Samuel J Hund1,2, Benjamin R Brown1, Coline L Lemale3,4, Prahlad G Menon1,5, Kirk A Easley6, Jens P Dreier3,4,7,8,9, Stephen C Jones10. 1. CerebroScope, SciencePlusPlease LLC, Pittsburgh, PA, USA. 2. SimulationSolutions, Pittsburgh, PA, USA. 3. Center for Stroke Research, Charité, - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany. 4. Department of Experimental Neurology, Charité, - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany. 5. Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA. 6. Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA, USA. 7. Department of Neurology, Charité, - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany. 8. Bernstein Center for Computational Neuroscience Berlin, Berlin, Germany. 9. Einstein Center for Neurosciences Berlin, Berlin, Germany. 10. CerebroScope, SciencePlusPlease LLC, Pittsburgh, PA, USA. sjones@cerebro-scope.com.
Abstract
BACKGROUND: Cortical spreading depolarization (SD) is a propagating depolarization wave of neurons and glial cells in the cerebral gray matter. SD occurs in all forms of severe acute brain injury, as documented by using invasive detection methods. Based on many experimental studies of mechanical brain deformation and concussion, the occurrence of SDs in human concussion has often been hypothesized. However, this hypothesis cannot be confirmed in humans, as SDs can only be detected with invasive detection methods that would require either a craniotomy or a burr hole to be performed on athletes. Typical electroencephalography electrodes, placed on the scalp, can help detect the possible presence of SD but have not been able to accurately and reliably identify SDs. METHODS: To explore the possibility of a noninvasive method to resolve this hurdle, we developed a finite element numerical model that simulates scalp voltage changes that are induced by a brain surface SD. We then compared our simulation results with retrospectively evaluated data in patients with aneurysmal subarachnoid hemorrhage from Drenckhahn et al. (Brain 135:853, 2012). RESULTS: The ratio of peak scalp to simulated peak cortical voltage, Vscalp/Vcortex, was 0.0735, whereas the ratio from the retrospectively evaluated data was 0.0316 (0.0221, 0.0527) (median [1st quartile, 3rd quartile], n = 161, p < 0.001, one sample Wilcoxon signed-rank test). These differing values provide validation because their differences can be attributed to differences in shape between concussive SDs and aneurysmal subarachnoid hemorrhage SDs, as well as the inherent limitations in human study voltage measurements. This simulated scalp surface potential was used to design a virtual scalp detection array. Error analysis and visual reconstruction showed that 1 cm is the optimal electrode spacing to visually identify the propagating scalp voltage from a cortical SD. Electrode spacings of 2 cm and above produce distorted images and high errors in the reconstructed image. CONCLUSIONS: Our analysis suggests that concussive (and other) SDs can be detected from the scalp, which could confirm SD occurrence in human concussion, provide concussion diagnosis on the basis of an underlying physiological mechanism, and lead to noninvasive SD detection in the setting of severe acute brain injury.
BACKGROUND: Cortical spreading depolarization (SD) is a propagating depolarization wave of neurons and glial cells in the cerebral gray matter. SD occurs in all forms of severe acute brain injury, as documented by using invasive detection methods. Based on many experimental studies of mechanical brain deformation and concussion, the occurrence of SDs in human concussion has often been hypothesized. However, this hypothesis cannot be confirmed in humans, as SDs can only be detected with invasive detection methods that would require either a craniotomy or a burr hole to be performed on athletes. Typical electroencephalography electrodes, placed on the scalp, can help detect the possible presence of SD but have not been able to accurately and reliably identify SDs. METHODS: To explore the possibility of a noninvasive method to resolve this hurdle, we developed a finite element numerical model that simulates scalp voltage changes that are induced by a brain surface SD. We then compared our simulation results with retrospectively evaluated data in patients with aneurysmal subarachnoid hemorrhage from Drenckhahn et al. (Brain 135:853, 2012). RESULTS: The ratio of peak scalp to simulated peak cortical voltage, Vscalp/Vcortex, was 0.0735, whereas the ratio from the retrospectively evaluated data was 0.0316 (0.0221, 0.0527) (median [1st quartile, 3rd quartile], n = 161, p < 0.001, one sample Wilcoxon signed-rank test). These differing values provide validation because their differences can be attributed to differences in shape between concussive SDs and aneurysmal subarachnoid hemorrhage SDs, as well as the inherent limitations in human study voltage measurements. This simulated scalp surface potential was used to design a virtual scalp detection array. Error analysis and visual reconstruction showed that 1 cm is the optimal electrode spacing to visually identify the propagating scalp voltage from a cortical SD. Electrode spacings of 2 cm and above produce distorted images and high errors in the reconstructed image. CONCLUSIONS: Our analysis suggests that concussive (and other) SDs can be detected from the scalp, which could confirm SD occurrence in human concussion, provide concussion diagnosis on the basis of an underlying physiological mechanism, and lead to noninvasive SD detection in the setting of severe acute brain injury.
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