Quantitative computational analysis and cotside correlation of cardiac magnetic resonance imaging in newborn infants

Lead Research Organisation: Imperial College London
Department Name: Dept of Medicine

Abstract

While great advances have been made in providing breathing support for premature babies, a large number of infants still die or suffer long term disability caused by failure of the premature heart. Heart failure in the premature newborn cannot reliably be detected by currently available methods, and the best treatments for heart failure are unknown.
This study aims to develop new magnetic resonance (MR) and echocardiography techniques to help doctors understand why the heart fails in some premature infants, and to support future studies comparing treatments in randomised trials.
This research will be carried out by a team of doctors, physicists and computational scientists working at Imperial College London who will perform MR and echocardiography scans in the carefully controlled environment of their neonatal intensive care unit. This group has previously produced significant advances in understanding of brain development in premature infants using MR technology, and now aims to turn its unique expertise to improving management of the circulation.
The group believe that in the long term improved ability to monitor and support heart function in premature babies will help infants to survive, and survive free from disability.

Technical Summary

Aims and Objectives
To develop novel computational analysis techniques and cardiac magnetic resonance (CMR) imaging of newborn infants to:
1. Improve understanding of neonatal cardiovascular function in health and disease
2. Employ as biomarker endpoints in clinical trials of existing and emerging therapies
3. Allow standardisation of cotside echocardiographic techniques to apply improvements in patient care to the largest number of sick newborn infants.
The long-term goal of the research is to reduce mortality and morbidity through improved management of the cardiovascular system.
Research Hypothesis
Systemic inflammatory conditions such as sepsis/necrotising enterocolitis, and birth prior to 28 weeks gestation create specific abnormalities precipitating cardiac dysfunction in newborn infants which can be accurately delineated by CMR computational analysis techniques.
Design and Methodology:
Year 1 - Study of 40 stable preterm and term infants to optimise CMR image acquisition, particularly for tagged and phase contrast sequences. Refinement of computational post-processing techniques to allow semi-automated tag-tracking assessment of myocardial motion, calculation of systemic blood flow volume, and intra-cardiac vortex production. Optimisation of tissue Doppler imaging modality and correlation of multiple TDI measures with CMR measures of contractility.
Year 2-4 - Application of CMR (balanced fast field echo assessment of 3-dimensional cardiac filling and stroke volume; tagging analysis of longitudinal and rotational myocardial motion; phase contrast assessment of intra- and extra-cardiac blood flow) and TDI (isovolumic acceleration; peak tissue velocity; strain rate; AV valve displacement) techniques to 40 healthy term control infants, 40 preterm (<28 weeks) infants, and 40 infants with sepsis/necrotising enterocolitis. This protocol will produce a comprehensive assessment of preload, contractility, afterload and systemic perfusion in septic and premature infants who have high rates of mortality and morbidity.
Scientific and Medical Opportunities: (1) CMR will improve understanding of the contributions of abnormalities in preload, contractility, afterload and fetal shunting in producing circulatory failure in septic or premature newborn infants. (2) CMR will provide novel precise, reproducible biomarkers to act as endpoints for future studies of therapeutic studies of neonatal circulatory support. (3) By equipping clinicians with standardised tissue Doppler imaging techniques this research will rapidly translate into improved point-of-care assessment of circulatory function in the maximum number of sick infants. (4) Future directions of this research could include advances in cerebral perfusion quantification with arterial spin labelling, advanced (HARP) tissue tagging techniques, and study of the genetic associations of circulatory failure in the newborn.

Publications

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Broadhouse KM (2014) Cardiovascular magnetic resonance of cardiac function and myocardial mass in preterm infants: a preliminary study of the impact of patent ductus arteriosus. in Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance

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Broadhouse KM (2015) 4D phase contrast MRI in the preterm infant: visualisation of patent ductus arteriosus. in Archives of disease in childhood. Fetal and neonatal edition

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Cox DJ (2012) Inotropes in preterm infants--evidence for and against. in Acta paediatrica (Oslo, Norway : 1992)

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Ficial B (2014) Superior vena flow quantification in the newborn: reply to a letter by Kluckow and Evans. in Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography

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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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Foran A (2009) Patterns of brain injury and outcome in term neonates presenting with postnatal collapse. in Archives of disease in childhood. Fetal and neonatal edition

 
Description Neonatal Echocardiography Courses
Geographic Reach Europe 
Policy Influence Type Influenced training of practitioners or researchers
 
Description BHF Clinical Training Fellowship
Amount £113,403 (GBP)
Organisation British Heart Foundation (BHF) 
Sector Charity/Non Profit
Country United Kingdom
Start 09/2011 
End 09/2013
 
Description BRC Call for proposals for research projects in translational medicine - February 2010
Amount £91,153 (GBP)
Organisation National Institute for Health Research 
Department NIHR Imperial Biomedical Research Centre
Sector Charity/Non Profit
Country United Kingdom
Start 09/2010 
End 09/2011
 
Description Clinical Research Fellow Scheme
Amount £115,878 (GBP)
Organisation Sparks 
Sector Charity/Non Profit
Country United Kingdom
Start 09/2012 
End 08/2015
 
Description Friedman Family Scholarship
Amount $126,000 (USD)
Organisation Friedman Family Foundation Clinical Scholar in Newborn Medicine 
Sector Charity/Non Profit
Country United States
Start 05/2014 
End 04/2017
 
Description Imperial College Healthcare Charity Research Grant
Amount £23,500 (GBP)
Organisation Imperial College Healthcare NHS Trust 
Department Imperial College Healthcare NHS Charity
Sector Charity/Non Profit
Country United Kingdom
Start 05/2010 
End 12/2010
 
Description MRC Centenary Award
Amount £79,965 (GBP)
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 12/2012 
End 11/2013
 
Description Project Grant
Amount £206,157 (GBP)
Organisation British Heart Foundation (BHF) 
Sector Charity/Non Profit
Country United Kingdom
Start 06/2012 
End 05/2015
 
Description Pump Priming
Amount £45,011 (GBP)
Organisation King's College London 
Sector Academic/University
Country United Kingdom
Start 11/2012 
End 03/2013
 
Description MRI Receive Coil Field Test 
Organisation Philips Medical Systems UK Ltd
Country United Kingdom 
Sector Private 
PI Contribution Field testing of new pre-market release MRI receive coil. Provision of example images and data on signal to noise ratio.
Collaborator Contribution Early access to new release MRI receive coils
Impact Abstract on coil SNR and CNR submitted to Society for Cardiovascular Magnetic Resonance Conference in February 2011.
Start Year 2010
 
Description Predictive Monitoring Collaboration 
Organisation University of Virginia (UVa)
Department Division of Neonatology
Country United States 
Sector Academic/University 
PI Contribution Initiation of International Neonatal Collaboration on Noninvasive predictive monitoring. Karen Fairchild, Virginia Randall Moorman, Virginia David Edwards, London Hammad Khan, London Chris Dewhurst, Liverpool
Collaborator Contribution Our introduction of the 'HeRO' predictive monitoring system has led to development of this collaborative group, with a collaborators meeting planned for December 2013, Washington, USA.
Impact One funding application already submitted (SPR, 2013, unsuccessful). Further applications to be discussed at collaborators meeting planned for December 2013, Washington, USA.
Start Year 2013
 
Description Visiting Research Fellow, Albert Einstein School of Medicine, New York, June - August 2010 
Organisation Albert Einstein College of Medicine
Country United States 
Sector Academic/University 
PI Contribution During the replacement I optimized protocols for analysis of speckle tracking and tissue Doppler imaging in the paediatric population. An abstract based on the data obtained has been presented at the EuroEcho meeting, and a full paper is currently in preparation.
Collaborator Contribution Dr Leo Lopez, first author of the American Society of Echocardiography's report on recommendations for quantifications methods during the performance of a pediatric echocardiogram. He provided background to speckle tracking analysis and introduced a collaboration with Philips Medical Systems.
Impact Abstract presentation at EuroEcho Meeting. Paper in preparation.
Start Year 2010
 
Description Neonatal Echocardiography Website 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Health professionals
Results and Impact Neonatal echocardiography training website set up to facilitate learning of skills and application to clinical practice.

Website receives over 2,500 unique visitors/month.
Year(s) Of Engagement Activity 2011,2012
 
Description Review Article in Industry Newsletter 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Primary Audience Public/other audiences
Results and Impact Review article written for Philips Medical Systems' in-house newsletter. Describing use of their MRI equipment to forward research in the field.

Supported further collaboration with Philips Medical Systems.
Year(s) Of Engagement Activity 2009