Abstract

We demonstrate the use of inspired oxygen and carbon dioxide as a possible route to increase contrast in optical imaging of cancerous tissue. Differential imaging in human xenograft rodent models of cancer exhibits significant variation in signal between normal and cancerous tissue. This differential cancer-specific contrast is stronger and more consistent than the conventional static contrast. This differential technique exploits the response of abnormal tumor vasculature to inhaled gases and could provide a promising alternative to supplement mainstream cancer imaging modalities such as x-rays and MRI.

© 2008 Optical Society of America

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    [CrossRef] [PubMed]

2007 (5)

N. Chaudary and R. P. Hill, “Hypoxia and metastasis,” Clin. Cancer Res. 13, 1947–1949 (2007).
[CrossRef] [PubMed]

M. W. Dewhirst, I. C. Navia, D. M. Brizel, C. Willett, and T. W. Secomb, “Multiple etiologies of tumor hypoxia require multifaceted solutions,” Clin. Cancer Res. 13, 375–377 (2007).
[CrossRef] [PubMed]

J. G. Rajendran and D. A. Mankoff, “Beyond detection: Novel applications for PET imaging to guide cancer therapy,” J. Nucl. Med. 48, 855–856 (2007).
[CrossRef] [PubMed]

N. Chan, M. Milosevic, and R. G. Bristow, “Tumor hypoxia, DNA repair and prostate cancer progression: new targets and new therapies,” Future Oncol. 3, 329–341 (2007).
[CrossRef] [PubMed]

E. M. C. Hillman and A. Moore, “All-optical anatomical co-registration for molecular imaging of small animals using dynamic contrast,” Nature Photonics 1, 526–530 (2007).
[CrossRef]

2006 (1)

U. Sunar, H. Quon, T. Durduran, J. Zhang, and J. Duet al., “Noninvasive diffuse optical measurement of blood flow and blood oxygenation for monitoring radiation therapy in patients with head and neck tumors: a pilot study,” J. Biomed. Opt. 11, 064021 (2006).
[CrossRef]

2005 (2)

C. Menon and D. L. Fraker, “Tumor oxygenation status as a prognostic marker,” Cancer Lett. 221, 225–235 (2005).
[CrossRef] [PubMed]

B. S. Sorg, B. J. Moeller, O. Donovan, Y. Cao, and M. W. Dewhirst, “Hyperspectral imaging of hemoglobin saturation in tumor microvasculature and tumor hypoxia development,” J. Biomed. Opt. 10, 044004 (2005).
[CrossRef]

2004 (7)

P. Büchler, H. A. Reber, R. S. Lavey, J. Tomlinson, M. W. Büchler, H. Friess, and O. J. Hines, “Tumor hypoxia correlates with metastatic tumor growth of pancreatic cancer in an orthotopic murine model,” J. Surg. Res. 120, 295–303 (2004).
[CrossRef] [PubMed]

J. M. Brown and W. R. Wilson, “Exploiting tumour hypoxia in cancer treatment,” Nat Rev Cancer 4, 437–447 (2004).
[CrossRef] [PubMed]

M. Tozaki, “Interpretation of breast MRI: correlation of kinetic and morphological parameters with pathological findings,” Magn Reson Med Sci 3, 189–197 (2004).
[CrossRef]

C. Baudelet and B. Gallez, “Effect of anesthesia on the signal intensity in tumors using BOLD-MRI: comparison with flow measurements by Laser Doppler flowmetry and oxygen measurements by luminescence-based probes,” Magn. Reson. Imaging 22, 905–912 (2004).
[CrossRef] [PubMed]

H. Liu, Y. Gu, J. G. Kim, and R. P. Mason, “Near-infrared spectroscopy and imaging of tumor vascular oxygenation,” Methods Enzymol. 386, 349–378 (2004).
[CrossRef] [PubMed]

H. W. Wang, M. E. Putt, M. J. Emanuele, D. B. Shin, E. Glatstein, A. G. Yodh, and T. M. Busch, “Treatment-induced changes in tumor oxygenation predict photodynamic therapy outcome,” Cancer Res. 64, 7553–7561 (2004).
[CrossRef] [PubMed]

K. T. Kotz, K. S. Kalogerakis, W. N. Boenig, K. Amin, and G. W. Faris, “Dynamic imaging of tumor vasculature in rodents: Carbogen-induced contrast enhancement,” Proc. SPIE 5312, 273–277 (2004).
[CrossRef]

2003 (2)

J. G. Kim, D. Zhao, Y. Song, A. Constantinescu, R. P. Mason, and H. Liu, “Interplay of tumor vascular oxygenation and tumor pO2 observed using near-infrared spectroscopy, an oxygen needle electrode, and 19F MR pO2 mapping,” J. Biomed. Opt. 8, 53–62 (2003).
[CrossRef] [PubMed]

K. S. Kalogerakis, K. T. Kotz, K. Rand, and G. W. Faris, “Animal imaging using immersion,” Proc. SPIE 4955, 145–153 (2003).
[CrossRef]

2002 (6)

O. Thews, D. K. Kelleher, and P. Vaupel, “Dynamics of tumor oxygenation and red blood cell flux in response to inspiratory hyperoxia combined with different levels of inspiratory hypercapnia,” Radiother. Oncol. 62, 77–85 (2002).
[CrossRef] [PubMed]

G. Ilangovan, H. Li, J. L. Zweier, M. C. Krishna, J. B. Mitchell, and P. Kuppusamy, “In vivo measurement of regional oxygenation and imaging of redox status in RIF-1 murine tumor: Effect of carbogen-breathing,” Magn. Reson. Med. 48, 723–730 (2002).
[CrossRef] [PubMed]

M. Stubbs, S. P. Robinson, C. Hui, N. M. Price, L. M. Rodrigues, F. A. Howe, and J. R. Griffiths, “The importance of tumor metabolism in cancer prognosis and therapy; pre-clinical studies on rodent tumors with agents that improve tumor oxygenation,” Adv. Enzyme Regul. 42, 131–141 (2002).
[CrossRef] [PubMed]

J. H. Kaanders, J. Bussink, and A. J. van der Kogel, “ARCON: A novel biology-based approach in radiotherapy,” Lancet Oncol. 3, 728–737 (2002).
[CrossRef] [PubMed]

J. H. Kaanders, L. A. Pop, H. A. Marres, I. Bruaset, F. J. van den Hoogen, M. A. Merkx, and A. J. van der Kogel, “ARCON: Experience in 215 patients with advanced head-and-neck cancer,” Int. J. Radiat. Oncol. Biol. Phys. 52, 769–778 (2002).
[CrossRef] [PubMed]

M. Rijpkema, J. H. Kaanders, F. B. Joosten, A. J. van der Kogel, and A. Heerschap, “Effects of breathing a hyperoxic hypercapnic gas mixture on blood oxygenation and vascularity of head-and-neck tumors as measured by magnetic resonance imaging,” Int. J. Radiat. Oncol. Biol. Phys. 53, 1185–1191 (2002).
[CrossRef] [PubMed]

2001 (3)

M. Hockel and P. Vaupel, “Tumor hypoxia: Definitions and current clinical, biologic, and molecular aspects,” J. Natl. Cancer Inst. 93, 266–276 (2001).
[CrossRef] [PubMed]

M. O. Leach, “Application of magnetic resonance imaging to angiogenesis in breast cancer,” Breast Cancer Res 3, 22–27 (2001).
[CrossRef] [PubMed]

R. L. Barbour, H. L. Graber, Y. Pei, S. Zhong, and C. H. Schmitz, “Optical tomographic imaging of dynamic features of dense-scattering media,” J. Opt. Soc. Am. A 18, 3018–3036 (2001).
[CrossRef]

2000 (3)

M. A. Franceschini, V. Toronov, M. E. Filiaci, E. Gratton, and S. Fantini, “On-line optical imaging of the human brain with 160-ms temporal resolution” Opt. Express 6, 49–57 (2000).
[CrossRef] [PubMed]

D. L. Conover, B. M. Fenton, T. H. Foster, and E. L. Hull, “An evaluation of near infrared spectroscopy and cryospectrophotometry estimates of haemoglobin oxygen saturation in a rodent mammary tumour model,” Phys. Med. Biol. 45, 2685–2700 (2000).
[CrossRef] [PubMed]

P. Carmeliet and R. K. Jain, “Angiogenesis in cancer and other diseases,” Nature 407, 249–257 (2000).
[CrossRef] [PubMed]

1999 (7)

J. E. Sinex, “Pulse oximetry: Principles and limitations,” Am. J. Emerg. Med. 17, 59–66 (1999).
[CrossRef] [PubMed]

C. Aquino-Parsons, P. Lim, A. Green, and A. I. Minchinton, “Carbogen inhalation in cervical cancer: Assessment of oxygenation change,” Gynecol. Oncol. 74, 259–264 (1999).
[CrossRef] [PubMed]

B. P. J. van der Sanden, A. Heerschap, L. Hoofd, A. W. Simonetti, K. Nicolay, A. van der Toorn, W. Colier, and A. J. van der Kogel, “Effect of carbogen breathing on the physiological profile of human glioma xenografts,” Magn. Reson. Med. 42, 490–499 (1999).
[CrossRef] [PubMed]

E. L. Hull, D. L. Conover, and T. H. Foster, “Carbogen-induced changes in rat mammary tumour oxygenation reported by near infrared spectroscopy,” Br. J. Cancer 79, 1709–1716 (1999).
[CrossRef] [PubMed]

V. Ntziachristos, B. Chance, and A. Yodh, “Differential diffuse optical tomography,” Opt. Express 5, 230–242 (1999).
[CrossRef] [PubMed]

M. Gerken and G. W. Faris, “Frequency-domain immersion technique for accurate optical property measurements of turbid media,” Opt. Lett. 24, 1726–1728 (1999).
[CrossRef]

X. Wu and G. W. Faris, “Compensated transillumination,” Appl. Opt. 38, 4262–4265 (1999).
[CrossRef]

1998 (3)

B. Chance, E. Anday, S. Nioka, S. Zhou, L. Hong, K. Worden, C. Li, T. Murray, Y. Ovetsky, D. Pidikiti, and R. Thomas, “A novel method for fast imaging of brain function, non-invasively, with light,” Opt. Express 2, 411–423 (1998).
[CrossRef] [PubMed]

V. Quaresima, R. Springett, M. Cope, J. T. Wyatt, D. T. Delpy, M. Ferrari, and C. E. Cooper, “Oxidation and reduction of cytochrome oxidase in the neonatal brain observed by in vivo near-infrared spectroscopy,” Biochim. Biophys. Acta 1366, 291–300 (1998).
[CrossRef] [PubMed]

S. P. Robinson, F. A. Howe, L. M. Rodrigues, M. Stubbs, and J. R. Griffiths, “Magnetic resonance imaging techniques for monitoring changes in tumor oxygenation and blood flow,” Semin. Radiat. Oncol. 8, 197–207 (1998).
[CrossRef] [PubMed]

1997 (1)

J. R. Griffiths, N. J. Taylor, F. A. Howe, M. I. Saunders, S. P. Robinson, P. J. Hoskin, M. E. B. Powell, M. Thoumine, L. A. Caine, and H. Baddeley, “The response of human tumors to carbogen breathing, monitored by Gradient-Recalled Echo Magnetic Resonance Imaging,” Int. J. Radiat. Oncol. Biol. Phys. 39, 697–701 (1997).
[CrossRef] [PubMed]

1995 (1)

S. J. Matcher, C. E. Elwell, C. E. Cooper, M. Cope, and D. T. Delpy, “Performance comparison of several published tissue near-infrared spectroscopy algorithms,” Anal. Biochem. 227, 54–68 (1995).
[CrossRef] [PubMed]

1992 (1)

J. W. Severinghaus and J. F. Kelleher, “Recent developments in pulse oximetry,” Anesthesiology 76, 1018–1038 (1992).
[CrossRef] [PubMed]

1989 (1)

1988 (1)

M. Cope, D. T. Delpy, E. O. Reynolds, S. Wray, J. Wyatt, and P. van der Zee, “Methods of quantitating cerebral near infrared spectroscopy data,” Adv. Exp. Med. Biol. 222, 183–189 (1988).
[PubMed]

1986 (1)

J. S. Wyatt, M. Cope, D. T. Delpy, S. Wray, and E. O. Reynolds, “Quantification of cerebral oxygenation and haemodynamics in sick newborn infants by near infrared spectrophotometry,” Lancet 2, 1063–1066 (1986).
[CrossRef] [PubMed]

1977 (1)

F. F. Jöbsis, “Noninvasive, infrared monitoring of cerebral and myocardial oxygen sufficiency and circulatory parameters,” Science 198, 1264–1267 (1977).
[CrossRef] [PubMed]

Amin, K.

K. T. Kotz, K. S. Kalogerakis, W. N. Boenig, K. Amin, and G. W. Faris, “Dynamic imaging of tumor vasculature in rodents: Carbogen-induced contrast enhancement,” Proc. SPIE 5312, 273–277 (2004).
[CrossRef]

Anday, E.

Aquino-Parsons, C.

C. Aquino-Parsons, P. Lim, A. Green, and A. I. Minchinton, “Carbogen inhalation in cervical cancer: Assessment of oxygenation change,” Gynecol. Oncol. 74, 259–264 (1999).
[CrossRef] [PubMed]

Baddeley, H.

J. R. Griffiths, N. J. Taylor, F. A. Howe, M. I. Saunders, S. P. Robinson, P. J. Hoskin, M. E. B. Powell, M. Thoumine, L. A. Caine, and H. Baddeley, “The response of human tumors to carbogen breathing, monitored by Gradient-Recalled Echo Magnetic Resonance Imaging,” Int. J. Radiat. Oncol. Biol. Phys. 39, 697–701 (1997).
[CrossRef] [PubMed]

Barbour, R. L.

Baudelet, C.

C. Baudelet and B. Gallez, “Effect of anesthesia on the signal intensity in tumors using BOLD-MRI: comparison with flow measurements by Laser Doppler flowmetry and oxygen measurements by luminescence-based probes,” Magn. Reson. Imaging 22, 905–912 (2004).
[CrossRef] [PubMed]

Boenig, W. N.

K. T. Kotz, K. S. Kalogerakis, W. N. Boenig, K. Amin, and G. W. Faris, “Dynamic imaging of tumor vasculature in rodents: Carbogen-induced contrast enhancement,” Proc. SPIE 5312, 273–277 (2004).
[CrossRef]

Bristow, R. G.

N. Chan, M. Milosevic, and R. G. Bristow, “Tumor hypoxia, DNA repair and prostate cancer progression: new targets and new therapies,” Future Oncol. 3, 329–341 (2007).
[CrossRef] [PubMed]

Brizel, D. M.

M. W. Dewhirst, I. C. Navia, D. M. Brizel, C. Willett, and T. W. Secomb, “Multiple etiologies of tumor hypoxia require multifaceted solutions,” Clin. Cancer Res. 13, 375–377 (2007).
[CrossRef] [PubMed]

Brown, J. M.

J. M. Brown and W. R. Wilson, “Exploiting tumour hypoxia in cancer treatment,” Nat Rev Cancer 4, 437–447 (2004).
[CrossRef] [PubMed]

Bruaset, I.

J. H. Kaanders, L. A. Pop, H. A. Marres, I. Bruaset, F. J. van den Hoogen, M. A. Merkx, and A. J. van der Kogel, “ARCON: Experience in 215 patients with advanced head-and-neck cancer,” Int. J. Radiat. Oncol. Biol. Phys. 52, 769–778 (2002).
[CrossRef] [PubMed]

Büchler, M. W.

P. Büchler, H. A. Reber, R. S. Lavey, J. Tomlinson, M. W. Büchler, H. Friess, and O. J. Hines, “Tumor hypoxia correlates with metastatic tumor growth of pancreatic cancer in an orthotopic murine model,” J. Surg. Res. 120, 295–303 (2004).
[CrossRef] [PubMed]

Büchler, P.

P. Büchler, H. A. Reber, R. S. Lavey, J. Tomlinson, M. W. Büchler, H. Friess, and O. J. Hines, “Tumor hypoxia correlates with metastatic tumor growth of pancreatic cancer in an orthotopic murine model,” J. Surg. Res. 120, 295–303 (2004).
[CrossRef] [PubMed]

Busch, T. M.

H. W. Wang, M. E. Putt, M. J. Emanuele, D. B. Shin, E. Glatstein, A. G. Yodh, and T. M. Busch, “Treatment-induced changes in tumor oxygenation predict photodynamic therapy outcome,” Cancer Res. 64, 7553–7561 (2004).
[CrossRef] [PubMed]

Bussink, J.

J. H. Kaanders, J. Bussink, and A. J. van der Kogel, “ARCON: A novel biology-based approach in radiotherapy,” Lancet Oncol. 3, 728–737 (2002).
[CrossRef] [PubMed]

Caine, L. A.

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J. H. Kaanders, L. A. Pop, H. A. Marres, I. Bruaset, F. J. van den Hoogen, M. A. Merkx, and A. J. van der Kogel, “ARCON: Experience in 215 patients with advanced head-and-neck cancer,” Int. J. Radiat. Oncol. Biol. Phys. 52, 769–778 (2002).
[CrossRef] [PubMed]

Powell, M. E. B.

J. R. Griffiths, N. J. Taylor, F. A. Howe, M. I. Saunders, S. P. Robinson, P. J. Hoskin, M. E. B. Powell, M. Thoumine, L. A. Caine, and H. Baddeley, “The response of human tumors to carbogen breathing, monitored by Gradient-Recalled Echo Magnetic Resonance Imaging,” Int. J. Radiat. Oncol. Biol. Phys. 39, 697–701 (1997).
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Prahl, S.

S. Prahl, “Optical absorption of hemoglobin,” (Oregon Medical Laser Center).

Price, N. M.

M. Stubbs, S. P. Robinson, C. Hui, N. M. Price, L. M. Rodrigues, F. A. Howe, and J. R. Griffiths, “The importance of tumor metabolism in cancer prognosis and therapy; pre-clinical studies on rodent tumors with agents that improve tumor oxygenation,” Adv. Enzyme Regul. 42, 131–141 (2002).
[CrossRef] [PubMed]

Putt, M. E.

H. W. Wang, M. E. Putt, M. J. Emanuele, D. B. Shin, E. Glatstein, A. G. Yodh, and T. M. Busch, “Treatment-induced changes in tumor oxygenation predict photodynamic therapy outcome,” Cancer Res. 64, 7553–7561 (2004).
[CrossRef] [PubMed]

Quaresima, V.

V. Quaresima, R. Springett, M. Cope, J. T. Wyatt, D. T. Delpy, M. Ferrari, and C. E. Cooper, “Oxidation and reduction of cytochrome oxidase in the neonatal brain observed by in vivo near-infrared spectroscopy,” Biochim. Biophys. Acta 1366, 291–300 (1998).
[CrossRef] [PubMed]

Quon, H.

U. Sunar, H. Quon, T. Durduran, J. Zhang, and J. Duet al., “Noninvasive diffuse optical measurement of blood flow and blood oxygenation for monitoring radiation therapy in patients with head and neck tumors: a pilot study,” J. Biomed. Opt. 11, 064021 (2006).
[CrossRef]

Rajendran, J. G.

J. G. Rajendran and D. A. Mankoff, “Beyond detection: Novel applications for PET imaging to guide cancer therapy,” J. Nucl. Med. 48, 855–856 (2007).
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K. S. Kalogerakis, K. T. Kotz, K. Rand, and G. W. Faris, “Animal imaging using immersion,” Proc. SPIE 4955, 145–153 (2003).
[CrossRef]

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P. Büchler, H. A. Reber, R. S. Lavey, J. Tomlinson, M. W. Büchler, H. Friess, and O. J. Hines, “Tumor hypoxia correlates with metastatic tumor growth of pancreatic cancer in an orthotopic murine model,” J. Surg. Res. 120, 295–303 (2004).
[CrossRef] [PubMed]

Reynolds, E. O.

M. Cope, D. T. Delpy, E. O. Reynolds, S. Wray, J. Wyatt, and P. van der Zee, “Methods of quantitating cerebral near infrared spectroscopy data,” Adv. Exp. Med. Biol. 222, 183–189 (1988).
[PubMed]

J. S. Wyatt, M. Cope, D. T. Delpy, S. Wray, and E. O. Reynolds, “Quantification of cerebral oxygenation and haemodynamics in sick newborn infants by near infrared spectrophotometry,” Lancet 2, 1063–1066 (1986).
[CrossRef] [PubMed]

Rijpkema, M.

M. Rijpkema, J. H. Kaanders, F. B. Joosten, A. J. van der Kogel, and A. Heerschap, “Effects of breathing a hyperoxic hypercapnic gas mixture on blood oxygenation and vascularity of head-and-neck tumors as measured by magnetic resonance imaging,” Int. J. Radiat. Oncol. Biol. Phys. 53, 1185–1191 (2002).
[CrossRef] [PubMed]

Robinson, S. P.

M. Stubbs, S. P. Robinson, C. Hui, N. M. Price, L. M. Rodrigues, F. A. Howe, and J. R. Griffiths, “The importance of tumor metabolism in cancer prognosis and therapy; pre-clinical studies on rodent tumors with agents that improve tumor oxygenation,” Adv. Enzyme Regul. 42, 131–141 (2002).
[CrossRef] [PubMed]

S. P. Robinson, F. A. Howe, L. M. Rodrigues, M. Stubbs, and J. R. Griffiths, “Magnetic resonance imaging techniques for monitoring changes in tumor oxygenation and blood flow,” Semin. Radiat. Oncol. 8, 197–207 (1998).
[CrossRef] [PubMed]

J. R. Griffiths, N. J. Taylor, F. A. Howe, M. I. Saunders, S. P. Robinson, P. J. Hoskin, M. E. B. Powell, M. Thoumine, L. A. Caine, and H. Baddeley, “The response of human tumors to carbogen breathing, monitored by Gradient-Recalled Echo Magnetic Resonance Imaging,” Int. J. Radiat. Oncol. Biol. Phys. 39, 697–701 (1997).
[CrossRef] [PubMed]

Rodrigues, L. M.

M. Stubbs, S. P. Robinson, C. Hui, N. M. Price, L. M. Rodrigues, F. A. Howe, and J. R. Griffiths, “The importance of tumor metabolism in cancer prognosis and therapy; pre-clinical studies on rodent tumors with agents that improve tumor oxygenation,” Adv. Enzyme Regul. 42, 131–141 (2002).
[CrossRef] [PubMed]

S. P. Robinson, F. A. Howe, L. M. Rodrigues, M. Stubbs, and J. R. Griffiths, “Magnetic resonance imaging techniques for monitoring changes in tumor oxygenation and blood flow,” Semin. Radiat. Oncol. 8, 197–207 (1998).
[CrossRef] [PubMed]

Saunders, M. I.

J. R. Griffiths, N. J. Taylor, F. A. Howe, M. I. Saunders, S. P. Robinson, P. J. Hoskin, M. E. B. Powell, M. Thoumine, L. A. Caine, and H. Baddeley, “The response of human tumors to carbogen breathing, monitored by Gradient-Recalled Echo Magnetic Resonance Imaging,” Int. J. Radiat. Oncol. Biol. Phys. 39, 697–701 (1997).
[CrossRef] [PubMed]

Schmitz, C. H.

Secomb, T. W.

M. W. Dewhirst, I. C. Navia, D. M. Brizel, C. Willett, and T. W. Secomb, “Multiple etiologies of tumor hypoxia require multifaceted solutions,” Clin. Cancer Res. 13, 375–377 (2007).
[CrossRef] [PubMed]

Severinghaus, J. W.

J. W. Severinghaus and J. F. Kelleher, “Recent developments in pulse oximetry,” Anesthesiology 76, 1018–1038 (1992).
[CrossRef] [PubMed]

Shin, D. B.

H. W. Wang, M. E. Putt, M. J. Emanuele, D. B. Shin, E. Glatstein, A. G. Yodh, and T. M. Busch, “Treatment-induced changes in tumor oxygenation predict photodynamic therapy outcome,” Cancer Res. 64, 7553–7561 (2004).
[CrossRef] [PubMed]

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B. P. J. van der Sanden, A. Heerschap, L. Hoofd, A. W. Simonetti, K. Nicolay, A. van der Toorn, W. Colier, and A. J. van der Kogel, “Effect of carbogen breathing on the physiological profile of human glioma xenografts,” Magn. Reson. Med. 42, 490–499 (1999).
[CrossRef] [PubMed]

Sinex, J. E.

J. E. Sinex, “Pulse oximetry: Principles and limitations,” Am. J. Emerg. Med. 17, 59–66 (1999).
[CrossRef] [PubMed]

Song, Y.

J. G. Kim, D. Zhao, Y. Song, A. Constantinescu, R. P. Mason, and H. Liu, “Interplay of tumor vascular oxygenation and tumor pO2 observed using near-infrared spectroscopy, an oxygen needle electrode, and 19F MR pO2 mapping,” J. Biomed. Opt. 8, 53–62 (2003).
[CrossRef] [PubMed]

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B. S. Sorg, B. J. Moeller, O. Donovan, Y. Cao, and M. W. Dewhirst, “Hyperspectral imaging of hemoglobin saturation in tumor microvasculature and tumor hypoxia development,” J. Biomed. Opt. 10, 044004 (2005).
[CrossRef]

Springett, R.

V. Quaresima, R. Springett, M. Cope, J. T. Wyatt, D. T. Delpy, M. Ferrari, and C. E. Cooper, “Oxidation and reduction of cytochrome oxidase in the neonatal brain observed by in vivo near-infrared spectroscopy,” Biochim. Biophys. Acta 1366, 291–300 (1998).
[CrossRef] [PubMed]

Stubbs, M.

M. Stubbs, S. P. Robinson, C. Hui, N. M. Price, L. M. Rodrigues, F. A. Howe, and J. R. Griffiths, “The importance of tumor metabolism in cancer prognosis and therapy; pre-clinical studies on rodent tumors with agents that improve tumor oxygenation,” Adv. Enzyme Regul. 42, 131–141 (2002).
[CrossRef] [PubMed]

S. P. Robinson, F. A. Howe, L. M. Rodrigues, M. Stubbs, and J. R. Griffiths, “Magnetic resonance imaging techniques for monitoring changes in tumor oxygenation and blood flow,” Semin. Radiat. Oncol. 8, 197–207 (1998).
[CrossRef] [PubMed]

Sunar, U.

U. Sunar, H. Quon, T. Durduran, J. Zhang, and J. Duet al., “Noninvasive diffuse optical measurement of blood flow and blood oxygenation for monitoring radiation therapy in patients with head and neck tumors: a pilot study,” J. Biomed. Opt. 11, 064021 (2006).
[CrossRef]

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J. R. Griffiths, N. J. Taylor, F. A. Howe, M. I. Saunders, S. P. Robinson, P. J. Hoskin, M. E. B. Powell, M. Thoumine, L. A. Caine, and H. Baddeley, “The response of human tumors to carbogen breathing, monitored by Gradient-Recalled Echo Magnetic Resonance Imaging,” Int. J. Radiat. Oncol. Biol. Phys. 39, 697–701 (1997).
[CrossRef] [PubMed]

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O. Thews, D. K. Kelleher, and P. Vaupel, “Dynamics of tumor oxygenation and red blood cell flux in response to inspiratory hyperoxia combined with different levels of inspiratory hypercapnia,” Radiother. Oncol. 62, 77–85 (2002).
[CrossRef] [PubMed]

Thomas, R.

Thoumine, M.

J. R. Griffiths, N. J. Taylor, F. A. Howe, M. I. Saunders, S. P. Robinson, P. J. Hoskin, M. E. B. Powell, M. Thoumine, L. A. Caine, and H. Baddeley, “The response of human tumors to carbogen breathing, monitored by Gradient-Recalled Echo Magnetic Resonance Imaging,” Int. J. Radiat. Oncol. Biol. Phys. 39, 697–701 (1997).
[CrossRef] [PubMed]

Tomlinson, J.

P. Büchler, H. A. Reber, R. S. Lavey, J. Tomlinson, M. W. Büchler, H. Friess, and O. J. Hines, “Tumor hypoxia correlates with metastatic tumor growth of pancreatic cancer in an orthotopic murine model,” J. Surg. Res. 120, 295–303 (2004).
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Tozaki, M.

M. Tozaki, “Interpretation of breast MRI: correlation of kinetic and morphological parameters with pathological findings,” Magn Reson Med Sci 3, 189–197 (2004).
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J. H. Kaanders, L. A. Pop, H. A. Marres, I. Bruaset, F. J. van den Hoogen, M. A. Merkx, and A. J. van der Kogel, “ARCON: Experience in 215 patients with advanced head-and-neck cancer,” Int. J. Radiat. Oncol. Biol. Phys. 52, 769–778 (2002).
[CrossRef] [PubMed]

van der Kogel, A. J.

J. H. Kaanders, L. A. Pop, H. A. Marres, I. Bruaset, F. J. van den Hoogen, M. A. Merkx, and A. J. van der Kogel, “ARCON: Experience in 215 patients with advanced head-and-neck cancer,” Int. J. Radiat. Oncol. Biol. Phys. 52, 769–778 (2002).
[CrossRef] [PubMed]

M. Rijpkema, J. H. Kaanders, F. B. Joosten, A. J. van der Kogel, and A. Heerschap, “Effects of breathing a hyperoxic hypercapnic gas mixture on blood oxygenation and vascularity of head-and-neck tumors as measured by magnetic resonance imaging,” Int. J. Radiat. Oncol. Biol. Phys. 53, 1185–1191 (2002).
[CrossRef] [PubMed]

J. H. Kaanders, J. Bussink, and A. J. van der Kogel, “ARCON: A novel biology-based approach in radiotherapy,” Lancet Oncol. 3, 728–737 (2002).
[CrossRef] [PubMed]

B. P. J. van der Sanden, A. Heerschap, L. Hoofd, A. W. Simonetti, K. Nicolay, A. van der Toorn, W. Colier, and A. J. van der Kogel, “Effect of carbogen breathing on the physiological profile of human glioma xenografts,” Magn. Reson. Med. 42, 490–499 (1999).
[CrossRef] [PubMed]

van der Sanden, B. P. J.

B. P. J. van der Sanden, A. Heerschap, L. Hoofd, A. W. Simonetti, K. Nicolay, A. van der Toorn, W. Colier, and A. J. van der Kogel, “Effect of carbogen breathing on the physiological profile of human glioma xenografts,” Magn. Reson. Med. 42, 490–499 (1999).
[CrossRef] [PubMed]

van der Toorn, A.

B. P. J. van der Sanden, A. Heerschap, L. Hoofd, A. W. Simonetti, K. Nicolay, A. van der Toorn, W. Colier, and A. J. van der Kogel, “Effect of carbogen breathing on the physiological profile of human glioma xenografts,” Magn. Reson. Med. 42, 490–499 (1999).
[CrossRef] [PubMed]

van der Zee, P.

M. Cope, D. T. Delpy, E. O. Reynolds, S. Wray, J. Wyatt, and P. van der Zee, “Methods of quantitating cerebral near infrared spectroscopy data,” Adv. Exp. Med. Biol. 222, 183–189 (1988).
[PubMed]

Vaupel, P.

O. Thews, D. K. Kelleher, and P. Vaupel, “Dynamics of tumor oxygenation and red blood cell flux in response to inspiratory hyperoxia combined with different levels of inspiratory hypercapnia,” Radiother. Oncol. 62, 77–85 (2002).
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M. Hockel and P. Vaupel, “Tumor hypoxia: Definitions and current clinical, biologic, and molecular aspects,” J. Natl. Cancer Inst. 93, 266–276 (2001).
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H. W. Wang, M. E. Putt, M. J. Emanuele, D. B. Shin, E. Glatstein, A. G. Yodh, and T. M. Busch, “Treatment-induced changes in tumor oxygenation predict photodynamic therapy outcome,” Cancer Res. 64, 7553–7561 (2004).
[CrossRef] [PubMed]

Willett, C.

M. W. Dewhirst, I. C. Navia, D. M. Brizel, C. Willett, and T. W. Secomb, “Multiple etiologies of tumor hypoxia require multifaceted solutions,” Clin. Cancer Res. 13, 375–377 (2007).
[CrossRef] [PubMed]

Wilson, B. C.

Wilson, W. R.

J. M. Brown and W. R. Wilson, “Exploiting tumour hypoxia in cancer treatment,” Nat Rev Cancer 4, 437–447 (2004).
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Wray, S.

M. Cope, D. T. Delpy, E. O. Reynolds, S. Wray, J. Wyatt, and P. van der Zee, “Methods of quantitating cerebral near infrared spectroscopy data,” Adv. Exp. Med. Biol. 222, 183–189 (1988).
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J. S. Wyatt, M. Cope, D. T. Delpy, S. Wray, and E. O. Reynolds, “Quantification of cerebral oxygenation and haemodynamics in sick newborn infants by near infrared spectrophotometry,” Lancet 2, 1063–1066 (1986).
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Wu, X.

Wyatt, J.

M. Cope, D. T. Delpy, E. O. Reynolds, S. Wray, J. Wyatt, and P. van der Zee, “Methods of quantitating cerebral near infrared spectroscopy data,” Adv. Exp. Med. Biol. 222, 183–189 (1988).
[PubMed]

Wyatt, J. S.

J. S. Wyatt, M. Cope, D. T. Delpy, S. Wray, and E. O. Reynolds, “Quantification of cerebral oxygenation and haemodynamics in sick newborn infants by near infrared spectrophotometry,” Lancet 2, 1063–1066 (1986).
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Wyatt, J. T.

V. Quaresima, R. Springett, M. Cope, J. T. Wyatt, D. T. Delpy, M. Ferrari, and C. E. Cooper, “Oxidation and reduction of cytochrome oxidase in the neonatal brain observed by in vivo near-infrared spectroscopy,” Biochim. Biophys. Acta 1366, 291–300 (1998).
[CrossRef] [PubMed]

Yodh, A.

Yodh, A. G.

H. W. Wang, M. E. Putt, M. J. Emanuele, D. B. Shin, E. Glatstein, A. G. Yodh, and T. M. Busch, “Treatment-induced changes in tumor oxygenation predict photodynamic therapy outcome,” Cancer Res. 64, 7553–7561 (2004).
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Zhang, J.

U. Sunar, H. Quon, T. Durduran, J. Zhang, and J. Duet al., “Noninvasive diffuse optical measurement of blood flow and blood oxygenation for monitoring radiation therapy in patients with head and neck tumors: a pilot study,” J. Biomed. Opt. 11, 064021 (2006).
[CrossRef]

Zhao, D.

J. G. Kim, D. Zhao, Y. Song, A. Constantinescu, R. P. Mason, and H. Liu, “Interplay of tumor vascular oxygenation and tumor pO2 observed using near-infrared spectroscopy, an oxygen needle electrode, and 19F MR pO2 mapping,” J. Biomed. Opt. 8, 53–62 (2003).
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Zhong, S.

Zhou, S.

Zweier, J. L.

G. Ilangovan, H. Li, J. L. Zweier, M. C. Krishna, J. B. Mitchell, and P. Kuppusamy, “In vivo measurement of regional oxygenation and imaging of redox status in RIF-1 murine tumor: Effect of carbogen-breathing,” Magn. Reson. Med. 48, 723–730 (2002).
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Adv. Enzyme Regul. (1)

M. Stubbs, S. P. Robinson, C. Hui, N. M. Price, L. M. Rodrigues, F. A. Howe, and J. R. Griffiths, “The importance of tumor metabolism in cancer prognosis and therapy; pre-clinical studies on rodent tumors with agents that improve tumor oxygenation,” Adv. Enzyme Regul. 42, 131–141 (2002).
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Adv. Exp. Med. Biol. (1)

M. Cope, D. T. Delpy, E. O. Reynolds, S. Wray, J. Wyatt, and P. van der Zee, “Methods of quantitating cerebral near infrared spectroscopy data,” Adv. Exp. Med. Biol. 222, 183–189 (1988).
[PubMed]

Am. J. Emerg. Med. (1)

J. E. Sinex, “Pulse oximetry: Principles and limitations,” Am. J. Emerg. Med. 17, 59–66 (1999).
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Anal. Biochem. (1)

S. J. Matcher, C. E. Elwell, C. E. Cooper, M. Cope, and D. T. Delpy, “Performance comparison of several published tissue near-infrared spectroscopy algorithms,” Anal. Biochem. 227, 54–68 (1995).
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Anesthesiology (1)

J. W. Severinghaus and J. F. Kelleher, “Recent developments in pulse oximetry,” Anesthesiology 76, 1018–1038 (1992).
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Appl. Opt. (2)

Biochim. Biophys. Acta (1)

V. Quaresima, R. Springett, M. Cope, J. T. Wyatt, D. T. Delpy, M. Ferrari, and C. E. Cooper, “Oxidation and reduction of cytochrome oxidase in the neonatal brain observed by in vivo near-infrared spectroscopy,” Biochim. Biophys. Acta 1366, 291–300 (1998).
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Br. J. Cancer (1)

E. L. Hull, D. L. Conover, and T. H. Foster, “Carbogen-induced changes in rat mammary tumour oxygenation reported by near infrared spectroscopy,” Br. J. Cancer 79, 1709–1716 (1999).
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Breast Cancer Res (1)

M. O. Leach, “Application of magnetic resonance imaging to angiogenesis in breast cancer,” Breast Cancer Res 3, 22–27 (2001).
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Cancer Lett. (1)

C. Menon and D. L. Fraker, “Tumor oxygenation status as a prognostic marker,” Cancer Lett. 221, 225–235 (2005).
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Cancer Res. (1)

H. W. Wang, M. E. Putt, M. J. Emanuele, D. B. Shin, E. Glatstein, A. G. Yodh, and T. M. Busch, “Treatment-induced changes in tumor oxygenation predict photodynamic therapy outcome,” Cancer Res. 64, 7553–7561 (2004).
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Clin. Cancer Res. (2)

N. Chaudary and R. P. Hill, “Hypoxia and metastasis,” Clin. Cancer Res. 13, 1947–1949 (2007).
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M. W. Dewhirst, I. C. Navia, D. M. Brizel, C. Willett, and T. W. Secomb, “Multiple etiologies of tumor hypoxia require multifaceted solutions,” Clin. Cancer Res. 13, 375–377 (2007).
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Future Oncol. (1)

N. Chan, M. Milosevic, and R. G. Bristow, “Tumor hypoxia, DNA repair and prostate cancer progression: new targets and new therapies,” Future Oncol. 3, 329–341 (2007).
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Gynecol. Oncol. (1)

C. Aquino-Parsons, P. Lim, A. Green, and A. I. Minchinton, “Carbogen inhalation in cervical cancer: Assessment of oxygenation change,” Gynecol. Oncol. 74, 259–264 (1999).
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Int. J. Radiat. Oncol. Biol. Phys. (3)

J. R. Griffiths, N. J. Taylor, F. A. Howe, M. I. Saunders, S. P. Robinson, P. J. Hoskin, M. E. B. Powell, M. Thoumine, L. A. Caine, and H. Baddeley, “The response of human tumors to carbogen breathing, monitored by Gradient-Recalled Echo Magnetic Resonance Imaging,” Int. J. Radiat. Oncol. Biol. Phys. 39, 697–701 (1997).
[CrossRef] [PubMed]

J. H. Kaanders, L. A. Pop, H. A. Marres, I. Bruaset, F. J. van den Hoogen, M. A. Merkx, and A. J. van der Kogel, “ARCON: Experience in 215 patients with advanced head-and-neck cancer,” Int. J. Radiat. Oncol. Biol. Phys. 52, 769–778 (2002).
[CrossRef] [PubMed]

M. Rijpkema, J. H. Kaanders, F. B. Joosten, A. J. van der Kogel, and A. Heerschap, “Effects of breathing a hyperoxic hypercapnic gas mixture on blood oxygenation and vascularity of head-and-neck tumors as measured by magnetic resonance imaging,” Int. J. Radiat. Oncol. Biol. Phys. 53, 1185–1191 (2002).
[CrossRef] [PubMed]

J. Biomed. Opt. (3)

U. Sunar, H. Quon, T. Durduran, J. Zhang, and J. Duet al., “Noninvasive diffuse optical measurement of blood flow and blood oxygenation for monitoring radiation therapy in patients with head and neck tumors: a pilot study,” J. Biomed. Opt. 11, 064021 (2006).
[CrossRef]

B. S. Sorg, B. J. Moeller, O. Donovan, Y. Cao, and M. W. Dewhirst, “Hyperspectral imaging of hemoglobin saturation in tumor microvasculature and tumor hypoxia development,” J. Biomed. Opt. 10, 044004 (2005).
[CrossRef]

J. G. Kim, D. Zhao, Y. Song, A. Constantinescu, R. P. Mason, and H. Liu, “Interplay of tumor vascular oxygenation and tumor pO2 observed using near-infrared spectroscopy, an oxygen needle electrode, and 19F MR pO2 mapping,” J. Biomed. Opt. 8, 53–62 (2003).
[CrossRef] [PubMed]

J. Natl. Cancer Inst. (1)

M. Hockel and P. Vaupel, “Tumor hypoxia: Definitions and current clinical, biologic, and molecular aspects,” J. Natl. Cancer Inst. 93, 266–276 (2001).
[CrossRef] [PubMed]

J. Nucl. Med. (1)

J. G. Rajendran and D. A. Mankoff, “Beyond detection: Novel applications for PET imaging to guide cancer therapy,” J. Nucl. Med. 48, 855–856 (2007).
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J. Opt. Soc. Am. A (1)

J. Surg. Res. (1)

P. Büchler, H. A. Reber, R. S. Lavey, J. Tomlinson, M. W. Büchler, H. Friess, and O. J. Hines, “Tumor hypoxia correlates with metastatic tumor growth of pancreatic cancer in an orthotopic murine model,” J. Surg. Res. 120, 295–303 (2004).
[CrossRef] [PubMed]

Lancet (1)

J. S. Wyatt, M. Cope, D. T. Delpy, S. Wray, and E. O. Reynolds, “Quantification of cerebral oxygenation and haemodynamics in sick newborn infants by near infrared spectrophotometry,” Lancet 2, 1063–1066 (1986).
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Lancet Oncol. (1)

J. H. Kaanders, J. Bussink, and A. J. van der Kogel, “ARCON: A novel biology-based approach in radiotherapy,” Lancet Oncol. 3, 728–737 (2002).
[CrossRef] [PubMed]

Magn Reson Med Sci (1)

M. Tozaki, “Interpretation of breast MRI: correlation of kinetic and morphological parameters with pathological findings,” Magn Reson Med Sci 3, 189–197 (2004).
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Magn. Reson. Imaging (1)

C. Baudelet and B. Gallez, “Effect of anesthesia on the signal intensity in tumors using BOLD-MRI: comparison with flow measurements by Laser Doppler flowmetry and oxygen measurements by luminescence-based probes,” Magn. Reson. Imaging 22, 905–912 (2004).
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Magn. Reson. Med. (2)

G. Ilangovan, H. Li, J. L. Zweier, M. C. Krishna, J. B. Mitchell, and P. Kuppusamy, “In vivo measurement of regional oxygenation and imaging of redox status in RIF-1 murine tumor: Effect of carbogen-breathing,” Magn. Reson. Med. 48, 723–730 (2002).
[CrossRef] [PubMed]

B. P. J. van der Sanden, A. Heerschap, L. Hoofd, A. W. Simonetti, K. Nicolay, A. van der Toorn, W. Colier, and A. J. van der Kogel, “Effect of carbogen breathing on the physiological profile of human glioma xenografts,” Magn. Reson. Med. 42, 490–499 (1999).
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Methods Enzymol. (1)

H. Liu, Y. Gu, J. G. Kim, and R. P. Mason, “Near-infrared spectroscopy and imaging of tumor vascular oxygenation,” Methods Enzymol. 386, 349–378 (2004).
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Nat Rev Cancer (1)

J. M. Brown and W. R. Wilson, “Exploiting tumour hypoxia in cancer treatment,” Nat Rev Cancer 4, 437–447 (2004).
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P. Carmeliet and R. K. Jain, “Angiogenesis in cancer and other diseases,” Nature 407, 249–257 (2000).
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E. M. C. Hillman and A. Moore, “All-optical anatomical co-registration for molecular imaging of small animals using dynamic contrast,” Nature Photonics 1, 526–530 (2007).
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Opt. Express (3)

Opt. Lett. (1)

Phys. Med. Biol. (1)

D. L. Conover, B. M. Fenton, T. H. Foster, and E. L. Hull, “An evaluation of near infrared spectroscopy and cryospectrophotometry estimates of haemoglobin oxygen saturation in a rodent mammary tumour model,” Phys. Med. Biol. 45, 2685–2700 (2000).
[CrossRef] [PubMed]

Proc. SPIE (2)

K. S. Kalogerakis, K. T. Kotz, K. Rand, and G. W. Faris, “Animal imaging using immersion,” Proc. SPIE 4955, 145–153 (2003).
[CrossRef]

K. T. Kotz, K. S. Kalogerakis, W. N. Boenig, K. Amin, and G. W. Faris, “Dynamic imaging of tumor vasculature in rodents: Carbogen-induced contrast enhancement,” Proc. SPIE 5312, 273–277 (2004).
[CrossRef]

Radiother. Oncol. (1)

O. Thews, D. K. Kelleher, and P. Vaupel, “Dynamics of tumor oxygenation and red blood cell flux in response to inspiratory hyperoxia combined with different levels of inspiratory hypercapnia,” Radiother. Oncol. 62, 77–85 (2002).
[CrossRef] [PubMed]

Science (1)

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[CrossRef] [PubMed]

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S. P. Robinson, F. A. Howe, L. M. Rodrigues, M. Stubbs, and J. R. Griffiths, “Magnetic resonance imaging techniques for monitoring changes in tumor oxygenation and blood flow,” Semin. Radiat. Oncol. 8, 197–207 (1998).
[CrossRef] [PubMed]

Other (1)

S. Prahl, “Optical absorption of hemoglobin,” (Oregon Medical Laser Center).

Supplementary Material (2)

» Media 1: AVI (2146 KB)     
» Media 2: AVI (2154 KB)     

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Figures (9)

Fig. 1.
Fig. 1.

Experimental apparatus to acquire transillumination images. The LED box consists of two arrays of LEDs at 780 and 840 nm. The mass flow controllers deliver precise concentrations of gases to the animal during the experiment. The temperature of the tissue phantom immersion medium is held constant at around 37 °C.

Fig. 2.
Fig. 2.

Direct images of mice in the ventral imaging position with the tumor facing away from the camera. (a) Normal, no tumor (#1), (b) U87 brain tumor (#3) and (c) DLD colon cancer (#6).

Fig. 3.
Fig. 3.

(a) Change in absorbance from the tumor in animal #3 at 780 and 840 nm. The various inspired gases are indicated by colored shading. The Air+CO2 mixture contains 5% CO2, the first carbogen mixture contains 5% CO2 and the second carbogen mixture contains 10% CO2. No color shading is used for inhalation of Air. (b) Changes in relative concentrations of Hb, HbO2 and Hbtotal for the same data.

Fig. 4.
Fig. 4.

Comparison between static transillumination images and relative HbO2 concentration maps for a normal mouse (#1) and two tumor bearing mice (#3, 6). Images from a particular animal are shown in a single row. Column (a) includes static transillumination images obtained at 780 nm. Column (b) shows relative HbO2 concentration maps when the animals breathe air. Column (c) shows the relative change in HbO2 concentration upon hyperoxic gas intervention (oxygen, carbogen and oxygen for #1, 3, and 6, respectively). Column (d) shows relative HbO2 concentrations fall back to those noted in column (b) when the hyperoxic gas is turned off. Tumor and animal outlines are shown in black. The units on the intensity scale bar for images in columns (b)–(d) are cm*mM/L. Note that U87 #3 is a relatively shallow and wide tumor while DLD #6 is a relatively deep and narrow tumor.

Fig. 5.
Fig. 5.

Direct images of mice in the dorsal imaging position with the tumor facing the camera. (a) U87 brain tumor (#3), (b) U87 brain tumor (#4) and (c) DLD colon cancer (#6).

Fig. 6.
Fig. 6.

Comparison between static transillumination images and relative HbO2 concentration maps for three tumor-bearing mice (#3, 4 and 6). Images from a particular animal are shown in a single row. Column (a) includes static transillumination images obtained at 780 nm. Column (b) shows relative HbO2 concentration maps when the animals breathe air. Column (c) shows the relative change in HbO2 concentration upon hyperoxic (oxygen) gas intervention. Column (d) shows relative HbO2 concentrations fall back to those noted in column (b) when the hyperoxic gas is turned off. Tumor and animal outlines are shown in black. The units on the intensity scale bar for images in columns (b)–(d) are cm*mM/L.

Fig. 7.
Fig. 7.

(2.1 MB) Movie showing the dynamic change in relative HbO2 concentration as a function of inspired gases for animal #3. The units on the intensity scale bar are cm*mM/L. [Media 1]

Fig. 8.
Fig. 8.

(2.1 MB) Movie showing the dynamic change in relative HbO2 concentration as a function of inspired gases for animal #4. The units on the intensity scale bar are cm*mM/L. [Media 2]

Fig. 9.
Fig. 9.

Dynamic change in the differential intensity observed for the tumor zone during the inhalation of various gases. The gas mixtures cycled over the entire experiment were in the following order: Air, carbogen (85% oxygen + 15% carbon dioxide in this case), oxygen (85% oxygen + 15% air) and carbon dioxide (85% air + 5% carbon dioxide).

Tables (1)

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Table 1. Mouse statistics.

Equations (6)

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Δ μ a 780 = ln ( 10 ) { ε Hb 780 Δ [ Hb ] + ε HbO 2 780 Δ [ Hb O 2 ] }
Δ μ a 840 = ln ( 10 ) { ε Hb 840 Δ [ Hb ] + ε HbO 2 840 Δ [ Hb O 2 ] }
ε Hb , Hb O 2 780 , 840 = λ ε ( λ ) I ( λ ) d λ .
1 L 780 ln ( I B I T ) 780 = ln ( 10 ) { ε Hb 780 Δ [ Hb ] + ε HbO 2 780 Δ [ HbO 2 ] }
1 L 840 ln ( I B I T ) 840 = ln ( 10 ) { ε Hb 840 Δ [ Hb ] + ε HbO 2 840 Δ [ HbO 2 ] }
( Δ [ Hb ] Δ [ HbO 2 ] ) = 1 ln ( 10 ) ( ε Hb 780 ε HbO 2 780 ε Hb 840 ε HbO 2 840 ) 1 ( 1 L 780 ln ( I B I T ) 780 1 L 840 ln ( I B I T ) 840 ) .

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