INTELLECTUAL MERIT: The aim of this research is to develop cardiovascular fluid mechanics tools that can analyze and predict the 3D vascular changes due to the growth and remodeling process (GR) during early embryonic cardiac development. Mechanical flow-induced loading, in addition to the genetic factors, is an essential regulator of this GR feedback process. Fluid-induced vascular 3D changes will be computed through transformative aims at the system and at the organ levels; that are coupled to the lower-level GR theories. At the system level, the rich diversity of circulation systems found in nature inspired a novel reduced-order lumped parameter circulation model (LPM). For the first-time, LPM is integrated with multi-scale continuum mechanics vascular GR theories in order to establish a numerical feed-back loop between the GR response and instantaneous hemodynamic circuit parameters. A general network-based LPM model is proposed, again for the first time that covers the entire hydrodynamic network space where the numbers of vascular compartments, ventricles and their branching patterns evolve freely, but are subject to the cost functions founded on the biological optimality principles. Formal engineering optimization routines and novel circuit similitude parameters that allow an unbiased energetic comparison will be developed to realize this aim. This framework will provide the global GR response of the entire circulation during development, energy/exergy budgets of complex congenital heart disease pathologies, and impact pediatric surgical treatments. At the organ level, integrated with a high-resolution in-house 3D immersed boundary computational fluid dynamics (CFD) solver, an innovative optimization based arterial GR paradigm that eliminates the need for commonly employed growth rate laws or micro-structurally motivated phenomenological models is proposed. A fully automated shape-optimizer, geometry parameterization and dedicated moving boundary Cartesian meshing will be achieved through a unique interdisciplinary engineering collaboration. The tools developed will also transform the broader patient-specific CFD technology, which is currently used in clinical decision making, by addressing the dynamic 3D morphologies and facilitating simulations at multiple biological time-points predicting the acute tissue response.
BROADER IMPACT: The educational component of this project seeks to convey the fascinating biomechanics of embryonic vascular development, biomedical engineering and the distinctive science of hemodynamics at all levels from pre-kindergarden through graduate school by providing excellent training and enrichment opportunities. A widespread high-impact outreach program is proposed: (1) Integrate all proposed research objectives to the institutional undergraduate and graduate teaching program. (2) Transform the teaching and research laboratory culture so that student teams are encouraged and supported in designing and executing innovative outreach activities themselves as part of their regular graduate or undergraduate program. (3) Train in-service and pre-service science teachers through biomedical engineering workshops and at Research Seminar courses collaborating with Leonard Gelfand Center for Service Learning and Outreach at Carnegie Mellon University and School of Education at University of Pittsburgh, respectively. (4) Within the framework of Carnegie Mellon Institute for Talented Elementary and Secondary Students Program (C-MITES), develop novel hands-on, interactive activities about cardiovascular fluid dynamics and bio-inspired engineering. (5) Collaborate with the regional early-education centers and organize pedagogical activities in the form of scientific games and attract scientific curiosity as early as possible particularly for girls and minorities. (6) Develop long-term contacts at regional museums and share ongoing research achievements by participating actively in their community events. Finally, the engineering aims of this project will have an important impact on the pediatric and fetal cardiology, and cardiovascular surgery by giving researchers access to quantitative physiological information from which new discoveries and biomedical applications will materialize. Embryonic cardiovascular fluid dynamics is an emerging research field that challenges the human-centric bias and apathetic viewpoint of the static mature and healthy cardiovascular system at all educational levels.
