# Exploring the Role of TSPO-PET Imaging Among MRI-Negative Patients with Temporal Lobe Epilepsy: From the Perspective of Heterogeneity

## TL;DR

TSPO-PET imaging reveals neuroinflammatory patterns in MRI-negative temporal lobe epilepsy patients, showing variability linked to seizure frequency and timing.

## Contribution

Demonstrates TSPO-PET's potential for detecting neuroinflammation in MRI-negative TLE and highlights clinical factors affecting imaging outcomes.

## Key findings

- TSPO-PET imaging with [18F] DPA-714 shows significant inter-individual neuroinflammatory heterogeneity in TLE patients.
- Elevated TSPO uptake and asymmetry index correlate with seizure frequency and time since last seizure.
- TSPO-PET detected subtle lesions confirmed by immunohistochemistry in three patients.

## Abstract

What are the main findings?
TSPO-PET/MRI with [18F] DPA-714 revealed marked inter-individual heterogeneity in neuroinflammatory distribution among temporal lobe epilepsy patients.Elevated TSPO uptake and asymmetry index were significantly associated with seizure frequency and the interval between the last seizure and PET imaging.

TSPO-PET/MRI with [18F] DPA-714 revealed marked inter-individual heterogeneity in neuroinflammatory distribution among temporal lobe epilepsy patients.

Elevated TSPO uptake and asymmetry index were significantly associated with seizure frequency and the interval between the last seizure and PET imaging.

What are the implications of the main findings?
TSPO-PET may serve as a sensitive tool for localizing epileptogenic foci, particularly in MRI-negative temporal lobe epilepsy.Clinical seizure-related factors like scanning timing should be considered when interpreting TSPO-PET signals, as they may contribute to variability in neuroinflammatory imaging patterns.

TSPO-PET may serve as a sensitive tool for localizing epileptogenic foci, particularly in MRI-negative temporal lobe epilepsy.

Clinical seizure-related factors like scanning timing should be considered when interpreting TSPO-PET signals, as they may contribute to variability in neuroinflammatory imaging patterns.

Background/Objectives: This study explored the heterogeneous distribution pattern of translocator protein 18kDa (TSPO)-PET/MRI using radioligand [18F] DPA-714 in temporal lobe epilepsy patients and identified clinical factors influencing imaging outcomes. Methods: The TSPO imaging in individual patient was evaluated with both visual reading and quantitative assessment using an asymmetry index based on cerebellum-normalized standardized uptake values. The association between clinical factors and TSPO imaging outcomes was assessed. Pathological evaluation was conducted in three patients. Results: Twenty-nine TLE patients and ten healthy controls were enrolled. Visual evaluation revealed increased [18F] DPA-714 uptake in twenty patients as compared to controls, predominantly in a unilateral regional brain, while the remaining nine patients showed visually undetectable uptake of [18F] DPA-714. Consistently, quantitative analysis revealed that 69% (20/29) patients exhibited at least one brain area with significant asymmetry index, notably in the temporal lobe (85%, 17/20). A high asymmetry index could also be observed in the parietal (13.8%, 4/29) and occipital lobe (17.2%, 5/29). Significant associations were identified between the asymmetry index and seizure frequency (p = 0.045, OR = 7.994), and the interval from last seizure to PET scan (p = 0.033, OR = 6.712). Moreover, we confirmed the pathology in three patients via immunohistochemistry, which underscored the potential of TSPO-PET in detecting minor lesion. Conclusions: TSPO-PET reveals patient-specific and network-level neuroinflammatory heterogeneity in MRI-negative TLE, supporting its potential role as a complementary tool for presurgical evaluation.