Rationale: We are pioneering the development of a bioimaging sensor technology, NMI, concomitantly with the development of innovative biosensors for diagnosing epilepsy patients. These are ongoing studies to image the neurotransmitter milieu in the intact neocortex of patients, in vivo, in NYU Tisch Hospital. Also ongoing are our studies in resected neocortical epileptogenic tissue which take place in CUNY. The purpose of this presentation is to compare NMI data derived during intra-operative imaging with NMI data derived from resected epileptogenic tissue.
Methods: The biosensor (BRODERICK PROBE®) is a laminar biocompatible micro/nano device, manufactured on site in CUNY; it is carbon-based, comprised of e.g. lipids. The biocables are designed and tested on site in CUNY and manufactured by Isotec, Seoul, Korea. We use a semiderivative voltammetric reduction circuit (Broderick, US Patent #5,938,903; 1999). NMI methods for epilepsy patients is published (Broderick & Pacia US Patent #7,112,319; 2006). Biosensors are γ-irradiated (11.6-12.7kGy) (Sterigenics,NJ). Neurochemicals are selectively imaged in neocortex during surgery and in cortical resected tissue. Intra-operative: After electroencephalographic (EEG) monitoring and placement of subdural grid and strip electrodes to identify epileptogenic cortex, biosensors (diameter 5 times less than epilepsy depth electrodes for invasive EEG) are placed by direct visualization in exposed cortical region destined for resection. Six recordings are taken for 1/2 hr, at 2 sites. Resected Tissue: Patient tissue (-80°C) is adapted to room temperature and biosensors are placed in 10 sites in the 6 layers of gray matter and 2 sites in white matter; recordings are taken for 2 hrs. In Vitro: Neurochemicals are aliquoted into phosphate buffer for calibration of signals/images (PA Broderick, SV Pacia, WK Doyle, O Devinsky, Brain Res. 878:48-63, 2000).
Results: Intra-operative Studies showed a predominance of L-tryptophan (L-TP) (precursor to 5-HT), and peptides (dynorphin (DYN A) and somatostatin (SRIF) over monoamines. Homovanillic acid (HVA) was present in higher concentrations during surgical imaging than recordings from resected tissue. Resected Tissue showed a predominance of L-TP, DYN A and SRIF over monoamines; monoamines in resected tissue were present in higher concentrations than was seen during surgical imaging. In Vitro Recordings showed each neurochemical imaged at experimentally derived signatures/oxidation potentials.
Conclusions: Preliminary results show that L-TP, DYN A and SRIF may be biomarkers for neurodegeneration. SRIF may be homeostatic whereas L-TP and DYN A (2-17) may be excitatory in epilepsy. The data suggest that voltage-gated calcium channels (VGCC) may be involved since glutamate release is modulated via N/P/Q and monoamines by L type VGCC (Haile et al., Amer. Soc. Anes. 2008). These studies will hopefully provide discovery of novel surgical and pharmacologic therapies for our epilepsy patients.