Feasibility of detecting myocardial infarction in the sheep fetus using late gadolinium enhancement CMR imaging

Abstract

BackgroundLate gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) imaging has enabled the accurate assessment of myocardial infarction (MI). However, LGE CMR has not been performed successfully in the fetus, where it could be useful for animal studies of interventions to promote cardiac regeneration. We believe that LGE imaging could allow us to document the presence, extent and effect of MI in utero and would thereby expand our capacity for conducting fetal sheep MI research. We therefore aimed to investigate the feasibility of using LGE to detect MI in sheep fetuses.MethodsSix sheep fetuses underwent a thoracotomy and ligation of a left anterior descending (LAD) coronary artery branch; while two fetuses underwent a sham surgery. LGE CMR was performed in a subset of fetuses immediately after the surgery and three days later. Early gadolinium enhancement (EGE) CMR was also performed in a subset of fetuses on both days. Cine imaging of the heart was performed to measure ventricular function.ResultsThe imaging performed immediately after LAD ligation revealed no evidence of infarct on LGE (n=3). Two of four infarcted fetuses (50%) showed hypoenhancement at the infarct site on the EGE images. Three days after the ligation, LGE images revealed a clear, hyper-enhanced infarct zone in four of the five infarcted fetuses (80%). No hyper-enhanced infarct zone was seen on the one sham fetus that underwent LGE CMR. No hypoenhancement could be seen in the EGE images in either the sham (n=1) or the infarcted fetus (n=1). No regional wall motion abnormalities were apparent in two of the five infarcted fetuses.ConclusionLGE CMR detected the MI three days after LAD ligation, but not immediately after. Using available methods, EGE imaging was less useful for detecting deficits in perfusion. Our study provides evidence for the ability of a non-invasive tool to monitor the progression of cardiac repair and damage in fetuses with MI. However, further investigation into the optimal timing of LGE and EGE scans and improvement of the sequences should be pursued with the aim of expanding our capacity to monitor cardiac regeneration after MI in fetal sheep.Electronic supplementary materialThe online version of this article (10.1186/s12968-017-0383-1) contains supplementary material, which is available to authorized users.

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 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 application of this kind of imaging technology in animal models represents an exciting advancement in the development of fetal cardiac MRI.…”

“…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. For example, the combination of fetal surgical preparation and 4D flow cardiac MRI has made it possible to characterize and quantify complex in utero flow patterns including the preferential streaming of oxygenated blood across the foramen ovale and into the ascending aorta via the umbilical vein and ductus venosus (online Video 11).…”

And the beat goes on

“…CMRI has recently been employed to study the fetal heart (Duan et al . ) and thus CMRI studies could be employed across the life course, beginning as early as fetal life, to identify changes in cardiac function in populations at increased risk of cardiovascular disease prior to the development of dysfunction.…”

“…For example, a severe 50% maternal nutrient restriction in late gestation increased myocardial fibrosis and altered the phosphorylation state of key contractile proteins in the fetal sheep right ventricle (Darby et al 2018). CMRI has recently been employed to study the fetal heart (Duan et al 2017) and thus CMRI studies could be employed across the life course, beginning as early as fetal life, to identify changes in cardiac function in populations at increased risk of cardiovascular disease prior to the development of dysfunction.…”