Accurate localization of epileptogenic tubers (ETs) in patients with tuberous sclerosis complex (TSC) is essential but challenging because ETs lack distinct pathological or genetic markers that differentiate them from other cortical tubers. Approximately 60% of patients fail to have their ETs identified through noninvasive preoperative evaluations, highlighting the clinical need for an efficient, noninvasive ET localization method.

Using MRI data from training datasets, we developed a novel noninvasive fusion model that combines a risk model based on lesion network mapping with a prediction model using brain functional connectivity and random forest algorithms. A retrospective analysis was conducted on TSC patients with epilepsy who underwent resective surgery. Tubers were classified as true-ETs, false-ETs, or true non-ETs based on resection locations and postoperative seizure-freedom. The model calculated and ranked the ET probability for each tuber for every patient, and its accuracy was assessed based on postoperative seizure outcomes.

Inclusion Criteria:

(1) male or female patients aged ≥6 months; (2) patients meeting the diagnostic criteria for TSC according to Northrup's guidelines;17 (3) patients in whom the clinical evaluation determined that a single surgical target, or hypothesized primary EZ, was identified by a multidisciplinary specialist team at epilepsy centers of Beijing Children's Hospital, PLA General Hospital, or Shenzhen Children's Hospital in China; (4) patients who underwent resective surgery between July 2016 and June 2023, with a 1-year follow-up completed by June 2024; and (5) availability of patients with available preoperative and postoperative MRI T2-Flair imaging.

Exclusion Criteria:

• (1) patients with a history of craniotomy, serious head injury, neuromodulation therapy, or corpus callosotomy before or within one year after the resective surgery; and (2) subjects lacking key clinical or MRI data. This study was approved by the Ethics Commission of Beijing Children's Hospital.