Epilepsy is a recurrent, episodic, and complex neurological syndrome characterized by an enduring predisposition to epileptic seizures and consequent neurological, cognitive, psychological, and social problems. [1] An epileptic seizure is a transient occurrence of symptoms (such as temporary confusion, staring spells, uncontrollable jerking, and loss of awareness) caused by abnormal neuronal electrical activities. [2] As a serious health problem, epilepsy affects ≈1% of the global population, [3] and nearly 5 million people worldwide are diagnosed with epilepsy every year. Although there are now more than 20 antiseizure medications (ASMs) in active clinical use, [4] ≈20-30% of epilepsy patients fail to achieve sustained seizure freedom after adequate trial of two appropriately chosen ASMs. [5] These drugresistant epilepsy (DRE) patients are at an increased risk of injury and death, [6] unbearable medication burden and adverse effects, increased psychiatric and neurocognitive comorbidities, [7] and socioeconomic disadvantage. Therefore, the management of DRE in the clinic is a major challenge.Resection of the epileptic foci (EF), defined as the minimum area of the brain tissue that must be resected or disconnected for the abolishment of seizures, [8] is the most efficient approach for the treatment of DRE patients. [9] First, epilepsy surgery increases the prospects of patients being seizure-free. [10] Approximately 52% of the patients have no disabling seizures for 5 years after surgery, and nearly half of the patients remain free from seizures for 10 years. [11] Second, surgical treatment reduces DRE patients' mortality by two to three times [12] and extends life expectancy by an average of 5 years in comparison to patients who have received drug therapy. [13] Third, epilepsy surgery reduces individual medical expenditures for families. [14] Overall, these results suggest that DRE is potentially curable with surgical intervention. Accurate identification of the EF is a prerequisite for achieving satisfactory postsurgical outcomes. [15] However, only a small percentage of patients is recommended for surgical treatment because of the difficulty in defining EF. First, an initial clinical assessment, including history of epilepsy, semiology information, drug history, and comorbidity, will be performed in the clinic to confirm whether the patients are suitable for surgery. Next, high-resolution structural magnetic resonance imaging (MRI) and long-term inpatient video electroencephalography (EEG) are conducted. [16] If MRI shows Excising epileptic foci (EF) is the most efficient approach for treating drugresistant epilepsy (DRE). However, owing to the vast heterogeneity of epilepsies, EF in one-third of patients cannot be accurately located, even after exhausting all current diagnostic strategies. Therefore, identifying biomarkers that truly represent the status of epilepsy and fabricating probes with high targeting specificity are prerequisites for identifying the "concealed" EF. However, no systematic summary of thi...