High-resolution pediatric age-specific 18F-FDG PET template: a pilot study in epileptogenic focus localization

Teng Zhang, Yuting Li, Shuilin Zhao, Yuanfan Xu, Xiaohui Zhang, Shuang Wu, Xiaofeng Dou, Congcong Yu, Jianhua Feng, Yao Ding, Junming Zhu, Zexin Chen, Hong Zhang, Mei Tian, Teng Zhang, Yuting Li, Shuilin Zhao, Yuanfan Xu, Xiaohui Zhang, Shuang Wu, Xiaofeng Dou, Congcong Yu, Jianhua Feng, Yao Ding, Junming Zhu, Zexin Chen, Hong Zhang, Mei Tian

Abstract

Background: PET 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.

Methods: We 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).

Results: Spatial 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%).

Conclusion: The 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://ichgcp.net/clinical-trials-registry/NCT04725162.

Keywords: Epilepsy; Pediatric age–specific; Positron emission tomography (PET); Template.

Conflict of interest statement

The authors declare no competing interests.

© 2021. The Author(s).

Figures

Fig. 1
Fig. 1
Flowchart of iterative registration-averaging optimization. This optimization approach iterated between registration and averaging steps to create unbiased brain template
Fig. 2
Fig. 2
Comparison of PET templates. A 6–10 years PAPT; B 11–18 years PAPT; C pediatric linear template; D adult PET template. Arrows point blurred cortical structures in linear and adult templates
Fig. 3
Fig. 3
Comparison of spatial normalization. A, B Registration similarities and global transformation for the 6–10 years group, respectively; C, D 11–18 years group
Fig. 4
Fig. 4
Regions of potential registration bias in spatial normalization. A 6–10 years group; B 11–18 years group
Fig. 5
Fig. 5
Localization results of patients whose foci were missed by routine visual assessment. A A 9-year-old boy: right frontal lobe hypo-metabolism, peak-t =  − 4.04, cluster size = 963; B 18-year-old boy: left frontal lobe hyper-metabolism, peak-t = 7.37, cluster size = 1387; C 15-year-old boy: left temporal lobe hyper-metabolism, peak-t = 8.16, cluster size = 452 (P < 0.01, cluster size > 100)
Fig. 6
Fig. 6
Localization results of patients who underwent epilepsy surgery. A Seizure-free 17-year-old girl who underwent right temporal lobe resection, peak-t =  − 5.43, cluster size = 30,951; B seizure-free 13-year-old girl who underwent left frontal lobe resection, peak-t =  − 6.07, cluster size = 29,482; C seizure-free 10-year-old boy who underwent left occipital lobe resection, peak-t =  − 3.05, cluster size = 174; D non-seizure-free 10-year-old boy who underwent left frontal lobe resection. Localization cluster was nearby but without the resection area, peak-t =  − 3.90, cluster size = 319 (P < 0.01, cluster size > 100)

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