Abstract

BackgroundPET imaging has been widely used in diagnosis of neurological disorders; however, its application to pediatric population is limited due to lacking pediatric age–specific PET template. This study aims to develop a pediatric age–specific PET template (PAPT) and conduct a pilot study of epileptogenic focus localization in pediatric epilepsy.MethodsWe recruited 130 pediatric patients with epilepsy and 102 age-matched controls who underwent 18F-FDG PET examination. High-resolution PAPT was developed by an iterative nonlinear registration-averaging optimization approach for two age ranges: 6–10 years (n = 17) and 11–18 years (n = 50), respectively. Spatial normalization to the PAPT was evaluated by registration similarities of 35 validation controls, followed by estimation of potential registration biases. In a pilot study, epileptogenic focus was localized by PAPT-based voxel-wise statistical analysis, compared with multi-disciplinary team (MDT) diagnosis, and validated by follow-up of patients who underwent epilepsy surgery. Furthermore, epileptogenic focus localization results were compared among three templates (PAPT, conventional adult template, and a previously reported pediatric linear template).ResultsSpatial normalization to the PAPT significantly improved registration similarities (P < 0.001), and nearly eliminated regions of potential biases (< 2% of whole brain volume). The PAPT-based epileptogenic focus localization achieved a substantial agreement with MDT diagnosis (Kappa = 0.757), significantly outperforming localization based on the adult template (Kappa = 0.496) and linear template (Kappa = 0.569) (P < 0.05). The PAPT-based localization achieved the highest detection rate (89.2%) and accuracy (80.0%). In postsurgical seizure-free patients (n = 40), the PAPT-based localization also achieved a substantial agreement with resection areas (Kappa = 0.743), and the highest detection rate (95%) and accuracy (80.0%).ConclusionThe PAPT can significantly improve spatial normalization and epileptogenic focus localization in pediatric epilepsy. Future pediatric neuroimaging studies can also benefit from the unbiased spatial normalization by PAPT.Trial registration.NCT04725162: https://clinicaltrials.gov/ct2/show/NCT04725162

Highlights

  • Positron emission tomography (PET) imaging provides an in-depth evaluation of physiological and pathological processes of in vivo brains and has been widely used in the investigation of neurological disorders [1, 2]

  • We developed a novel age-specific 18F-FDG PET template to improve diagnosis of pediatric PET imaging and evaluate its efficiency in pediatric epilepsy

  • To the best of our knowledge, the PAPT we developed is the first pediatric age–specific PET template created by nonlinear methods

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Summary

Introduction

Positron emission tomography (PET) imaging provides an in-depth evaluation of physiological and pathological processes of in vivo brains and has been widely used in the investigation of neurological disorders [1, 2]. Many magnetic resonance imaging (MRI) studies developed pediatric age–specific MRI templates, which can significantly improve spatial normalization, morphological analysis, and clinical diagnosis [10,11,12]. Age ranges were not well matched between MRI template and PET data in the previous study, which may introduce systematic biases to spatial normalization due to rapid brain development during childhood [11, 12]. This study aims to develop a pediatric age–specific PET template (PAPT) and conduct a pilot study of epileptogenic focus localization in pediatric epilepsy. Epileptogenic focus was localized by PAPT-based voxel-wise statistical analysis, compared with multi-disciplinary team (MDT) diagnosis, and validated by follow-up of patients who underwent epilepsy surgery.

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