The hybrid brain PET/MRI method with 18F-FDG in the diagnostics of focal cortical dysplasia in patients with focal drug-resistant epilepsy
- Authors: Rostovtseva T.M.1, Dolgushin M.B.1, Dvoryanchikov A.V.1, Nadelyaev R.V.1, Karalkina M.A.1, Dzhafarov V.M.1, Rubleva Y.V.1, Baranova E.A.1, Patsap O.I.1, Burd S.G.1
-
Affiliations:
- Federal Center of Brain Research and Neurotechnologies
- Issue: Vol 16, No 4 (2025)
- Pages: 42-53
- Section: Original Study Articles
- Submitted: 03.10.2025
- Accepted: 06.11.2025
- Published: 03.01.2026
- URL: https://clinpractice.ru/clinpractice/article/view/691913
- DOI: https://doi.org/10.17816/clinpract691913
- EDN: https://elibrary.ru/MKMBEB
- ID: 691913
Cite item
Abstract
BACKGROUND: Up to 30% of the patients with epilepsy are resistant to drug therapy. One of the leading causes of drug-resistant epilepsy in adults and children is the focal cortical dysplasia. The complete resection of the epileptogenic focus in 60–70% of the cases results in the complete resolving of epileptic seizures, however, its detection and determining its margins by using magnetic resonance imaging (MRI) could be a difficult task. Positron emission tomography combined with MRI (PET/MRI) is a new hybrid method of diagnostics, which can be used in case of negative and indefinite MRI results, as well as in case of non-compliance of the MRI findings to the data from videoelectroencephalography (video-EEG-monitoring). AIM: To evaluate the diagnostic possibilities of the hybrid brain PET/MRI method with the use of the radiopharmaceutical — Fluorodeoxyglucose (18F-FDG) in detecting the focal cortical dysplasia in patients with focal drug-resistant epilepsy and to analyze the metabolic patterns in cases of focal cortical dysplasia of various type and location. METHODS: The retrospective analysis of data from 23 patients included the comparison of data from the brain PET/MRI with 18F-FDG, from the MRI and from the video-EEG-monitoring, as well as the analysis of 18F-FDG hypometabolism patterns in cases of focal cortical dysplasia of various types and locations. RESULTS: Focal cortical dysplasia was found in 13 (56.5%) patients by means of MRI, in 22 (95.6%) — by means of PET/MRI with 18F-FDG; 6 (26.1%) were MRI-negative, while in 3 (13%) cases the signs of focal cortical dysplasia were found upon the retrospective targeted analysis of MRI images in the 18F-FDG hypometabolism zone. Small focal area of 18F-FDG hypometabolism in our research was found only when the epileptogenic focus was located in the frontal lobe, which was 75% of the cases of the frontal variant of FCD. In all the cases of the temporal location, the zone was spreading to two and more gyri. As of the moment of article publication, the absence of seizures acc. to the classification by J. Engel (Engel I) in the postoperative period was reported for 11 (84.6%) of 13 operated patients, the Engel II class outcome was registered in 1 (4.3%) patient. CONCLUSION: Brain PET/MRI with 18F-FDG in patients with focal drug-resistant epilepsy increases the detection rates of focal cortical dysplasia by 39% comparing to MRI, including the MRI-negative patients and the patients with minor structural changes. The analysis of PET/MRI images in patients with suspected presence of epileptogenic focus of frontal location requires special attention.
Full Text
BACKGROUND
Epilepsy is one of the most widespread neurological diseases, which affects more than 50 million people worldwide1. The most common form of epilepsy is the focal one [1]. Approximately 30% of the patients with epilepsy are resistant to anti-epileptic therapy and the most optimal treatment method for the patients with drug-resistant focal epilepsy is the surgical one [2]. Focal cortical dysplasia (FCD) is one of the leading causes of drug-resistant epilepsy in adults and children, and it is associated with severe forms of the disease, requiring specific approach to therapy and often requiring the surgical intervention. Up to 70% of the cases of cortical malformations are related to the FCD, which makes it one of the main factors in the development of drug-resistant epilepsy [3].
FCD is a local disorder in the normal development and organization of the brain cortex, developing as a result of impaired proliferation, migration or differentiation of neurons in the intrauterine period [4]. The classification of FCD, proposed by I. Blümcke et al. in 2011 [5], remained commonly used up until recently. The differences between the subtypes of FCD type I (abnormal cortex with impaired cytoarchitectonics, but without the dysmorphic neurons or balloon cells) in this classification are determined by the type of cortical dyslamination (Ia — radial, Ib — tangential, Ic — combined); the subtypes of FCD type II (with the presence of dysmorphic neurons) are characterized by the presence of balloon cells (presence of dysmorphic neurons without the balloon cells in cases of subtype IIa and both types of cells — in cases of subtype IIb); FCD type III is a combination of FCD type Ic with other abnormalities (IIIa — with hippocampal sclerosis, IIIb — with glioneuronal tumors, IIIc — with vascular malformations, IIId — with zones of gliosis of various origin) [5]. The topical classification of FCD, proposed in 2022 by the International League Against Epilepsy (ILAE), is based on the principles of combined diagnostics and includes, besides the classical pathomorphological types, new categories, reflecting the histological, the genetic and the neuroimaging data, among which, the mild malformation of cortical development (mMCD), the mild malformation of cortical development with oligodendroglial hyperplasia and frontal epilepsy (MOGHE), as well as the absence of FCD according to the pathomorphological examination data [6].
In a number of research works, in cases of the complete surgical resection of FCD, the long-term remission and the absence of seizures acc. to the classification by J. Engel (Engel I) is being achieved in 60–70% of the cases [7, 8]. Partial resection or incomplete resection of focus, on the contrary, are associated with a lower level of seizure control (14–22%) and higher risk of recurrences [8]. One of the important prognostic factors is also the type of FCD: patients with type II FCD more often get seizure-free status (up to 75–80%), while in patients with type I FCD and with mMCD, the resection results are worse, but still significant [8, 9].
The algorithm of examining the epilepsy patients includes, generally, the video-electroencephalography (EEG-video-monitoring, EEG-VM) and the magnetic resonance imaging (MRI). Typical MRI signs found in FCD are characterized by cortical thickening, by the blurred margin between the gray and the white matters, by the increased signal when using the T2-FLAIR mode (T2-Fluid-Attenuated Inversion Recovery), by the presence of transmantle signs [linear focus of increased intensity of the MRI-signal in the Т2-weighed image (Т2-WI) and in the FLAIR pulse sequence from the cortex to the wall of the lateral ventricle, characteristic for FCD subtype IIb and by the changes in the shape of the gyri [10]. The detection and the precise estimation of the FCD borders using the MRI in many cases can be difficult, and in a number of cases — impossible. In cases when the structural changes within the brain matter are not detected using the MRI, when the MRI and EEG findings do not match, as well as in patients with bilateral or multifocal lesions, the verification of the location and the resectability of epileptogenic zone could be aided by the additional radionuclide diagnostic methods — the single-photon emission tomography and the positron-emission tomography (PET) [11]. The new hybrid method allowing for consecutive or instantaneous evaluation of the structural and the metabolic changes in the brain within a single scanning is the combined PET/MRI method.
Research aim — to evaluate the diagnostic possibilities of the hybrid brain PET/MRI method with the Fluorodeoxyglucose (18F-FDG) radiopharmaceutical in detecting FCD in patients with focal drug-resistant epilepsy and to analyze the metabolic patterns in cases of FCD of various type and location.
METHODS
Research design
A retrospective single-group cohort study was arranged. Data analyzed included the results of brain PET/MRI with 18F-FDG conducted during the period from 2023 until 2025 in 23 patients (11 men, 12 women; age — from 19 to 51 years, mean age — 31.48 years) with focal drug-resistant epilepsy. The comparison involved the number of FCD cases detected using MRI, PET and combined PET/MRI scans. The analyzed data also included the 18F-FDG hypometabolism patterns depending on the type and the location of FCD.
Conformity criteria
Inclusion criteria: patients with an established diagnosis of focal drug-resistant epilepsy.
Non-inclusion criteria: the presence of generalized epilepsy and other forms of epilepsy, except for the focal one; the presence of focal epilepsy without drug resistance; the presence of epileptic syndrome related to the mass lesions in the brain, arteriovenous malformations, cerebral infarction, craniocerebral injury or other possible causes, except for FCD.
Research facilities
The treatment of the patients and all the examinations were carried out within the premises of the Federal State Budgetary Institution “Federal Center of Brain Research and Neurotechnologies” under the Federal Medical-Biological Agency (FSBI FCBRN of FMBA of Russia).
Research Duration
The enrollment of the patients was carried out in 2023–2025, the analysis of the results — in 2025.
Medical Procedure Description
All the patients enrolled into the research were receiving anti-epileptic drugs as the polytherapy mode with partial effect or with its absence.
All the patients were undergoing the clinical-neurological examination — the prolonged EEG-VM, the hybrid brain PET/MRI scanning with 18F-FDG; and the analysis of the functional, structural and metabolic changes of the brain was conducted. In all the cases, FCD was detected or suspected.
Later on, each clinical case was discussed during the consilium with the participation of epileptologists, neurophysiologists, radiologists, roentgenologists and neurosurgeons: comparison was made for the clinical data and the results of conducted examinations with further making a decision on the further tactics of managing the patient, in particular, the surgical resection of the epileptogenic focus, the invasive EEG-VM, the minimally invasive surgical interventions, the correction of therapy or the dynamic follow-up. Thus, stereo-EEG-video-monitoring (stereo-EEG-VM) was performed in 12 patients, surgical resection of the epileptogenic zone — in 13 (of which 10 patients before surgical resection underwent the invasive EEG-VM).
Methods for registration of outcomes
The prolonged EEG-VM was carried out using the “Neuron-Spectrum-4/P” and the “Neuron-Spectrum-65” devices (“Neurosoft”, Russia) in accordance with the recommendations from the International Federation of Clinical Neurophysiology (IFCN) using 21 electrodes with their positioning according to the 10-20 scheme and with applying the additional ECG channels. During the EEG-VM, the investigated parameter was the bioelectrical activity of the brain with recording the seizure patterns.
The PET/MRI procedures were conducted using the integrated PET/MRI system (SIGNA PET/MR 3Т, GE Healthcare, USA), which allows for simultaneously conducting both the PET and the MR-visualization of the brain. For all the PET/MRI procedures, the 8-channel coil for high-resolution neuroradiology scans was used. In all the cases, during a period of not less than 2 hours before the examination, the patients were supervised by the medical staff; in case of developing the epileptic seizure, the examination was shifted to the other day. Before the brain PET/MRI with 18F-FDG, the patients were receiving the preliminary preparation standard for 18F-FDG-PET scanning procedures [12]: intravenous injection of the radiopharmaceutical based on 18F-FDG at a dosage prescribed by the Radiology Physician, calculated by the body weight and by the height of the patient (125–250 MBq, an average of 180 MBq). After the injection of the radiopharmaceutical, the patient was placed for 20–30 minutes into the dark room under the supervision of the medical staff, following the mode of comfortable lying position with the eyes closed and avoiding the use of mobile devices, not listening to music, not reading or doing any active motions.
The protocol of hybrid PET/MRI-scanning was compiled in the following way: when acquiring the PET data (15 minutes, matrix dimensions 192×192) based on the technical capabilities of the system and on the recommended HARNESS-MRI protocol (Harmonized Neuroimaging of Epilepsy Structural Sequences-Magnetic Resonance Imaging) for patients with epilepsy (ILAE-2019 recommendations), the following high-resolution MRI-sequences were employed [13]:
- 3D T1-weighed sequence with inversion recovery (IR-FSPGR) in the sagittal plane: field of vision — 25.6 cm; slice thickness 1.2 mm; tilt angle — 12; frequency resolution 256; phase resolution 256; bandwidth 31.25 kHz;
- 3D T2-weighed sequence (Cube T2) in the sagittal plane: field of vision 25.6 cm; TR (repetition time) 2500 ms; TE (echo time) — maximal; ETL (echo train length) 125; frequency resolution 320; phase resolution 320; bandwidth 50 kHz;
- 3D T2-FLAIR-weighed sequence (Cube T2-FLAIR) in the sagittal plane: field of vision 25.6 cm; slice thickness 1.2 mm; TR 6500 ms; TE 90 ms; ETL 140; frequency resolution 256; phase resolution 256; bandwidth 31.25 kHz;
- 2D coronal T2-weighed sequence with rapid spin-echo (FRFSE-XL): field of vision 20 cm; slice thickness 2.0 mm; inter-slice distance 0.2 mm; TR 4877ms; TE 120ms; tilt angle 111; ETL 14; frequency resolution 288; phase resolution 224; bandwidth 19.23 kHz.
Besides the sequences described above, the acquired data also included the magnetic resonance attenuation correction (MR AC) with the duration of 18 seconds, used for mapping the corrections based on the atlas data for obtaining the pseudo-CT scans, which includes the information on the continuous attenuation for the head area using the single head map based on CT-images.
Independently from one another, two radiology physicians and two roentgenologists have conducted the visual analysis of the obtained hybrid scanning images. Besides the visual analysis, data processing included the use of the Advantage Workstation 4.6 (AWS, GE Healthcare, USA) with the CortexID Suite specialized clinical software ver. 1.04-5.
The analysis of PET/MRI by means of the specialized clinical software was conducted consecutively: first of all, MRI images were viewed with analyzing the structural changes within the brain matter. Later on, qualitative and quantitative evaluation of the 18F-FDG metabolism within the brain matter was done. Based on the PET data, the asymmetry of 18F-FDG metabolism was estimated in the contralateral areas of the brain matter. The quantitative analysis included the measurements of the standard uptake values (SUVmax, SUVmean) in the region of interest (ROI) and in the areas of corrected uptake (COROA), the calculations of the 18F-FDG metabolism asymmetry index in the suspected epileptogenic zone comparing to the contralateral area of the brain matter; the volume of the selected ROI was 400–600 mm3.
At the final stage, comparison was done for the structural changes detected using the MRI, for the metabolism zones detected by PET and for the EEG-VM data. In cases of discordance in the results, a repeated detailed analysis of the structural changes in the brain matter was done for the detected zones of 18F-FDG hypometabolism.
Research outcomes
The main research outcome: the diagnostic effectiveness of the hybrid brain PET/MRI with 18F-FDG, determined as the rate of detecting the FCD in the tested cohort of patients with focal drug-resistant epilepsy, comparing to standard MRI.
Additional research outcomes: the analysis of 18F-FDG hypometabolism patterns for various types and locations of FCD, comparison of the PET/MRI data to the EEG-VM and MRI results, as well as the post-operative outcomes (Engel) in patients which underwent the resection of the epileptogenic focus.
Subgroup analysis
The patients were divided into subgroups depending on the location and the type of FCD, as well as on the presence of characteristic structural changes in the MRI data. In the 12 operated patients, the type of FCD was determined according to the data from the pathomorphological examination, in other cases — according to the MRI data. In all the MRI-negative patients enrolled into the research, the FCD type was determined according to the pathomorphological examination findings.
Methods for registration of outcomes
The registration of the main and the additional research outcomes was carried out based on the results of analyzing all the PET/MRI data with the participation of two independent experts-radiologists (with an employment history of not less than 5 years, with the experience in neurovisualization) and with using the standard protocols for the quantitative and the visual evaluation of hypometabolism foci.
Statistical analysis
The statistical analysis of the results was conducted using the SPSS Statistics software package, version 23.0 (IBM, USA), as well as using the SciPy and Matplotlib libraries (Python Software Foundation, USA). The quantitative data were presented as the medians with standard deviations (M±SD) or as the median with the interquartile range depending on the distribution type. The normality was checked using the Shapiro–Wilk test. The comparison of the independent groups with normal distribution was done using the Student t-test, with non-normal — the Mann-Whitney U-criterion. For comparing the dependent samples, the paired t-test or the Wilcoxon criterion were used. The correlation analysis was performed with calculating the Pearson’s or Spearman correlation coefficients depending on the type of data. The statistical significance of differences was claimed with the p < 0.05.
RESULTS
Research sample (participants)
The data analyzed included the results of brain 18F-FDG PET/MRI hybrid examinations from 23 FCD patients.
Primary findings
FCD was detected in 13 (56.5%) patients by means of MRI, in 22 (95.6%) — by means of 18F-FDG PET/MRI hybrid examination, of which 6 (26.1%) patients were MRI-negative, and 3 (13%) cases had signs of FCD detected in the MRI scans during the repeated targeted analysis of the images showing the 18F-FDG hypometabolism zone (Fig. 1). In a single MRI-negative case, the 18F-FDG hypometabolism zone was found retrospectively upon the revision of PET/MRI images after an invasive EEG-VM.
Fig. 1. Combined positron-emission tomography with magnetic resonance imaging (PET/MRI) of the brain with 18F-FDG in a patient with focal cortical dysplasia located at the bottom of the sulcus in the left frontal lobe: а (combined PET/MRI image in the coronal plane) — 18F-FDG hypometabolism focus in the area of the focal cortical dysplasia (circle); b (Т1-WI in the coronal plane) — a small area of decreased grey-white matter demarcation in the sulcus bottom in the left frontal lobe (circle); c (Т2-FLAIR in the coronal plane) — a small area of increased intensity of the MRI-signal and of decreased grey-white matter demarcation in the sulcus bottom in the left frontal lobe (circle); d (Т2-WI in the axial plane) — a small area of decreased grey-white matter demarcation in the sulcus bottom in the left frontal lobe (circle); e (histological slide, staining with hematoxylin and eosin, ×400) — dysmorphic neurons.
Of the 13 patients, which after PET/MRI underwent the invasive EEG-VM, the location of the seizure onset zone was completely matching to the 18F-FDG hypometabolism zone in 12 (92.3%) cases. In a single case, the zone of seizure onset was also detected in the contralateral cyngulate gyrus, which had no signs of structural or metabolic changes.
The resection of the FCD was done in 13 patients, the follow-up during the postoperative period varies from 4 to 25 months, with more than 12 months in 5/13 (38.5%).
Absence of seizures (Engel I) during the postoperative period as of the moment of publication was reported in 11 (84.6%) cases. The Engel II class outcome was registered in 1 (7.69%), Engel III class outcome — in 1 (7.69%) MRI-negative patient: before the resection, the location of the epileptogenic focus was confirmed by means of an invasive EEG-VM.
The distribution by the FCD types was the following: type I — 4 (17.4%) patients, type II — 16 (69.6%) and type III — 3 (13.0%). The analysis of the topographic location of the hypometabolic zones has shown that frontal location is the most common one (43.5% of all the cases), followed by the insular location (26.1%) and the parietal one (17.4%). The evaluation of the type of spreading of the metabolic disorders has demonstrated that the “several gyri” pattern was observed in 39.1% of the cases and the “focal area” pattern — in 30.4%.
The statistical analysis with the using the Pearson chi-square test did not reveal a significant inter-relation between the FCD type and the location of the hypometabolism zone (p=0.450), as well as between the type of FCD and the pattern of spreading of the metabolic changes, which can be resulting from the relatively small sample size and uneven subgroup distribution.
The following patterns of 18F-FDG hypometabolism were revealed as observed in cases of FCD: small focal area of 18F-FDG hypometabolism; zone of 18F-FDG hypometabolism spreading within a single gyrus; 18F-FDG hypometabolism zone spreading to two or more gyri. The patterns of 18F-FDG hypometabolism were evaluated depending on the FCD location. The focal pattern of 18F-FDG hypometabolism (limited hypometabolism) was practically completely associated with the frontal location of FCD: such a pattern was found in 75% of the patients with frontal location of the FCD and was not registered in other FCD locations. The pattern of “several gyri” predominates in cases of lesions in the insular, the parietal, the occipital and the temporal zones, reflecting the most widespread type of hypometabolism in these areas. As for the insular and the parietal lobes, their predominant feature is the multifocal distribution of metabolic changes, while the single impaired gyrus was found extremely rarely. As for the occipital, the parietal and the insular locations of FCD, the 18F-FDG hypometabolism zone more often involves several adjacent gyri, which complicates the clear localization of the focus.
Additional research findings
In 2 patients with FCD showing parietal location, the 18F-FDG hypometabolism zone was not matching to the location of the structural changes in the MRI scans, but it was rather located in the neighboring areas of the brain matter (Fig. 2, 3). Upon performing the stereo-EEG-VM in these patients, the epileptiform activity was detected in the zone of detected structural changes and was not registered in the zone of metabolic changes.
Fig. 2. Combined positron-emission tomography with magnetic resonance imaging (PET/MRI) of the brain with 18F-FDG in a patient with focal cortical dysplasia in the left parietal lobe: а (combined PET-MRI scans in the axial plane) — absence of signs of 18F-FDG hypometabolism in the area of the focal cortical dysplasia (arrow); b (Т2-WI in the axial plane) — the area of increased MRI-signal intensity and a decrease in the grey-white matter demarcation in the left parietal lobe (arrow); c (combined PET-MRI scan in the axial plane) — 18F-FDG hypometabolism zone in the paramedian areas of the left frontal lobe (circle); d (Т2-WI in the axial plane) — absence of pathological structural changes in the 18F-FDG hypometabolism zone (circle).
Fig. 3. Data from the stereo-electroencephalography: during the monitoring period of 24 hours, the total registered findings include 13 focal non-motor seizures with the transition to the motor ones and with an initiation on the left side under the ‘PSF-PC’ electrode (posterior upper frontal gyrus — posterior part of the callosal gyrus, 8 contacts).
In 3 patients with FCD types I and II, in the zone of FCD location, besides the zone of 18F-FDG hypometabolism, additional 18F-FDG hypometabolism zones were found in the other areas of the cortex of brain hemispheres with no signs of structural changes shown by MRI, and in 2 cases, according to the data from stereo-EEG-VM, these areas were showing the epileptiform activity, while in a single case stereo-EEG-VM was not done and after the FCD resection, the Engel class II outcome was achieved.
DISCUSSION
PET with 18F-FDG is to be done, generally, at the phase between the seizures and allows for detecting the 18F-FDG hypometabolism zones in the epileptogenic foci. The decrease in the 18F-FDG accumulation in the potential foci is sensitive, but non-specific for epilepsy: 18F-FDG hypometabolism can be also observed in cases of other pathological conditions of the brain matter, such as the infarction, the tumor, the consequences of injury, while the location of the hypometabolism zone does not always precisely correspond to the minor epileptogenic focus, which is why it is critically important to compare the PET data to the CT or MRI findings for the purpose of defining the exact anatomical location of the 18F-FDG hypometabolism, for the purpose of evaluating its structure, margins and inter-relations with the surrounding brain matter [14]. In a number of research works, PET with 18F-FDG demonstrates significant benefits comparing to MRI in detecting small developmental defects (such as the focal cortical dysplasia), which, when using the PET, get detected in 72–83% of the cases, with the MRI showing only 21–39% [15, 16].
The hybrid method of PET/MRI has a number of advantages when examining the patients with drug-resistant epilepsy. In particular, the method is devoid of the drawbacks characteristic for PET/CT, such as the low anatomic detailing of the small structures in the brain, as well as the excessive radiation exposure due to the computed tomography [17]. The PET/MRI technology is especially convenient if used in Pediatrics due to the decreased radiation exposure and lesser anesthesia duration [18, 19].
The research works on the efficiency of the hybrid PET/MRI method have demonstrated better diagnostic results and more precise identification of focal epileptogenic foci (including the patients with refractory epilepsy) comparing to the isolated use of PET or MRI, as well as comparing to the PET-CT method [20]. In our research, the PET/MRI with 18F-FDG has provided the ability to increase the FCD detection rates by 39% due to the MRI-negative cases, as well as due to the targeted repeated reviewing of MRI scans with taking into consideration the metabolic data. In the retrospective research by K. Guo et al. [21], the addition of the PET component to MRI has allowed for increasing the number of patients with a single focus suspicious for being the epileptogenic zone, from 35% to 74%, which, in turn, was a potent prognostic factor for favorable outcome of the surgical resection of the epileptogenic focus (Engel I). In the majority of literature sources, it is reported that the dimensions of the 18F-FDG hypometabolism zone, generally, are more than the dimensions of the epileptogenic focus, which should be kept in mind during the pre-operative planning and when evaluating the extent of resection [22–24]. The 18F-FDG hypometabolism zone, probably, includes the area of the initiation and the spreading of excitation, besides, vast 18F-FDG hypometabolism can be related to the spreading of the epileptic activity along the neuronal networks, as well as to the propagation phenomenon or the involvement of functionally related areas [10, 19].
In our research, small focal area of 18F-FDG hypometabolism was reported solely with the FCD located at the frontal lobe, which was 75% of the cases of the frontal FCD variant. In cases of FCD with temporal location, in all the cases the 18F-FDG hypometabolism zone was vast and was spreading to two and more gyri. Similar data were obtained in the research by X. Wang et al. [15], in which foci of the 18F-FDG hypometabolism with lesser longitude were found in cases of FCD localizing at the frontal lobes, comparing to other locations, as well as in cases of FCD type II comparing to type I. Thus, when suspecting the presence of the FCD with frontal location, the analysis of the images requires special attention. In the research by H. Yokota et al. [25], the dimensions of the 18F-FDG hypometabolism zone with temporal location of FCD also exceeded the dimensions of the 18F-FDG hypometabolism zone observed in cases of FCD with other locations.
The part of detected 18F-FDG hypometabolism foci does not find endorsement by the MRI data, nevertheless, the surgical resection of this area conducted using the EEG-VM, in the majority of cases results in the improvement of clinical symptoms up to the complete regress of seizures. PET with 18F-FDG in a number of cases can detect the epileptogenic zone in case of MRI-negative epilepsy, besides, the topical location of the hypometabolism area in the PET scans helps detecting the organic abnormalities upon the revision of MRI scans, which is especially characteristic for small focal cortical dysplasias [15].
In our research, the epileptogenic focus was detected using PET/MRI with 18F-FDG in 6 (26.1%) patients with negative MRI signs. In the research by H. Li et al. [26], the combined registration with PET and MRI has allowed for topically localizing the hypometabolism zones in 46% MRI-negative patients and confirming 12% of doubtful MRI results, which has increased the rate of detecting focal cortical abnormalities up to 94%. This is also related to the possibility of reviewing the MRI data in case of detecting any metabolism abnormalities, which allows for detecting small structural changes, unnoticed or underestimated previously. In our research, in case of targeted reviewing of MRI images with taking into consideration the metabolic changes, signs of FCD were detected in 3 (13%) patients. Besides, PET/MRI allows for detecting more potential targets when planning the locations of electrodes for stereo-EEG-VM and by this increasing the number of detected epileptogenic zones, even in cases of MRI-negative forms of epilepsy [27].
In our research, 5 patients with FCD types I and II, additional foci of 18F-FDG hypometabolism were detected in the cortex of brain hemispheres, 2 patients underwent the invasive EEG-VM, which has shown the presence of epileptiform activity in these areas. According to the data from literature sources, it is worth noting that in some patients the MRI-negative epileptic focus is visualized in the areas contralateral to the EEG data: in such cases, the high priority tasks are the data from stereo-EEG-VM [28].
In the research described by us, the contralaterally located areas of 18F-FDG hypometabolism were not registered, however, in 2 patients the location of the structural and the metabolic changes did not match, the zones of 18F-FDG hypometabolism were located in the brain areas adjacent to the FCD and, probably, were representing the zone of functional deficit. According to the data from invasive EEG-VM, the epileptiform activity in such patients was registered in the zone of detected structural changes and was not registered in the zone of metabolic changes. The non-conformity between the location of the 18F-FDG hypometabolism zone according to the PET data, the epileptogenic zone detected by EEG, and the clinical signs can be the predictor of unfavorable outcome for the surgical treatment. In the research by Z.M. Wang et al. [28] the combined analysis of PET data together with the MRI findings in case of the conformity of data obtained using these methods, has allowed for detecting up to 89% of the patients with the favorable outcome of surgical treatment.
According to our findings, the Engel class outcome I was achieved in 84.6% of operated patients, of which only in 39% the follow-up period was more than 12 months, thus, the obtained data are deemed the preliminary result.
Research limitations
The research retrospectively included the patients in which the epileptogenic focus was detected by means of PET/MRI, or the patients without the detected focus, the diagnosis in which was set using the stereo-EEG-VM and the surgical resection. Despite the fact that before the PET examination, as well as during the examination itself, all the patients were supervised by the medical staff and they had no registered clinical manifestations of epileptic seizures, the fact that directly before the examination patients were not undergoing the scalp EEG-VM, could also affect the examination results towards the positive side.
CONCLUSION
The application of the new hybrid method of brain PET/MRI with 18F-FDG in the algorithm of pre-operational examination for the patients with focal drug-resistant epilepsy allows for increasing the detection rates of FCD (95.6% for PET/MRI, 56.5% for MRI) due to the MRI-negative patients and the patients with small structural changes within the brain matter.
The least longitudinal foci of 18F-FDG hypometabolism were observed in patients with the FCD located in the frontal lobes: thus, suspecting the presence of FCD with frontal location required the most careful and detailed analysis of the PET/MRI scans.
The use of PET/MRI allows for detecting the additional potentially epileptogenic foci, which can be used for the verifying the stereo-EEG-VM electrodes location, as well as for planning and evaluating the prognosis of surgical resection.
ADDITIONAL INFORMATION
Author contributions: T.M. Rostovtseva, R.V. Nadelyaev, writing the text of the article; A.V. Dvoryanchikov, M.A. Karalkina, search and analytical work; M.B. Dolgushin, S.G. Burd, conception, discussion of the results of the study; V.M. Dzhafarov, surgical resection of the epileptogenic lesions; Yu.V. Rubleva, treatment of the patients; E.A. Baranova, scalp and stereo video EEG monitoring; O.I. Patsap, pathomorphological study. Thereby, all authors provided approval of the version to be published and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Ethics approval: The research protocol was approved by the Ethics Committee at the Federal State Budgetary Institution “Federal Center of Brain Research and Neurotechnologies” of the Federal Medical Biological Agency (extract from Protocol No. 12/05-12-22 dated 2022 Dec 05). All the study participants voluntarily signed an informed consent form before being included in the research.
Funding source: This study was conducted as part of the research project “Developing indications for the use of hybrid PET/MRI when planning surgery in patients with pharmacoresistant epilepsy”, code 03,02.VY.
Disclosure of interests: The authors declare that they have no competing interests.
Statement of originality: The authors did not use previously published information (text, illustrations, data) while conducting this work.
Data availability statement: The editorial policy regarding data sharing does not apply to this work, data can be published as open access.
Generative AI: Generative AI technologies were not used for this article creation.
LIST OF ABBREVIATIONS
CT — computed tomography
MRI — magnetic resonance imaging
PET/MRI — the technology of combined positron emission tomography with magnetic resonance imaging
FCD — focal cortical dysplasia
EEG — electroencephalography
EEG-VM (EEG-video-monitoring) — video-electroencephalography
stereo-EEG-VM (stereo-EEG-video-monitoring) — stereo-electroencephalography
18F-FDG ([18F]Fluorodeoxyglucose, [18F]FDG) — radiopharmaceutical medicinal product [18F]Fluorodeoxyglucose
Т1-/Т2-WI — Т1-/Т2-weighted image
T2-FLAIR (T2-Fluid-Attenuated Inversion Recovery) — the mode of magnetic resonance imaging representing the pulse sequence named «Inversion recovery with free fluid signal suppression»
1 World Health Organization [Internet]. Epilepsy: a public health imperative. Geneva: World Health Organization; 2019. Access mode: https://apps.who.int/iris/handle/10665/325293. Date of request: 15.10.2025.
About the authors
Tatiana M. Rostovtseva
Federal Center of Brain Research and Neurotechnologies
Author for correspondence.
Email: rostovtsevat@mail.ru
ORCID iD: 0000-0001-6541-179X
SPIN-code: 5840-7590
Russian Federation, Moscow
Mikhail B. Dolgushin
Federal Center of Brain Research and Neurotechnologies
Email: dolgushin.m@fccps.ru
ORCID iD: 0000-0003-3930-5998
SPIN-code: 6388-9644
MD, PhD, Professor of the Russian Academy of Sciences
Russian Federation, MoscowAndrey V. Dvoryanchikov
Federal Center of Brain Research and Neurotechnologies
Email: dvoryanchikov.a@fccps.ru
ORCID iD: 0009-0009-0678-7821
SPIN-code: 3169-8708
Russian Federation, Moscow
Rostislav V. Nadelyaev
Federal Center of Brain Research and Neurotechnologies
Email: nadelyaev.r@fccps.ru
SPIN-code: 8189-3021
Russian Federation, Moscow
Mariya A. Karalkina
Federal Center of Brain Research and Neurotechnologies
Email: karalkina.m@fccps.ru
ORCID iD: 0000-0002-9267-3602
SPIN-code: 9812-0420
Russian Federation, Moscow
Vidzhai M. Dzhafarov
Federal Center of Brain Research and Neurotechnologies
Email: djafarov.v@fccps.ru
ORCID iD: 0000-0002-5337-8715
SPIN-code: 1737-2522
Russian Federation, Moscow
Yulia V. Rubleva
Federal Center of Brain Research and Neurotechnologies
Email: rubleva@fccps.ru
ORCID iD: 0000-0002-3746-1797
SPIN-code: 8100-0855
Russian Federation, Moscow
Elena A. Baranova
Federal Center of Brain Research and Neurotechnologies
Email: baranova.e@fccps.ru
ORCID iD: 0000-0002-9200-9234
SPIN-code: 6791-2193
Russian Federation, Moscow
Olga I. Patsap
Federal Center of Brain Research and Neurotechnologies
Email: patsap.o@fccps.ru
ORCID iD: 0000-0003-4620-3922
SPIN-code: 6460-1758
Russian Federation, Moscow
Sergey G. Burd
Federal Center of Brain Research and Neurotechnologies
Email: burd.s@fccps.ru
ORCID iD: 0000-0001-6256-2576
SPIN-code: 1484-0178
Russian Federation, Moscow
References
- Schefer IE, Berkovic S, Capovilla G, et al. ILAE classifcation of the epilepsies: position paper of the ILAE Commission for Classifcation and Terminology. Epilepsia. 2017;58(4):512–521. doi: 10.1111/epi.13709
- Sultana B, Panzini MA, Carpentier AV, et al. Incidence and prevalence of drug-resistant epilepsy: a systematic review and meta-analysis. Neurology. 2021;96(17):805–817. doi: 10.1212/WNL.0000000000011839
- Pitkänen A, Löscher W. Epileptogenesis and drug-resistant focal cortical dysplasias. Epilepsy Behav. 2023;145:109241. doi: 10.1016/j.yebeh.2023.109241
- Mohsin SN, Grezenko H, Khan S, et al. Bridging development and disruption: comprehensive insights into focal cortical dysplasia and epileptic management. Cureus. 2023;15(9):e45996. doi: 10.7759/cureus.45996 EDN: GWDNQE
- Blümcke I, Thom M, Aronica E, et al. The clinicopathologic spectrum of focal cortical dysplasias: a consensus classification proposed by an ad hoc task force of the ILAE Diagnostic Methods Commission. Epilepsia. 2011;52(1):158–174. doi: 10.1111/j.1528-1167.2010.02777.x
- Najm I, Lal D, Vanegas MA, et al. The ILAE consensus classification of focal cortical dysplasia: an update proposed by an ad hoc task force of the ILAE diagnostic methods commission. Epilepsia. 2022;63(8):1899–1919. doi: 10.1111/epi.17301 EDN: ZWSMDN
- Агрба С.Б., Козлова А.Б., Шишкина Л.В., и др. Хирургическое лечение эпилепсии у детей с фокальными кортикальными дисплазиями центральных извилин // Вопросы нейрохирургии им. Н.Н. Бурденко. 2023. Т. 87, № 2. С. 17–21. [Agrba SB, Kozlova AB, Shishkina LV, et al. Surgical treatment of epilepsy in children with focal cortical dysplasia in central gyri. Burdenko’s journal of neurosurgery. 2023;87(2):17–21]. doi: 10.17116/neiro20238702117 EDN: ZCWLNI
- Choi SA, Kim KJ. The surgical and cognitive outcomes of focal cortical dysplasia. J Korean Neurosurg Soc. 2019;62(3):321–327. doi: 10.3340/jkns.2019.0005
- Veersema TJ, Swampillai B, Ferrier CH, et al. Long-term seizure outcome after epilepsy surgery in patients with mild malformation of cortical development and focal cortical dysplasia. Epilepsia Open. 2018;4(1):170–175. doi: 10.1002/epi4.12289
- Urbach H, Kellner E, Kremers N, et al. MRI of focal cortical dysplasia. Neuroradiology. 2022;64(3):443–452. doi: 10.1007/s00234-021-02865-x EDN: FPTDNO
- Kurian M, Spinelli L, Delavelle J, et al. Multimodality imaging for focus localization in pediatric pharmacoresistant epilepsy. Epileptic Disord. 2007;9(1):20–31.
- Guedj E, Varrone A, Boellaard R, et al. EANM procedure guidelines for brain PET imaging using [18F]FDG, version 3. Eur J Nucl Med Mol Imaging. 2022;49(2):632–651. doi: 10.1007/s00259-021-05603-w. Erratum in: Eur J Nucl Med Mol Imaging. 2022;49(6):2100–2101. doi: 10.1007/s00259-022-05755-3
- Bernasconi A, Cendes F, Theodore WH, et al. Recommendations for the use of structural magnetic resonance imaging in the care of patients with epilepsy: a consensus report from the International League Against Epilepsy Neuroimaging Task Force. Epilepsia. 2019;60(6):1054–1068. doi: 10.1111/epi.15612
- Kikuchi K, Togao O, Yamashita K, et al. Diagnostic accuracy for the epileptogenic zone detection in focal epilepsy could be higher in FDG-PET/MRI than in FDG-PET/CT. Eur Radiol. 2021;31(5):2915–2922. doi: 10.1007/s00330-020-07389-1 EDN: PDDUEE
- Wang X, Hu W, Shao X, et al. Hypometabolic patterns of focal cortical dysplasia in PET-MRI co-registration imaging: a retrospective evaluation in a series of 83 patients. Front Neurosci. 2023;17:1173534. doi: 10.3389/fnins.2023.1173534 EDN: UHSAGG
- Bacon EJ, Jin C, He D, et al. Cortical surface analysis for focal cortical dysplasia diagnosis by using PET images. Heliyon. 2023;10(1):e23605. doi: 10.1016/j.heliyon.2023.e23605 EDN: WZMUEJ
- Наделяев Р.В., Долгушин М.Б., Ростовцева Т.М., и др. Гибридные методы лучевой диагностики в оценке эпилептогенных очагов: разбор диагностического случая // Медицина экстремальных ситуаций. 2025. Т. 27, №2. С. 176–182. [Nadelyaev RV, Dolgushin MB, Rostovtseva TM, et al. Hybrid imaging techniques in the assessment of epileptic foci: a clinical case. Extreme medicine. 2025;27(2):176–182]. doi: 10.47183/mes.2025-240 EDN: BWDXID
- Ponisio MR, Zempel JM, Willie JT, et al. FDG-PET/MRI in the presurgical evaluation of pediatric epilepsy. Pediatr Radiol. 2024;54(10):1589–1602. doi: 10.1007/s00247-024-06011-6 EDN: SWULXQ
- Pedersen C, Aboian M, Messina SA, et al. PET/MRI applications in pediatric epilepsy. World J Nucl Med. 2023;22(2):78–86. doi: 10.1055/s-0043-1764303 EDN: EZLQLO
- Borbély K, Emri M, Kenessey I, et al. PET/MRI in the presurgical evaluation of patients with epilepsy: a concordance analysis. Biomedicines. 2022;10(5):949. doi: 10.3390/biomedicines10050949 EDN: YDOOHG
- Guo K, Hu J, Cui B, et al. Simultaneous 18F-FDG PET/MRI predicting favourable surgical outcome in refractory epilepsy patients. Neuroradiology. 2025;67(1):89–97. doi: 10.1007/s00234-024-03446-4 EDN: EFHDME
- Sarikaya I. PET studies in epilepsy. Am J Nucl Med Mol Imaging. 2015;5(5):416–430. eCollection 2015
- Ponisio MR, Zempel JM, Day BK, et al. The role of SPECT and PET in epilepsy. Am J Roentgenol. 2021;216(3):759–768. doi: 10.2214/AJR.20.23336 EDN: NALPSS
- Abdul Aziz AF, Mohamed AR, Murugesu S, et al. 18F-FDG PET/CT for the pre-surgical localization of epileptogenic focus among paediatric patients with drug resistant epilepsy in Malaysia: perspective of a nuclear medicine physician. Med J Malaysia. 2021;76(4):502–509.
- Yokota H, Uetani H, Tatekawa H, et al. Focal cortical dysplasia imaging discrepancies between MRI and FDG-PET: unique association with temporal lobe location. Seizure. 2020;81:180–185. doi: 10.1016/j.seizure.2020.08.017 EDN: MWDOOV
- Li H, Zhang M, Lin Z, et al. Utility of hybrid PET/MRI in stereoelectroencephalography guided radiofrequency thermocoagulation in MRI negative epilepsy patients. Front Neurosci. 2023;17:1163946. doi: 10.3389/fnins.2023.1163946 EDN: YBJWLK
- Карлов В.А. Учение об эпилептической системе. Заслуга отечественной научной школы // Эпилепсия и пароксизмальные состояния. 2017. Т. 9, № 4. С. 76–85. [Karlov VA. The concept of the «epileptic system» is credited to russian medical science. Epilepsy and paroxysmal conditions. 2017;9(4):76–85]. doi: 10.17749/2077-8333.2017.9.4.076-085 EDN: YQDIAL
- Wang ZM, Wei PH, Wang C, et al. Combined [18F]FDG-PET with MRI structural patterns in predicting post-surgical seizure outcomes in temporal lobe epilepsy patients. Eur Radiol. 2022;32(12):8423–8431. doi: 10.1007/s00330-022-08912-2 EDN: VHUMNC
Supplementary files





