All ETDs from UAB

Advisory Committee Chair

Jerzy P Szaflarski

Advisory Committee Members

Mark Bolding

Adam Goodman

Christianne Strang

Jarred Younger

Document Type

Dissertation

Date of Award

2023

Degree Name by School

Doctor of Philosophy (PhD) Heersink School of Medicine

Abstract

Epilepsy affects over 70 million people worldwide with a global incidence of 2.4 million new cases per year. In many of these patients, neuroinflammation (NI) is a key pathological contributor to focal seizure generation and maintenance. Sustained NI degrades the blood–brain barrier, leads to neuronal death, and ultimately decreases seizure threshold. Finding ways to image and treat NI is especially important for the >30% of patients with treatment-resistant epilepsy (TRE) who cannot achieve seizure freedom with standard antiseizure medications. Cannabidiol (CBD) effectively reduces seizure frequency and severity in many TRE patients, although its antiepileptic effects remain poorly understood. Atypically high brain temperature (>38°C) is a surrogate measure for the biochemical consequences of NI, and may be useful for studying the effects of CBD on human NI. Brain temperature can be non-invasively measured by volumetric magnetic resonance spectroscopic imaging and thermometry (MRSI-t). To date, no study has tested the reproducibility of MRSI-t or established the bounds of typical brain temperatures. Further, no study has investigated whether patients with TRE have brain temperature elevations as measured by MRSI-t, or if such abnormalities correspond to microstructural damage or resolve with targeted treatment. This dissertation uses multimodal imaging to address these gaps. Aim 1 establishes the stability of MRSI-t in healthy controls, scanned twice, ~12 weeks apart. Aim 2 measures the spatial concordance between MRSI-t brain temperature elevations and edema. Lastly, iii Aim 3 demonstrates brain temperature reductions in the ictal onset zones of patients with TRE imaged before and after CBD treatment initiation. This is the first prospective, longitudinal study to map changes in brain temperature in typical and diseased brains. Additionally, this work provides a first glimpse into how brain temperature changes after initiating CBD, thus advancing our understanding of the antiepileptic properties of CBD in humans. Together, these studies indicate MRSI-t–measured brain temperature mapping is a promising imaging-based biomarker for noninvasively visualizing NI and tracking response to CBD treatment. These findings provide a critical foundation for further research into imaging-based assessments of brain temperature and the relationship between brain temperature and NI in epilepsy.

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