Electronic Thesis and Dissertation Repository

Thesis Format

Integrated Article

Degree

Master of Science

Program

Medical Biophysics

Supervisor

Anazodo, Udunna C.

Affiliation

Lawson Health Research Institute

2nd Supervisor

Thiessen, Jonathan D.

Affiliation

Lawson Health Research Institute

Co-Supervisor

Abstract

Hybrid PET/MRI can non-invasively improve epileptic focus (EF) localization prior to surgical resection in drug-resistant epilepsy (DRE), especially when MRI is negative. In this thesis, we developed an 18F-fluorodeoxyglucose (FDG) PET-guided diffusion tractography (PET/DTI) approach to assess white matter (WM) integrity in MRI-negative DRE and evaluated its potential impact on epilepsy surgical planning. To validate the potential of PET/MRI, we first evaluated the diagnostic competence of PET/MRI in DRE and found that PET/MRI provides similar diagnostic information as PET/CT (current clinical standard). For the PET/DTI approach, we used asymmetry index (AI) mapping of FDG-PET to guide WM fiber tractography around glucose hypometabolic brain regions (potential EF). Fiber tractography was repeated in the contralateral brain region (opposite to EF), which served as a control for this study. WM fibers were quantified by calculating the fiber count, mean fractional anisotropy (FA), mean fiber length, and mean cross-section of each fiber bundle. WM integrity was assessed through fiber visualization and by normalizing ipsilateral fiber measurements to contralateral fiber measurements. The added value of PET/DTI in clinical decision-making was assessed by an experienced epileptologist. In over 60% of the patient cohort (n = 14), AI mapping findings were concordant with clinical reports on seizure-onset zone. Mean FA, fiber count, and mean fiber length were decreased in 14/14 (100%), 13/14 (93%), and 12/14 (86%) patients, respectively. PET/DTI improved diagnostic confidence in 10/14 (71%) patients and indicated surgical candidacy be reassessed in 3/6 (50%) patients who had not undergone surgery. FDG-PET coupled with diffusion tractography can be a powerful tool for detecting EF and assessing WM integrity around EF in MRI-negative epilepsy. PET/DTI could further enhance clinical decision-making in epilepsy surgery.

Summary for Lay Audience

Drug-resistant epilepsy (DRE) is a serious neurological condition affecting approximately one in three epilepsy patients. Surgical resection of the seizure-onset zone in the brain can alleviate seizure occurrence and improve quality of life. However, about 50% of DRE patients continue to have seizures after surgery. Poor surgical outcomes can occur when the seizure-onset zone and its relationships with surrounding brain regions are not properly characterized. Furthermore, absence of a clear structural lesion in the brain can further decrease a patient’s chances of achieving long-term seizure freedom after surgery. Recent advances in medical imaging have seen the increased use of MRI and PET to non-invasively map out brain structure and function in epilepsy. Specifically, multimodal brain imaging combining PET and MRI (hybrid PET/MRI) can improve detection of the seizure-onset zone prior to surgical resection and could potentially improve surgical outcomes, especially in MRI-negative epilepsy. In this thesis, we developed a hybrid PET/MRI approach combining PET and diffusion tractography to non-invasively assess structural integrity around seizure-onset zones in MRI-negative DRE and then evaluated the potential clinical impact of this PET/MRI approach on epilepsy surgical planning. To validate the potential of PET/MRI, we first assessed the diagnostic competence of PET/MRI in DRE and found that PET/MRI provides similar diagnostic information as PET/CT (current clinical standard). For the PET/MRI approach, we used PET to detect seizure foci as brain regions showing decreased PET activity and then used diffusion tractography to assess structural integrity around seizure foci. The added value of the PET/MRI approach in guiding clinical decision-making was evaluated by a senior neurologist. Our PET/MRI approach revealed structural alterations around seizure foci and improved diagnostic confidence in the majority of our DRE patient cohort. Furthermore, the PET/MRI approach indicated surgical candidacy be reassessed in some patients who had not undergone surgery. PET/MRI can be a powerful tool for detecting seizure foci and assessing structural integrity around seizure foci in DRE. Our hybrid PET/MRI approach could be used to further enhance clinical decision-making in epilepsy surgery.

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