Abstract

We present initial results obtained during the course of a Phase I clinical trial of 2-1[hexyloxyethyl]-2-devinylpyropheophorbide-a (HPPH)-mediated photo-dynamic therapy (PDT) in a head and neck cancer patient. We quantified blood flow, oxygenation and HPPH drug photobleaching before and after therapeutic light treatment by utilizing fast, non-invasive diffuse optical methods. Our results showed that HPPH-PDT induced significant drug photobleaching, and reduction in blood flow and oxygenation suggesting significant vascular and cellular reaction. These changes were accompanied by cross-linking of the signal transducer and activator of transcription 3 (STAT3), a molecular measure for the oxidative photoreaction. These preliminary results suggest diffuse optical spectroscopies permit non-invasive monitoring of PDT in clinical settings of head and neck cancer patients.

© 2010 OSA

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2009 (2)

P. Zakharov, A. C. Völker, M. T. Wyss, F. Haiss, N. Calcinaghi, C. Zunzunegui, A. Buck, F. Scheffold, and B. Weber, “Dynamic laser speckle imaging of cerebral blood flow,” Opt. Express 17(16), 13904–13917 (2009).
[CrossRef] [PubMed]

B. Kruijt, S. Kascakova, H. S. de Bruijn, A. van der Ploeg-van den Heuvel, H. J. Sterenborg, D. J. Robinson, and A. Amelink, “In vivo quantification of chromophore concentration using fluorescence differential path length spectroscopy,” J. Biomed. Opt. 14(3), 034022 (2009).
[CrossRef] [PubMed]

2008 (4)

A. Amelink, O. P. Kaspers, H. J. Sterenborg, J. E. van der Wal, J. L. Roodenburg, and M. J. Witjes, “Non-invasive measurement of the morphology and physiology of oral mucosa by use of optical spectroscopy,” Oral Oncol. 44(1), 65–71 (2008).
[CrossRef]

R. A. Schwarz, W. Gao, D. Daye, M. D. Williams, R. Richards-Kortum, and A. M. Gillenwater, “Autofluorescence and diffuse reflectance spectroscopy of oral epithelial tissue using a depth-sensitive fiber-optic probe,” Appl. Opt. 47(6), 825–834 (2008).
[CrossRef] [PubMed]

D. Roblyer, R. Richards-Kortum, K. Sokolov, A. K. El-Naggar, M. D. Williams, C. Kurachi, and A. M. Gillenwater, “Multispectral optical imaging device for in vivo detection of oral neoplasia,” J. Biomed. Opt. 13(2), 024019 (2008).
[CrossRef] [PubMed]

E. H. Moriyama, A. Kim, A. Bogaards, L. Lilge, and B. Wilson, “A ratiometric fluorescence imaging system for surgical guidance,” Adv. Opt. Technol. 2008, 532368 (2008).

2007 (5)

C. Sheng, P. J. Hoopes, T. Hasan, and B. W. Pogue, “Photobleaching-based dosimetry predicts deposited dose in ALA-PpIX PDT of rodent esophagus,” Photochem. Photobiol. 83(3), 738–748 (2007).
[CrossRef] [PubMed]

A. Bogaards, H. J. Sterenborg, and B. Wilson, “In vivo quantification of fluorescent molecular markers in real-time: A review to evaluate the performance of five existing methods,” Photodiagn. Photodyn. Ther. 4(3), 170–178 (2007).
[CrossRef]

M. A. Biel, “Photodynamic therapy treatment of early oral and laryngeal cancers,” Photochem. Photobiol. 83(5), 1063–1068 (2007).
[CrossRef] [PubMed]

B. W. Henderson, C. Daroqui, E. Tracy, L. A. Vaughan, G. M. Loewen, M. T. Cooper, and H. Baumann, “Cross-linking of signal transducer and activator of transcription 3--a molecular marker for the photodynamic reaction in cells and tumors,” Clin. Cancer Res. 13(11), 3156–3163 (2007).
[CrossRef] [PubMed]

U. Sunar, S. Makonnen, C. Zhou, T. Durduran, G. Yu, H. W. Wang, W. M. F. Lee, and A. G. Yodh, “Hemodynamic responses to antivascular therapy and ionizing radiation assessed by diffuse optical spectroscopies,” Opt. Express 15(23), 15507–15516 (2007).
[CrossRef] [PubMed]

2006 (7)

T. Binzoni, T. S. Leung, D. Rüfenacht, and D. T. Delpy, “Absorption and scattering coefficient dependence of laser-Doppler flowmetry models for large tissue volumes,” Phys. Med. Biol. 51(2), 311–333 (2006).
[CrossRef] [PubMed]

U. Sunar, H. Quon, T. Durduran, J. Zhang, J. Du, C. Zhou, G. Yu, R. Choe, A. Kilger, R. Lustig, L. Loevner, S. Nioka, B. Chance, and A. G. Yodh, “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(6), 064021 (2006).
[CrossRef]

G. Yu, T. Durduran, C. Zhou, T. C. Zhu, J. C. Finlay, T. M. Busch, S. B. Malkowicz, S. M. Hahn, and A. G. Yodh, “Real-time in situ monitoring of human prostate photodynamic therapy with diffuse light,” Photochem. Photobiol. 82(5), 1279–1284 (2006).
[CrossRef] [PubMed]

C. Zhou, G. Yu, D. Furuya, J. Greenberg, A. Yodh, and T. Durduran, “Diffuse optical correlation tomography of cerebral blood flow during cortical spreading depression in rat brain,” Opt. Express 14(3), 1125–1144 (2006).
[CrossRef] [PubMed]

P. Zakharov, A. Völker, A. Buck, B. Weber, and F. Scheffold, “Quantitative modeling of laser speckle imaging,” Opt. Lett. 31(23), 3465–3467 (2006).
[CrossRef] [PubMed]

D. A. Bellnier, W. R. Greco, G. M. Loewen, H. Nava, A. R. Oseroff, and T. J. Dougherty, “Clinical pharmacokinetics of the PDT photosensitizers porfimer sodium (Photofrin), 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a (Photochlor) and 5-ALA-induced protoporphyrin IX,” Lasers Surg. Med. 38(5), 439–444 (2006).
[CrossRef] [PubMed]

W. J. Cottrell, A. R. Oseroff, and T. H. Foster, “Portable instrument that integrates irradiation with fluorescence and reflectance spectroscopies during clinical photodynamic therapy of cutaneous disease,” Rev. Sci. Instrum. 77(6), 064302 (2006).
[CrossRef]

2005 (7)

M. P. Bard, A. Amelink, V. N. Hegt, W. J. Graveland, H. J. Sterenborg, H. C. Hoogsteden, and J. G. Aerts, “Measurement of hypoxia-related parameters in bronchial mucosa by use of optical spectroscopy,” Am. J. Respir. Crit. Care Med. 171(10), 1178–1184 (2005).
[CrossRef] [PubMed]

R. L. P. Veen, A. Amelink, M. Menke-Pluymers, C. Pol, and H. J. C. M. Sterenborg, “Optical biopsy of breast tissue using differential path-length spectroscopy,” Phys. Med. Biol. 50(11), 2573–2581 (2005).
[CrossRef] [PubMed]

D. C. de Veld, M. Skurichina, M. J. Witjes, R. P. Duin, H. J. Sterenborg, and J. L. Roodenburg, “Autofluorescence and diffuse reflectance spectroscopy for oral oncology,” Lasers Surg. Med. 36(5), 356–364 (2005).
[CrossRef] [PubMed]

P. R. Bargo, S. A. Prahl, T. T. Goodell, R. A. Sleven, G. Koval, G. Blair, and S. L. Jacques, “In vivo determination of optical properties of normal and tumor tissue with white light reflectance and an empirical light transport model during endoscopy,” J. Biomed. Opt. 10(3), 034018 (2005).
[CrossRef] [PubMed]

H. W. Wang, T. C. Zhu, M. E. Putt, M. Solonenko, J. Metz, A. Dimofte, J. Miles, D. L. Fraker, E. Glatstein, S. M. Hahn, and A. G. Yodh, “Broadband reflectance measurements of light penetration, blood oxygenation, hemoglobin concentration, and drug concentration in human intraperitoneal tissues before and after photodynamic therapy,” J. Biomed. Opt. 10(1), 014004 (2005).
[CrossRef]

G. Yu, T. Durduran, C. Zhou, H. W. Wang, M. E. Putt, H. M. Saunders, C. M. Sehgal, E. Glatstein, A. G. Yodh, and T. M. Busch, “Noninvasive monitoring of murine tumor blood flow during and after photodynamic therapy provides early assessment of therapeutic efficacy,” Clin. Cancer Res. 11(9), 3543–3552 (2005).
[CrossRef] [PubMed]

T. Durduran, R. Choe, G. Yu, C. Zhou, J. C. Tchou, B. J. Czerniecki, and A. G. Yodh, “Diffuse optical measurement of blood flow in breast tumors,” Opt. Lett. 30(21), 2915–2917 (2005).
[CrossRef] [PubMed]

2004 (1)

W. Liu, A. R. Oseroff, and H. Baumann, “Photodynamic therapy causes cross-linking of signal transducer and activator of transcription proteins and attenuation of interleukin-6 cytokine responsiveness in epithelial cells,” Cancer Res. 64(18), 6579–6587 (2004).
[CrossRef] [PubMed]

2003 (3)

D. A. Bellnier, W. R. Greco, G. M. Loewen, H. Nava, A. R. Oseroff, R. K. Pandey, T. Tsuchida, and T. J. Dougherty, “Population pharmacokinetics of the photodynamic therapy agent 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a in cancer patients,” Cancer Res. 63(8), 1806–1813 (2003).
[PubMed]

J. P. Culver, T. Durduran, D. Furuya, C. Cheung, J. H. Greenberg, and A. G. Yodh, “Diffuse optical tomography of cerebral blood flow, oxygenation, and metabolism in rat during focal ischemia,” J. Cereb. Blood Flow Metab. 23(8), 911–924 (2003).
[CrossRef] [PubMed]

S. Gross, A. Gilead, A. Scherz, M. Neeman, and Y. Salomon, “Monitoring photodynamic therapy of solid tumors online by BOLD-contrast MRI,” Nat. Med. 9(10), 1327–1331 (2003).
[CrossRef] [PubMed]

2001 (4)

T. H. Pham, R. Hornung, M. W. Berns, Y. Tadir, and B. J. Tromberg, “Monitoring tumor response during photodynamic therapy using near-infrared photon-migration spectroscopy,” Photochem. Photobiol. 73(6), 669–677 (2001).
[CrossRef] [PubMed]

C. Cheung, J. P. Culver, K. Takahashi, J. H. Greenberg, and A. G. Yodh, “In vivo cerebrovascular measurement combining diffuse near-infrared absorption and correlation spectroscopies,” Phys. Med. Biol. 46(8), 2053–2065 (2001).
[CrossRef] [PubMed]

M. G. Müller, I. Georgakoudi, Q. Zhang, J. Wu, and M. S. Feld, “Intrinsic fluorescence spectroscopy in turbid media: disentangling effects of scattering and absorption,” Appl. Opt. 40(25), 4633–4646 (2001).
[CrossRef]

J. C. Finlay, D. L. Conover, E. L. Hull, and T. H. Foster, “Porphyrin bleaching and PDT-induced spectral changes are irradiance dependent in ALA-sensitized normal rat skin in vivo,” Photochem. Photobiol. 73(1), 54–63 (2001).
[CrossRef] [PubMed]

1999 (1)

H. J. Feldmann, M. Molls, and P. Vaupel, “Blood flow and oxygenation status of human tumors,” Strahlenther. Onkol. 175(1), 1–9 (1999).
[CrossRef] [PubMed]

1998 (2)

I. Georgakoudi and T. H. Foster, “Singlet oxygen- versus nonsinglet oxygen-mediated mechanisms of sensitizer photobleaching and their effects on photodynamic dosimetry,” Photochem. Photobiol. 67(6), 612–625 (1998).
[PubMed]

G. A. Wagnières, W. M. Star, and B. C. Wilson, “In vivo fluorescence spectroscopy and imaging for oncological applications,” Photochem. Photobiol. 68(5), 603–632 (1998).
[PubMed]

1997 (6)

1996 (1)

S. L. Jacques, “Origins of tissue optical properties in the UVA, visible, and NIR regions,” OSA Trends in Optics and Photonics on Advances in Optical Imaging and Photon Migration 2, 364–371 (1996).

1995 (1)

D. A. Boas, L. E. Campbell, and A. G. Yodh, “Scattering and Imaging with Diffusing Temporal Field Correlations,” Phys. Rev. Lett. 75(9), 1855–1858 (1995).
[CrossRef] [PubMed]

1993 (2)

J. Wu, M. S. Feld, and R. P. Rava, “Analytical model for extracting intrinsic fluorescence in turbid media,” Appl. Opt. 32(19), 3585–3595 (1993).
[CrossRef] [PubMed]

D. A. Bellnier, B. W. Henderson, R. K. Pandey, W. R. Potter, and T. J. Dougherty, “Murine pharmacokinetics and antitumor efficacy of the photodynamic sensitizer 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a,” J. Photochem. Photobiol. B 20(1), 55–61 (1993).
[CrossRef] [PubMed]

1992 (1)

T. J. Farrell, M. S. Patterson, and B. Wilson, “A diffusion theory model of spatially resolved, steady-state diffuse reflectance for the noninvasive determination of tissue optical properties in vivo,” Med. Phys. 19(4), 879–888 (1992).
[CrossRef] [PubMed]

1989 (1)

P. Vaupel, F. Kallinowski, and P. Okunieff, “Blood flow, oxygen and nutrient supply, and metabolic microenvironment of human tumors: a review,” Cancer Res. 49(23), 6449–6465 (1989).
[PubMed]

1988 (1)

D. J. Pine, D. A. Weitz, P. M. Chaikin, and E. Herbolzheimer, “Diffusing wave spectroscopy,” Phys. Rev. Lett. 60(12), 1134–1137 (1988).
[CrossRef] [PubMed]

1987 (1)

G. Maret and P. E. Wolf, “Multiple Light-Scattering from Disordered Media - the Effect of Brownian-Motion of Scatterers,” Z. Phys. B Condens. Matter 65(4), 409–413 (1987).
[CrossRef]

Aerts, J. G.

M. P. Bard, A. Amelink, V. N. Hegt, W. J. Graveland, H. J. Sterenborg, H. C. Hoogsteden, and J. G. Aerts, “Measurement of hypoxia-related parameters in bronchial mucosa by use of optical spectroscopy,” Am. J. Respir. Crit. Care Med. 171(10), 1178–1184 (2005).
[CrossRef] [PubMed]

Amelink, A.

B. Kruijt, S. Kascakova, H. S. de Bruijn, A. van der Ploeg-van den Heuvel, H. J. Sterenborg, D. J. Robinson, and A. Amelink, “In vivo quantification of chromophore concentration using fluorescence differential path length spectroscopy,” J. Biomed. Opt. 14(3), 034022 (2009).
[CrossRef] [PubMed]

A. Amelink, O. P. Kaspers, H. J. Sterenborg, J. E. van der Wal, J. L. Roodenburg, and M. J. Witjes, “Non-invasive measurement of the morphology and physiology of oral mucosa by use of optical spectroscopy,” Oral Oncol. 44(1), 65–71 (2008).
[CrossRef]

M. P. Bard, A. Amelink, V. N. Hegt, W. J. Graveland, H. J. Sterenborg, H. C. Hoogsteden, and J. G. Aerts, “Measurement of hypoxia-related parameters in bronchial mucosa by use of optical spectroscopy,” Am. J. Respir. Crit. Care Med. 171(10), 1178–1184 (2005).
[CrossRef] [PubMed]

R. L. P. Veen, A. Amelink, M. Menke-Pluymers, C. Pol, and H. J. C. M. Sterenborg, “Optical biopsy of breast tissue using differential path-length spectroscopy,” Phys. Med. Biol. 50(11), 2573–2581 (2005).
[CrossRef] [PubMed]

Bard, M. P.

M. P. Bard, A. Amelink, V. N. Hegt, W. J. Graveland, H. J. Sterenborg, H. C. Hoogsteden, and J. G. Aerts, “Measurement of hypoxia-related parameters in bronchial mucosa by use of optical spectroscopy,” Am. J. Respir. Crit. Care Med. 171(10), 1178–1184 (2005).
[CrossRef] [PubMed]

Bargo, P. R.

P. R. Bargo, S. A. Prahl, T. T. Goodell, R. A. Sleven, G. Koval, G. Blair, and S. L. Jacques, “In vivo determination of optical properties of normal and tumor tissue with white light reflectance and an empirical light transport model during endoscopy,” J. Biomed. Opt. 10(3), 034018 (2005).
[CrossRef] [PubMed]

Baumann, H.

B. W. Henderson, C. Daroqui, E. Tracy, L. A. Vaughan, G. M. Loewen, M. T. Cooper, and H. Baumann, “Cross-linking of signal transducer and activator of transcription 3--a molecular marker for the photodynamic reaction in cells and tumors,” Clin. Cancer Res. 13(11), 3156–3163 (2007).
[CrossRef] [PubMed]

W. Liu, A. R. Oseroff, and H. Baumann, “Photodynamic therapy causes cross-linking of signal transducer and activator of transcription proteins and attenuation of interleukin-6 cytokine responsiveness in epithelial cells,” Cancer Res. 64(18), 6579–6587 (2004).
[CrossRef] [PubMed]

Bellnier, D. A.

D. A. Bellnier, W. R. Greco, G. M. Loewen, H. Nava, A. R. Oseroff, and T. J. Dougherty, “Clinical pharmacokinetics of the PDT photosensitizers porfimer sodium (Photofrin), 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a (Photochlor) and 5-ALA-induced protoporphyrin IX,” Lasers Surg. Med. 38(5), 439–444 (2006).
[CrossRef] [PubMed]

D. A. Bellnier, W. R. Greco, G. M. Loewen, H. Nava, A. R. Oseroff, R. K. Pandey, T. Tsuchida, and T. J. Dougherty, “Population pharmacokinetics of the photodynamic therapy agent 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a in cancer patients,” Cancer Res. 63(8), 1806–1813 (2003).
[PubMed]

D. A. Bellnier, B. W. Henderson, R. K. Pandey, W. R. Potter, and T. J. Dougherty, “Murine pharmacokinetics and antitumor efficacy of the photodynamic sensitizer 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a,” J. Photochem. Photobiol. B 20(1), 55–61 (1993).
[CrossRef] [PubMed]

Berns, M. W.

T. H. Pham, R. Hornung, M. W. Berns, Y. Tadir, and B. J. Tromberg, “Monitoring tumor response during photodynamic therapy using near-infrared photon-migration spectroscopy,” Photochem. Photobiol. 73(6), 669–677 (2001).
[CrossRef] [PubMed]

Biel, M. A.

M. A. Biel, “Photodynamic therapy treatment of early oral and laryngeal cancers,” Photochem. Photobiol. 83(5), 1063–1068 (2007).
[CrossRef] [PubMed]

Bigio, I. J.

Binzoni, T.

T. Binzoni, T. S. Leung, D. Rüfenacht, and D. T. Delpy, “Absorption and scattering coefficient dependence of laser-Doppler flowmetry models for large tissue volumes,” Phys. Med. Biol. 51(2), 311–333 (2006).
[CrossRef] [PubMed]

Blair, G.

P. R. Bargo, S. A. Prahl, T. T. Goodell, R. A. Sleven, G. Koval, G. Blair, and S. L. Jacques, “In vivo determination of optical properties of normal and tumor tissue with white light reflectance and an empirical light transport model during endoscopy,” J. Biomed. Opt. 10(3), 034018 (2005).
[CrossRef] [PubMed]

Boas, D. A.

D. A. Boas and A. G. Yodh, “Spatially varying dynamical properties of turbid media probed with diffusing temporal light correlation,” J. Opt. Soc. Am. A 14(1), 192–215 (1997).
[CrossRef]

D. A. Boas, L. E. Campbell, and A. G. Yodh, “Scattering and Imaging with Diffusing Temporal Field Correlations,” Phys. Rev. Lett. 75(9), 1855–1858 (1995).
[CrossRef] [PubMed]

Bogaards, A.

E. H. Moriyama, A. Kim, A. Bogaards, L. Lilge, and B. Wilson, “A ratiometric fluorescence imaging system for surgical guidance,” Adv. Opt. Technol. 2008, 532368 (2008).

A. Bogaards, H. J. Sterenborg, and B. Wilson, “In vivo quantification of fluorescent molecular markers in real-time: A review to evaluate the performance of five existing methods,” Photodiagn. Photodyn. Ther. 4(3), 170–178 (2007).
[CrossRef]

Boyer, J.

Buck, A.

Busch, T. M.

G. Yu, T. Durduran, C. Zhou, T. C. Zhu, J. C. Finlay, T. M. Busch, S. B. Malkowicz, S. M. Hahn, and A. G. Yodh, “Real-time in situ monitoring of human prostate photodynamic therapy with diffuse light,” Photochem. Photobiol. 82(5), 1279–1284 (2006).
[CrossRef] [PubMed]

G. Yu, T. Durduran, C. Zhou, H. W. Wang, M. E. Putt, H. M. Saunders, C. M. Sehgal, E. Glatstein, A. G. Yodh, and T. M. Busch, “Noninvasive monitoring of murine tumor blood flow during and after photodynamic therapy provides early assessment of therapeutic efficacy,” Clin. Cancer Res. 11(9), 3543–3552 (2005).
[CrossRef] [PubMed]

Calcinaghi, N.

Campbell, L. E.

D. A. Boas, L. E. Campbell, and A. G. Yodh, “Scattering and Imaging with Diffusing Temporal Field Correlations,” Phys. Rev. Lett. 75(9), 1855–1858 (1995).
[CrossRef] [PubMed]

Chaikin, P. M.

D. J. Pine, D. A. Weitz, P. M. Chaikin, and E. Herbolzheimer, “Diffusing wave spectroscopy,” Phys. Rev. Lett. 60(12), 1134–1137 (1988).
[CrossRef] [PubMed]

Chance, B.

U. Sunar, H. Quon, T. Durduran, J. Zhang, J. Du, C. Zhou, G. Yu, R. Choe, A. Kilger, R. Lustig, L. Loevner, S. Nioka, B. Chance, and A. G. Yodh, “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(6), 064021 (2006).
[CrossRef]

Cheung, C.

J. P. Culver, T. Durduran, D. Furuya, C. Cheung, J. H. Greenberg, and A. G. Yodh, “Diffuse optical tomography of cerebral blood flow, oxygenation, and metabolism in rat during focal ischemia,” J. Cereb. Blood Flow Metab. 23(8), 911–924 (2003).
[CrossRef] [PubMed]

C. Cheung, J. P. Culver, K. Takahashi, J. H. Greenberg, and A. G. Yodh, “In vivo cerebrovascular measurement combining diffuse near-infrared absorption and correlation spectroscopies,” Phys. Med. Biol. 46(8), 2053–2065 (2001).
[CrossRef] [PubMed]

Choe, R.

U. Sunar, H. Quon, T. Durduran, J. Zhang, J. Du, C. Zhou, G. Yu, R. Choe, A. Kilger, R. Lustig, L. Loevner, S. Nioka, B. Chance, and A. G. Yodh, “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(6), 064021 (2006).
[CrossRef]

T. Durduran, R. Choe, G. Yu, C. Zhou, J. C. Tchou, B. J. Czerniecki, and A. G. Yodh, “Diffuse optical measurement of blood flow in breast tumors,” Opt. Lett. 30(21), 2915–2917 (2005).
[CrossRef] [PubMed]

Conover, D. L.

J. C. Finlay, D. L. Conover, E. L. Hull, and T. H. Foster, “Porphyrin bleaching and PDT-induced spectral changes are irradiance dependent in ALA-sensitized normal rat skin in vivo,” Photochem. Photobiol. 73(1), 54–63 (2001).
[CrossRef] [PubMed]

Cooper, M. T.

B. W. Henderson, C. Daroqui, E. Tracy, L. A. Vaughan, G. M. Loewen, M. T. Cooper, and H. Baumann, “Cross-linking of signal transducer and activator of transcription 3--a molecular marker for the photodynamic reaction in cells and tumors,” Clin. Cancer Res. 13(11), 3156–3163 (2007).
[CrossRef] [PubMed]

Cottrell, W. J.

W. J. Cottrell, A. R. Oseroff, and T. H. Foster, “Portable instrument that integrates irradiation with fluorescence and reflectance spectroscopies during clinical photodynamic therapy of cutaneous disease,” Rev. Sci. Instrum. 77(6), 064302 (2006).
[CrossRef]

Culver, J. P.

J. P. Culver, T. Durduran, D. Furuya, C. Cheung, J. H. Greenberg, and A. G. Yodh, “Diffuse optical tomography of cerebral blood flow, oxygenation, and metabolism in rat during focal ischemia,” J. Cereb. Blood Flow Metab. 23(8), 911–924 (2003).
[CrossRef] [PubMed]

C. Cheung, J. P. Culver, K. Takahashi, J. H. Greenberg, and A. G. Yodh, “In vivo cerebrovascular measurement combining diffuse near-infrared absorption and correlation spectroscopies,” Phys. Med. Biol. 46(8), 2053–2065 (2001).
[CrossRef] [PubMed]

Czerniecki, B. J.

Daroqui, C.

B. W. Henderson, C. Daroqui, E. Tracy, L. A. Vaughan, G. M. Loewen, M. T. Cooper, and H. Baumann, “Cross-linking of signal transducer and activator of transcription 3--a molecular marker for the photodynamic reaction in cells and tumors,” Clin. Cancer Res. 13(11), 3156–3163 (2007).
[CrossRef] [PubMed]

Daye, D.

de Bruijn, H. S.

B. Kruijt, S. Kascakova, H. S. de Bruijn, A. van der Ploeg-van den Heuvel, H. J. Sterenborg, D. J. Robinson, and A. Amelink, “In vivo quantification of chromophore concentration using fluorescence differential path length spectroscopy,” J. Biomed. Opt. 14(3), 034022 (2009).
[CrossRef] [PubMed]

de Veld, D. C.

D. C. de Veld, M. Skurichina, M. J. Witjes, R. P. Duin, H. J. Sterenborg, and J. L. Roodenburg, “Autofluorescence and diffuse reflectance spectroscopy for oral oncology,” Lasers Surg. Med. 36(5), 356–364 (2005).
[CrossRef] [PubMed]

Delpy, D. T.

T. Binzoni, T. S. Leung, D. Rüfenacht, and D. T. Delpy, “Absorption and scattering coefficient dependence of laser-Doppler flowmetry models for large tissue volumes,” Phys. Med. Biol. 51(2), 311–333 (2006).
[CrossRef] [PubMed]

Dimofte, A.

H. W. Wang, T. C. Zhu, M. E. Putt, M. Solonenko, J. Metz, A. Dimofte, J. Miles, D. L. Fraker, E. Glatstein, S. M. Hahn, and A. G. Yodh, “Broadband reflectance measurements of light penetration, blood oxygenation, hemoglobin concentration, and drug concentration in human intraperitoneal tissues before and after photodynamic therapy,” J. Biomed. Opt. 10(1), 014004 (2005).
[CrossRef]

Dougherty, T. J.

D. A. Bellnier, W. R. Greco, G. M. Loewen, H. Nava, A. R. Oseroff, and T. J. Dougherty, “Clinical pharmacokinetics of the PDT photosensitizers porfimer sodium (Photofrin), 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a (Photochlor) and 5-ALA-induced protoporphyrin IX,” Lasers Surg. Med. 38(5), 439–444 (2006).
[CrossRef] [PubMed]

D. A. Bellnier, W. R. Greco, G. M. Loewen, H. Nava, A. R. Oseroff, R. K. Pandey, T. Tsuchida, and T. J. Dougherty, “Population pharmacokinetics of the photodynamic therapy agent 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a in cancer patients,” Cancer Res. 63(8), 1806–1813 (2003).
[PubMed]

D. A. Bellnier, B. W. Henderson, R. K. Pandey, W. R. Potter, and T. J. Dougherty, “Murine pharmacokinetics and antitumor efficacy of the photodynamic sensitizer 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a,” J. Photochem. Photobiol. B 20(1), 55–61 (1993).
[CrossRef] [PubMed]

Du, J.

U. Sunar, H. Quon, T. Durduran, J. Zhang, J. Du, C. Zhou, G. Yu, R. Choe, A. Kilger, R. Lustig, L. Loevner, S. Nioka, B. Chance, and A. G. Yodh, “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(6), 064021 (2006).
[CrossRef]

Duin, R. P.

D. C. de Veld, M. Skurichina, M. J. Witjes, R. P. Duin, H. J. Sterenborg, and J. L. Roodenburg, “Autofluorescence and diffuse reflectance spectroscopy for oral oncology,” Lasers Surg. Med. 36(5), 356–364 (2005).
[CrossRef] [PubMed]

Durduran, T.

U. Sunar, S. Makonnen, C. Zhou, T. Durduran, G. Yu, H. W. Wang, W. M. F. Lee, and A. G. Yodh, “Hemodynamic responses to antivascular therapy and ionizing radiation assessed by diffuse optical spectroscopies,” Opt. Express 15(23), 15507–15516 (2007).
[CrossRef] [PubMed]

G. Yu, T. Durduran, C. Zhou, T. C. Zhu, J. C. Finlay, T. M. Busch, S. B. Malkowicz, S. M. Hahn, and A. G. Yodh, “Real-time in situ monitoring of human prostate photodynamic therapy with diffuse light,” Photochem. Photobiol. 82(5), 1279–1284 (2006).
[CrossRef] [PubMed]

U. Sunar, H. Quon, T. Durduran, J. Zhang, J. Du, C. Zhou, G. Yu, R. Choe, A. Kilger, R. Lustig, L. Loevner, S. Nioka, B. Chance, and A. G. Yodh, “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(6), 064021 (2006).
[CrossRef]

C. Zhou, G. Yu, D. Furuya, J. Greenberg, A. Yodh, and T. Durduran, “Diffuse optical correlation tomography of cerebral blood flow during cortical spreading depression in rat brain,” Opt. Express 14(3), 1125–1144 (2006).
[CrossRef] [PubMed]

G. Yu, T. Durduran, C. Zhou, H. W. Wang, M. E. Putt, H. M. Saunders, C. M. Sehgal, E. Glatstein, A. G. Yodh, and T. M. Busch, “Noninvasive monitoring of murine tumor blood flow during and after photodynamic therapy provides early assessment of therapeutic efficacy,” Clin. Cancer Res. 11(9), 3543–3552 (2005).
[CrossRef] [PubMed]

T. Durduran, R. Choe, G. Yu, C. Zhou, J. C. Tchou, B. J. Czerniecki, and A. G. Yodh, “Diffuse optical measurement of blood flow in breast tumors,” Opt. Lett. 30(21), 2915–2917 (2005).
[CrossRef] [PubMed]

J. P. Culver, T. Durduran, D. Furuya, C. Cheung, J. H. Greenberg, and A. G. Yodh, “Diffuse optical tomography of cerebral blood flow, oxygenation, and metabolism in rat during focal ischemia,” J. Cereb. Blood Flow Metab. 23(8), 911–924 (2003).
[CrossRef] [PubMed]

El-Naggar, A. K.

D. Roblyer, R. Richards-Kortum, K. Sokolov, A. K. El-Naggar, M. D. Williams, C. Kurachi, and A. M. Gillenwater, “Multispectral optical imaging device for in vivo detection of oral neoplasia,” J. Biomed. Opt. 13(2), 024019 (2008).
[CrossRef] [PubMed]

Farrell, T. J.

T. J. Farrell, M. S. Patterson, and B. Wilson, “A diffusion theory model of spatially resolved, steady-state diffuse reflectance for the noninvasive determination of tissue optical properties in vivo,” Med. Phys. 19(4), 879–888 (1992).
[CrossRef] [PubMed]

Feld, M. S.

Feldmann, H. J.

H. J. Feldmann, M. Molls, and P. Vaupel, “Blood flow and oxygenation status of human tumors,” Strahlenther. Onkol. 175(1), 1–9 (1999).
[CrossRef] [PubMed]

Finlay, J. C.

G. Yu, T. Durduran, C. Zhou, T. C. Zhu, J. C. Finlay, T. M. Busch, S. B. Malkowicz, S. M. Hahn, and A. G. Yodh, “Real-time in situ monitoring of human prostate photodynamic therapy with diffuse light,” Photochem. Photobiol. 82(5), 1279–1284 (2006).
[CrossRef] [PubMed]

J. C. Finlay, D. L. Conover, E. L. Hull, and T. H. Foster, “Porphyrin bleaching and PDT-induced spectral changes are irradiance dependent in ALA-sensitized normal rat skin in vivo,” Photochem. Photobiol. 73(1), 54–63 (2001).
[CrossRef] [PubMed]

Foster, T. H.

W. J. Cottrell, A. R. Oseroff, and T. H. Foster, “Portable instrument that integrates irradiation with fluorescence and reflectance spectroscopies during clinical photodynamic therapy of cutaneous disease,” Rev. Sci. Instrum. 77(6), 064302 (2006).
[CrossRef]

J. C. Finlay, D. L. Conover, E. L. Hull, and T. H. Foster, “Porphyrin bleaching and PDT-induced spectral changes are irradiance dependent in ALA-sensitized normal rat skin in vivo,” Photochem. Photobiol. 73(1), 54–63 (2001).
[CrossRef] [PubMed]

I. Georgakoudi and T. H. Foster, “Singlet oxygen- versus nonsinglet oxygen-mediated mechanisms of sensitizer photobleaching and their effects on photodynamic dosimetry,” Photochem. Photobiol. 67(6), 612–625 (1998).
[PubMed]

I. Georgakoudi, M. G. Nichols, and T. H. Foster, “The mechanism of Photofrin photobleaching and its consequences for photodynamic dosimetry,” Photochem. Photobiol. 65(1), 135–144 (1997).
[CrossRef] [PubMed]

Fraker, D. L.

H. W. Wang, T. C. Zhu, M. E. Putt, M. Solonenko, J. Metz, A. Dimofte, J. Miles, D. L. Fraker, E. Glatstein, S. M. Hahn, and A. G. Yodh, “Broadband reflectance measurements of light penetration, blood oxygenation, hemoglobin concentration, and drug concentration in human intraperitoneal tissues before and after photodynamic therapy,” J. Biomed. Opt. 10(1), 014004 (2005).
[CrossRef]

Furuya, D.

C. Zhou, G. Yu, D. Furuya, J. Greenberg, A. Yodh, and T. Durduran, “Diffuse optical correlation tomography of cerebral blood flow during cortical spreading depression in rat brain,” Opt. Express 14(3), 1125–1144 (2006).
[CrossRef] [PubMed]

J. P. Culver, T. Durduran, D. Furuya, C. Cheung, J. H. Greenberg, and A. G. Yodh, “Diffuse optical tomography of cerebral blood flow, oxygenation, and metabolism in rat during focal ischemia,” J. Cereb. Blood Flow Metab. 23(8), 911–924 (2003).
[CrossRef] [PubMed]

Fuselier, T.

Gao, W.

Georgakoudi, I.

M. G. Müller, I. Georgakoudi, Q. Zhang, J. Wu, and M. S. Feld, “Intrinsic fluorescence spectroscopy in turbid media: disentangling effects of scattering and absorption,” Appl. Opt. 40(25), 4633–4646 (2001).
[CrossRef]

I. Georgakoudi and T. H. Foster, “Singlet oxygen- versus nonsinglet oxygen-mediated mechanisms of sensitizer photobleaching and their effects on photodynamic dosimetry,” Photochem. Photobiol. 67(6), 612–625 (1998).
[PubMed]

I. Georgakoudi, M. G. Nichols, and T. H. Foster, “The mechanism of Photofrin photobleaching and its consequences for photodynamic dosimetry,” Photochem. Photobiol. 65(1), 135–144 (1997).
[CrossRef] [PubMed]

Gilead, A.

S. Gross, A. Gilead, A. Scherz, M. Neeman, and Y. Salomon, “Monitoring photodynamic therapy of solid tumors online by BOLD-contrast MRI,” Nat. Med. 9(10), 1327–1331 (2003).
[CrossRef] [PubMed]

Gillenwater, A. M.

R. A. Schwarz, W. Gao, D. Daye, M. D. Williams, R. Richards-Kortum, and A. M. Gillenwater, “Autofluorescence and diffuse reflectance spectroscopy of oral epithelial tissue using a depth-sensitive fiber-optic probe,” Appl. Opt. 47(6), 825–834 (2008).
[CrossRef] [PubMed]

D. Roblyer, R. Richards-Kortum, K. Sokolov, A. K. El-Naggar, M. D. Williams, C. Kurachi, and A. M. Gillenwater, “Multispectral optical imaging device for in vivo detection of oral neoplasia,” J. Biomed. Opt. 13(2), 024019 (2008).
[CrossRef] [PubMed]

Glatstein, E.

G. Yu, T. Durduran, C. Zhou, H. W. Wang, M. E. Putt, H. M. Saunders, C. M. Sehgal, E. Glatstein, A. G. Yodh, and T. M. Busch, “Noninvasive monitoring of murine tumor blood flow during and after photodynamic therapy provides early assessment of therapeutic efficacy,” Clin. Cancer Res. 11(9), 3543–3552 (2005).
[CrossRef] [PubMed]

H. W. Wang, T. C. Zhu, M. E. Putt, M. Solonenko, J. Metz, A. Dimofte, J. Miles, D. L. Fraker, E. Glatstein, S. M. Hahn, and A. G. Yodh, “Broadband reflectance measurements of light penetration, blood oxygenation, hemoglobin concentration, and drug concentration in human intraperitoneal tissues before and after photodynamic therapy,” J. Biomed. Opt. 10(1), 014004 (2005).
[CrossRef]

Goodell, T. T.

P. R. Bargo, S. A. Prahl, T. T. Goodell, R. A. Sleven, G. Koval, G. Blair, and S. L. Jacques, “In vivo determination of optical properties of normal and tumor tissue with white light reflectance and an empirical light transport model during endoscopy,” J. Biomed. Opt. 10(3), 034018 (2005).
[CrossRef] [PubMed]

Graveland, W. J.

M. P. Bard, A. Amelink, V. N. Hegt, W. J. Graveland, H. J. Sterenborg, H. C. Hoogsteden, and J. G. Aerts, “Measurement of hypoxia-related parameters in bronchial mucosa by use of optical spectroscopy,” Am. J. Respir. Crit. Care Med. 171(10), 1178–1184 (2005).
[CrossRef] [PubMed]

Greco, W. R.

D. A. Bellnier, W. R. Greco, G. M. Loewen, H. Nava, A. R. Oseroff, and T. J. Dougherty, “Clinical pharmacokinetics of the PDT photosensitizers porfimer sodium (Photofrin), 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a (Photochlor) and 5-ALA-induced protoporphyrin IX,” Lasers Surg. Med. 38(5), 439–444 (2006).
[CrossRef] [PubMed]

D. A. Bellnier, W. R. Greco, G. M. Loewen, H. Nava, A. R. Oseroff, R. K. Pandey, T. Tsuchida, and T. J. Dougherty, “Population pharmacokinetics of the photodynamic therapy agent 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a in cancer patients,” Cancer Res. 63(8), 1806–1813 (2003).
[PubMed]

Greenberg, J.

Greenberg, J. H.

J. P. Culver, T. Durduran, D. Furuya, C. Cheung, J. H. Greenberg, and A. G. Yodh, “Diffuse optical tomography of cerebral blood flow, oxygenation, and metabolism in rat during focal ischemia,” J. Cereb. Blood Flow Metab. 23(8), 911–924 (2003).
[CrossRef] [PubMed]

C. Cheung, J. P. Culver, K. Takahashi, J. H. Greenberg, and A. G. Yodh, “In vivo cerebrovascular measurement combining diffuse near-infrared absorption and correlation spectroscopies,” Phys. Med. Biol. 46(8), 2053–2065 (2001).
[CrossRef] [PubMed]

Gross, S.

S. Gross, A. Gilead, A. Scherz, M. Neeman, and Y. Salomon, “Monitoring photodynamic therapy of solid tumors online by BOLD-contrast MRI,” Nat. Med. 9(10), 1327–1331 (2003).
[CrossRef] [PubMed]

Hahn, S. M.

G. Yu, T. Durduran, C. Zhou, T. C. Zhu, J. C. Finlay, T. M. Busch, S. B. Malkowicz, S. M. Hahn, and A. G. Yodh, “Real-time in situ monitoring of human prostate photodynamic therapy with diffuse light,” Photochem. Photobiol. 82(5), 1279–1284 (2006).
[CrossRef] [PubMed]

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Adv. Opt. Technol. (1)

E. H. Moriyama, A. Kim, A. Bogaards, L. Lilge, and B. Wilson, “A ratiometric fluorescence imaging system for surgical guidance,” Adv. Opt. Technol. 2008, 532368 (2008).

Am. J. Respir. Crit. Care Med. (1)

M. P. Bard, A. Amelink, V. N. Hegt, W. J. Graveland, H. J. Sterenborg, H. C. Hoogsteden, and J. G. Aerts, “Measurement of hypoxia-related parameters in bronchial mucosa by use of optical spectroscopy,” Am. J. Respir. Crit. Care Med. 171(10), 1178–1184 (2005).
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Cancer Res. (3)

D. A. Bellnier, W. R. Greco, G. M. Loewen, H. Nava, A. R. Oseroff, R. K. Pandey, T. Tsuchida, and T. J. Dougherty, “Population pharmacokinetics of the photodynamic therapy agent 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a in cancer patients,” Cancer Res. 63(8), 1806–1813 (2003).
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B. W. Henderson, C. Daroqui, E. Tracy, L. A. Vaughan, G. M. Loewen, M. T. Cooper, and H. Baumann, “Cross-linking of signal transducer and activator of transcription 3--a molecular marker for the photodynamic reaction in cells and tumors,” Clin. Cancer Res. 13(11), 3156–3163 (2007).
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G. Yu, T. Durduran, C. Zhou, H. W. Wang, M. E. Putt, H. M. Saunders, C. M. Sehgal, E. Glatstein, A. G. Yodh, and T. M. Busch, “Noninvasive monitoring of murine tumor blood flow during and after photodynamic therapy provides early assessment of therapeutic efficacy,” Clin. Cancer Res. 11(9), 3543–3552 (2005).
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J. Biomed. Opt. (5)

U. Sunar, H. Quon, T. Durduran, J. Zhang, J. Du, C. Zhou, G. Yu, R. Choe, A. Kilger, R. Lustig, L. Loevner, S. Nioka, B. Chance, and A. G. Yodh, “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(6), 064021 (2006).
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D. Roblyer, R. Richards-Kortum, K. Sokolov, A. K. El-Naggar, M. D. Williams, C. Kurachi, and A. M. Gillenwater, “Multispectral optical imaging device for in vivo detection of oral neoplasia,” J. Biomed. Opt. 13(2), 024019 (2008).
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D. C. de Veld, M. Skurichina, M. J. Witjes, R. P. Duin, H. J. Sterenborg, and J. L. Roodenburg, “Autofluorescence and diffuse reflectance spectroscopy for oral oncology,” Lasers Surg. Med. 36(5), 356–364 (2005).
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Figures (3)

Fig. 1
Fig. 1

Schematic diagram of the instrument and fiber optic probe. a) The combined DCS, DFS and DRS setup with fiber optic probe. DCS consists of 785 nm laser, single photon counting detector (SPCD), a custom correlator (Corr), and a laptop (PC-1). DFS and DRS mainly consist of a dual channel spectrometer, 410 nm blue laser and a whitelight source. Data acquisition card (DAQ) switches the blue and whitelight sources via a laptop (PC-2). b) Diagram of source-detector fiber configuration. bfs: the blood flow laser, d1,..d4 are DCS detector fibers, wls: white light source fiber, bls: blue light source fiber, bld: blue light detector fiber, wld: white light detector fiber. The distances between bfs-d1, bfs-d2, bfs-d3, and bfs-d4 are 0.6, 1.2, 0.8 and 1.6mm, respectively. The distance between wls-wld is 1.6mm and that between bls-bld is 0.8mm. c) Diagram of the fiber optic probe. d) Picture of the probe.

Fig. 2
Fig. 2

a) Representative curves (tumor site) of normalized autocorrelation functions, g1(r,τ) (decay rate is related to blood flow) b) normalized DRS data and c) normalized fluorescence pre- and post-PDT. d) HPPH spectra obtained in cuvette, autofluorescence spectra obtained from a patient, and HPPH spectra from an oral tissue simulating phantom. Cuvette and autofluorescence data is normalized to 1. Intralipid data is normalized to 0.5 for better view compared to cuvette data.

Fig. 3
Fig. 3

Extracted functional parameters from a head and neck patient before and after PDT. a) Relative blood flow (rBF(%)). b) Blood volume fraction (BVF (%)). c) Blood oxygen saturation (StO2 (%)). d) HPPH concentration (µM). e) HPPH fluorescence (normalized). f) STAT3 cross-linking.

Equations (2)

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μ a ( λ ) = B V F × ( S t O 2 × μ a o x y ( λ ) + ( 1 S t O 2 ) × μ a d e o x y ( λ ) ) + w f × μ a w a t e r ( λ ) + C H P P H × μ a H P P H ( λ ) ,
  F n ( λ )   = C H P P H × F H P P H ( λ ) + C a f × F a f ( λ ) .  

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