Feasibility of phase-contrast cine magnetic resonance imaging for measuring blood flow in the sheep fetus

Abstract

Phase-contrast cine MRI (PC-MRI) is the gold-standard non-invasive technique for measuring vessel blood flow and has previously been applied in the human fetal circulation. We aimed to assess the feasibility of using PC-MRI to define the distribution of the fetal circulation in sheep. Fetuses were catheterized at 119-120 days gestation (term, 150 days) and underwent MRI at 123 days gestation under isoflurane anesthesia, ventilated at a FiO of 1.0. PC-MRI was performed using a fetal arterial blood pressure catheter signal for cardiac triggering. Blood flows were measured in the major fetal vessels, including the main pulmonary artery, ascending and descending aorta, superior vena cava, ductus arteriosus, left and right pulmonary arteries, umbilical vein, ductus venosus, and common carotid artery; and were indexed to estimated fetal weight. The combined ventricular output, pulmonary blood flow and flow across the foramen ovale were calculated from vessel flows. Intra-observer, inter-observer agreement and reproducibility were assessed. Blood flow measurements were successfully obtained in 61 out of 74 vessels (82.4%) interrogated in 9 fetuses. There was good intra-observer (R=0.998, P<0.0001; ICC=0.997) and inter-observer agreement (R=0.996, P<0.0001; ICC=0.996). Repeated MRI measurements showed good reproducibility (R=0.989, P=0.0002; ICC=0.990). We conclude that PC-MRI using fetal catheters for gating triggers is feasible in the major vessels of late gestation fetal sheep. This approach may provide a useful new tool for assessing the circulatory characteristics of fetal sheep models of human disease, including fetal growth restriction and congenital heart disease.

Technique for comprehensive fetal hepatic blood flow assessment in sheep using 4D flow MRI

“…Techniques to measure flow distribution include historical studies using the injection and downstream counting of radio-or fluorescently-labelled microspheres in animal models of pregnancy, but these required invasive tissue collection (Rudolph & Heymann, 1967;Edelstone & Rudolph, 1979;Poudel et al 2015). More recent non-invasive imaging studies have used ultrasound to measure fetal velocity waveforms (Schmidt et al 1996;Zhou et al 2014) and single-slice 2D phase-contrast (PC) MRI to quantify blood flow in fetal target vessels (Seed et al 2012;Duan et al 2019). These latter, more clinically applied techniques, while proving elucidative in fetal flow physiology, do not directly and comprehensively capture the intricate three-dimensional (3D) circulatory patterns within the fetal vasculature, particularly of smaller vessels.…”

“…Resulting blood velocity fields can be visualized and interactively probed using particle traces illustrating paths followed by virtual particles released into the time-dependent velocity field. Additionally, the use of MRI in animal models of pregnancy together with fetal instrumentation has allowed for more in-depth probing of fetal physiology (Yamamura et al 2009;Morrison et al 2018;Duan et al 2019).…”

Understanding Fetal Hemodynamics Using Cardiovascular Magnetic Resonance Imaging

“…The pressure trace is obtained using an indwelling fetal arterial catheter and imaging quality is optimized using maternal anesthesia to restrict maternal and fetal motion. Examples of applications of fetal CMR that have been used to study animal models include the visualization of myocardial infarcts induced by coronary artery ligation and the quantification of the distribution of blood flow across the fetal sheep circulation [50,51]. Thus, the fetal sheep physiology work that inspired the development of human fetal CMR may now be enhanced by this versatile imaging medium for examining cardiovascular physiology, which now provides an alternative to conventional invasive techniques.…”

MR imaging of the fetal heart

“…The ability to accurately measure ventricular mass, end‐diastolic and systolic volumes, and right and left ventricular ejection fractions could be of considerable interest in a number of situations. The utility of this approach has been explored in the setting of a fetal sheep model of myocardial infarction . In that study, the presence of myocardial infarcts induced by ligation of a coronary artery was also delineated using late gadolinium enhancement .…”

“…The utility of this approach has been explored in the setting of a fetal sheep model of myocardial infarction. 73 In that study, the presence of myocardial infarcts induced by ligation of a coronary artery was also delineated using late gadolinium enhancement. 74 The application of this kind of imaging technology in animal models represents an exciting advancement in the development of fetal cardiac MRI.…”