Improving MRI-Negative Epilepsy Localization: Synergy of Dual-Probe PET/MR (18F-FDG/11C-FMZ)

Summary

Here, we describe a protocol using dual-probe ¹⁸F-FDG/¹¹C-FMZ PET/MRI that precisely localizes the epileptogenic focus in MRI-negative refractory epilepsy, thereby optimizing diagnosis and treatment.

Abstract

The localization of refractory epilepsy, especially MRI-negative cases, is a critical challenge in diagnosing and treating neurological disorders. To address this challenge, this study proposes a standardized protocol for localizing the epileptogenic focus using a dual-probe Positron Emission Tomography/Magnetic Resonance Imaging (PET/MR) technique. The protocol focuses on radiotracer selection, imaging sequence design, and image interpretation strategies. Radiotracers selection: This imaging combines ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) metabolic imaging and ¹¹C-flumazenil (¹¹C-FMZ) GABA_A receptor imaging to locate epileptogenic focus in refractory epilepsy patients by detecting glucose metabolism abnormalities and GABA_A receptor density changes; imaging sequence design: FDG PET/MR scans were done first, followed by FMZ PET/MR scans 24 h later, MRI Sequence images including structural and functional images; image interpretation strategy: The dual-probe evaluation strategy identifies potential epileptogenic focus through FDG hypometabolism and FMZ binding reduction, with concurrent findings providing strong evidence, quantitative analysis involves standardized uptake values (SUV) and asymmetry index (AI) of FDG and FMZ images. This study details the preparation process of radiotracers, scanning parameters, and image fusion methods, validating the protocol's effectiveness through representative results. The adoption of dual-probe PET/MR imaging technology may enhance the accuracy of epileptogenic focus localization, thereby supporting more precise assessments and improving treatment outcomes. Currently, this protocol has completed methodological validation, and preliminary results indicate its potential to guide preoperative assessment for clinical epileptogenic focus resection (successful surgery was performed in 3 patients based on localization results, with no post-operative seizures). To address technical limitations (e.g., short ¹¹C-FMZ half-life, cyclotron dependency), optimization directions include developing long-half-life analogues and exploring multi-tracer combinations. Future integration with AI-assisted image analysis and lesion identification is also feasible. In summary, this study offers novel insights for precision epilepsy diagnosis and treatment, holding significant implications for improving patient outcomes.

Introduction

Refractory epilepsy, characterized by resistance to two or more appropriately selected and dosed antiepileptic drugs^1,2,3, often presents as focal epilepsy accompanied by neurocognitive impairment and comorbid mental disorders^4,5,6. When pharmacological treatments fail, surgical resection of the epileptogenic focus becomes a critical intervention, making precise preoperative localization a key prerequisite for successful outcomes.

Conventional magnetic res....

Protocol

The study has received approval from the local medical ethics committee. This study adheres to the principles of the Declaration of Helsinki. Patients or their legal guardians must sign a written informed consent form that details the invasive procedures, radiation exposure, and follow-up requirements.

1. Preparation and quality control of radiotracers

NOTE: It is essential to adhere to the established principles of biological occupational protection and radiological occupational protection. Additionally, it is important to follow the guidelines for the proper and compliant disposal of medical and ....

Results

All case images in this study were subjected to a strict quality control process as specified in paragraph 7.1 and section 8 of this protocol. They were included in the analysis only after ensuring that they met the following criteria: (1) the MRI images had no obvious motion artifacts or geometric distortion; (2) the tracer distribution of PET images was uniform, and the signal-to-noise ratio met the requirements for quantitative analysis; and (3) the automated fusion of the PET and MRI images was successful, and it was.......

Discussion

The primary objective of this study was to establish and delineate a standardized operational protocol for dual-probe (¹⁸F-FDG/¹¹C-FMZ) PET/MR in the evaluation of MRI-negative refractory epilepsy. The pressing clinical need for such a protocol stems from the current lack of uniform specifications across centers, which leads to inconsistencies in imaging acquisition, analysis, and interpretation, thereby hindering the comparability of results and broader clinical adoption. This protocol aims to.......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
18O-rich water	Taiyo Nippon Sanso,Japan	24-0091
Acetonitrile	ABX,Germany	TF-A1-231207002
Air filter membrane (Millex-25)	Merck,Germany	SLFGN25VS
Anhydrous ethanol	Sinopharm Chemical Reagent,Shanghai,China	10009293
C18 Bonded Silica Chromatography Column	Macherey-Nagel,Germany	715412.100
Cyclotron	GE,USA	MINITRACE
Desmethylflumazenil	Jiangsu Huayi Technology Co., Ltd.,China	DFBE-95-0001A
Dimethylformamide (DMF)	Bailingwei Technology Co., Ltd., China	983353
EtOH	ABX,Germany	10009216
HPLC Semi-Preparative Analysis System	SYKNM,Germany	S-1122
K2CO3 Solution	ABX,Germany	TF-K1-230724001
Kryptofix[2.2.2](K222)	ABX,Germany	800
liquid filter membrane (Millex-GV)	Merck,Germany	SLGVR33RB
NaH	Bailingwei Technology Co., Ltd., China	114895
PET/MR	GE,USA	Signa
QMA column	Waters,USA	186002350
Radionuclide activity	Capintec,USA	CRC-25R
Reference Standard Flumazenil	Jiangsu Huayi Technology Co., Ltd.,China	FBE-97-0001A
Sep-Pak C18 chromatography column	Waters, USA	046933248A
Trifluoromethanesulfonic acid	Sigma-Aldrich,USA	MKBW5282V