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Electrophysiology & Neurochemistry Sensor for Stroke Studies
Victor NekrasovP.I. Professor Patrick J. RouscheMasters Student Peter Tek
Neural Engineering Applications LabUIC Bioengineering
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Purpose of Study
– To better understand the complex electrophysiological and neurochemical changes during stroke
– Developing a sensor that detects the various spatiotemporal changes that occur in neural tissue during and after stroke
– In the future the research will help with rehabilitation after stroke by possible electrical and chemical stimulation of neural tissue surrounding the stroke
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I mpact of Stroke in the U.S.
700,000 people suffer annually150,000 people killed each year3rd leading cause of death behind heart disease and cancerAnnual economic burden of $62.7 billion
American Heart Association: Heart Disease and Stroke Statistics – 2007 Update; Rosamond, W. et al. Circulation 2007;115:e69-e171
American Stroke Victims
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What is a Stroke
Damage to the brain– Ischemic Stroke– Hemorrhagic Stroke
Outcomes of Stroke– Death – 24%– Loss of one or more normal
functionsPermanent – 15-30%Temporary – 50-70%
Focus on Ischemic Stroke
http://www.hmc.psu.edu/neurosurgery/services/diseases/Stroke.htmAmerican Stroke Association, Stroke Treatment; http://www.massgeneral.org/vascularcenter/page.asp?id=stroke
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Stroke Treatment
Tissue PlasminogenActivator (tPA) Thrombolytic drug: Dissolves clot & restores blood flow1-3% of stroke victims are eligible
– Therapy started within 3 hours of stoke onset
– Increased risk of bleeding into the brain
American Stroke Association, Stroke Treatment; http://www.massgeneral.org/vascularcenter/page.asp?id=stroke
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Proposed Device
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Fiber Optic Probe to Induce Stroke
Use micromanipulator to position fiber optic light probe
– Precise target location– Ischemia size control
Illumination for 20 min following dye injection
Light ExposureReactive Oxygen
Radicals
BiomolecularEvent Cascade Thrombosis
Comparative Electrophysiological Response Dynamics During Stroke, Terry C. Chiganos, PhD Thesis (2006)
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Neurotransmitter Analysis
Microdialysis technique to collect samplesHPLC technology to identify and quantify specific neurotransmitters Create a spatial and temporal “roadmap” of neurochemical changes
http://www.sfn.org/index.cfm?pagename=brainBriefings_nMDAReceptorBlockers
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Electrophysiological
Microwire electrodes– Multiple lengths – Different Brain Layers
II/II “integrating” and V “output”
Brain Signals– Amplified – Analyzed using TDT– Before, During, and After
Stroke
http://brain.web-us.com/brain/PhysiologyOrdinaryConsciousness.htm
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Prototype Electrode
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Cranial Window Prototype
Attached to the skull of the ratIncorporates– Microdialysis– Multi-depth microwire electrode array– Cannula for photo-thrombosis fiber optic
Made using 3D printer– Dimension Elite
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Electrochemical Impedance Spectroscopy
Electrochemical impedance spectroscopy (EIS) – powerful technique for the characterization of electrochemical systems
Applications in the field of materials characterizationTool for investigation of mechanisms involving passivity and localized corrosion studiesEvaluating properties of surface modified and coated materials
Like Resistance, Impedance is a measure of the ability of a circuit to resist the flow of electrical current
Ohms Law: V = IZ where V is Voltage, I is Current, and Z is Impedance
http://www.metrohm.com.sg/other-products/eco-pgstat302.jpg
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How EIS Works
Potentiostat or GalvanostatPotentiostat: Sets up a voltage between working and reference electrode, measures current in the cellGalvanostat: Sets up a current between the two electrodes, measures potential of the cellImpedance is then calculated Z = V/I
http://www.gamry.com/App_Notes/EIS_Of_Coatings/EIS_Of_Coatings.htm
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Electrochemical Cell
3 electrodes in electrolyte liquidWorking Electrode
– Electrode under study– Point at which the voltage is controlled and current is measured, or
visa versa. Reference Electrode
– Constant electrochemical potential when no current flows throughit
– Used in measuring working electrode potential– Typically Ag/AgCl or Saturated Calomel Electrode (SCE)
Counter (Auxiliary) Electrode– Conductor that completes the electrical circuit of the cell– Inert conductor like platinum or graphite
Electrodes emmersed in electrolyte solution– PBS – Phosphate Buffer Saline
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EIS Data for First Electrodes
0 500 1000 1500 2000 2500 3000 3500 4000 4500 50000
5
10
15x 10
4
Impe
danc
e (O
hms)
Frequency (Hz)
E1 Sites (1)(2)(3) Averages: Impedance vs. Frequency
Site 1Site 2Site 3
0 500 1000 1500 2000 2500 3000 3500 4000 4500 50000
5
10
15x 104
Impe
danc
e (O
hms)
Frequency (Hz)
Electrode1 EIS: Impedance vs. Frequency
Recording electrodes: Low impedance necessary
Stimulating electrodes: High impedance is preferred
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EIS Data for Redesigned Electrode
Impedance Vs. Frequency
0
200000
400000
600000
800000
1000000
1200000
0 2000 4000 6000 8000 10000 12000
Frequency (Hz)
Impe
danc
e (O
hms)
Site1Site2Site3Site4Site5Site6Total Avg
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TDT Data from Electrode Array
Full
1 Min
1 Spike
Vol
ts
Milliseconds
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Conclusion
Purpose of study is to better understand the complex spatiotemporal events that occur during a stroke and during the recovery processSensor will give us a tool to quantitatively look at what happens to neural tissue Allow for more affective treatment of stroke in the future
– Aide in rehabilitation – Prevention of the devastating damage during stroke
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Acknowledgements
DoD-ASSURE and NSF-REU Programs– For financial support Grant NSF EEC 0453432
Dr. Patrick J. Rousche– P.I. of Neural Engineering Applications Lab
Peter Tek– Masters Student N.E.A.L.
Dr. Christos G. Takoudis– Summer 2007 REU Program