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11C-flumazenil PET in patients with refractory temporal lobe epilepsy and normal MRI
Background:
Using 11C-flumazenil (FMZ) PET with correction for partial-volume effect, reductions of central benzodiazepine receptor (cBZR) binding can be detected reliably in vivo on remaining neurons in sclerotic hippocampi of patients with mesial temporal lobe epilepsy (TLE).
Objective:
To delineate abnormalities of 11C-FMZ binding in patients with medically refractory TLE and normal quantitative MRI.
Methods:
Analysis of parametric images of FMZ volume of distribution (Vd) using two complementary approaches: 1) MRI-based volume of interest (VOI) approach with partial volume effect correction for multiple hippocampal and extrahippocampal VOIs; and 2) statistical parametric mapping (SPM) to localize significant 11C-FMZ binding changes objectively on a voxel-by-voxel basis.
Results:
Significant abnormalities of absolute FMZ-Vd were found after partial volume effect correction in 5 of 10 patients: unilateral decrease in the amygdala ipsilateral to the EEG focus (1), unilateral hippocampal decreases and bilateral temporal and extratemporal neocortical decreases (2), unilateral increase in the temporal neocortex together with extratemporal neocortical increases (1), and bilateral posterior hippocampal increases together with temporal neocortical increases (1). In the three patients with extratemporal neocortical changes, the concomitant unilateral hippocampal or temporal neocortical changes were contralateral to the presumed epileptic focus. Significant asymmetries of FMZ-Vd between homologous regions were found in six patients. In four of those patients, absolute FMZ-Vd for the homologous regions were within normal limits, with two of the four patients showing relatively higher hippocampal values ipsilateral to the presumed epileptic focus. SPM analysis localized significant abnormalities of FMZ-Vd in similar locations in three of the seven patients in whom VOI analysis detected significant changes. In addition, SPM indicated significant unilateral contralateral hippocampal decreases in an eighth patient. However, both methods failed to localize epileptic foci in two patients identified by depth-EEG recordings.
Conclusions:
11C-FMZ PET showed focal increases as well as decreases of FMZ binding in 80% of patients with refractory TLE and normal high-quality MRI but was not consistently helpful in localizing the epileptic foci.
Insights
Positron emission tomography (PET) with 11C-flumazenil (FMZ) detected abnormalities in 80% of refractory temporal lobe epilepsy (TLE) patients with normal MRI. However, FMZ PET was not consistently effective in pinpointing the exact epileptic foci.
Area of Science:
- Neuroscience
- Medical Imaging
- Radiochemistry
Background:
- 11C-flumazenil (FMZ) Positron Emission Tomography (PET) can detect central benzodiazepine receptor (cBZR) binding reductions in sclerotic hippocampi of mesial temporal lobe epilepsy (TLE) patients.
- Partial-volume effect correction is crucial for accurate in vivo assessment of cBZR binding on remaining neurons.
Purpose of the Study:
- To identify abnormalities in 11C-FMZ binding in patients with medically refractory TLE and normal quantitative MRI.
- To evaluate the utility of 11C-FMZ PET in localizing epileptic foci in this patient cohort.
Main Methods:
- Analysis of FMZ volume of distribution (Vd) parametric images using MRI-based volume of interest (VOI) with partial volume effect correction.
- Application of statistical parametric mapping (SPM) for voxel-wise analysis of 11C-FMZ binding changes.
- Comparison of VOI and SPM findings for localizing abnormalities.
Main Results:
- Significant FMZ-Vd abnormalities were detected in 80% of patients (5/10) after partial volume effect correction.
- Abnormalities included focal decreases and increases in the hippocampus, amygdala, and neocortical regions.
- SPM identified similar abnormalities in some patients and detected additional contralateral hippocampal decreases in one patient.
- Both methods failed to localize epileptic foci in two patients confirmed by depth-EEG.
Conclusions:
- 11C-FMZ PET reveals focal binding increases and decreases in most refractory TLE patients with normal MRI.
- The technique shows promise for detecting neurobiological changes but is not consistently reliable for epileptic focus localization.