
 
Description fetal movement studies 
Organisation Imperial College London
Country United Kingdom 
Sector Academic/University 
PI Contribution we have provided fetal MR videos. collaborations on further funding applications
Collaborator Contribution on going work studying movement on these videos. Publications
Impact publications 26534772, 20170593 news coverage https://www.nature.com/articles/d41586-018-01117-y?utm_source=twt&utm_medium=social&utm_campaign=naturemarketinghttp://www.sciencemag.org/news/2018/01/babies-womb-pack-more-4-kilograms-force-kick?utm_source=newsfromscience&utm_medium=twitter&utm_campaign=inthewomb-17494
Start Year 2015
 
Description molnar 
Organisation University of Oxford
Department Department of Physiology, Anatomy and Genetics
Country United Kingdom 
Sector Academic/University 
PI Contribution provision of human brain tissue, knowledge of the developing brain, interpretation of images
Collaborator Contribution collaborative studies investigating subplate in human cortex.
Impact 20727056
Start Year 2009
 
Title SNAPIR 
Description A T1 weighted MR sequence "resistant" to the motion for the fetal brain 
IP Reference Insufficient Information 
Protection Patent granted
Year Protection Granted
Licensed No
Impact This sequence is now used routinely in our clinical fetal MR examinations
 
Description 360 degrees 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Participants in your research and patient groups
Results and Impact article about our latest fetal imaging techniques

nil of note
Year(s) Of Engagement Activity 2009
 
Description AMR 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Participants in your research and patient groups
Results and Impact Summary of our fetal research

Obtained further funding from same organisation
Year(s) Of Engagement Activity 2008
 
Description BBC video interview 
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 Public/other audiences
Results and Impact Video interview of the fetal imaging set up Patienet and group head interview

contacted by further news stations CNN,
Year(s) Of Engagement Activity 2009
 
Description Houses of Parliament 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Presntation of our work funded by AMR at the Houses of Parliament. For donors.

Obtained further funding from AMR
Year(s) Of Engagement Activity 2009
 
Description Moonbeam website 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact written report on our fetal imaging programme for lay reader

continued funding for our research fellows
Year(s) Of Engagement Activity 2009
 
Description Pint of Science 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Pint of Science activities. Organise an evening of presentations around a scientific topic. Usually held in a pub and open to the public through purchase of tickets. Just over 50 people in audience. Mixed professionals and students.
Year(s) Of Engagement Activity 2015
 
Description Presentation at Kingston University Hospital. London 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact presentation on imaging neonatal brain . between 50-100 mixed disciplinary audience. doctors midwives, nurses.
Year(s) Of Engagement Activity 2017
 
Description Presentation at Luton and Dunstable Hospital. London 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact presentation on imaging the neonatal brain . Case presentations and discussion
Year(s) Of Engagement Activity 2016
 
Description Presentation on fetal imaging Darent Valley Hospital 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact Presentation about fetal MR imaging to mixed disciplinary group of doctors, nurses and midwives.
Year(s) Of Engagement Activity 2016
 
Description University of Cambridge case review 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact Case presentation and review of images, and developmental outcomes.
Year(s) Of Engagement Activity 2016
 
Description case review Kingston 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact case review
Year(s) Of Engagement Activity 2019
 
Description case review cambridge 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact case review
Year(s) Of Engagement Activity 2018
 
Description case review watford 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact case review
Year(s) Of Engagement Activity 2018
 
Description demonstration at Science week 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact demonstrations of microscope use , histology findings in association with our studies
Year(s) Of Engagement Activity 2015
 
Description involvement in Science week 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact demonstrations about our work.
Year(s) Of Engagement Activity 2016
 
Description newspaper article 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Type Of Presentation Paper Presentation
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact Supplied material for an article on MR imaging of the developing brain published in the Sunday Times . February 2013

some volunteer recrutiment for our MR studies
Year(s) Of Engagement Activity 2013
 
Description presentation on fetal MR Imaging Medway Hospital 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact presentation and discussion about fetal MR imaging . case review. approximately 50 multidisciplinary participants
Year(s) Of Engagement Activity 2015
 
Description presntation 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Presentation to group Priorities in Perinatal care in South Africa . approximately 200 participants form various professional groups. doctors, midwives , nurses
Year(s) Of Engagement Activity 2017
 
Description supplied images to BBC 
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 Public/other audiences
Results and Impact Images supplied to BBC for documentray, still being made on fetal development.

none as yet
Year(s) Of Engagement Activity 2010
 
Description videos of fetal imaging 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Patients, carers and/or patient groups
Results and Impact making cine clips with voice overs for best beginnings charity
Year(s) Of Engagement Activity 2018