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

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.

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.