A Biomechanical-Physiological Model for Preclinical Investigation of Blast Wave TBI

In Operation Iraqi Freedom (OIF) 61% of soldiers injured in explosion blast events experienced Traumatic Brain Injury (TBI). The current incomplete understanding of TBI mechanisms limits the development of protection and therapeutic measures. Animal testing, in vitro study, and analysis of clinical data, while useful and necessary, are slow, expensive, and often inconclusive. Anatomy and physiology based mathematical modeling tools of small animal blast brain injury will provide complementary capabilities to better understand blast wave brain injury mechanisms, assess and improve protective armor, and speed development of better treatment protocols. The overall project objective is to develop and validate high-fidelity and reduced order multiscale modeling tools for the analysis of blast wave primary TBI mechanisms in animal models. In Phase I we developed a Virtual Rat anatomical model which was further advanced by generation of a Geometry/Mesh Virtual Rat model. We performed CoBi model validation using WRAIR shock tube data for the whole body rat front and side and the rat brain in direct impact and blast. We developed a rat phantom for use in Phase II. In Phase II we will develop virtual mouse and pig models and databases for high-fidelity and multiscale modeling of blast wave TBI (BW-TBI). We will adapt the CoBi tools for multiscale modeling of coupled biomechanics-physiology-neurobiology events during BW-TBI. The model will be validated using physical phantom and animal test data. We will conduct parametric simulations to understand injury mechanisms and thresholds, demonstrate rat-pig-human injury scaling, and explore methods of TBI protection.