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Objective In the presurgical workup of MRI-negative (MRI−, or “nonlesional”) pharmacoresistant focal epilepsy (PFE) patients, discovering a previously undetected lesion can drastically change the evaluation and likely improve surgical outcome. Our study utilizes a voxel-based MRI post-processing technique, implemented in a morphometric analysis program (MAP), to facilitate detection of subtle abnormalities in a consecutive cohort of MRI− surgical candidates. Methods Included in this retrospective study was a consecutive cohort of 150 MRI-surgical patients. MAP was performed on T1-weighted MRI, with comparison to a scanner-specific normal database. Review and analysis of MAP were performed blinded to patients’ clinical information. The pertinence of MAP+ areas was confirmed by surgical outcome and pathology. Results MAP showed a 43% positive rate, sensitivity of 0.9 and specificity of 0.67. Overall, patients with MAP+ region completely resected had the best seizure outcomes, followed by the MAP− patients, and patients who had no/partial resection of the MAP+ region had the worst outcome (p<0.001). Subgroup analysis revealed that visually identified subtle findings are more likely correct if also MAP+. False-positive rate in 52 normal controls was 2%. Surgical pathology of the resected MAP+ areas contained mainly non-balloon-cell FCD. Multiple MAP+ regions were present in 7% of patients. Conclusions MAP can be a practical and valuable tool to: (1) guide the search for subtle MRI abnormalities, and (2) confirm visually identified questionable abnormalities in patients with PFE due to suspected FCD. A MAP+ region, when concordant with the patient’s electro-clinical presentation, should provide a legitimate target for surgical exploration.

Objective MRI-negative (MRI–) pharmacoresistant focal epilepsy (PFE) patients are most challenging for epilepsy surgical management. This study utilizes a voxel-based MRI postprocessing technique, implemented using a morphometric analysis program (MAP), aiming to facilitate detection of subtle focal cortical dysplasia (FCD) in MRI– patients. Furthermore, the study examines the concordance between MAP-identified regions and localization from magnetic source imaging (MSI). Methods Included in this retrospective study were 25 MRI– surgical patients. MAP was performed on T1-weighted MRI, with comparison to a normal database. The pertinence of MAP+ areas was confirmed by MSI, surgical outcome and pathology. Analyses of MAP and MSI were performed blindly from patients' clinical information and independently from each other. Results The detection rate of subtle changes by MAP was 48% (12/25). Once MAP+ areas were resected, patients were more likely to be seizure-free (p = 0.02). There were no false positives in the 25 age-matched normal controls. Seven patients had a concordant MSI correlate. Patients in whom a concordant area was identified by both MAP and MSI had a significantly higher chance of achieving a seizure-free outcome following complete resection of this area (p = 0.008). In the 9 resected MAP+ areas, pathology revealed FCD type IA in 7 and type IIB in 2. Interpretation MAP shows promise in identifying subtle FCD abnormalities and increasing the diagnostic yield of conventional MRI visual analysis in presurgical evaluation of PFE. Concordant MRI postprocessing and MSI analyses may lead to the noninvasive identification of a structurally and electrically abnormal subtle lesion that can be surgically targeted.

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