Novel analysis for improved validity in semi-quantitative 2-deoxyglucose autoradiographic imaging
The original [ 14C]-2-deoxyglucose autoradiographic imaging technique allows for the quantitative determination of local cerebral glucose utilisation (LCMRglu) [Sokoloff L, Reivich, M, Kennedy C, Desrosiers M, Patlak C, Pettigrew K, et al. The 2-deoxyglucose-C-14 method for measurement of local cere...
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Published in | Journal of neuroscience methods Vol. 175; no. 1; pp. 25 - 35 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
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Elsevier B.V
30.10.2008
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Abstract | The original [
14C]-2-deoxyglucose autoradiographic imaging technique allows for the quantitative determination of local cerebral glucose utilisation (LCMRglu) [Sokoloff L, Reivich, M, Kennedy C, Desrosiers M, Patlak C, Pettigrew K, et al. The 2-deoxyglucose-C-14 method for measurement of local cerebral glucose utilisation—theory, procedure and normal values in conscious and anestherized albino rats. J Neurochem 1977;28:897–916]. The range of applications to which the quantitative method can be readily applied is limited, however, by the requirement for the intermittent measurement of arterial radiotracer and glucose concentrations throughout the experiment, via intravascular cannulation. Some studies have applied a modified, semi-quantitative approach to estimate LCMRglu while circumventing the requirement for intravascular cannulation [Kelly S, Bieneman A, Uney J, McCulloch J. Cerebral glucose utilization in transgenic mice over-expressing heat shock protein 70 is altered by dizocilpine. Eur J Neurosci 2002;15(6):945–52; Jordan GR, McCulloch J, Shahid M, Hill DR, Henry B, Horsburgh K. Regionally selective and dose-dependent effects of the ampakines Org 26576 and Org 24448 on local cerebral glucose utilisation in the mouse as assessed by C-14-2-deoxyglucose autoradiography. Neuropharmacology 2005;49(2):254–64]. In this method only a terminal blood sample is collected for the determination of plasma [
14C] and [glucose] and the rate of LCMRglu in each brain region of interest (RoI) is estimated by comparing the [
14C] concentration in each region relative to a selected control region, which is proposed to demonstrate metabolic stability between the experimental groups. Here we show that the semi-quantitative method has reduced validity in the measurement of LCMRglu as compared to the quantitative method and that the validity of this technique is further compromised by the inability of the methods applied within the analysis to appropriately determine metabolic stability in the selected standard region. To address these issues we have developed a novel form of analysis that provides an index of LCMRglu (iLCMRglu) for application when using the semi-quantitative approach. Provided that the methodological constraints inherent in 2-deoxyglucose autoradiography (e.g. normoglycaemia) are met this analytical technique both increases the validity of LCMRglu estimation by the semi-quantitative method and also allows for its broader experimental application. |
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AbstractList | The original [
14C]-2-deoxyglucose autoradiographic imaging technique allows for the quantitative determination of local cerebral glucose utilisation (LCMRglu) [Sokoloff L, Reivich, M, Kennedy C, Desrosiers M, Patlak C, Pettigrew K, et al. The 2-deoxyglucose-C-14 method for measurement of local cerebral glucose utilisation—theory, procedure and normal values in conscious and anestherized albino rats. J Neurochem 1977;28:897–916]. The range of applications to which the quantitative method can be readily applied is limited, however, by the requirement for the intermittent measurement of arterial radiotracer and glucose concentrations throughout the experiment, via intravascular cannulation. Some studies have applied a modified, semi-quantitative approach to estimate LCMRglu while circumventing the requirement for intravascular cannulation [Kelly S, Bieneman A, Uney J, McCulloch J. Cerebral glucose utilization in transgenic mice over-expressing heat shock protein 70 is altered by dizocilpine. Eur J Neurosci 2002;15(6):945–52; Jordan GR, McCulloch J, Shahid M, Hill DR, Henry B, Horsburgh K. Regionally selective and dose-dependent effects of the ampakines Org 26576 and Org 24448 on local cerebral glucose utilisation in the mouse as assessed by C-14-2-deoxyglucose autoradiography. Neuropharmacology 2005;49(2):254–64]. In this method only a terminal blood sample is collected for the determination of plasma [
14C] and [glucose] and the rate of LCMRglu in each brain region of interest (RoI) is estimated by comparing the [
14C] concentration in each region relative to a selected control region, which is proposed to demonstrate metabolic stability between the experimental groups. Here we show that the semi-quantitative method has reduced validity in the measurement of LCMRglu as compared to the quantitative method and that the validity of this technique is further compromised by the inability of the methods applied within the analysis to appropriately determine metabolic stability in the selected standard region. To address these issues we have developed a novel form of analysis that provides an index of LCMRglu (iLCMRglu) for application when using the semi-quantitative approach. Provided that the methodological constraints inherent in 2-deoxyglucose autoradiography (e.g. normoglycaemia) are met this analytical technique both increases the validity of LCMRglu estimation by the semi-quantitative method and also allows for its broader experimental application. The original [(14)C]-2-deoxyglucose autoradiographic imaging technique allows for the quantitative determination of local cerebral glucose utilisation (LCMRglu) [Sokoloff L, Reivich, M, Kennedy C, Desrosiers M, Patlak C, Pettigrew K, et al. The 2-deoxyglucose-C-14 method for measurement of local cerebral glucose utilisation-theory, procedure and normal values in conscious and anestherized albino rats. J Neurochem 1977;28:897-916]. The range of applications to which the quantitative method can be readily applied is limited, however, by the requirement for the intermittent measurement of arterial radiotracer and glucose concentrations throughout the experiment, via intravascular cannulation. Some studies have applied a modified, semi-quantitative approach to estimate LCMRglu while circumventing the requirement for intravascular cannulation [Kelly S, Bieneman A, Uney J, McCulloch J. Cerebral glucose utilization in transgenic mice over-expressing heat shock protein 70 is altered by dizocilpine. Eur J Neurosci 2002;15(6):945-52; Jordan GR, McCulloch J, Shahid M, Hill DR, Henry B, Horsburgh K. Regionally selective and dose-dependent effects of the ampakines Org 26576 and Org 24448 on local cerebral glucose utilisation in the mouse as assessed by C-14-2-deoxyglucose autoradiography. Neuropharmacology 2005;49(2):254-64]. In this method only a terminal blood sample is collected for the determination of plasma [(14)C] and [glucose] and the rate of LCMRglu in each brain region of interest (RoI) is estimated by comparing the [(14)C] concentration in each region relative to a selected control region, which is proposed to demonstrate metabolic stability between the experimental groups. Here we show that the semi-quantitative method has reduced validity in the measurement of LCMRglu as compared to the quantitative method and that the validity of this technique is further compromised by the inability of the methods applied within the analysis to appropriately determine metabolic stability in the selected standard region. To address these issues we have developed a novel form of analysis that provides an index of LCMRglu (iLCMRglu) for application when using the semi-quantitative approach. Provided that the methodological constraints inherent in 2-deoxyglucose autoradiography (e.g. normoglycaemia) are met this analytical technique both increases the validity of LCMRglu estimation by the semi-quantitative method and also allows for its broader experimental application. The original [[super]14C]-2-deoxyglucose autoradiographic imaging technique allows for the quantitative determination of local cerebral glucose utilisation (LCMRglu) [Sokoloff L, Reivich, M, Kennedy C, Desrosiers M, Patlak C, Pettigrew K, et al. The 2-deoxyglucose-C-14 method for measurement of local cerebral glucose utilisation - theory, procedure and normal values in conscious and anestherized albino rats. J Neurochem 1977; 28:897-916]. The range of applications to which the quantitative method can be readily applied is limited, however, by the requirement for the intermittent measurement of arterial radiotracer and glucose concentrations throughout the experiment, via intravascular cannulation. Some studies have applied a modified, semi-quantitative approach to estimate LCMRglu while circumventing the requirement for intravascular cannulation [Kelly S, Bieneman A, Uney J, McCulloch J. Cerebral glucose utilization in transgenic mice over-expressing heat shock protein 70 is altered by dizocilpine. Eur J Neurosci 2002; 15(6):945-52; Jordan GR, McCulloch J, Shahid M, Hill DR, Henry B, Horsburgh K. Regionally selective and dose-dependent effects of the ampakines Org 26576 and Org 24448 on local cerebral glucose utilisation in the mouse as assessed by C-14-2-deoxyglucose autoradiography. Neuropharmacology 2005; 49(2):254-64]. In this method only a terminal blood sample is collected for the determination of plasma [[super]14C] and [glucose] and the rate of LCMRglu in each brain region of interest (RoI) is estimated by comparing the [[super]14C] concentration in each region relative to a selected control region, which is proposed to demonstrate metabolic stability between the experimental groups. Here we show that the semi-quantitative method has reduced validity in the measurement of LCMRglu as compared to the quantitative method and that the validity of this technique is further compromised by the inability of the methods applied within the analysis to appropriately determine metabolic stability in the selected standard region. To address these issues we have developed a novel form of analysis that provides an index of LCMRglu (iLCMRglu) for application when using the semi-quantitative approach. Provided that the methodological constraints inherent in 2-deoxyglucose autoradiography (e.g. normoglycaemia) are met this analytical technique both increases the validity of LCMRglu estimation by the semi-quantitative method and also allows for its broader experimental application. |
Author | Dawson, Neil Ferrington, Linda Olverman, Henry J. Kelly, Paul A.T. |
Author_xml | – sequence: 1 givenname: Neil surname: Dawson fullname: Dawson, Neil email: N.Dawson@ed.ac.uk organization: Centre for Cognitive and Neural Systems, University of Edinburgh, 1 George Square, Edinburgh EH8 9JZ, United Kingdom – sequence: 2 givenname: Linda surname: Ferrington fullname: Ferrington, Linda organization: Centre for Neuroscience Research, University of Edinburgh, 1 George Square, Edinburgh EH8 9JZ, United Kingdom – sequence: 3 givenname: Henry J. surname: Olverman fullname: Olverman, Henry J. – sequence: 4 givenname: Paul A.T. surname: Kelly fullname: Kelly, Paul A.T. |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/18762213$$D View this record in MEDLINE/PubMed |
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Cites_doi | 10.1046/j.1460-9568.2002.01931.x 10.1016/0006-8993(80)90874-4 10.1038/jcbfm.1981.4 10.1016/0006-8993(83)90782-5 10.1016/S0893-133X(99)00127-X 10.1007/s00213-004-1784-z 10.1016/j.neuroscience.2004.03.052 10.1023/A:1022534709672 10.1161/01.RES.44.1.127 10.1016/0306-4522(88)90044-9 10.1038/jcbfm.1990.134 10.1038/jcbfm.1995.96 10.1111/j.1471-4159.1982.tb07937.x 10.1038/jcbfm.1982.56 10.1111/j.1471-4159.1977.tb10649.x 10.1016/0028-3908(89)90128-7 10.1016/j.neuropharm.2005.03.011 |
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References | Kelly, Davis, Goodwin (bib3) 1988; 25 Quate, McBean, Ritchie, Olverman, Kelly (bib10) 2004; 173 Kelly, Bieneman, Uney, McCulloch (bib2) 2002; 15 Kelly, McCulloch (bib4) 1982; 39 Quelven, Roussin, Zajac (bib11) 2004; 126 Reivich, Kuhl, Wolf, Greenberg, Phelps, Ido (bib12) 1979; 44 Sokoloff (bib15) 1999; 24 Sokoloff (bib14) 1981; 1 Schuier, Orzi, Suda, Lucignani, Kennedy, Sokoloff (bib13) 1981; 10 Kelly, Ritchie, Arbuthnott (bib6) 1995; 15 McCulloch, Kelly, Ford (bib7) 1982; 2 Meibach, Glick, Ross, Cox, Maavani (bib8) 1980; 195 Wilkerson, London (bib17) 1989; 28 Jordan, McCulloch, Shahid, Hill, Henry, Horsburgh (bib1) 2005; 49 Miyamoto, Leipzig, Lieberman, Duncan (bib9) 2000; 22 Sokoloff, Reivich, Kennedy, Desrosiers, Patlak, Pettigrew (bib16) 1977; 28 Kelly, McCulloch (bib5) 1983; 260 Sokoloff (10.1016/j.jneumeth.2008.07.020_bib14) 1981; 1 Wilkerson (10.1016/j.jneumeth.2008.07.020_bib17) 1989; 28 Kelly (10.1016/j.jneumeth.2008.07.020_bib3) 1988; 25 McCulloch (10.1016/j.jneumeth.2008.07.020_bib7) 1982; 2 Quate (10.1016/j.jneumeth.2008.07.020_bib10) 2004; 173 Sokoloff (10.1016/j.jneumeth.2008.07.020_bib16) 1977; 28 Meibach (10.1016/j.jneumeth.2008.07.020_bib8) 1980; 195 Sokoloff (10.1016/j.jneumeth.2008.07.020_bib15) 1999; 24 Quelven (10.1016/j.jneumeth.2008.07.020_bib11) 2004; 126 Kelly (10.1016/j.jneumeth.2008.07.020_bib5) 1983; 260 Kelly (10.1016/j.jneumeth.2008.07.020_bib2) 2002; 15 Kelly (10.1016/j.jneumeth.2008.07.020_bib4) 1982; 39 Miyamoto (10.1016/j.jneumeth.2008.07.020_bib9) 2000; 22 Reivich (10.1016/j.jneumeth.2008.07.020_bib12) 1979; 44 Schuier (10.1016/j.jneumeth.2008.07.020_bib13) 1981; 10 Jordan (10.1016/j.jneumeth.2008.07.020_bib1) 2005; 49 Kelly (10.1016/j.jneumeth.2008.07.020_bib6) 1995; 15 |
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Snippet | The original [
14C]-2-deoxyglucose autoradiographic imaging technique allows for the quantitative determination of local cerebral glucose utilisation (LCMRglu)... The original [(14)C]-2-deoxyglucose autoradiographic imaging technique allows for the quantitative determination of local cerebral glucose utilisation... The original [[super]14C]-2-deoxyglucose autoradiographic imaging technique allows for the quantitative determination of local cerebral glucose utilisation... |
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SubjectTerms | 2-Deoxyglucose Animals Autoradiography Blood Glucose - drug effects Blood Glucose - metabolism Brain - blood supply Brain - drug effects Brain metabolism Carbon Isotopes - metabolism Cerebrovascular Circulation - drug effects Cerebrovascular Circulation - physiology Deoxyglucose - metabolism Male N-Methyl-3,4-methylenedioxyamphetamine - pharmacology Rats Reproducibility of Results Serotonin Agents |
Title | Novel analysis for improved validity in semi-quantitative 2-deoxyglucose autoradiographic imaging |
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