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Optical monitoring of oxygen tension in cortical microvessels with confocal microscopy
Mohammad A. Yaseen, Vivek J. Srinivasan, Sava Sakadžić, Weicheng Wu, Svetlana Ruvinskaya, Sergei A. Vinogradov, and David A. Boas »View Author Affiliations
1Photon Migration Imaging Laboratory, MGH/MIT/HMS Athinuola A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital/Harvard Medical School,Building 149Room 2301,13 Street, Charlestown, MA 02129, USA
2Department of Biochemistry and Biophysics, University of Pennsylvania, 3700 Hamilton Walk, Philadelphia, PA 19104, USA
*Corresponding author: dboas@nmr.mgh.harvard.edu
Optics Express, Vol. 17, Issue 25, pp. 22341-22350 (2009)
http://dx.doi.org/10.1364/OE.17.022341
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Abstract
Evaluating cerebral oxygenation is of critical importance for the understanding of brain function and several neuropathologies. Although several techniques exist for measuring cerebral oxygenation in vivo, the most widely accepted techniques offer limited spatial resolution. We have developed a confocal imaging system for minimally invasive measurement of oxygen tension (pO2) in cerebral microvessels with high spatial and temporal resolution. The system relies on the phosphorescence quenching method using exogenous porphyrin-based dendritic oxygen probes. Here we present high-resolution phosphorescence images of cortical microvasculature and temporal pO2 profiles from multiple locations in response to varied fraction of inspired oxygen and functional activation.
© 2009 OSA
OCIS Codes
(170.1470) Medical optics and biotechnology : Blood or tissue constituent monitoring
(170.3650) Medical optics and biotechnology : Lifetime-based sensing
(180.1790) Microscopy : Confocal microscopy
ToC Category:
Medical Optics and Biotechnology
History
Original Manuscript: September 4, 2009
Revised Manuscript: October 18, 2009
Manuscript Accepted: October 22, 2009
Published: November 23, 2009
Virtual Issues
Vol. 5, Iss. 1 Virtual Journal for Biomedical Optics
Citation
Mohammad A. Yaseen, Vivek J. Srinivasan, Sava Sakadžić, Weicheng Wu, Svetlana Ruvinskaya, Sergei A. Vinogradov, and David A. Boas, "Optical monitoring of oxygen tension in cortical microvessels with confocal microscopy," Opt. Express 17, 22341-22350 (2009)
http://www.opticsinfobase.org/vjbo/abstract.cfm?URI=oe-17-25-22341
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- J. L. Tatum, G. J. Kelloff, R. J. Gillies, J. M. Arbeit, J. M. Brown, K. S. C. Chao, J. D. Chapman, W. C. Eckelman, A. W. Fyles, A. J. Giaccia, R. P. Hill, C. J. Koch, M. C. Krishna, K. A. Krohn, J. S. Lewis, R. P. Mason, G. Melillo, A. R. Padhani, G. Powis, J. G. Rajendran, R. Reba, S. P. Robinson, G. L. Semenza, H. M. Swartz, P. Vaupel, D. Yang, B. Croft, J. Hoffman, G. Liu, H. Stone, and D. Sullivan, “Hypoxia: Importance in tumor biology, noninvasive measurement by imaging, and value of its measurement in the management of cancer therapy,” Int. J. Radiat. Biol. 82(10), 699–757 (2006). [CrossRef] [PubMed]
- O. S. Finikova, A. Y. Lebedev, A. Aprelev, T. Troxler, F. Gao, C. Garnacho, S. Muro, R. M. Hochstrasser, and S. A. Vinogradov, “Oxygen Microscopy by Two-Photon-Excited Phosphorescence,” ChemPhysChem 9(12), 1673–1679 (2008). [CrossRef] [PubMed]
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- J. L. Tatum, G. J. Kelloff, R. J. Gillies, J. M. Arbeit, J. M. Brown, K. S. C. Chao, J. D. Chapman, W. C. Eckelman, A. W. Fyles, A. J. Giaccia, R. P. Hill, C. J. Koch, M. C. Krishna, K. A. Krohn, J. S. Lewis, R. P. Mason, G. Melillo, A. R. Padhani, G. Powis, J. G. Rajendran, R. Reba, S. P. Robinson, G. L. Semenza, H. M. Swartz, P. Vaupel, D. Yang, B. Croft, J. Hoffman, G. Liu, H. Stone, and D. Sullivan, “Hypoxia: Importance in tumor biology, noninvasive measurement by imaging, and value of its measurement in the management of cancer therapy,” Int. J. Radiat. Biol. 82(10), 699–757 (2006). [CrossRef] [PubMed]
- K. Nagata, M. Sato, Y. Satoh, Y. Watahiki, Y. Kondoh, M. Sugawara, G. Box, D. Wright, S. Leung, H. Yuya, and E. Shimosegawa, “Hemodynamic aspects of Alzheimer’s Disease,” Ann. N. Y. Acad. Sci. 977(1), 391–402 (2002). [CrossRef] [PubMed]
- P. B. Jones, H. K. Shin, D. A. Boas, B. T. Hyman, M. A. Moskowitz, C. Ayata, and A. K. Dunn, “Simultaneous multispectral reflectance imaging and laser speckle flowmetry of cerebral blood flow and oxygen metabolism in focal cerebral ischemia,” J. Biomed. Opt. 13(4), 044007 (2008). [CrossRef] [PubMed]
- R. G. Shulman, F. Hyder, and D. L. Rothman, “Biophysical basis of brain activity: implications for neuroimaging,” Q. Rev. Biophys. 35(3), 287–325 (2002). [CrossRef] [PubMed]
- E. M. C. Hillman, A. Devor, M. B. Bouchard, A. K. Dunn, G. W. Krauss, J. Skoch, B. J. Bacskai, A. M. Dale, and D. A. Boas, “Depth-resolved optical imaging and microscopy of vascular compartment dynamics during somatosensory stimulation,” Neuroimage 35(1), 89–104 (2007). [CrossRef] [PubMed]
- J. L. Tatum, G. J. Kelloff, R. J. Gillies, J. M. Arbeit, J. M. Brown, K. S. C. Chao, J. D. Chapman, W. C. Eckelman, A. W. Fyles, A. J. Giaccia, R. P. Hill, C. J. Koch, M. C. Krishna, K. A. Krohn, J. S. Lewis, R. P. Mason, G. Melillo, A. R. Padhani, G. Powis, J. G. Rajendran, R. Reba, S. P. Robinson, G. L. Semenza, H. M. Swartz, P. Vaupel, D. Yang, B. Croft, J. Hoffman, G. Liu, H. Stone, and D. Sullivan, “Hypoxia: Importance in tumor biology, noninvasive measurement by imaging, and value of its measurement in the management of cancer therapy,” Int. J. Radiat. Biol. 82(10), 699–757 (2006). [CrossRef] [PubMed]
- K. Nagata, M. Sato, Y. Satoh, Y. Watahiki, Y. Kondoh, M. Sugawara, G. Box, D. Wright, S. Leung, H. Yuya, and E. Shimosegawa, “Hemodynamic aspects of Alzheimer’s Disease,” Ann. N. Y. Acad. Sci. 977(1), 391–402 (2002). [CrossRef] [PubMed]
- J. L. Tatum, G. J. Kelloff, R. J. Gillies, J. M. Arbeit, J. M. Brown, K. S. C. Chao, J. D. Chapman, W. C. Eckelman, A. W. Fyles, A. J. Giaccia, R. P. Hill, C. J. Koch, M. C. Krishna, K. A. Krohn, J. S. Lewis, R. P. Mason, G. Melillo, A. R. Padhani, G. Powis, J. G. Rajendran, R. Reba, S. P. Robinson, G. L. Semenza, H. M. Swartz, P. Vaupel, D. Yang, B. Croft, J. Hoffman, G. Liu, H. Stone, and D. Sullivan, “Hypoxia: Importance in tumor biology, noninvasive measurement by imaging, and value of its measurement in the management of cancer therapy,” Int. J. Radiat. Biol. 82(10), 699–757 (2006). [CrossRef] [PubMed]
- J. L. Tatum, G. J. Kelloff, R. J. Gillies, J. M. Arbeit, J. M. Brown, K. S. C. Chao, J. D. Chapman, W. C. Eckelman, A. W. Fyles, A. J. Giaccia, R. P. Hill, C. J. Koch, M. C. Krishna, K. A. Krohn, J. S. Lewis, R. P. Mason, G. Melillo, A. R. Padhani, G. Powis, J. G. Rajendran, R. Reba, S. P. Robinson, G. L. Semenza, H. M. Swartz, P. Vaupel, D. Yang, B. Croft, J. Hoffman, G. Liu, H. Stone, and D. Sullivan, “Hypoxia: Importance in tumor biology, noninvasive measurement by imaging, and value of its measurement in the management of cancer therapy,” Int. J. Radiat. Biol. 82(10), 699–757 (2006). [CrossRef] [PubMed]
- H. M. Swartz, “Measuring real levels of oxygen in vivo: opportunities and challenges,” Biochem. Soc. Trans. 30(2), 248–252 (2002). [CrossRef] [PubMed]
- K. Masamoto, T. Kurachi, N. Takizawa, H. Kobayashi, and K. Tanishita, “Successive depth variations in microvascular distribution of rat somatosensory cortex,” Brain Res. 995(1), 66–75 (2004). [CrossRef]
- K. Masamoto, T. Kurachi, N. Takizawa, H. Kobayashi, and K. Tanishita, “Successive depth variations in microvascular distribution of rat somatosensory cortex,” Brain Res. 995(1), 66–75 (2004). [CrossRef]
- J. L. Tatum, G. J. Kelloff, R. J. Gillies, J. M. Arbeit, J. M. Brown, K. S. C. Chao, J. D. Chapman, W. C. Eckelman, A. W. Fyles, A. J. Giaccia, R. P. Hill, C. J. Koch, M. C. Krishna, K. A. Krohn, J. S. Lewis, R. P. Mason, G. Melillo, A. R. Padhani, G. Powis, J. G. Rajendran, R. Reba, S. P. Robinson, G. L. Semenza, H. M. Swartz, P. Vaupel, D. Yang, B. Croft, J. Hoffman, G. Liu, H. Stone, and D. Sullivan, “Hypoxia: Importance in tumor biology, noninvasive measurement by imaging, and value of its measurement in the management of cancer therapy,” Int. J. Radiat. Biol. 82(10), 699–757 (2006). [CrossRef] [PubMed]
- I. P. Torres Filho, H. Kerger, and M. Intaglietta, “pO2 Measurements in Arteriolar Networks,” Microvasc. Res. 51(2), 202–212 (1996). [CrossRef] [PubMed]
- I. P. Torres Filho and M. Intaglietta, “Microvessel PO2 measurements by phosphorescence decay method,” Am. J. Physiol. 265(4 Pt 2), H1434–H1438 (1993). [PubMed]
- O. S. Finikova, A. Y. Lebedev, A. Aprelev, T. Troxler, F. Gao, C. Garnacho, S. Muro, R. M. Hochstrasser, and S. A. Vinogradov, “Oxygen Microscopy by Two-Photon-Excited Phosphorescence,” ChemPhysChem 9(12), 1673–1679 (2008). [CrossRef] [PubMed]
- A. G. Tsai, B. Friesenecker, M. C. Mazzoni, H. Kerger, D. G. Buerk, P. C. Johnson, and M. Intaglietta, “Microvascular and tissue oxygen gradients in the rat mesentery,” Proc. Natl. Acad. Sci. U.S.A. 95(12), 6590–6595 (1997). [CrossRef]
- W. L. Rumsey, J. M. Vanderkooi, and D. F. Wilson, “Imaging of Phosphorescence: A Novel Method for Measuring Oxygen Distribution in Perfused Tissue,” Science 241(4873), 1649–1651 (1988). [CrossRef] [PubMed]
- J. L. Tatum, G. J. Kelloff, R. J. Gillies, J. M. Arbeit, J. M. Brown, K. S. C. Chao, J. D. Chapman, W. C. Eckelman, A. W. Fyles, A. J. Giaccia, R. P. Hill, C. J. Koch, M. C. Krishna, K. A. Krohn, J. S. Lewis, R. P. Mason, G. Melillo, A. R. Padhani, G. Powis, J. G. Rajendran, R. Reba, S. P. Robinson, G. L. Semenza, H. M. Swartz, P. Vaupel, D. Yang, B. Croft, J. Hoffman, G. Liu, H. Stone, and D. Sullivan, “Hypoxia: Importance in tumor biology, noninvasive measurement by imaging, and value of its measurement in the management of cancer therapy,” Int. J. Radiat. Biol. 82(10), 699–757 (2006). [CrossRef] [PubMed]
- D. S. Vikram, J. L. Zweier, and P. Kuppusamy, “Methods for Noninvasive Imaging of Tissue Hypoxia,” Antioxid. Redox Signal. 9(10), 1745–1756 (2007). [CrossRef] [PubMed]
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- S. Sakadžić, S. Yuan, E. Dilekoz, S. Ruvinskaya, S. A. Vinogradov, C. Ayata, and D. A. Boas, “Simultaneous imaging of cerebral partial pressure of oxygen and blood flow during functional activation and cortical spreading depression,” Appl. Opt. 48(10), D169–D177 (2009). [CrossRef] [PubMed]
- O. S. Finikova, A. Y. Lebedev, A. Aprelev, T. Troxler, F. Gao, C. Garnacho, S. Muro, R. M. Hochstrasser, and S. A. Vinogradov, “Oxygen Microscopy by Two-Photon-Excited Phosphorescence,” ChemPhysChem 9(12), 1673–1679 (2008). [CrossRef] [PubMed]
- D. F. Wilson, S. A. Vinogradov, P. Grosul, M. N. Vaccarezza, A. Kuroki, and J. Bennett, “Oxygen distribution and vascular injury in the mouse eye measured by phosphorescence-lifetime imaging,” Appl. Opt. 44(25), 5239–5248 (2005). [CrossRef] [PubMed]
- I. Dunphy, S. A. Vinogradov, and D. F. Wilson, “Oxyphor R2 and G2: phosphors for measuring oxygen by oxygen-dependent quenching of phosphorescence,” Anal. Biochem. 310(2), 191–198 (2002). [CrossRef] [PubMed]
- S. A. Vinogradov, L.-W. Lo, and D. F. Wilson, “Dendritic Polyglutamic Porphyrins: Probing Porphyrin Protection by Oxygen-Dependent Quenching of Phosphorescence,” Chem. Eur. J. 5(4), 1338–1347 (1999). [CrossRef]
- S. A. Vinogradov, L.-W. Lo, W. T. Jenkins, S. M. Evans, C. Koch, and D. F. Wilson, “Noninvasive Imaging of the Distribution in Oxygen in Tissue In Vivo Using Near-Infrared Phosphors,” Biophys. J. 70(4), 1609–1617 (1996). [CrossRef] [PubMed]
- E. P. Vovenko, “Distribution of oxygen tension on the surface of arterioles, capillaries, and venules of brain cortex and in tissue in normoxia: an experimental study on rats,” Pfluegers Arch. Eur. J. Physiol. 437(4), 617–623 (1999). [CrossRef]
- K. Nagata, M. Sato, Y. Satoh, Y. Watahiki, Y. Kondoh, M. Sugawara, G. Box, D. Wright, S. Leung, H. Yuya, and E. Shimosegawa, “Hemodynamic aspects of Alzheimer’s Disease,” Ann. N. Y. Acad. Sci. 977(1), 391–402 (2002). [CrossRef] [PubMed]
- A. Y. Lebedev, A. V. Cheprakov, S. Sakadžić, D. A. Boas, D. F. Wilson, and S. A. Vinogradov, “Dendritic Phosphorescent Probes for Oxygen Imaging in Biological Systems,” ACS Applied Materials & Interfaces 1(6), 1292–1304 (2009). [CrossRef]
- D. F. Wilson, S. A. Vinogradov, P. Grosul, M. N. Vaccarezza, A. Kuroki, and J. Bennett, “Oxygen distribution and vascular injury in the mouse eye measured by phosphorescence-lifetime imaging,” Appl. Opt. 44(25), 5239–5248 (2005). [CrossRef] [PubMed]
- I. Dunphy, S. A. Vinogradov, and D. F. Wilson, “Oxyphor R2 and G2: phosphors for measuring oxygen by oxygen-dependent quenching of phosphorescence,” Anal. Biochem. 310(2), 191–198 (2002). [CrossRef] [PubMed]
- S. A. Vinogradov, L.-W. Lo, and D. F. Wilson, “Dendritic Polyglutamic Porphyrins: Probing Porphyrin Protection by Oxygen-Dependent Quenching of Phosphorescence,” Chem. Eur. J. 5(4), 1338–1347 (1999). [CrossRef]
- S. A. Vinogradov, L.-W. Lo, W. T. Jenkins, S. M. Evans, C. Koch, and D. F. Wilson, “Noninvasive Imaging of the Distribution in Oxygen in Tissue In Vivo Using Near-Infrared Phosphors,” Biophys. J. 70(4), 1609–1617 (1996). [CrossRef] [PubMed]
- R. D. Shonat, D. F. Wilson, C. E. Riva, and M. Pawlowski, “Oxygen distribution in the retinal and choroidal vessels of the cat as measured by a new phosphorescence imaging method,” Appl. Opt. 31(19), 3711–3718 (1992). [CrossRef] [PubMed]
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- I. Filho, M. Leunig, F. Yuan, M. Intaglietta, and R. K. Jain, “Noninvasive measurement of microvascular and interstitial oxygen profiles in a human tumor in SCID mice,” Proc. Natl. Acad. Sci. U.S.A. 91(6), 2081–2085 (1994). [CrossRef] [PubMed]
- K. Nagata, M. Sato, Y. Satoh, Y. Watahiki, Y. Kondoh, M. Sugawara, G. Box, D. Wright, S. Leung, H. Yuya, and E. Shimosegawa, “Hemodynamic aspects of Alzheimer’s Disease,” Ann. N. Y. Acad. Sci. 977(1), 391–402 (2002). [CrossRef] [PubMed]
- D. S. Vikram, J. L. Zweier, and P. Kuppusamy, “Methods for Noninvasive Imaging of Tissue Hypoxia,” Antioxid. Redox Signal. 9(10), 1745–1756 (2007). [CrossRef] [PubMed]
ACS Applied Materials & Interfaces
- A. Y. Lebedev, A. V. Cheprakov, S. Sakadžić, D. A. Boas, D. F. Wilson, and S. A. Vinogradov, “Dendritic Phosphorescent Probes for Oxygen Imaging in Biological Systems,” ACS Applied Materials & Interfaces 1(6), 1292–1304 (2009). [CrossRef]
Am. J. Physiol.
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Am. J. Physiol. Heart Circ. Physiol.
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Am. J. Physiol. Renal Physiol.
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Anal. Biochem.
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Anat. Rec.
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Ann. N. Y. Acad. Sci.
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Antioxid. Redox Signal.
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Appl. Opt.
- R. D. Shonat, D. F. Wilson, C. E. Riva, and M. Pawlowski, “Oxygen distribution in the retinal and choroidal vessels of the cat as measured by a new phosphorescence imaging method,” Appl. Opt. 31(19), 3711–3718 (1992). [CrossRef] [PubMed]
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- D. F. Wilson, S. A. Vinogradov, P. Grosul, M. N. Vaccarezza, A. Kuroki, and J. Bennett, “Oxygen distribution and vascular injury in the mouse eye measured by phosphorescence-lifetime imaging,” Appl. Opt. 44(25), 5239–5248 (2005). [CrossRef] [PubMed]
Appl. Spectrosc.
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Biochem. Soc. Trans.
- H. M. Swartz, “Measuring real levels of oxygen in vivo: opportunities and challenges,” Biochem. Soc. Trans. 30(2), 248–252 (2002). [CrossRef] [PubMed]
Biophys. J.
- S. A. Vinogradov, L.-W. Lo, W. T. Jenkins, S. M. Evans, C. Koch, and D. F. Wilson, “Noninvasive Imaging of the Distribution in Oxygen in Tissue In Vivo Using Near-Infrared Phosphors,” Biophys. J. 70(4), 1609–1617 (1996). [CrossRef] [PubMed]
Brain Res.
- K. Masamoto, T. Kurachi, N. Takizawa, H. Kobayashi, and K. Tanishita, “Successive depth variations in microvascular distribution of rat somatosensory cortex,” Brain Res. 995(1), 66–75 (2004). [CrossRef]
Cardiovasc. Res.
- M. Intaglietta, P. C. Johnson, and R. M. Winslow, “Microvascular and tissue oxygen distribution,” Cardiovasc. Res. 32(4), 632–643 (1996). [PubMed]
Cereb. Cortex (Cary)
- R. V. Harrison, N. Harel, J. Panesar, and R. J. Mount, “Blood Capillary Distribution Correlates with Hemodynamic-based Functional Imaging in Cerebral Cortex,” Cereb. Cortex (Cary) 12(3), 225–233 (2002). [CrossRef]
Chem. Eur. J.
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ChemPhysChem
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Int. J. Radiat. Biol.
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J. Biomed. Opt.
- P. B. Jones, H. K. Shin, D. A. Boas, B. T. Hyman, M. A. Moskowitz, C. Ayata, and A. K. Dunn, “Simultaneous multispectral reflectance imaging and laser speckle flowmetry of cerebral blood flow and oxygen metabolism in focal cerebral ischemia,” J. Biomed. Opt. 13(4), 044007 (2008). [CrossRef] [PubMed]
Microvasc. Res.
- I. P. Torres Filho, H. Kerger, and M. Intaglietta, “pO2 Measurements in Arteriolar Networks,” Microvasc. Res. 51(2), 202–212 (1996). [CrossRef] [PubMed]
Neuroimage
- E. M. C. Hillman, A. Devor, M. B. Bouchard, A. K. Dunn, G. W. Krauss, J. Skoch, B. J. Bacskai, A. M. Dale, and D. A. Boas, “Depth-resolved optical imaging and microscopy of vascular compartment dynamics during somatosensory stimulation,” Neuroimage 35(1), 89–104 (2007). [CrossRef] [PubMed]
Opt. Lett.
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Pfluegers Arch. Eur. J. Physiol.
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Proc. Natl. Acad. Sci. U.S.A.
- A. G. Tsai, B. Friesenecker, M. C. Mazzoni, H. Kerger, D. G. Buerk, P. C. Johnson, and M. Intaglietta, “Microvascular and tissue oxygen gradients in the rat mesentery,” Proc. Natl. Acad. Sci. U.S.A. 95(12), 6590–6595 (1997). [CrossRef]
- I. Filho, M. Leunig, F. Yuan, M. Intaglietta, and R. K. Jain, “Noninvasive measurement of microvascular and interstitial oxygen profiles in a human tumor in SCID mice,” Proc. Natl. Acad. Sci. U.S.A. 91(6), 2081–2085 (1994). [CrossRef] [PubMed]
Q. Rev. Biophys.
- R. G. Shulman, F. Hyder, and D. L. Rothman, “Biophysical basis of brain activity: implications for neuroimaging,” Q. Rev. Biophys. 35(3), 287–325 (2002). [CrossRef] [PubMed]
Science
- W. L. Rumsey, J. M. Vanderkooi, and D. F. Wilson, “Imaging of Phosphorescence: A Novel Method for Measuring Oxygen Distribution in Perfused Tissue,” Science 241(4873), 1649–1651 (1988). [CrossRef] [PubMed]
Other
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2009, Lebedev, ACS Applied Materials & Interfaces
- A. Y. Lebedev, A. V. Cheprakov, S. Sakadžić, D. A. Boas, D. F. Wilson, and S. A. Vinogradov, “Dendritic Phosphorescent Probes for Oxygen Imaging in Biological Systems,” ACS Applied Materials & Interfaces 1(6), 1292–1304 (2009). [CrossRef]
- A. S. Golub and R. N. Pittman, “PO2 measurements in the microcirculation using phosphorescence quenching microscopy at high magnification,” Am. J. Physiol. Heart Circ. Physiol. 294(6), 2905–2916 (2008). [CrossRef]
- O. S. Finikova, A. Y. Lebedev, A. Aprelev, T. Troxler, F. Gao, C. Garnacho, S. Muro, R. M. Hochstrasser, and S. A. Vinogradov, “Oxygen Microscopy by Two-Photon-Excited Phosphorescence,” ChemPhysChem 9(12), 1673–1679 (2008). [CrossRef] [PubMed]
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