Intracranial Strain in Mild Traumatic Head Injury

Washington University, Saint Louis MO

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Abstract

DESCRIPTION (provided by applicant): The goal of this project is to develop the technology needed to measure deformation and strain fields in the brain of the mouse or rat during mild traumatic closed-head injury. The project addresses the need for information on neuronal strain in closed-head trauma and its relationship to subsequent injury and impairment. The technology will be applied to the immature rat; it also is applicable to the mouse and mature rat. Our long-term objectives are to: (1) determine the strain fields within the brain that result from impacts or skull accelerations; (2) characterize the response of the intact brain to high strains. Measurement of brain deformation will increase our understanding of brain injury and will advance trauma therapy and prevention. Injury and degeneration can be studied with respect to the fundamental parameter: strain. Results for the immature rat are relevant to brain injury in young children. Specific aims are: AIM 1: Develop instrumentation and MR tagging procedures to obtain images of deformation in the immature rat brain during mild head injury: An MR-compatible system to deliver calibrated impacts will be developed. MR images of deformed tag lines in the brain of a prone, anesthetized, immature rat will be acquired during delivery of light, sub-concussive impacts to the head. Impact energy and velocity will be prescribed within a range based on prior published studies and on pilot studies using euthanized animals. Motion will be repeated to acquire resolved images of the deformed tag lines. The imaging procedure will be directly analogous to that used in cardiac MRI cine studies in the rat and mouse heart. In vivo studies will provide fundamental data on brain deformation in this trauma model. AIM 2: Develop software to estimate strain fields, quantify strain, and compare to overall levels of neuronal degeneration. Software developed for analysis of cardiac strain will be adapted to compute strain fields in the brain and to characterize strain as a function of location and impact characteristics (amplitude, duration). Histopathological studies will be performed post-trauma in rats that receive multiple light impacts during imaging, and in rats receiving a single larger impact, to determine total neuronal degeneration. Hypotheses: Strain will increase predictably with impact energy. In both groups, total neuronal degeneration is expected to increase with peak strain and the area of high strain in a manner characterized by sigmoid "dose-response" curves. This is an inter-disciplinary project involving impact mechanics, MR tagging, histopathology, and brain injury.