Multi-Fidelity TBI
Abstract
This effort originates from an ARO funded, Applied Research Associates, Inc. (ARA) study to develop a proof of-concept fractal model of the cerebral microvasculature restructuring that occurs after a traumatic brain injury (TBI). ARA developed a vascular endothelial growth factor (VEGF) driven multiscale model that incorporated the diffusion of VEGF into the cerebral tissue and initiated angiogenesis. The modeled process used a reaction-diffusion model and adapted a structured morphologic bifurcating tree to calculate physiological response and induced microvascular restructuring. The model highlighted the macro and micro-scale events that occur within the two weeks following the injury. The model was compared to available data for each step: 1. The behavior of a healthy cerebral vascular system prior to a TBI 2. The release and diffusion of VEGF into the tissue after the brain injury 3. The angiogenesis and cerebral microvascular restructuring driven by the VEGF 4. The changes in cerebral blood flow due to the microvascular restructuring. The importance of continuing this research is that understanding cerebral microvasculature restructuring after a TBI can allow development of injury-specific treatments to provide better recovery opportunities for the leading cause of death and long-term disability among U.S. soldiers. Understanding the complex nature of TBI and potential treatments aligns well with ongoing military initiatives that seek to improve a soldierÕs mental and physical resilience. Recent published literature supports the idea that monitoring oxygen levels and increasing oxygenation of the brain tissue can significantly reduce patient death following a severe TBI. Our work will help the military research community understand TBI severities and begin defining guidelines for injury specific treatments. The main goals of this work include a mathematically rigorous validation of the existing models and a formal extension to the overall model fidelity to evaluate: 1. Oxygen transport and distribution along the microvascular network in the brain 2. Interaction between oxygenation of the tissue and the formation of VEGF 3. Handling of VEGF receptors responsible for angiogenesis Current models of TBI events and subsequent recovery do not connect the changes of cerebral vasculature, cell signaling and altered flow as a codependent system. A discriminator is that our work will consider micro and macro time scales, which will model short and long-term protein release/diffusion and the resulting changes to cerebral blood flow after the initial trauma. Development of a comprehensive multiscale TBI model allows for injury-specific analysis to determine possible interventions for best outcomes.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 11, 2018
- Source ID
- W911NF1710572
Entities
People
- Charles R. Fisher
Organizations
- Applied Research Associates (United States)
- Army Contracting Command
- United States Army