1. Academic Validation
  2. A Neuronal Signal Sorting and Amplifying Nanosensor for EEG-Concordant Imaging-Guided Precision Epilepsy Ablation

A Neuronal Signal Sorting and Amplifying Nanosensor for EEG-Concordant Imaging-Guided Precision Epilepsy Ablation

  • Adv Mater. 2024 Dec 15:e2408864. doi: 10.1002/adma.202408864.
Qiyue Wang 1 2 Sirui Cui 3 Dao Shi 2 Pan Tao 2 Chencheng Zhang 4 Fang Wang 5 Peihua Lin 2 Fangyuan Li 1 3 Daishun Ling 2
Affiliations

Affiliations

  • 1 Department of Clinical Laboratory, Songjiang Research Institute, Shanghai Key Laboratory of Emotions and Affective Disorders (LEAD), Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 201600, China.
  • 2 Frontiers Science Center for Transformative Molecules, School of Chemistry and Chemical Engineering, School of Biomedical Engineering, National Center for Translational Medicine, State Key Laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University, Shanghai, 200240, China.
  • 3 Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.
  • 4 Department of Neurosurgery, Clinical Neuroscience Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
  • 5 Clinical Research Center for Mental Disorders, Shanghai Pudong New Area Mental Health Center, School of Medicine, Tongji University, Shanghai, 200124, China.
Abstract

Surgery remains an essential treatment for managing drug-resistant focal epilepsy, but its accessibility and efficacy are limited in patients without distinct structural abnormalities on magnetic resonance imaging (MRI). Potassium ion (K+), a critical marker for seizure-associated Neuronal Signaling, shows significant promise for designing sensors targeting hidden epileptic foci. However, existing sensors cannot cross the blood-brain barrier and lack the ability to specifically enrich and amplify K+ signals in the brain with high temporal and spatial resolution. Here, an intravenously administered neuronal signal sorting and amplifying nanosensor (NSAN) is reported that combines real-time dynamic reversible K+ fluorescence imaging with high-resolution structural MRI, enabling electroencephalogram-concordant imaging of MRI-negative epileptic foci. Guided by NSANs, minimally invasive surgery is successfully performed in both intrahippocampal kainic acid (KA) epilepsy model with foci confined to the ipsilateral hippocampus, and intraperitoneal KA model where foci are randomly distributed, resulting in sustained seizure control and cognitive improvement. These findings highlight the NSAN as a transformative tool for visualizing hidden epileptic foci, thereby broadening eligibility for minimally invasive and precision surgical intervention.

Keywords

dual‐mode imaging; imaging‐guided surgery; nanosensors; neurological disease; potassium ions.

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