18F-FDG PET-guided diffusion tractography reveals white matter abnormalities around the epileptic focus in medically refractory epilepsy: implications for epilepsy surgical evaluation

Stefan E Poirier,Lina Samargandy,Jorge G Burneo,David A Steven,Michael T Jurkiewicz,Jonathan Romsa,Udunna C Anazodo,Victor Lam Shin Cheung,Benjamin Y M Kwan,Jonathan D Thiessen,Frank S Prato,Ana Suller-Marti,Ali R Khan

doi:10.1186/s41824-020-00079-7

Abstract

BackgroundHybrid PET/MRI can non-invasively improve localization and delineation of the epileptic focus (EF) prior to surgical resection in medically refractory epilepsy (MRE), especially when MRI is negative or equivocal. In this study, we developed a PET-guided diffusion tractography (PET/DTI) approach combining 18F-fluorodeoxyglucose PET (FDG-PET) and diffusion MRI to investigate white matter (WM) integrity in MRI-negative MRE patients and its potential impact on epilepsy surgical planning.MethodsFDG-PET and diffusion MRI of 14 MRI-negative or equivocal MRE patients were used to retrospectively pilot the PET/DTI approach. We used asymmetry index (AI) mapping of FDG-PET to detect the EF as brain areas showing the largest decrease in FDG uptake between hemispheres. Seed-based WM fiber tracking was performed on DTI images with a seed location in WM 3 mm from the 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 evaluated by a senior neurologist.ResultsIn over 60% of the patient cohort, AI mapping findings were concordant with clinical reports on seizure-onset localization and lateralization. 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 that surgical candidacy be reassessed in 3/6 (50%) patients who had not undergone surgery.ConclusionsWe demonstrate here the utility of AI mapping in detecting the EF based on brain regions showing decreased FDG-PET activity and, when coupled with DTI, could be a powerful tool for detecting EF and assessing WM integrity in MRI-negative epilepsy. PET/DTI could be used to further enhance clinical decision-making in epilepsy surgery.

Highlights

Refractory epilepsy (MRE) affects approximately 30% of epilepsy patients and is defined as a chronic neurological disorder where seizures persist despite administration of anti-epileptic drugs (AEDs) (Helmstaedter et al 2003; Richardson et al 2004; Jiang et al 2017)
We demonstrate here the utility of asymmetry index (AI) mapping in detecting the epileptic focus (EF) based on brain regions showing decreased FDG-positron emission tomography (PET) activity and, when coupled with diffusion tensor imaging (DTI), could be a powerful tool for detecting EF and assessing white matter (WM) integrity in MRInegative epilepsy
AI mapping of fluorodeoxyglucose PET (FDG-PET) for EF localization and lateralization in medically refractory epilepsy (MRE) AI mapping was used to detect the EF based on regions showing significant metabolic asymmetry between hemispheres in the brain

Summary

Introduction

Refractory epilepsy (MRE) affects approximately 30% of epilepsy patients and is defined as a chronic neurological disorder where seizures persist despite administration of anti-epileptic drugs (AEDs) (Helmstaedter et al 2003; Richardson et al 2004; Jiang et al 2017). In some MRE patients, surgical resection of the epileptic focus (EF)— the brain region responsible for seizures—can alleviate seizure occurrence and improve overall quality of life (Richardson et al 2004; Caciagli et al 2014; Cahill et al 2019). Positive surgical outcomes are highly dependent on accurate identification of the EF to ensure the epileptic region is safely removed without harming surrounding healthy brain tissue (Bettus et al 2009). Hybrid PET/MRI can non-invasively improve localization and delineation of the epileptic focus (EF) prior to surgical resection in medically refractory epilepsy (MRE), especially when MRI is negative or equivocal. We developed a PET-guided diffusion tractography (PET/DTI) approach combining 18F-fluorodeoxyglucose PET (FDG-PET) and diffusion MRI to investigate white matter (WM) integrity in MRI-negative MRE patients and its potential impact on epilepsy surgical planning

Methods

Results

Conclusion