A multiscale computational platform in the design of a geometrically tunable blood shunt

Ellen Elizabeth Garven

doi:10.17918/00001877

Single ventricle malformations are a severe form of congenital heart defect in which one of the two normal ventricles of the heart is missing or malformed. Infants born with single ventricle defects require cardiac surgery shortly after birth as these defects are fatal without immediate intervention. In the first of several staged palliative surgeries, the Norwood procedure establishes a circulation that delivers blood to both the lungs and the body with a single functional ventricle. This is achieved through the implantation of an artificial graft called a shunt, which redirects a portion of the blood flow from the aortic arch and into the pulmonary artery. The shunt remains in place for approximately four to six months before the next surgical stage. The Norwood procedure is the riskiest stage of the single ventricle palliation plan, and the risk associated with it extends throughout the period that the shunt remains in place. Despite advances in the field and in overall patient care, the Norwood procedure remains challenging and is associated with elevated rates of morbidity and mortality. With the placement of the shunt, the Norwood results in a mixture of oxygenated and deoxygenated blood in the ventricle. This configuration is suitable to sustain the patient given that the mixture is properly balanced, with adequate blood saturation and sufficient body perfusion. Maintaining this balance is critical, but is highly dependent on the conditions within the shunt because it solely supplies all of the blood flow to the lungs. An excess in volume of either systemic or pulmonary flow would put the patient at risk for hypoxia. Thus, the clinical stability of the Norwood patient depends on a delicate balance within the shunt. The task of maintaining sufficient blood oxygenation is further complicated by the duration of the interstage period. During the four to six months that the shunt remains in place, the infant should experience a significant period of growth and development. It is expected that the infant will gain weight and grow during this time, increasing their body surface area, oxygen consumption, and cardiac output. Other growth-related changes or adaptations to the univentricular circulation may alter the size, shape, and tone of various vessels and cardiac structures. These factors all have an impact on the hemodynamics and thus all have the potential to alter the blood oxygenation balance. Given the numerous physiological changes that occur in the first few months of infancy, a fixed diameter shunt theoretically cannot maintain adequate blood oxygenation and stable hemodynamics across the entire period. Motivated by this idea in the context of the clinical challenges, the BioCirc Laboratory at Drexel University and its collaborators have begun investigation into the design of a geometrically tunable blood shunt. This shunt would address the limitations of the current clinical design with an inner lumen diameter that could be adjusted over the duration of use. The inner diameter would be customized by modulating the cross-linking density of a hydrogel coating along the interior wall of the shunt, thereby altering the effective internal resistance of the shunt. This diameter changing mechanism is a novel methodology to adjust the ratio of blood oxygenation in a Norwood patient. The first phases of research have established the design concept and efforts are ongoing in the developmental process. In this study, we sought to characterize how the inner lumen of the shunt should change over time in a Norwood patient. To accomplish that goal, computational models of blood flow were used to simulate the hemodynamics within the system. First, we developed a multiscale modeling methodology that would capture all of the relevant variables surrounding the shunt, using a computational fluid dynamics model coupled to a lumped parameter model. The methodology was verified by recreating the conditions and results of a patient-specific model that was published previously. The hemodynamic conditions were then characterized under the existing shunt design. Using patient-specific data, multiscale models were created that represented two points in time spanning the period between the Norwood and the next surgical stage. The resulting set of models captured growth related changes to the geometric and hemodynamic conditions within the patient. This process was repeated with an additional patient. While the Norwood has been studied extensively using computational models, our simulations are among the first to study the Norwood at multiple timepoints and the results provided hemodynamic insights about a clinically complicated period. Finally, the models of growth-related changes across the Norwood duration were leveraged to simulate the tunable shunt with the goal of maintaining reasonable hemodynamics. The diameters of the tunable shunt that positively impacted the hemodynamic balance were identified through iterative simulations. By comparing the identified diameters between timepoints, we established how the tunable shunt diameter would ideally change over time. In both patient-specific models, a diameter change of 12 - 13% was found to rebalance the Q_P/Q_S between timepoints. While this percentage was lower than our previous estimates, a comparison of the two patient models also demonstrated a significant variety of hemodynamic conditions at the first timepoint. While the shunt may not need to change significantly over time in a single patient, the shunt would need to be adaptable to a broad range of possible conditions that necessitates a wide range of possible diameters. This work established a computational platform of the Norwood across the interstage period in two patient-specific models. Given the heterogeneity in the Norwood patient population, the contrast in these models was used to study the tunable shunt in a range of clinical conditions and will help ensure a robust design. The results quantified how the inner lumen of the tunable shunt should adjust in geometry in order to better maintain the hemodynamic balance in a model of growth-related changes. With the ratio of flow through the shunt maintained at a specified level, the tunable shunt design should allow for sufficient blood oxygenation across infancy. Beyond the current research goals, the computational platform that was created will continue to serve as a valuable resource for future design and development investigations.

A multiscale computational platform in the design of a geometrically tunable blood shunt

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A multiscale computational platform in the design of a geometrically tunable blood shunt

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