Real-time electrochemical monitoring of brain tissue oxygen: A surrogate for functional magnetic resonance imaging in rodents

Long-term in-vivo electrochemistry (LIVE) enables real-time monitoring and measurement of brain metabolites. In this study we have simultaneously obtained blood oxygenation level dependent (BOLD) fMRI and amperometric tissue O(2) data from rat cerebral cortex, during both increases and decreases in inspired O(2) content. BOLD and tissue O(2) measurements demonstrated close correlation (r=0.7898) during complete (0%) O(2) removal, with marked negative responses occurring ca. 30s after the onset of O(2) removal. Conversely, when the inspired O(2) was increased (50, 70 and 100% O(2) for 1min) similar positive rapid changes (ca. 15s) in both the BOLD and tissue O(2) signals were observed. These findings demonstrate, for the first time, the practical feasibility of obtaining real-time metabolite information during fMRI acquisition, and that tissue O(2) concentration monitored using an O(2) sensor can serve as an index of changes in the magnitude of the BOLD response. As LIVE O(2) sensors can be used in awake animals performing specific behavioural tasks the technique provides a viable animal surrogate of human fMRI experimentation.

[1]  B. Westerink,et al.  Handbook of Microdialysis: Methods, Applications and Perspectives , 2007 .

[2]  M. Fillenz,et al.  Characterization of carbon paste electrodes in vitro for simultaneous amperometric measurement of changes in oxygen and ascorbic acid concentrations in vivo. , 1996, The Analyst.

[3]  Grant R. Gordon,et al.  Brain metabolism dictates the polarity of astrocyte control over arterioles , 2008, Nature.

[4]  Richard J. K. Taylor,et al.  Electrochemical studies on glassy carbon electrodes: II. Oxygen reduction in solutions of high pH (pH>10) , 1975 .

[5]  Zimmerman Jb,et al.  Simultaneous electrochemical measurements of oxygen and dopamine in vivo. , 1991 .

[6]  Paul M. Matthews,et al.  Confounding effects of anesthesia on functional activation in rodent brain: a study of halothane and α-chloralose anesthesia , 2005, NeuroImage.

[7]  J. B. Justice,et al.  Probing brain chemistry. , 1996, Analytical chemistry.

[8]  John P. Lowry,et al.  Relation between Cerebral Blood Flow and Extracellular Glucose in Rat Striatum during Mild Hypoxia and Hyperoxia , 1998, Developmental Neuroscience.

[9]  Ravi S. Menon,et al.  Intrinsic signal changes accompanying sensory stimulation: functional brain mapping with magnetic resonance imaging. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[10]  Giammario Calia,et al.  Real-time monitoring of brain tissue oxygen using a miniaturized biotelemetric device implanted in freely moving rats. , 2009, Analytical chemistry.

[11]  Martyn G Boutelle,et al.  Measurement of brain tissue oxygen at a carbon paste electrode can serve as an index of increases in regional cerebral blood flow , 1997, Journal of Neuroscience Methods.

[12]  C Delalande,et al.  Comparison of ultrasmall particles of iron oxide (USPIO)-enhanced T2-weighted, conventional T2-weighted, and gadolinium-enhanced T1-weighted MR images in rats with experimental autoimmune encephalomyelitis. , 1999, AJNR. American journal of neuroradiology.

[13]  Mark R. Symms,et al.  Functional Magnetic Resonance Neuroimaging of Drug Dependence: Naloxone-Precipitated Morphine Withdrawal , 2002, NeuroImage.

[14]  Ping Wang,et al.  Trial-by-trial relationship between neural activity, oxygen consumption, and blood flow responses , 2008, NeuroImage.

[15]  Myles Jones,et al.  Polarographic Electrode Measures of Cerebral Tissue Oxygenation: Implications for Functional Brain Imaging , 2008, Sensors.

[16]  G. Houston,et al.  Mapping of brain activation in response to pharmacological agents using fMRI in the rat. , 2001, Magnetic resonance imaging.

[17]  P. Nilsson,et al.  Long-term in vivo experience of an electrochemical sensor using the potential step technique for measurement of mixed venous oxygen pressure. , 1998, Biosensors & bioelectronics.

[18]  W. Ward,et al.  Continuous amperometric monitoring of subcutaneous oxygen in rabbit by telemetry , 2002, Journal of medical engineering & technology.

[19]  C. Hsia,et al.  Respiratory function of hemoglobin. , 1998, The New England journal of medicine.

[20]  M. Hitchman,et al.  Measurement of Dissolved Oxygen , 1978 .

[21]  G. S. Wilson,et al.  In vitro and in vivo evaluation of oxygen effects on a glucose oxidase based implantable glucose sensor , 1993 .

[22]  R. Wightman,et al.  Correlation of local changes in extracellular oxygen and pH that accompany dopaminergic terminal activity in the rat caudate–putamen , 2003, Journal of neurochemistry.

[23]  Mark Preece,et al.  Detection of pharmacologically mediated changes in cerebral activity by functional magnetic resonance imaging: the effects of sulpiride in the brain of the anaesthetised rat , 2001, Brain Research.

[24]  R. Freeman,et al.  High-resolution neurometabolic coupling revealed by focal activation of visual neurons , 2004, Nature Neuroscience.

[25]  Steven C.R. Williams,et al.  Functional magnetic resonance neuroimaging of drug dependence , 2002 .

[26]  Stamford Ja,et al.  Probing brain chemistry. , 1996 .

[27]  Nicholas Jones,et al.  Examining the neural targets of the AMPA receptor potentiator LY404187 in the rat brain using pharmacological magnetic resonance imaging , 2005, Psychopharmacology.

[28]  Nikolas Offenhauser,et al.  Activity‐induced tissue oxygenation changes in rat cerebellar cortex: interplay of postsynaptic activation and blood flow , 2005, The Journal of physiology.

[29]  C. Iadecola,et al.  Glial regulation of the cerebral microvasculature , 2007, Nature Neuroscience.

[30]  R P Travis,et al.  Changes in evoked brain oxygen during sensory stimulation and conditioning. , 1965, Electroencephalography and clinical neurophysiology.

[31]  M. Mas,et al.  Monitoring brain chemistry in vivo: voltammetric techniques, sensors, and behavioral applications. , 1998, Critical reviews in neurobiology.

[32]  T. Ohsaka,et al.  Quasi-reversible two-electron reduction of oxygen at gold electrodes modified with a self-assembled submonolayer of cysteine , 2003 .

[33]  L. C. Clark,et al.  Chronically implanted polarographic electrodes. , 1958, Journal of applied physiology.

[34]  Baowang Li,et al.  High-Resolution Neurometabolic Coupling in the Lateral Geniculate Nucleus , 2007, The Journal of Neuroscience.

[35]  Craig A. Grimes,et al.  Encyclopedia of Sensors , 2006 .

[36]  R. Freeman,et al.  Single-Neuron Activity and Tissue Oxygenation in the Cerebral Cortex , 2003, Science.

[37]  Richard J. K. Taylor,et al.  Electrochemical studies on glassy carbon electrodes: I. Electron transfer kinetics , 1973 .

[38]  R. Freeman,et al.  Neurometabolic coupling in cerebral cortex reflects synaptic more than spiking activity , 2007, Nature Neuroscience.

[39]  M. Raichle.  Behind the scenes of functional brain imaging: a historical and physiological perspective. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[40]  V. C. Austin,et al.  Differences in the BOLD fMRI response to direct and indirect cortical stimulation in the rat , 2003, Magnetic resonance in medicine.

[41]  Ralph D Freeman,et al.  Separate Spatial Scales Determine Neural Activity-Dependent Changes in Tissue Oxygen within Central Visual Pathways , 2005, The Journal of Neuroscience.

[42]  R. Wightman,et al.  Simultaneous electrochemical measurements of oxygen and dopamine in vivo. , 1991, Analytical chemistry.

[43]  B. Covino,et al.  Effects of anesthesia , 1985 .

[44]  Kazuto Masamoto,et al.  Biphasic Changes in Tissue Partial Pressure of Oxygen Closely Related to Localized Neural Activity in Guinea Pig Auditory Cortex , 2003, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[45]  David J. Dubowitz,et al.  CBF/CMRO2 coupling measured with calibrated BOLD fMRI: Sources of bias , 2007, NeuroImage.

[46]  T. L. Davis,et al.  Calibrated functional MRI: mapping the dynamics of oxidative metabolism. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[47]  R D O'Neill,et al.  Microvoltammetric techniques and sensors for monitoring neurochemical dynamics in vivo. A review. , 1994, The Analyst.

[48]  John P. Lowry,et al.  Brain Tissue Oxygen: In Vivo Monitoring with Carbon Paste Electrodes , 2005, Sensors (Basel, Switzerland).

[49]  R R Edelman,et al.  Effect of oxygen inhalation on relaxation times in various tissues , 1997, Journal of magnetic resonance imaging : JMRI.

[50]  S.C.R. Williams,et al.  Mapping the effects of the selective dopamine D2/D3 receptor agonist quinelorane using pharmacological magnetic resonance imaging , 2005, Neuroscience.

[51]  Daniel Thomas,et al.  Electrochemical study of d-glucose oxidase autoinactivation , 1982 .

[52]  J. Detre,et al.  Temporal dynamics of the partial pressure of brain tissue oxygen during functional forepaw stimulation in rats , 2001, Neuroscience Letters.

[53]  R. S. Hinks,et al.  Time course EPI of human brain function during task activation , 1992, Magnetic resonance in medicine.

[54]  Ji-Kyung Choi,et al.  Exogenous contrast agent improves sensitivity of gradient‐echo functional magnetic resonance imaging at 9.4 T , 2004, Magnetic resonance in medicine.

[55]  R. Cooper,et al.  Local changes of intra-cerebral blood flow and oxygen in humans , 1963, Medical electronics and biological engineering.