David J Cox

Validation Study of the Accuracy of Echocardiographic Measurements of Systemic Blood Flow Volume in Newborn Infants

Background The echocardiographic assessment of circulatory function in sick newborn infants has the potential to improve patient care. However, measurements are prone to error and have not been sufficiently validated. Phase-contrast magnetic resonance imaging (MRI) provides highly validated measures of blood flow and has recently been applied to the newborn population. The aim of this study was to validate measures of left ventricular output and superior vena caval flow volume in newborn infants. Methods Echocardiographic and MRI assessments were performed within 1 working day of each other in a cohort of newborn infants. Results Examinations were performed in 49 infants with a median corrected gestational age at scan of 34.43 weeks (range, 27.43–40 weeks) and a median weight at scan of 1,880 g (range, 660–3,760 g). Echocardiographic assessment of left ventricular output showed a strong correlation with MRI assessment (R2 = 0.83; mean bias, −9.6 mL/kg/min; limits of agreement, −79.6 to +60.0 mL/kg/min; repeatability index, 28.2%). Echocardiographic assessment of superior vena caval flow showed a poor correlation with MRI assessment (R2 = 0.22; mean bias, −13.7 mL/kg/min; limits of agreement, −89.1 to +61.7 mL/kg/min; repeatability index, 68.0%). Calculating superior vena caval flow volume from an axial area measurement and applying a 50% reduction to stroke distance to compensate for overestimation gave a slightly improved correlation with MRI (R2 = 0.29; mean bias, 2.6 mL/kg/min; limits of agreement, −53.4 to +58.6 mL/kg/min; repeatability index, 54.5%). Conclusions Echocardiographic assessment of left ventricular output appears relatively robust in newborn infant. Echocardiographic assessment of superior vena caval flow is of limited accuracy in this population, casting doubt on the utility of the measurement for diagnostic decision making.

Machine-learning to characterise neonatal functional connectivity in the preterm brain

Brain development is adversely affected by preterm birth. Magnetic resonance image analysis has revealed a complex fusion of structural alterations across all tissue compartments that are apparent by term-equivalent age, persistent into adolescence and adulthood, and associated with wide-ranging neurodevelopment disorders. Although functional MRI has revealed the relatively advanced organisational state of the neonatal brain, the full extent and nature of functional disruptions following preterm birth remain unclear. In this study, we apply machine-learning methods to compare whole-brain functional connectivity in preterm infants at term-equivalent age and healthy term-born neonates in order to test the hypothesis that preterm birth results in specific alterations to functional connectivity by term-equivalent age. Functional connectivity networks were estimated in 105 preterm infants and 26 term controls using group-independent component analysis and a graphical lasso model. A random forest–based feature selection method was used to identify discriminative edges within each network and a nonlinear support vector machine was used to classify subjects based on functional connectivity alone. We achieved 80% cross-validated classification accuracy informed by a small set of discriminative edges. These edges connected a number of functional nodes in subcortical and cortical grey matter, and most were stronger in term neonates compared to those born preterm. Half of the discriminative edges connected one or more nodes within the basal ganglia. These results demonstrate that functional connectivity in the preterm brain is significantly altered by term-equivalent age, confirming previous reports of altered connectivity between subcortical structures and higher-level association cortex following preterm birth.

A modified echocardiographic approach improves reliability of superior vena caval flow quantification

Objective To assess accuracy and repeatability of a modified echocardiographic approach to quantify superior vena cava (SVC) flow volume that uses a short-axis view to directly measure SVC area and a suprasternal view to measure flow velocity, both at the level of the right pulmonary artery. Setting Three tertiary-level neonatal intensive care units. Design This was a multicentre, prospective, observational study. Accuracy of the traditional and modified approach was first assessed by comparing echo measurements according to both techniques with Phase contrast MRI (PCMRI) assessments, in a cohort of 10 neonates. In a second cohort of 40 neonates, intraobserver scan–rescan repeatability and interobserver analysis–reanalysis repeatability were assessed by repeated SVC flow echo measurements, according to both techniques. Results The traditional echocardiographic approach to assessment of SVC flow had a moderate agreement with PCMRI (r2 0.259), a scan–rescan intraobserver repeatability index (RI) of 37% (limits of agreement (LOA) −47/+51 mL/kg/min) and an interobserver analysis–reanalysis RI of 31% (LOA −38/+40 mL/kg/min). The modified approach showed a stronger agreement with PCMRI (r2 0.775), an improved intraobserver scan–rescan repeatability (RI 22%, LOA −24/+18 mL/kg/min) and improved interobserver analysis–reanalysis repeatability (RI 18%, LOA −18/+20 mL/kg/min). Conclusions Echocardiographic assessment of SVC flow volume by tracing area from a short-axis view and measuring velocity–time integral from a suprasternal view offered an improvement in accuracy and repeatability, building on the traditional approach previously described.

Chloral hydrate sedation for magnetic resonance imaging in newborn infants.

The aim of this study was to look for clinically significant adverse effects of chloral hydrate used in a large cohort of infants sedated for magnetic resonance imaging.

Inotropes in preterm infants – evidence for and against

There is significant uncertainty regarding the optimal circulatory management of preterm infants, with research in the field limited by the paucity of safe, reproducible biomarkers of circulatory function. This review discusses the physiology and pathophysiology of circulatory function in preterm infants, describes the mode of action and evidence for and against commonly used and recently trialled inotropic therapies and provides recommendations for managing circulatory dysfunction in the transitional period and in the context of sepsis/necrotizing enterocolitis. We recommend a pragmatic approach of assessing multiple aspects of circulatory function (blood pressure alone correlates weakly with volume of flow) in each infant, tailoring therapy on the basis of the change in function desired and frequently reassessing response to intervention.

Neonatal cardiac MRI using prolonged balanced SSFP imaging at 3T with active frequency stabilization

Cardiac MRI in neonates holds promise as a tool that can provide detailed functional information in this vulnerable group. However, their small size, rapid heart rate, and inability to breath‐hold, pose particular challenges that require prolonged high‐contrast and high‐SNR methods. Balanced‐steady state free precession (SSFP) offers high SNR efficiency and excellent contrast, but is vulnerable to off‐resonance effects that cause banding artifacts. This is particularly problematic in the blood‐pool, where off‐resonance flow artifacts severely degrade image quality. Methods: In this article, we explore active frequency stabilization, combined with image‐based shimming, to achieve prolonged SSFP imaging free of banding artifacts. The method was tested using 2D multislice SSFP cine acquisitions on 18 preterm infants, and the functional measures derived were validated against phase‐contrast flow assessment. Results: Significant drifts in the resonant frequency (165 ± 23Hz) were observed during 10‐min SSFP examinations. However, full short‐axis stacks free of banding artifacts were achieved in 16 subjects with stabilization; the cardiac output obtained revealed a mean difference of 9.0 ± 8.5% compared to phase‐contrast flow measurements. Conclusion: Active frequency stabilization has enabled the use of prolonged SSFP acquisitions for neonatal cardiac imaging at 3T. The findings presented could have broader implications for other applications using prolong SSFP acquisitions. Magn Reson Med 70:776–784, 2013.

Cardiovascular magnetic resonance of cardiac function and myocardial mass in preterm infants: a preliminary study of the impact of patent ductus arteriosus

BackgroundMany pathologies seen in the preterm population are associated with abnormal blood supply, yet robust evaluation of preterm cardiac function is scarce and consequently normative ranges in this population are limited. The aim of this study was to quantify and validate left ventricular dimension and function in preterm infants using cardiovascular magnetic resonance (CMR). An initial investigation of the impact of the common congenital defect patent ductus arteriosus (PDA) was then carried out.MethodsSteady State Free Procession short axis stacks were acquired. Normative ranges of left ventricular end diastolic volume (EDV), stroke volume (SV), left ventricular output (LVO), ejection fraction (EF), left ventricular (LV) mass, wall thickness and fractional thickening were determined in “healthy” (control) neonates. Left ventricular parameters were then investigated in PDA infants. Unpaired student t-tests compared the 2 groups. Multiple linear regression analysis assessed impact of shunt volume in PDA infants, p-value ≤ 0.05 being significant.Results29 control infants median (range) corrected gestational age at scan 34+6(31+1-39+3) weeks were scanned. EDV, SV, LVO, LV mass normalized by weight and EF were shown to decrease with increasing corrected gestational age (cGA) in controls. In 16 PDA infants (cGA 30+3(27+3-36+1) weeks) left ventricular dimension and output were significantly increased, yet there was no significant difference in ejection fraction and fractional thickening between the two groups. A significant association between shunt volume and increased left ventricular mass correcting for postnatal age and corrected gestational age existed.ConclusionCMR assessment of left ventricular function has been validated in neonates, providing more robust normative ranges of left ventricular dimension and function in this population. Initial investigation of PDA infants would suggest that function is relatively maintained.

4D phase contrast MRI in the preterm infant: visualisation of patent ductus arteriosus

Persistently patent ductus arteriosus (PDA) is correlated with multiple adverse outcomes; however, whether this association is causal or casual remains unclear.1 Echocardiography offers high sensitivity for detection of PDA, but has limited ability to quantify flow within the duct and surrounding vessels. Consequently, the haemodynamic significance can only be inferred.2 Four-dimensional (4D) phase contrast MRI (PCMRI) allows visualisation and quantitative analysis of haemodynamics at almost any anatomical location throughout the cardiac cycle.3 Should …

Quantification of aortic pulse wave velocity in preterm infants using 4D phase contrast MRI

Background 4D phase contrast (PC) MRI sequences providing full coverage of the aortic arch were acquired in neonates. Aortic pulse wave velocity (PWV) was then calculated from flow measurements taken at 5 to 8 locations along the arch and the aortic length between each location. Neonatal PWV values were compared with previously published adult values. Mechanical compliance within the healthy and diseased aorta has been well documented in adults and paediatrics [1,2]. Metafratzi et al [1] reported a PWV range from 4 to 10 ms-1 in the healthy adult aorta, whilst Vulliemoz et al found a mean PWV of 4.4 ms-1 [3]. PWV is an inverse measure of vessel compliance and marker for vessel stiffness. A significant increase in PWV has been found in paediatric subjects born prematurely at low birthweight when studied at ~8yrs and may explain the increase in cardiac disease in this population[2]. However PWV models do not extend back to preterm infants. Recent studies in adults have used PC MRI flow data to determine PWV [4].

PS-011 Quantitative Assessment Of Preterm Left Ventricular Anatomical Development And Remodelling Using Neonatal Cardiac Mri And Atlasing Techniques

Background and aims Cardiac development and myocardial maturation continues through the third trimester of gestation. Moderately preterm birth at 30–36 weeks adversely affects long-term cardiovascular health and impacts left ventricular size and geometry at young adulthood. We aim to quantify and characterise normal and pathological neonatal cardiac development using cardiac MRI and computational atlas construction. Methods Preterm neonates and healthy term controls underwent neonatal 3 Tesla cardiac MRI. Data from short axis stack sequences was manually segmented at end-diastole (ITK-SNAP software) providing volumetric measurements of the left ventricular myocardium and blood pool. Sub-group analysis compared 10 preterm neonates born at 32–35 weeks, scanned within 7 days of birth and at term-corrected age, with 4 healthy term controls (39–42 weeks). Results Weight-corrected left ventricular mass (LVM, g/kg) and end-diastolic volume (EDV, cm3/kg) for the preterm cohort at term-corrected age (LVM - mean 1.89, 95% CI 1.89 ± 0.21; EDV – mean 3.42, 95% CI 3.42 ± 0.34) were significantly greater than both the preterm cohort at birth (LVM 1.05, 1.05 ± 0.08, p = 0.0002; EDV 4.89, 4.89 ± 0.59, p = 0.0008) and healthy term controls (LVM 0.95, 0.95 ± 0.18, p = 0.001; EDV 2.16, 2.16 ± 0.38, p = 0.0006). Conclusions Neonatal MRI with manual ventricular segmentation quantifies preterm gross ex-utero left ventricular growth, highlighting differences from in-utero cardiac development. Increases in preterm LVM and EDV may represent pathological remodelling or physiological ex-utero adaptation. We have constructed provisional computational atlases that currently allow visual comparisons of size and shape, but which after further analysis will enable more sophisticated quantification and characterisation of preterm ventricular growth and remodelling. Abstract PS-011 Figure 1 Abstract PS-011 Figure 1