OBJECTIVE: To explore the utility of high frequency oscillations (HFO) and long-range temporal correlations (LRTCs) in preoperative assessment of epilepsy.
METHODS: MEG ripples were detected in 59 drug-resistant epilepsy patients, comprising 5 with parietal lobe epilepsy (PLE), 21 with frontal lobe epilepsy (FLE), 14 with lateral temporal lobe epilepsy (LTLE), and 19 with mesial temporal lobe epilepsy (MTLE) to identify the epileptogenic zone (EZ). The results were compared with clinical MEG reports and resection area. Subsequently, LRTCs were quantified at the source-level by detrended fluctuation analysis (DFA) and life/waiting -time at 5 bands for 90 cerebral cortex regions. The brain regions with larger DFA exponents and standardized life-waiting biomarkers were compared with the resection results.
RESULTS: Compared to MEG sensor-level data, ripple sources were more frequently localized within the resection area. Moreover, source-level analysis revealed a higher proportion of DFA exponents and life-waiting biomarkers with relatively higher rankings, primarily distributed within the resection area (p<0.01). Moreover, these two LRCT indices across five distinct frequency bands correlated with EZ.
CONCLUSIONS: HFO and source-level LRTCs are correlated with EZ. Integrating HFO and LRTCs may be an effective approach for presurgical evaluation of epilepsy.

OBJECTIVE: Accurate detection of focal cortical dysplasia (FCD) through magnetic resonance imaging (MRI) plays a pivotal role in the preoperative assessment of epilepsy. The integration of multimodal imaging has demonstrated substantial value in both diagnosing FCD and devising effective surgical strategies. This study aimed to enhance MRI post-processing by incorporating positron emission tomography (PET) analysis. We sought to compare the diagnostic efficacy of diverse image post-processing methodologies in patients presenting MRI-negative FCD.
METHODS: In this retrospective investigation, we assembled a cohort of patients with negative preoperative MRI results. T1-weighted volumetric sequences were subjected to morphometric analysis program (MAP) and composite parametric map (CPM) post-processing techniques. We independently co-registered images derived from various methods with PET scans. The alignment was subsequently evaluated, and its correlation was correlated with postoperative seizure outcomes.
RESULTS: A total of 41 patients were enrolled in the study. In the PET-MAP(p = 0.0189) and PET-CPM(p = 0.00041) groups, compared with the non-overlap group, the overlap group significantly associated with better postoperative outcomes. In PET(p = 0.234), CPM(p = 0.686) and MAP(p = 0.672), there is no statistical significance between overlap and seizure-free outcomes. The sensitivity of using the CPM alone outperformed the MAP (0.65 vs 0.46). The use of PET-CPM demonstrated superior sensitivity (0.96), positive predictive value (0.83), and negative predictive value (0.91), whereas the MAP displayed superior specificity (0.71).
CONCLUSIONS: Our findings suggested a superiority in sensitivity of CPM in detecting potential FCD lesions compared to MAP, especially when it is used in combination with PET for diagnosis of MRI-negative epilepsy patients. Moreover, we confirmed the superiority of synergizing metabolic imaging (PET) with quantitative maps derived from structural imaging (MAP or CPM) to enhance the identification of subtle epileptogenic zones (EZs). This study serves to illuminate the potential of integrated multimodal techniques in advancing our capability to pinpoint elusive pathological features in epilepsy cases.

OBJECTIVE: Interictal blood-brain barrier dysfunction in chronic epilepsy has been demonstrated in animal models and pathological specimens. Ictal blood-brain barrier dysfunction has been shown in humans in vivo using an experimental quantitative magnetic resonance imaging (MRI) protocol. Here, we hypothesized that interictal blood-brain barrier dysfunction is also present in people with drug-resistant epilepsy.
METHODS: Thirty-nine people (21 females, mean age at MRI ± SD = 30 ± 8 years) with drug-resistant epilepsy were prospectively recruited and underwent interictal T1-relaxometry before and after administration of a paramagnetic contrast agent. Likewise, quantitative T1 was acquired in 29 people without epilepsy (12 females, age at MRI = 48 ± 18 years). Quantitative T1 difference maps were calculated and served as a surrogate imaging marker for blood-brain barrier dysfunction. Values of quantitative T1 difference maps inside hemispheres ipsilateral to the presumed seizure onset zone were then compared, on a voxelwise level and within presumed seizure onset zones, to the contralateral side of people with epilepsy and to people without epilepsy.
RESULTS: Compared to the contralateral side, ipsilateral T1 difference values were significantly higher in white matter (corrected p < .05), gray matter (uncorrected p < .05), and presumed seizure onset zones (p = .04) in people with epilepsy. Compared to people without epilepsy, significantly higher T1 difference values were found in the anatomical vicinity of presumed seizure onset zones (p = .004). A subgroup of people with hippocampal sclerosis demonstrated significantly higher T1 difference values in the ipsilateral hippocampus and in regions strongly interconnected with the hippocampus compared to people without epilepsy (corrected p < .01). Finally, z-scores reflecting the deviation of T1 difference values within the presumed seizure onset zone were associated with verbal memory performance (p = .02) in people with temporal lobe epilepsy.
CONCLUSIONS: Our results indicate a blood-brain barrier dysfunction in drug-resistant epilepsy that is detectable interictally in vivo, anatomically related to the presumed seizure onset zone, and associated with cognitive deficits.

Epilepsy is one of the most frequent neurological conditions with an estimated prevalence of more than 50 million people worldwide and an annual incidence of two million. Although pharmacotherapy with anti-seizure medication (ASM) is the treatment of choice, ~30% of patients with epilepsy do not respond to ASM and become drug resistant. Focal epilepsy is the most frequent form of epilepsy. In patients with drug-resistant focal epilepsy, epilepsy surgery is a treatment option depending on the localisation of the seizure focus for seizure relief or seizure freedom with consecutive improvement in quality of life. Beside examinations such as scalp video/electroencephalography (EEG) telemetry, structural, and functional magnetic resonance imaging (MRI), which are primary standard tools for the diagnostic work-up and therapy management of epilepsy patients, molecular neuroimaging using different radiopharmaceuticals with single-photon emission computed tomography (SPECT) and positron emission tomography (PET) influences and impacts on therapy decisions. To date, there are no literature-based praxis recommendations for the use of Nuclear Medicine (NM) imaging procedures in epilepsy. The aims of these guidelines are to assist in understanding the role and challenges of radiotracer imaging for epilepsy; to provide practical information for performing different molecular imaging procedures for epilepsy; and to provide an algorithm for selecting the most appropriate imaging procedures in specific clinical situations based on current literature. These guidelines are written and authorized by the European Association of Nuclear Medicine (EANM) to promote optimal epilepsy imaging, especially in the presurgical setting in children, adolescents, and adults with focal epilepsy. They will assist NM healthcare professionals and also specialists such as Neurologists, Neurophysiologists, Neurosurgeons, Psychiatrists, Psychologists, and others involved in epilepsy management in the detection and interpretation of epileptic seizure onset zone (SOZ) for further treatment decision. The information provided should be applied according to local laws and regulations as well as the availability of various radiopharmaceuticals and imaging modalities.

We aimed to develop a new approach for identifying the localization of the seizure onset zone (SOZ) based on corticocortical evoked potentials (CCEPs) and to compare the connectivity patterns in patients with different clinical phenotypes.
Fifty patients who underwent stereoelectroencephalography and CCEP procedures were included. Logistic regression was used in the model, and six CCEP metrics were input as features: root mean square of the first peak (N1RMS) and second peak (N2RMS), peak latency, onset latency, width duration, and area.
The area under the curve (AUC) for localizing the SOZ ranged from 0.88 to 0.93. The N1RMS values in the hippocampus sclerosis (HS) group were greater than that of the focal cortical dysplasia (FCD) IIa group (p < 0.001), independent of the distance between the recorded and stimulated sites. The sensitivity of localization was higher in the seizure-free group than in the non-seizure-free group (p = 0.036).
This new method can be used to predict the SOZ localization in various focal epilepsy phenotypes.
This study proposed a machine-learning approach for localizing the SOZ. Moreover, we examined how clinical phenotypes impact large-scale abnormality of the epileptogenic networks.

OBJECTIVE: Individuals with drug-resistant epilepsy may benefit from epilepsy surgery. In nonlesional cases, where no epileptogenic lesion can be detected on structural magnetic resonance imaging, multimodal neuroimaging studies are required. Breath-hold-triggered BOLD fMRI (bh-fMRI) was developed to measure cerebrovascular reactivity in stroke or angiopathy and highlights regional network dysfunction by visualizing focal impaired flow increase after vasodilatory stimulus. This regional dysfunction may correlate with the epileptogenic zone. In this prospective single-center single-blind pilot study, we aimed to establish the feasibility and safety of bh-fMRI in individuals with drug-resistant non-lesional focal epilepsy undergoing presurgical evaluation.
METHODS: In this prospective study, 10 consecutive individuals undergoing presurgical evaluation for drug-resistant focal epilepsy were recruited after case review at a multidisciplinary patient management conference. Electroclinical findings and results of other neuroimaging were used to establish the epileptogenic zone hypothesis. To calculate significant differences in cerebrovascular reactivity in comparison to the normal population, bh-fMRIs of 16 healthy volunteers were analyzed. The relative flow change of each volume of interest (VOI) of the atlas was then calculated compared to the flow change of the whole brain resulting in an atlas of normal cerebral reactivity. Consequently, the mean flow change of every VOI of each patient was tested against the healthy volunteers group. Areas with significant impairment of cerebrovascular reactivity had decreased flow change and were compared to the epileptogenic zone localization hypothesis in a single-blind design.
RESULTS: Acquisition of bh-fMRI was feasible in 9/10 cases, with one patient excluded due to noncompliance with breathing maneuvers. No adverse events were observed, and breath-hold for intermittent hypercapnia was well tolerated. On blinded review, we observed full or partial concordance of the local network dysfunction seen on bh-fMRI with the electroclinical hypothesis in 6/9 cases, including cases with extratemporal lobe epilepsy and those with nonlocalizing 18F-fluorodeoxyglucose positron emission tomography (FDG-PET).
CONCLUSIONS: This represents the first report of bh-fMRI in individuals with epilepsy undergoing presurgical evaluation. We found bh-fMRI to be feasible and safe, with a promising agreement to electroclinical findings. Thus, bh-fMRI may represent a potential modality in the presurgical evaluation of epilepsy. Further studies are needed to establish clinical utility.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is the seventh leading cause of cancer-related deaths worldwide. Surgical resection is the main driver to improving survival in resectable tumors, while neoadjuvant treatment based on chemotherapy (and radiotherapy) is the best option-treatment for a non-primally resectable disease. CT-based imaging has a central role in detecting, staging, and managing PDAC. As several authors have proposed radiomics for risk stratification in patients undergoing surgery for PADC, in this narrative review, we have explored the actual fields of interest of radiomics tools in PDAC built on pre-surgical imaging and clinical variables, to obtain more objective and reliable predictors.
METHODS: The PubMed database was searched for papers published in the English language no earlier than January 2018.
RESULTS: We found 301 studies, and 11 satisfied our research criteria. Of those included, four were on resectability status prediction, three on preoperative pancreatic fistula (POPF) prediction, and four on survival prediction. Most of the studies were retrospective.
CONCLUSIONS: It is possible to conclude that many performing models have been developed to get predictive information in pre-surgical evaluation. However, all the studies were retrospective, lacking further external validation in prospective and multicentric cohorts. Furthermore, the radiomics models and the expression of results should be standardized and automatized to be applicable in clinical practice.

Diffusion tensor imaging (DTI)-tractography and functional magnetic resonance imaging (fMRI) have dynamically entered the presurgical evaluation context of brain surgery during the past decades, providing novel perspectives in surgical planning and lesion access approaches. However, their application in the presurgical setting requires significant time and effort and increased costs, thereby raising questions regarding efficiency and best use. In this work, we set out to evaluate DTI-tractography and combined fMRI/DTI-tractography during intra-operative neuronavigation in resective brain surgery using lesion-related preoperative neurological deficit (PND) outcomes as metrics. We retrospectively reviewed medical records of 252 consecutive patients admitted for brain surgery. Standard anatomical neuroimaging protocols were performed in 127 patients, 69 patients had additional DTI-tractography, and 56 had combined DTI-tractography/fMRI. fMRI procedures involved language, motor, somatic sensory, sensorimotor and visual mapping. DTI-tractography involved fiber tracking of the motor, sensory, language and visual pathways. At 1 month postoperatively, DTI-tractography patients were more likely to present either improvement or preservation of PNDs (p = 0.004 and p = 0.007, respectively). At 6 months, combined DTI-tractography/fMRI patients were more likely to experience complete PND resolution (p < 0.001). Low-grade lesion patients (N = 102) with combined DTI-tractography/fMRI were more likely to experience complete resolution of PNDs at 1 and 6 months (p = 0.001 and p < 0.001, respectively). High-grade lesion patients (N = 140) with combined DTI-tractography/fMRI were more likely to have PNDs resolved at 6 months (p = 0.005). Patients with motor symptoms (N = 80) were more likely to experience complete remission of PNDs at 6 months with DTI-tractography or combined DTI-tractography/fMRI (p = 0.008 and p = 0.004, respectively), without significant difference between the two imaging protocols (p = 1). Patients with sensory symptoms (N = 44) were more likely to experience complete PND remission at 6 months with combined DTI-tractography/fMRI (p = 0.004). The intraoperative neuroimaging modality did not have a significant effect in patients with preoperative seizures (N = 47). Lack of PND worsening was observed at 6 month follow-up in patients with combined DTI-tractography/fMRI. Our results strongly support the combined use of DTI-tractography and fMRI in patients undergoing resective brain surgery for improving their postoperative clinical profile.

This work investigates verbal memory functional MRI (fMRI) versus language fMRI in terms of lateralization, and assesses the validity of performing word recognition during the functional scan.
Thirty patients with a diagnosis of epilepsy underwent verbal memory, visuospatial memory, and language fMRI. We used word encoding, word recognition, image encoding, and image recognition memory tasks, and semantic description, reading comprehension, and listening comprehension language tasks. We used three common lateralization metrics: network spatial distribution, maximum statistical value, and laterality index (LI).
Lateralization of signal spatial distribution resulted in poor similarity between verbal memory and language fMRI tasks. Signal maximum lateralization showed significant (>.8) but not perfect (1) similarity. Word encoding LI showed significant correlation only with listening comprehension LI (p = .016). Word recognition LI was significantly correlated with expressive language semantic description LI (p = .024) and receptive language reading and listening comprehension LIs (p = .015 and p = .019, respectively). There was no correlation between LIs of the visuospatial tasks and LIs of the language tasks.
Our results support the association between language and verbal memory lateralization, optimally determined by LI quantification, and the introduction of quantitative means for language fMRI interpretation in clinical settings where verbal memory lateralization is imperative.

BACKGROUND: High-density EEG (hdEEG) is a validated tool in presurgical evaluation of people with epilepsy. The aim of this national survey is to estimate diffusion and knowledge of hdEEG to develop a network among Italian epilepsy centers.
METHODS: A survey of 16 items (and 15 additional items) was distributed nationwide by email to all members of the Italian League Against Epilepsy and the Italian Society of Clinical Neurophysiology. The data obtained were analyzed using descriptive statistics.
RESULTS: A total of 104 respondents were collected from 85 centers, 82% from the Centre-North of Italy; 27% of the respondents had a hdEEG. The main applications were for epileptogenic focus characterization in the pre-surgical evaluation (35%), biomarker research (35%) and scientific activity (30%). The greatest obstacles to hdEEG were economic resources (35%), acquisition of dedicated personnel (30%) and finding expertise (17%). Dissemination was limited by difficulties in finding expertise and dedicated personnel (74%) more than buying devices (9%); 43% of the respondents have already published hdEEG data, and 91% of centers were available to participate in multicenter hdEEG studies, helping in both pre-processing and analysis. Eighty-nine percent of respondents would be interested in referring patients to centers with established experience for clinical and research purposes.
CONCLUSIONS: In Italy, hdEEG is mainly used in third-level epilepsy centers for research and clinical purposes. HdEEG diffusion is limited not only by costs but also by lack of trained personnel. Italian centers demonstrated a high interest in educational initiatives on hdEEG as well as in clinical and research collaborations.