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UBC Theses and Dissertations

Structural and functional imaging of tauopathies Smith-Forrester, Jenna Rae

Abstract

Repetitive head trauma is a known cause of tau protein accumulation and the leading cause of chronic traumatic encephalopathy (CTE). Currently, no robust method for in vivo detection of CTE exists and definitive diagnosis can only be made post-mortem. This thesis aimed to address two gaps in the literature surrounding head injury and tau accumulation. First, we sought to evaluate the effects of concussion on adolescent brain structure using mathematical modeling applied to diffusion tensor imaging (DTI). In our study, 12 adolescent athletes completed DTI in the sub-acute phase of recovery from concussion. The primary outcome measures included Complex Network Analysis metrics related to efficiency, nodal clustering, and fibre tract length. These measures were applied to diffusivity output (FA, MD, and number of tracts) in subnetworks of vulnerability, with specific focus on the Default Mode Network (DMN). Here we found microstructural changes in the DMN of concussed athletes with increased clustering and shorter path lengths, indicating increased local efficiency. A corresponding decrease in global efficiency and alterations in core hubs may underlie the clinical profile, suggesting concussion results in large-scale network disconnection. Longitudinal studies with network analysis may serve as a marker of collective injury and provide early detection of pathological structural organization. Second, we established the baseline measures of a novel positron emission tomography (PET) radioligand, ¹¹C-PBB3, which is specific for hyperphosphorylated tau protein. We collected data on healthy, elderly individuals (n = 8), and tested the tracer in a probable (n = 1) and severe (n = 1) case of Progressive Supranuclear Palsy (PSP), a known tauopathy. We found that tracer circulated in the venous sinuses in our healthy controls with little to no deposition in brain tissue. We also present preliminary findings of tracer accumulation in the basal ganglia and thalamus in the PSP cases. These results suggest ¹¹C-PBB3 is a viable tracer for use in other tauopathies, including CTE. Longitudinal studies with combined DTI and PET are necessary to elucidate the potentially synergistic interactions between damage to white matter tracts, tau accumulation, inflammation, and the initiation of processes leading to CTE and other tauopathies.

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Attribution-NonCommercial-NoDerivs 2.5 Canada

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