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Thesis Format

Integrated Article

Degree

Doctor of Philosophy

Program

Medical Biophysics

Supervisor

Bartha, Robert

Abstract

Mild traumatic brain injury (mTBI) has become a focal point within the medical community due to its increased prevalence in recent years. Unfortunately, there is currently no neuroimaging technique able to accurately diagnose and monitor mTBI in-vivo. One technique that has shown great promise is neurite orientation dispersion and density imaging (NODDI). NODDI is a diffusion MRI (dMRI) technique used to characterize microstructural complexity through the compartmental modelling of neural water fractions into Intra-neurite, Extra-neurite and CSF volume fractions. The overreaching theme of this thesis was to validate NODDI in a preclinical setting to then be applied to imaging of early mTBI. In the first study, NODDI was shown to have high precision and repeatability both between and within subject. Furthermore, it was found that small biological changes (

Summary for Lay Audience

Mild traumatic brain injury (mTBI) has become an important public health concern as these injuries have become increasingly common in recent years. Unfortunately, there is no current medical imaging technique that allows accurate diagnosis and monitoring of mTBI. This is because many neuroimaging techniques such as computed tomography (CT) and positron emission tomography (PET) lack the specificity to identify the subtle damage present in the brains of those suffering from mTBI. Magnetic resonance imaging (MRI) is a good candidate to identify these changes due to its strong soft tissue contrast. One specific MRI technique that has shown promise in detecting subtle brain microstructural changes is neurite orientation dispersion and density imaging (NODDI). NODDI is able to quantify the density and spatial organization of various anatomical structures in the brain such as axons and dendrites and as such presents an opportunity to monitor brain health after injury. In this thesis, NODDI was first developed for use in a preclinical MRI setting. As animal models present a unique opportunity to study the extremely early stages of mTBI it was first necessary to redevelop this technique from clinical use in humans to rodent use in a preclinical MRI scanner. Once NODDI was validated for pre-clinical use it was then applied in the extremely early stages of a rodent model of mTBI. NODDI was able to detect changes in the neuronal structures of rodents within the first hour of mTBI, representing a potential opportunity to map out these changes over time. Following this successful application, NODDI was applied to a rodent model of repetitive mTBI, a model particularly relevant to sporting situations. Many athletes experience multiple mTBI’s over the course of a season and the cumulative effect of these injuries is still unknown. NODDI was able to detect extremely early changes in the brain of rodents after both a first and second mTBI. Further it was shown that some of these changes did not return to normal between the two injuries, potentially providing a window into the changes within the brain.

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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