Multiscale Modelling of Blast-Induced TBI Mechanobiology - From Body to Neuron to Molecule

Raj K. Gupta; X. Gary Tan; Mahadevabharath R. Somayaji; Andrzej J. Przekwas

doi:10.14429/dlsj.2.10369

Raj K. Gupta US Army Medical Research and Materiel Command, Fort Detrick - 217 02
X. Gary Tan CFD Research Corporation, 701 McMillian Way NW, Huntsville - 35 806
Mahadevabharath R. Somayaji CFD Research Corporation, 701 McMillian Way NW, Huntsville - 35 806
Andrzej J. Przekwas CFD Research Corporation, 701 McMillian Way NW, Huntsville - 35 806

DOI: https://doi.org/10.14429/dlsj.2.10369

Keywords: Blast wave, Mechanobiology military medicine, Multiscale modelling, Traumatic brain injury

Abstract

Blast induced Traumatic Brain Injury (bTBI) has become a signature wound of the recent military operations and is becoming a significant factor of recent civilian blast explosion events. In spite of significant clinical and preclinical research on TBI, current understanding of injury mechanisms is limited and little is known about the short and long-term outcomes. Mathematical models of bTBI may provide capabilities to study brain injury mechanisms, perhaps accelerating the development of neuroprotective strategies and aiding in the development of improved personal protective equipment. The paper presents a novel multiscale simulation framework that couples the body/brain scale biomechanics with micro-scale mechanobiology to study the effects of “primary” micro-damage to neuro-axonal structures with the “secondary” injury and repair mechanisms. Our results show that oligodendrocyte myelinating processes distribute strains among neighbor axons and cause their off-axis deformations. Similar effects have been observed at the finer scale for the Tau-Microtubule interaction. The paper also discusses the need for coupled modeling of primary injury biomechanics, secondary injury mechanobiology and model based assessment of injury severity scores. A new integrated computational and experimental approach is described coupling micro-scale injury criteria for the primary micro-mechanical damage to brain tissue/cells as well as to investigate various secondary injury mechanisms.

Author Biographies

Raj K. Gupta, US Army Medical Research and Materiel Command, Fort Detrick - 217 02

Dr Raj K. Gupta PhD from Washington State University, Pullman, Washington. Working as a Deputy Director and Senior Science Advisor of the DoD Blast Injury Research Program Coordinating Office at the US Army Medical Research and Materiel Command (USAMRMC), Fort Detrick, Maryland. He is Level III certified as a systems planning, research, development & engineering – Science and technology manager.

X. Gary Tan, CFD Research Corporation, 701 McMillian Way NW, Huntsville - 35 806

Dr. X. Gary Tan is the Mechanical Engineer at the U.S. Naval Research Laboratory. Until 2015 he was the Technical Fellow at the CFD Research Corporation. His research is focused on the computational mechanics and development of methods for multi-physics systems. The solid-shell element he developed was adopted in CFD-ACE+ and ABAQUS. He is a primary developer of multi-physics solver CoBi. He was the principal investigator on projects related toblast-induced human body and brain injury.

Mahadevabharath R. Somayaji, CFD Research Corporation, 701 McMillian Way NW, Huntsville - 35 806

Dr Mahadevabharath R. Somayaji received his PhD in Chemical Engineeringfrom University of Illinois at Chicago, MTech (Chemical Engineering) from Anna University, India and BTech (Chemical Engineering) from University of Madras, India. Currently works as a Manager in the Computational Medicine and Biology division at CFD Research Corporation. His research interests include multiscale modelling of chemical and biological systems, disease biophysics, microphysiological systems, computational physiology and pharmacology for personalised medicine. He has disseminated his research outcomes in peer-reviewed journals and conferences.

Andrzej J. Przekwas, CFD Research Corporation, 701 McMillian Way NW, Huntsville - 35 806

Dr Andrzej Przekwas, CTO and Sr. Vice President for Research obtained his PhD from Wroclaw Institute of Technology, Poland, and Post Doc from the Imperial College of Science and Technology, University of London, England. At present he is heading the Computational Medicine and Biology Division at CFDRC working on the development of computational multiphysics tools, CoBi, for modelling human physiology, biomechanics and injury. The main focus is on the military medicine applications such as traumatic brain injury, pilot biomechanics-physiology responses in extreme conditions, and optimisation of soldier’s performance. He has been the PI on several projects with DARPA, US Army, Air Force, Navy, NASA, NIH, and CDC.