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Cascade-Amplified Ratiometric Fluorescent Probe for Time-Locked Imaging Epilepsy.

Xin Wang1, Bohan Li1, Min Li1

  • 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.

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Summary
This summary is machine-generated.

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.

Keywords:
epilepsyfluorescenceimaging‐guided surgerypolymerratiometric imaging

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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.