One outstanding challenge for machine learning in diagnostic biomedical imaging is algorithm interpretability. A key application is the identification of subtle epileptogenic focal cortical dysplasias (FCDs) from structural MRI. FCDs are difficult to visualize on structural MRI but are often amenable to surgical resection. We aimed to develop an open-source, interpretable, surface-based machine-learning algorithm to automatically identify FCDs on heterogeneous structural MRI data from epilepsy surgery centres worldwide. The Multi-centre Epilepsy Lesion Detection (MELD) Project collated and harmonized a retrospective MRI cohort of 1015 participants, 618 patients with focal FCD-related epilepsy and 397 controls, from 22 epilepsy centres worldwide. We created a neural network for FCD detection based on 33 surface-based features. The network was trained and cross-validated on 50% of the total cohort and tested on the remaining 50% as well as on 2 independent test sites. Multidimensional feature analysis and integrated gradient saliencies were used to interrogate network performance. Our pipeline outputs individual patient reports, which identify the location of predicted lesions, alongside their imaging features and relative saliency to the classifier. On a restricted ‘gold-standard’ subcohort of seizure-free patients with FCD type IIB who had T1 and fluid-attenuated inversion recovery MRI data, the MELD FCD surface-based algorithm had a sensitivity of 85%. Across the entire withheld test cohort the sensitivity was 59% and specificity was 54%. After including a border zone around lesions, to account for uncertainty around the borders of manually delineated lesion masks, the sensitivity was 67%. This multicentre, multinational study with open access protocols and code has developed a robust and interpretable machine-learning algorithm for automated detection of focal cortical dysplasias, giving physicians greater confidence in the identification of subtle MRI lesions in individuals with epilepsy.

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Objective:Focal cortical dysplasia (FCD) has been associated with poorer post-surgical seizure outcomes compared to other pathologies. FCD surgical series have been assembled on the basis of a histological diagnosis, including patients with abnormal as well as normal pre-operative MRI. However, in clinical workflow, patient selection for surgery is based on pre-operative findings, including MRI. We performed a systematic review and meta-analysis of the literature to determine the rate and predictors of favorable seizure outcome after surgery for MRI-detected FCD.Methods:We devised our study protocol in accordance with PRISMA guidelines and registered the protocol with PROSPERO. We searched MEDLINE, EMBASE, and Web of Science for studies of patients followed for ≥12 months after resective surgery for drug-resistant epilepsy with MRI-detected FCD. Random-effects meta-analysis was used to calculate the proportion of patients attaining a favorable outcome, defined as Engel Class I, ILAE Classes 1-2, or “seizure-free” status. Meta-regression was performed to investigate sources of heterogeneity.Results:Our search identified 3,745 references. Of these, 35 studies (total of 1,353 patients) were included. Most studies (89%) followed patients for ≥24 months post-surgery. The overall post-surgical favorable outcome rate was 70% (95% CI: 64-75). There was high inter-study heterogeneity. Favorable outcome was associated with complete resection of the FCD lesion [risk ratio, RR=2.42 (95% CI: 1.55-3.76), p<0.001] and location of the FCD lesion in the temporal lobe [RR=1.38 (95% CI: 1.07-1.79), p=0013], but not lesion extent, intracranial EEG use, or FCD histological type. The number of FCD histological types included in the same study accounted for 7.6% of the observed heterogeneity.Conclusions:70% of patients with drug-resistant epilepsy and MRI features of FCD attain a favorable seizure outcome following resective surgery. Our findings can be incorporated in routine pre-operative counselling and reinforce the importance of resecting completely the MRI-detected FCD where this is safe and feasible.