Document Type

Dissertation

Date of Award

8-31-2020

Degree Name

Doctor of Philosophy in Biomedical Engineering - (Ph.D.)

Department

Biomedical Engineering

First Advisor

N. Chandra

Second Advisor

Bryan J. Pfister

Third Advisor

Joshua R. Berlin

Fourth Advisor

Kevin Pang

Fifth Advisor

Saikat Pal

Sixth Advisor

Maciej Skotak

Abstract

Blast-induced traumatic brain injury (bTBI) has become one of the leading injury modalities in military personnel and is considered a signature injury in veterans returning from conflicts in the Middle East. One of the main concerns in studying bTBI is translating animal experiments to clinical applications that can service veterans. Significant advances have been made using animal models in relating external shock waves to emerging neuropathophysiological and behavioral outcomes. However, it is unknown if these results are applicable to humans; and if so, can an interspecies transfer function be developed based on size, shape, and material response. This work aims to focus on relating mechanical loading (insults) between animals and humans, with the assumption that similar insults, at the tissue level, result in similar injuries. To this end, it is hypothesized that biomechanical transfer functions can be derived using a comparison of tissue level loading between live rodents, postmortem rodents, and human surrogates, based on the consideration of interspecies differences in size, material properties, and skull thickness. To accomplish this, a field validated compressed-gas driven shock tube is used to expose increasingly complex surrogates. Beginning with simple geometry surrogates, the effect of specimen size, window thickness, and material on surface loading and internal loading is investigated. Next, surrogates are developed to match the geometry of murine models and the effects of material properties on intracranial loading were elucidated. Finally, postmortem surrogates are prepared for murine and human head forms and used to investigate interspecies loading differences.

Simple geometry studies are conducted using plates of various cross-sectional areas and materials to investigate their effects on loading at three discrete incident overpressures, selected specifically based on rodent survival dose-response curves. Combined with numerical simulations, results offer insight into how surface loading varies with size and material. In three-dimensional studies, boxes were constructed and filled with previously studied brain simulants. These studies allow for the investigation of material thickness and brain simulant on both surface and internal shock loading. Results show that thicker materials offer improved protection and that 20% porcine gelatin is a potential brain simulant, based on the biomechanical performance.

Furthermore, potential brain and skin simulants are assessed by comparing intracranial pressure and skull strain between increasingly complex murine surrogates and live rats. By using geometrically similar surrogates and only altering materials, results elucidate how shock waves load biological structures on the surface and interior.

The study of postmortem surrogates allows for comparison of interspecies differences on insults. The use of similar external loading conditions allows for one-to-one comparisons between the two species. Using multiple linear regression, biomechanical transfer functions for intracranial pressure and impulse are derived based on specimen skull thickness, as well as, incident shock parameters. Based on these functions, the combination of skull thickness and incident loading parameters predict tissue independent of species. Thus, the transfer function developed in this thesis between animal models and humans, under primary blast loading conditions based on experimental data, can be used to apply animal results to humans as a good first step.

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