Open or closed: Changes in ductus arteriosus flow patterns at birth using 4D flow MRI in newborn piglets

Abstract

The ductus arteriosus (DA) functionally closes during the transition from fetal to postnatal life because of lung aeration and corresponding cardiovascular changes. The thorough and explicit measurement and visualization of the right and left heart output during this transition has not been previously accomplished. We combined 4D flow MRI (dynamic volumetric blood flow measurements) and T2 relaxometry (oxygen delivery quantification) in surgically instrumented newborn piglets to assess the DA. This was performed in Large White‐Landrace‐Duroc piglets ( n = 34) spanning four age groups: term‐9 days, term‐3, term+1, and term+5. Subject's DA status was classified using 4D flow: closed DA, forward DA flow, reversed DA flow, and bidirectional DA flow. Over all states, vessel diameters and flows normalized to body weight increased with age (for example in the ascending aorta flow—term‐9: 126.6 ± 45.4; term+5: 260.2 ± 80.0 ml/min per kg; p = 0.0005; ascending aorta diameter—term‐9: 5.2 ± 0.8; term+5: 7.7 ± 0.4 mm; p = 0.0004). In subjects with reversed DA blood flow there was lower common carotid artery blood flow (forward: 37.5 ± 9.0; reversed: 20.0 ± 7.4 ml/min per kg; p = 0.032). Linear regression revealed that as net DA flow decreases, common carotid artery flow decreases (R 2 = 0.32, p = 0.004), and left (R 2 = 0.33, p = 0.003) and right (R 2 = 0.34, p = 0.003) pulmonary artery flow increases. Bidirectional DA blood flow changed oxygen saturation as determined by MRI between the ascending and descending aorta (ascending aorta: 90.1% ± 8.4%; descending aorta: 75.6% ± 14.2%; p < 0.05). Expanded use of these techniques in preterm animal models will aid in providing new understandings of normal versus abnormal DA transition, as well as to test the effectiveness of related clinical interventions.

Advanced imaging of fetal cardiac function

“…Darby et al ( 51 ) then used 4D flow in combination with T2 oximetry to show that pharmacologically induced dilation of the ductus venosus results in an increased shunting of umbilical venous return through the ductus venosus without resulting in increased cerebral oxygen delivery. This method was also applied to visualize hepatic blood flow ( 152 ) and changes in flow through the ductus arteriosus at birth ( 49 ). Owing to motion corruption during human fetal MRI, direct 3D imaging is often challenging.…”

“…While administering gadolinium contrast agents is contraindicated in pregnant patients, a combination of late gadolinium enhancement and cardiac cine imaging has been used to evaluate the biology of myocardial infarctions and ventricular function in preclinical fetal and postnatal sheep studies (44,45). A combination of vessel flow and magnetic resonance oximetry has also been applied in sheep to assess the distribution of blood flow and oxygen transport across the fetal circulation, and as an approach to comprehensively quantifying the placental oxygen transfer (31,(46)(47)(48)(49)(50)(51). Fetal CMR has been used in human pregnancies to study the effect of congenital cardiac malformations on fetal cardiovascular physiology, particularly through the implementation of cine phase contrast for quantifying vessel flow and relaxometry for characterizing vessel oxygen saturation and hematocrit, techniques that have also been applied in the setting of fetal growth restriction and anemia (19,25,29,33,37,38,50,(52)(53)(54)(55)(56)(57)(58)(59)(60)(61)(62)(63)(64).…”

Impact of the Addition of a Centrifugal Pump in a Preterm Miniature Pig Model of the Artificial Placenta

“…Nevertheless, it seems likely that the fetal deterioration we observed on both pumped and pumpless AP circuits was more likely to be a consequence of abnormal cardiac loading than fetal hyperglycemia. Although we observed no change in lactate between controls and animals on the AP, it should be noted that both glucose and lactate are higher in pigs than sheep fetuses (Darby et al, 2019(Darby et al, , 2021Aujla et al, 2021;Charest-Pekeski et al, 2021;Schrauben et al, 2021). Mean blood pressure in the UV is 6-8 mmHg in near-term sheep and human fetuses (Rudolph, 2009;Acharya et al, 2016).…”

“…In a subset of fetuses ( n = 11/13 successful pumped AP experiments), a small incision was made along the right side of the neck to expose the jugular vein (JV) and CA ( Darby et al, 2021 ; Schrauben et al, 2021 ). A size-matched custom-made PVC tubing was then inserted in the JV and CA for monitoring of central venous pressure (CVP) and fetal mean arterial pressure (MAP), respectively.…”