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Cascade-Amplified Ratiometric Fluorescent Probe for Time-Locked Imaging Epilepsy
1School of Pharmacy, MOE Key Laboratory of Smart Drug Delivery, MOE Innovative Center For New Drug Development of Immune Inflammatory Diseases, Department of Pharmacy, Zhongshan Hospital, Fudan University, Shanghai, China.
Advanced Materials (Deerfield Beach, Fla.)
|January 5, 2026
Summary
A new fluorescent probe, CAR-FM, precisely maps the epileptogenic network (EN) in epilepsy by detecting acidosis and neuroinflammation. This imaging strategy significantly improves seizure reduction after surgery.
Area of Science:
- Biomedical Imaging
- Neuroscience
- Materials Science
Background:
- Drug-resistant epilepsy affects over 15 million globally, necessitating accurate surgical targeting of the epileptogenic network (EN).
- Current EN localization methods lack specificity and sensitivity, leading to variable surgical success rates (30-70%).
- Transient epileptiform discharges and sustained neuroinflammation are key pathological features of the EN.
Purpose of the Study:
- To develop a novel imaging strategy for precise, sensitive, and specific intraoperative visualization of the EN.
- To address the limitations of current EN detection methods in drug-resistant epilepsy.
Main Methods:
- Development of a cascade-amplified ratiometric imaging probe (CAR-FM) targeting acidosis and neuroinflammation.
- Utilizing dual-cascade amplification for enhanced fluorescence ratio (>150-fold) with improved specificity and sensitivity.
- Testing CAR-FM in four epilepsy models for time-locked EN delineation up to 100 hours.
Main Results:
- CAR-FM achieved >150-fold fluorescence ratio enhancement, demonstrating superior specificity and sensitivity.
- The probe enabled time-locked EN delineation for up to 100 hours across multiple epilepsy models.
- CAR-FM-guided resection in mouse models resulted in a 67% greater reduction in seizure burden compared to conventional methods.
Conclusions:
- CAR-FM offers a highly sensitive and specific imaging tool for intraoperative EN visualization.
- This clinically translatable strategy has the potential to improve surgical outcomes and expand eligibility for epilepsy surgery.
- CAR-FM addresses critical unmet needs in the surgical management of drug-resistant epilepsy.
