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Exploring Hippocampal Microstructural Differences in Temporal Lobe Epilepsy at an Ultra-High Field MRI

Abstract

Epilepsy affects over 51 million people worldwide, presenting debilitating symptoms, such as recurring seizures and cognitive deficits, that may significantly impact patients’ quality of life. Temporal Lobe Epilepsy (TLE) is the most common form of drug-resistant adult epilepsy and poses a challenge for treatment because patients are MRI-negative in about 30% of all clinical cases. TLE is often associated with hippocampal microstructural abnormalities that may not be visible on conventional MRI due to its limited spatial resolution and tissue contrast. Diffusion MRI (dMRI) provides a non-invasive method for probing tissue microstructure; however, standard diffusion tensor metrics are limited in their sensitivity to fibre orientation and extracellular free-water contamination. In this thesis, we applied microscopic fractional anisotropy (µFA) with a free-water elimination (FWE) technique to improve the characterization of hippocampal subfield-specific differences between 33 TLE patients and 22 healthy controls using ultra-high-field 7T dMRI. We observe subfield-specific hippocampal reductions in µFA that depend on the lateralization of the seizure onset, suggesting disruption of tissue microstructure beyond volumetric loss. These observed microstructural patterns align with histopathological evidence of axonal degeneration and neuronal loss, supporting µFA as a promising non-invasive biomarker for presurgical evaluation. Additionally, FWE may provide complementary information to conventional diffusion metrics to improve the detection and characterization of hippocampal abnormalities in epilepsy.

Summary for Lay Audience

Epilepsy affects more than 51 million people worldwide and can greatly reduce quality of life through recurring seizures and difficulties with memory and thinking. Temporal Lobe Epilepsy (TLE) is the most common form of epilepsy that does not respond to medication in adults. Although brain imaging is critical for guiding surgical treatments, standard MRI scans appear normal in about one-third of all cases, complicating the identification of abnormal brain regions responsible for seizure generation. Many of these changes are thought to occur in the hippocampus, a region in the brain, but they are often too subtle to be detected with conventional imaging. Using diffusion MRI (dMRI), a method that tracks the random motion of water molecules within the brain, we examined the microstructural anatomy of the hippocampus in patients with TLE and conducted comparisons with healthy individuals. These techniques allowed us to detect subtle changes in specific hippocampal regions that differed depending on which side of the brain the seizures originated from. Overall, this work demonstrates that advanced dMRI techniques may improve the detection of subtle brain abnormalities in TLE and have the potential to support better surgical planning for patients.

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Keywords

Hippocampus, Temporal Lobe Epilepsy, Diffusion MRI, Epilepsy, MRI, Free Water Elimination, Microstructural Abnormalities

DOI

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