Background:When investigating suitability for epilepsy surgery, people with drug-refractory focal epilepsy may have intracranial EEG (iEEG) electrodes implanted to localise seizure onset. Diffusion-weighted magnetic resonance imaging (dMRI) may be acquired to identify key white matter tracts for surgical avoidance. Here, we investigate whether structural connectivity abnormalities, inferred from dMRI, may be used in conjunction with functional iEEG abnormalities to aid localisation of the epileptogenic zone (EZ), improving surgical outcomes in epilepsy. Methods:We retrospectively investigated data from 43 patients with epilepsy who had surgery following iEEG. Twenty-five patients (58%) were free from disabling seizures (ILAE 1 or 2) at one year. Interictal iEEG functional, and dMRI structural connectivity abnormalities were quantified by comparison to a normative map and healthy controls. We explored whether the resection of maximal abnormalities related to improved surgical outcomes, in both modalities individually and concurrently. Additionally, we suggest how connectivity abnormalities may inform the placement of iEEG electrodes pre-surgically using a patient case study. Findings:Seizure freedom was 15 times more likely in patients with resection of maximal connectivity and iEEG abnormalities (p=0.008). Both modalities separately distinguished patient surgical outcome groups and when used simultaneously, a decision tree correctly separated 36 of 43 (84%) patients. Interpretation:Our results suggest that both connectivity and iEEG abnormalities may localise epileptogenic tissue, and that these two modalities may provide complementary information in pre-surgical evaluations. Funding:This research was funded by UKRI, CDT in Cloud Computing for Big Data, NIH, MRC, Wellcome Trust and Epilepsy Research UK.

The identification of abnormal electrographic activity is important in a wide range of neurological disorders, including epilepsy for localising epileptogenic tissue. However, this identification may be challenging during non-seizure (interictal) periods, especially if abnormalities are subtle compared to the repertoire of possible healthy brain dynamics. Here, we investigate if such interictal abnormalities become more salient by quantitatively accounting for the range of healthy brain dynamics in a location-specific manner. To this end, we constructed a normative map of brain dynamics, in terms of relative band power, from interictal intracranial recordings from 234 subjects (21,598 electrode contacts). We then compared interictal recordings from 62 patients with epilepsy to the normative map to identify abnormal regions. We hypothesised that if the most abnormal regions were spared by surgery, then patients would be more likely to experience continued seizures post-operatively. We first confirmed that the spatial variations of band power in the normative map across brain regions were consistent with healthy variations reported in the literature. Second, when accounting for the normative variations, regions which were spared by surgery were more abnormal than those resected only in patients with persistent post-operative seizures (t=-3.6, p=0.0003), confirming our hypothesis. Third, we found that this effect discriminated patient outcomes (AUC=0.75 p=0.0003). Normative mapping is a well-established practice in neuroscientific research. Our study suggests that this approach is feasible to detect interictal abnormalities in intracranial EEG, and of potential clinical value to identify pathological tissue in epilepsy. Finally, we make our normative intracranial map publicly available to facilitate future investigations in epilepsy and beyond.

Neocortical epilepsy surgery fails to achieve post-operative seizure freedom in 30-40% of cases. It is not fully understood why surgical interventions in some patients are unsuccessful. Comparing interictal MEG bandpower from patient data to normative maps, which describe healthy spatial and population variability, we identify patient specific abnormalities relating to surgical failure. Here we propose three possible mechanisms that could contribute to a poor surgical outcome; 1) failure to resect the epileptogenic abnormalities (mislocalisation), 2) failing to remove all of the epileptogenic abnormalities (partial resection), and 3) insufficiently impacting the overall cortical abnormality. In this study we develop markers of these mechanisms, validating them against patient outcomes. Resting-state eyes-closed MEG recordings were acquired for 70 healthy controls and 32 patients with refractory neocortical epilepsy. Relative band power spatial maps for five frequency bands were computed using source localised recordings from healthy controls. Patient and region-specific bandpower abnormalities were estimated as the maximum absolute z-score across all five frequency bands using healthy data as a baseline. Resected regions were identified using postoperative T1w MRI. We hypothesised that our mechanistically interpretable markers would discriminate patients with and without post-operative seizure freedom (ILAE 1 vs ILAE 2+). targeted: AUC=0.80, p=0.003, Partial resection of the epileptogenic zone: AUC=0.68, p=0.053, Insufficient cortical abnormality impact: AUC=0.64, p=0.096), performing as well as commonly collected clinical demographics. Leveraging all mechanisms together found that 95% of those who were not seizure free had markers of surgical failure for at least one of the three proposed mechanisms. In contrast, of those patients without markers for any mechanism, 80% were ultimately seizure-free post-surgically.

ObjectivesAutomated planning of stereoelectroencephalography (SEEG) electrode trajectories is dependent on vessel segmentation.1We quantify imaging protocols ability to measure trajectory-to-vessel distance.DesignRetrospective analysis.SubjectsTen consecutive patients were selected whom had SEEG implantation (95 electrodes) and Digital Catheter Subtraction Angiography (DSA) with catheterization of carotid or vertebral arteries, post-gadolinium T1-weighted (GAD), phase-contrast MR angiography and MR venography (MR) acquired.MethodsSEEG trajectories were planned manually with DSA. Minimum distance to vessels and risk1were computed for each trajectory using vessel segmentation from GAD, MR, or DSA. Vessel size was considered by including DSA vessels diameters above 1, 2, 3, or 4 mm.ResultsMinimum distance to a vessel was 6.2±3.9 mm (GAD), 2.5±1.6 mm (MR), and 1.5±1.2 mm (DSA). Based on DSA vessel size minimum distances were 2.0±1.5 mm (DSA >1 mm), 3.4±2.6 (DSA >2 mm), 6.6±4.6 mm (DSA >3 mm), and 11.8±7.9 mm (DSA >4 mm). Risk was 0.4±0.4 (GAD), 0.8±0.4 (MR), and 1.1±0.2 (all DSA), 1.0±0.2 (DSA >1 mm), 0.7±0.4 (DSA >2 mm), 0.4±0.5 (DSA >3 mm), and 0.2±0.3 (DSA >4 mm).ConclusionsDSA is best able to segment vessels. MR has metrics similar to DSA vessels above 2 mm. GAD has metrics similar to DSA vessels above 3 mm.

Background Breathing pattern cannot be controlled in small children, so multiple breath washout SnIII analysis has to exclude inadequate volume breaths. Aim To compare an existing mathematical breath exclusion algorithm with a physiological method. Methods School age children with CF (30) and controls (30) performed SF6MBW with mass spectrometer, with uncontrolled tidal breathing. Two different breath exclusion methods were compared, with exclusion based on: 1) Expired tidal volume (VT) deviating by >25% of the median VT1 2) VT <3 Langley dead space2 volume or 90% bigger than the median VT Runs with >33% excluded breaths were removed. Volume corrected Scond was calculated from subjects with 3 valid runs. Results Far fewer subjects were excluded by the physiological Langley method, than by the mathematical method (Table). The mean and SD for Scond was identical by both methods, implying that the mathematical algorithm excludes valid data. Conclusion A physiological approach to data cleaning prior to SnIII analysis allows retention of data that would be inappropriately excluded mathematically. References Bigler A, et al. Paediatric Pulmonol 2015;50(8):805–13. Langley FE, et al. Colloques INSERM 1975;51:209–212.