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.