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Published on: July 6, 2022
Ultrabright ratiometric Raman-guided epilepsy surgery by intraoperatively visualizing proinflammatory microglia
Cong Wang1, Zhi Li2, Xiao Zhu3
1MOE Key Laboratory of Smart Drug Delivery, MOE Innovative Center for New Drug Development of Immune Inflammatory Diseases, School of Pharmacy, Zhongshan Hospital, Fudan University, Shanghai, China; Greater Bay Area Institute of Precision Medicine (Guangzhou), Fudan University, Guangzhou, China; The Key Laboratory of Biomedical Imaging Science and System, Chinese Academy of Sciences, State Key Laboratory of Biomedical Imaging Science and System, Shenzhen 518055, China.
A new nanosensor, ultraHOCls, identifies activated microglia to precisely locate the epileptic focus (EF) for epilepsy surgery. This method significantly reduces seizure burden and offers a promising alternative to traditional electrocorticography mapping.
Area of Science:
- Neuroscience
- Biomaterials Science
- Surgical Innovation
Background:
- Drug-resistant focal epilepsy requires precise surgical removal of the epileptic focus (EF).
- Current intraoperative mapping using electrocorticography (ECoG) is limited by time, labor, and anesthetic interference.
- Activated microglia are potential biomarkers for identifying the EF.
Purpose of the Study:
- To develop and validate a novel nanosensor for visualizing activated microglia as biomarkers for EF localization.
- To compare the efficacy of ultraHOCl-guided surgery with ECoG-guided surgery in reducing seizure burden.
- To assess the diagnostic performance of ultraHOCls in discriminating epileptic from non-epileptic human brain tissue.
Main Methods:
- Development of a ratiometric Raman nanosensor, ultraHOCls, for visualizing proinflammatory microglia.
- Application of ultraHOCls in live epileptic mouse models for intraoperative EF delineation.
- Surgical intervention guided by ultraHOCl visualization versus ECoG in mouse models.
- Testing ultraHOCls on freshly excised human brain tissues for diagnostic accuracy.
Main Results:
- ultraHOCls successfully visualized proinflammatory microglia in live epileptic mice, enabling anesthesia-free EF delineation.
- ultraHOCl-guided surgery led to a 61% reduction in total seizure burden compared to ECoG-guided surgery.
- ultraHOCls demonstrated high sensitivity (94.89%) and specificity (93.3%) in discriminating epileptic human brain tissue.
Conclusions:
- Activated microglia visualized by ultraHOCls serve as reliable biomarkers for precise EF localization during epilepsy surgery.
- ultraHOCl-guided surgery offers a significant improvement in seizure control compared to traditional ECoG methods.
- This nanosensor technology presents a transformative approach for intraoperative EF delineation, potentially enhancing surgical outcomes for epilepsy patients.
