A Computational Model of the Fetal Circulation to Quantify Blood Redistribution in Intrauterine Growth Restriction

Abstract

Intrauterine growth restriction (IUGR) due to placental insufficiency is associated with blood flow redistribution in order to maintain delivery of oxygenated blood to the brain. Given that, in the fetus the aortic isthmus (AoI) is a key arterial connection between the cerebral and placental circulations, quantifying AoI blood flow has been proposed to assess this brain sparing effect in clinical practice. While numerous clinical studies have studied this parameter, fundamental understanding of its determinant factors and its quantitative relation with other aspects of haemodynamic remodeling has been limited. Computational models of the cardiovascular circulation have been proposed for exactly this purpose since they allow both for studying the contributions from isolated parameters as well as estimating properties that cannot be directly assessed from clinical measurements. Therefore, a computational model of the fetal circulation was developed, including the key elements related to fetal blood redistribution and using measured cardiac outflow profiles to allow personalization. The model was first calibrated using patient-specific Doppler data from a healthy fetus. Next, in order to understand the contributions of the main parameters determining blood redistribution, AoI and middle cerebral artery (MCA) flow changes were studied by variation of cerebral and peripheral-placental resistances. Finally, to study how this affects an individual fetus, the model was fitted to three IUGR cases with different degrees of severity. In conclusion, the proposed computational model provides a good approximation to assess blood flow changes in the fetal circulation. The results support that while MCA flow is mainly determined by a fall in brain resistance, the AoI is influenced by a balance between increased peripheral-placental and decreased cerebral resistances. Personalizing the model allows for quantifying the balance between cerebral and peripheral-placental remodeling, thus providing potentially novel information to aid clinical follow up.

The Aortic Isthmus: A Significant yet Underexplored Watershed of the Fetal Circulation

“…In a fetal sheep model with stepwise compression of umbilical veins, as well as in a computer-based fetal circulation model, the appearance of net retrograde flow in the AoI physiologically demonstrates cerebral hypoxia despite local vasodilation and preservation of cerebral blood flow. This is due to poorly oxygenated preplacental blood coming from the RV contaminating the ascending aortic blood (coming from the LV) destined for the brain, resulting in a reduction in mean oxygen tension in the cerebral vascular bed [52,53,54,55]. Additionally, these fetuses cannot shift their RV CO from the pulmonary circulation through the foramen ovale.…”

Assessment of Haemodynamic Remodeling in Fetal Aortic Coarctation Using a Lumped Model of the Circulation

“…All the data were obtained from the same control fetus as used to validate the model described in [8].…”

“…Still, these measurements have low sensitivity and specificity [6,7]. On the other hand, patient-specific lumped models of the fetal circulation have shown to be a great approach to understand the underlying mechanisms of fetal hemodynamics, both under healthy and pathological conditions, such as shown in Garcia-Canadilla et al [8,9]. Thereby, our purpose is to re-implement the fetal circulation model proposed in [9] in CellML using OpenCOR, an open-source cross-platform modelling environment [10], which favors model reuse amongst researchers.…”

Simulation and Analysis of Umbilical Blood Flow using Markov-based Mathematical Model

“…Hence, the use of a mathematical model is very helpful in the assessment of fetal well-being. Computational studies based on mathematical models of fetal cardiovascular blood flow redistribution [28,29] are already present. Some are based on fetal lamb circulation [30].…”