Stroke penumbra defined by an MRI-based oxygen challenge technique: 1. Validation using [14C]2-deoxyglucose autoradiography

Craig A Robertson, Christopher McCabe, Lindsay Gallagher, Maria del Rosario Lopez-Gonzalez, William M Holmes, Barrie Condon, Keith W Muir, Celestine Santosh, I Mhairi Macrae

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Accurate identification of ischemic penumbra will improve stroke patient selection for reperfusion therapies and clinical trials. Current magnetic resonance imaging (MRI) techniques have limitations and lack validation. Oxygen challenge T(2)(*) MRI (T(2)(*) OC) uses oxygen as a biotracer to detect tissue metabolism, with penumbra displaying the greatest T(2)(*) signal change during OC. [(14)C]2-deoxyglucose (2-DG) autoradiography was combined with T(2)(*) OC to determine metabolic status of T(2)(*)-defined penumbra. Permanent middle cerebral artery occlusion was induced in anesthetized male Sprague-Dawley rats (n=6). Ischemic injury and perfusion deficit were determined by diffusion- and perfusion-weighted imaging, respectively. At 147 ± 32 minutes after stroke, T(2)(*) signal change was measured during a 5-minute 100% OC, immediately followed by 125 μCi/kg 2-DG, intravenously. Magnetic resonance images were coregistered with the corresponding autoradiograms. Regions of interest were located within ischemic core, T(2)(*)-defined penumbra, equivalent contralateral structures, and a region of hyperglycolysis. A T(2)(*) signal increase of 9.22% ± 3.9% (mean ± s.d.) was recorded in presumed penumbra, which displayed local cerebral glucose utilization values equivalent to contralateral cortex. T(2)(*) signal change was negligible in ischemic core, 3.2% ± 0.78% in contralateral regions, and 1.41% ± 0.62% in hyperglycolytic tissue, located outside OC-defined penumbra and within the diffusion abnormality. The results support the utility of OC-MRI to detect viable penumbral tissue following stroke.

LanguageEnglish
Pages1778-1787
Number of pages10
JournalJournal of Cerebral Blood Flow and Metabolism
Volume31
Issue number8
Early online date11 May 2011
DOIs
Publication statusPublished - Aug 2011

Fingerprint

Deoxyglucose
Magnetic resonance
Autoradiography
Stroke
Magnetic Resonance Imaging
Oxygen
Imaging techniques
Tissue
Perfusion Imaging
Middle Cerebral Artery Infarction
Patient Selection
Reperfusion
Sprague Dawley Rats
Magnetic Resonance Spectroscopy
Perfusion
Metabolism
Clinical Trials
Glucose
Rats
Wounds and Injuries

Keywords

  • animals
  • autoradiography
  • brain
  • deoxyglucose
  • glycolysis
  • magnetic resonance imaging
  • male
  • metabolism
  • oxygen
  • rats
  • rats, sprague-dawley
  • stroke
  • mri-based oxygen challenge technique

Cite this

Robertson, Craig A ; McCabe, Christopher ; Gallagher, Lindsay ; Lopez-Gonzalez, Maria del Rosario ; Holmes, William M ; Condon, Barrie ; Muir, Keith W ; Santosh, Celestine ; Macrae, I Mhairi. / Stroke penumbra defined by an MRI-based oxygen challenge technique : 1. Validation using [14C]2-deoxyglucose autoradiography. In: Journal of Cerebral Blood Flow and Metabolism. 2011 ; Vol. 31, No. 8. pp. 1778-1787.
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abstract = "Accurate identification of ischemic penumbra will improve stroke patient selection for reperfusion therapies and clinical trials. Current magnetic resonance imaging (MRI) techniques have limitations and lack validation. Oxygen challenge T(2)(*) MRI (T(2)(*) OC) uses oxygen as a biotracer to detect tissue metabolism, with penumbra displaying the greatest T(2)(*) signal change during OC. [(14)C]2-deoxyglucose (2-DG) autoradiography was combined with T(2)(*) OC to determine metabolic status of T(2)(*)-defined penumbra. Permanent middle cerebral artery occlusion was induced in anesthetized male Sprague-Dawley rats (n=6). Ischemic injury and perfusion deficit were determined by diffusion- and perfusion-weighted imaging, respectively. At 147 ± 32 minutes after stroke, T(2)(*) signal change was measured during a 5-minute 100{\%} OC, immediately followed by 125 μCi/kg 2-DG, intravenously. Magnetic resonance images were coregistered with the corresponding autoradiograms. Regions of interest were located within ischemic core, T(2)(*)-defined penumbra, equivalent contralateral structures, and a region of hyperglycolysis. A T(2)(*) signal increase of 9.22{\%} ± 3.9{\%} (mean ± s.d.) was recorded in presumed penumbra, which displayed local cerebral glucose utilization values equivalent to contralateral cortex. T(2)(*) signal change was negligible in ischemic core, 3.2{\%} ± 0.78{\%} in contralateral regions, and 1.41{\%} ± 0.62{\%} in hyperglycolytic tissue, located outside OC-defined penumbra and within the diffusion abnormality. The results support the utility of OC-MRI to detect viable penumbral tissue following stroke.",
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Robertson, CA, McCabe, C, Gallagher, L, Lopez-Gonzalez, MDR, Holmes, WM, Condon, B, Muir, KW, Santosh, C & Macrae, IM 2011, 'Stroke penumbra defined by an MRI-based oxygen challenge technique: 1. Validation using [14C]2-deoxyglucose autoradiography' Journal of Cerebral Blood Flow and Metabolism, vol. 31, no. 8, pp. 1778-1787. https://doi.org/10.1038/jcbfm.2011.66

Stroke penumbra defined by an MRI-based oxygen challenge technique : 1. Validation using [14C]2-deoxyglucose autoradiography. / Robertson, Craig A; McCabe, Christopher; Gallagher, Lindsay; Lopez-Gonzalez, Maria del Rosario; Holmes, William M; Condon, Barrie; Muir, Keith W; Santosh, Celestine; Macrae, I Mhairi.

In: Journal of Cerebral Blood Flow and Metabolism, Vol. 31, No. 8, 08.2011, p. 1778-1787.

Research output: Contribution to journalArticle

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T1 - Stroke penumbra defined by an MRI-based oxygen challenge technique

T2 - Journal of Cerebral Blood Flow and Metabolism

AU - Robertson, Craig A

AU - McCabe, Christopher

AU - Gallagher, Lindsay

AU - Lopez-Gonzalez, Maria del Rosario

AU - Holmes, William M

AU - Condon, Barrie

AU - Muir, Keith W

AU - Santosh, Celestine

AU - Macrae, I Mhairi

PY - 2011/8

Y1 - 2011/8

N2 - Accurate identification of ischemic penumbra will improve stroke patient selection for reperfusion therapies and clinical trials. Current magnetic resonance imaging (MRI) techniques have limitations and lack validation. Oxygen challenge T(2)(*) MRI (T(2)(*) OC) uses oxygen as a biotracer to detect tissue metabolism, with penumbra displaying the greatest T(2)(*) signal change during OC. [(14)C]2-deoxyglucose (2-DG) autoradiography was combined with T(2)(*) OC to determine metabolic status of T(2)(*)-defined penumbra. Permanent middle cerebral artery occlusion was induced in anesthetized male Sprague-Dawley rats (n=6). Ischemic injury and perfusion deficit were determined by diffusion- and perfusion-weighted imaging, respectively. At 147 ± 32 minutes after stroke, T(2)(*) signal change was measured during a 5-minute 100% OC, immediately followed by 125 μCi/kg 2-DG, intravenously. Magnetic resonance images were coregistered with the corresponding autoradiograms. Regions of interest were located within ischemic core, T(2)(*)-defined penumbra, equivalent contralateral structures, and a region of hyperglycolysis. A T(2)(*) signal increase of 9.22% ± 3.9% (mean ± s.d.) was recorded in presumed penumbra, which displayed local cerebral glucose utilization values equivalent to contralateral cortex. T(2)(*) signal change was negligible in ischemic core, 3.2% ± 0.78% in contralateral regions, and 1.41% ± 0.62% in hyperglycolytic tissue, located outside OC-defined penumbra and within the diffusion abnormality. The results support the utility of OC-MRI to detect viable penumbral tissue following stroke.

AB - Accurate identification of ischemic penumbra will improve stroke patient selection for reperfusion therapies and clinical trials. Current magnetic resonance imaging (MRI) techniques have limitations and lack validation. Oxygen challenge T(2)(*) MRI (T(2)(*) OC) uses oxygen as a biotracer to detect tissue metabolism, with penumbra displaying the greatest T(2)(*) signal change during OC. [(14)C]2-deoxyglucose (2-DG) autoradiography was combined with T(2)(*) OC to determine metabolic status of T(2)(*)-defined penumbra. Permanent middle cerebral artery occlusion was induced in anesthetized male Sprague-Dawley rats (n=6). Ischemic injury and perfusion deficit were determined by diffusion- and perfusion-weighted imaging, respectively. At 147 ± 32 minutes after stroke, T(2)(*) signal change was measured during a 5-minute 100% OC, immediately followed by 125 μCi/kg 2-DG, intravenously. Magnetic resonance images were coregistered with the corresponding autoradiograms. Regions of interest were located within ischemic core, T(2)(*)-defined penumbra, equivalent contralateral structures, and a region of hyperglycolysis. A T(2)(*) signal increase of 9.22% ± 3.9% (mean ± s.d.) was recorded in presumed penumbra, which displayed local cerebral glucose utilization values equivalent to contralateral cortex. T(2)(*) signal change was negligible in ischemic core, 3.2% ± 0.78% in contralateral regions, and 1.41% ± 0.62% in hyperglycolytic tissue, located outside OC-defined penumbra and within the diffusion abnormality. The results support the utility of OC-MRI to detect viable penumbral tissue following stroke.

KW - animals

KW - autoradiography

KW - brain

KW - deoxyglucose

KW - glycolysis

KW - magnetic resonance imaging

KW - male

KW - metabolism

KW - oxygen

KW - rats

KW - rats, sprague-dawley

KW - stroke

KW - mri-based oxygen challenge technique

U2 - 10.1038/jcbfm.2011.66

DO - 10.1038/jcbfm.2011.66

M3 - Article

VL - 31

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EP - 1787

JO - Journal of Cerebral Blood Flow and Metabolism

JF - Journal of Cerebral Blood Flow and Metabolism

SN - 0271-678X

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ER -