Abstract

We investigate in vivo detection of mammary tumors in a rat model using autofluorescence imaging in the red and far-red spectral regions. The objective was to explore this method for non-invasive detection of malignant tumors and correlation between autofluorescence properties of tumors and their pathologic status. Eighteen tumor-bearing rats, bearing eight benign and seventeen malignant tumors were imaged. Autofluorescence images were acquired using spectral windows centered at 700-nm, 750-nm and 800-nm under laser excitation at 632.8-nm and 670-nm. Intensity in the autofluorescence images of malignant tumors under 670-nm excitation was higher than that of the adjacent normal tissue. whereas intensity of benign tumors was lower compared to normal tissue.

© 2006 Optical Society of America

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    [CrossRef]

2004 (4)

X. Gu, Q. Zhang, M. Bartlett, L. Schutz, L. L. Fajardo and H. Jiang, "Differentiation of cysts from solid tumors in the breast with diffuse optical tomography," Acad. Radiol. 11,53-60 (2004).
[CrossRef] [PubMed]

D. B. Jakubowski, A. E. Cerussi, F. Bevilacqua, N. Shah, D. Hsiang, J. Butler and B. J. Tromberg, "Monitoring neoadjuvant chemotherapy in breast cancer using quantitative diffuse optical spectroscopy: a case study," J. Biomed. Opt. 9,230-8 (2004).
[CrossRef] [PubMed]

Demos, S. G. , R. Gandour-Edwards, R. Ramsamooj and R. DeVere White, "Spectroscopic detection of bladder cancer using near-infrared imaging techniques," J. Biomed. Opt. 9, 767-71 (2004).
[CrossRef] [PubMed]

S. G. Demos, R. Gandour-Edwards, R. Ramsamooj and R. White, "Near-infrared autofluorescence imaging for detection of cancer," J. Biomed. Opt. 9,587-92 (2004).
[CrossRef] [PubMed]

2003 (1)

D. W. Chicken, A. C. Lee, G. M. Briggs, M. R. S. Keshtgar, K. S. Johnson, D. D. O. Pickard, I. J. Bigio and S. G. Bown, "Optical biopsy: A novel intraoperative diagnostic tool to determine sentinel lymph node status instantly in breast cancer," Breast Cancer Res. Treat. 82,S172-S174 (2003).

2002 (3)

T. M. Kolb, J. Lichy and J. H. Newhouse, "Comparison of the performance of screening mammography, physical examination, and breast US and evaluation of factors that influence them: an analysis of 27,825 patient evaluations," Radiology 225, 165-75 (2002).
[CrossRef] [PubMed]

A. S. Haka, K. E. Shafer-Peltier, M. Fitzmaurice, J. Crowe, R. R. Dasari and M. S. Feld, "Identifying microcalcifications in benign and malignant breast lesions by probing differences in their chemical composition using Raman spectroscopy," Cancer Res. 62,5375-80 (2002).
[PubMed]

T. Theodossiou and A. J. MacRobert, "Comparison of the photodynamic effect of exogenous photoprotoporphyrin and protoporphyrin IX on PAM 212 murine keratocytes.," Photochem. Photobiol. 76,530-537 (2002).
[CrossRef] [PubMed]

2000 (1)

V. Ntziachristos, A. G. Yodh, M. Schnall and B. Chance, "Concurrent MRI and diffuse optical tomography of breast after indocyanine green enhancement," Proc. Natl. Acad. Sci. U. S. A. 97,2767-72. (2000).
[CrossRef] [PubMed]

1999 (3)

G. Zhang, S. G. Demos and R. R. Alfano, "Far-red and NIR spectral wing emission from tissues under 532-nm and 632-nm photo-excitation," Lasers Life Sci. 9,1-16 (1999).

M. Inaguma and K. Hashimoto, "Porphyrin-like fluorescence in oral cancer: In vivo fluorescence spectral characterization of lesions by use of a near-ultraviolet excited autofluorescence diagnosis system and separation of fluorescent extracts by capillary electrophoresis," Cancer 86,2201-11. (1999).
[CrossRef] [PubMed]

M. Y. Su, Z. Wang, P. M. Carpenter, X. Lao, A. Muhler and O. Nalcioglu, "Characterization of N-ethyl-N-nitrosourea-induced malignant and benign breast tumors in rats by using three MR contrast agents," J. Magn. Reson. 9,177-86 (1999).
[CrossRef]

1998 (3)

H. Daldrup, D. M. Shames, M. Wendland, Y. Okuhata, T. M. Link, W. Rosenau, Y. Lu and R. C. Brasch, "Correlation of dynamic contrast-enhanced MR imaging with histologic tumor grade: comparison of macromolecular and small-molecular contrast media," AJR Am. J. Roentgenol. 171,941-9. (1998).
[PubMed]

G. A. Wagnieres, W. M. Star and B. C. Wilson, "In vivo fluorescence spectroscopy and imaging for oncological applications," Photochem. Photobiol. 68,603-32. (1998).
[PubMed]

R. Manoharan, K. Shafer, L. Perelman, J. Wu, K. Chen, G. Deinum, M. Fitzmaurice, J. Myles, J. Crowe, R. R. Dasari and M. S. Feld, "Raman spectroscopy and fluorescence photon migration for breast cancer diagnosis and imaging," Photochem. Photobiol. 67,15-22 (1998).
[CrossRef] [PubMed]

1996 (1)

S. G. Demos, H. Savage, A. S. Heerdt, S. Schantz and R. R. Alfano, "Time Resolved Degree of Polarization for Human Breast Tissue," Optics Commun. 124,439 (1996).
[CrossRef]

1994 (1)

C. J. Frank, D. C. Redd, T. S. Gansler and R. L. McCreery, "Characterization of human breast biopsy specimens with near-IR Raman spectroscopy," Anal. Chem. 66,319-26 (1994).
[CrossRef] [PubMed]

1992 (1)

M. M. el-Sharabasy, A. M. el-Waseef, M. M. Hafez and S. A. Salim, "Porphyrin metabolism in some malignant diseases," Br. J. Cancer 65,409-12. (1992).
[CrossRef] [PubMed]

1987 (1)

D. M. Harris and J. Werkhaven, "Endogenous porphyrin fluorescence in tumors," Lasers Surg. Med. 7,467-72. (1987).
[CrossRef] [PubMed]

1984 (1)

G. Stoica and A. Koestner, "Diverse spectrum of tumors in male Sprague-Dawley rats following single high doses of N-ethyl-N-nitrosourea (ENU)," Am. J. Pathol. 116,319-26 (1984).
[PubMed]

1979 (1)

B. Zawirska, "Comparative porphyrin content in tumors with contiguous non-neoplastic tissues," Neoplasma 26,223-9. (1979).
[PubMed]

1965 (1)

L. Rasetti, G. F. Rubino, L. Tettinatti and G. W. Drago, "Porphyrin porphobilinogen and amino ketone levels in tumor tissue," Panminerva Med. 7,105-110 (1965).

1929 (1)

M. Cutler, "Transillumination as an aid in the diagnosis of breast lesions.," Surg. Gynecol. Obstet. 48,721-729 (1929).

Alfano, R. R.

G. Zhang, S. G. Demos and R. R. Alfano, "Far-red and NIR spectral wing emission from tissues under 532-nm and 632-nm photo-excitation," Lasers Life Sci. 9,1-16 (1999).

S. G. Demos, H. Savage, A. S. Heerdt, S. Schantz and R. R. Alfano, "Time Resolved Degree of Polarization for Human Breast Tissue," Optics Commun. 124,439 (1996).
[CrossRef]

Bartlett, M.

X. Gu, Q. Zhang, M. Bartlett, L. Schutz, L. L. Fajardo and H. Jiang, "Differentiation of cysts from solid tumors in the breast with diffuse optical tomography," Acad. Radiol. 11,53-60 (2004).
[CrossRef] [PubMed]

Bevilacqua, F.

D. B. Jakubowski, A. E. Cerussi, F. Bevilacqua, N. Shah, D. Hsiang, J. Butler and B. J. Tromberg, "Monitoring neoadjuvant chemotherapy in breast cancer using quantitative diffuse optical spectroscopy: a case study," J. Biomed. Opt. 9,230-8 (2004).
[CrossRef] [PubMed]

Bigio, I. J.

D. W. Chicken, A. C. Lee, G. M. Briggs, M. R. S. Keshtgar, K. S. Johnson, D. D. O. Pickard, I. J. Bigio and S. G. Bown, "Optical biopsy: A novel intraoperative diagnostic tool to determine sentinel lymph node status instantly in breast cancer," Breast Cancer Res. Treat. 82,S172-S174 (2003).

Bown, S. G.

D. W. Chicken, A. C. Lee, G. M. Briggs, M. R. S. Keshtgar, K. S. Johnson, D. D. O. Pickard, I. J. Bigio and S. G. Bown, "Optical biopsy: A novel intraoperative diagnostic tool to determine sentinel lymph node status instantly in breast cancer," Breast Cancer Res. Treat. 82,S172-S174 (2003).

Brasch, R. C.

H. Daldrup, D. M. Shames, M. Wendland, Y. Okuhata, T. M. Link, W. Rosenau, Y. Lu and R. C. Brasch, "Correlation of dynamic contrast-enhanced MR imaging with histologic tumor grade: comparison of macromolecular and small-molecular contrast media," AJR Am. J. Roentgenol. 171,941-9. (1998).
[PubMed]

Briggs, G. M.

D. W. Chicken, A. C. Lee, G. M. Briggs, M. R. S. Keshtgar, K. S. Johnson, D. D. O. Pickard, I. J. Bigio and S. G. Bown, "Optical biopsy: A novel intraoperative diagnostic tool to determine sentinel lymph node status instantly in breast cancer," Breast Cancer Res. Treat. 82,S172-S174 (2003).

Butler, J.

D. B. Jakubowski, A. E. Cerussi, F. Bevilacqua, N. Shah, D. Hsiang, J. Butler and B. J. Tromberg, "Monitoring neoadjuvant chemotherapy in breast cancer using quantitative diffuse optical spectroscopy: a case study," J. Biomed. Opt. 9,230-8 (2004).
[CrossRef] [PubMed]

Carpenter, P. M.

M. Y. Su, Z. Wang, P. M. Carpenter, X. Lao, A. Muhler and O. Nalcioglu, "Characterization of N-ethyl-N-nitrosourea-induced malignant and benign breast tumors in rats by using three MR contrast agents," J. Magn. Reson. 9,177-86 (1999).
[CrossRef]

Cerussi, A. E.

D. B. Jakubowski, A. E. Cerussi, F. Bevilacqua, N. Shah, D. Hsiang, J. Butler and B. J. Tromberg, "Monitoring neoadjuvant chemotherapy in breast cancer using quantitative diffuse optical spectroscopy: a case study," J. Biomed. Opt. 9,230-8 (2004).
[CrossRef] [PubMed]

Chance, B.

V. Ntziachristos, A. G. Yodh, M. Schnall and B. Chance, "Concurrent MRI and diffuse optical tomography of breast after indocyanine green enhancement," Proc. Natl. Acad. Sci. U. S. A. 97,2767-72. (2000).
[CrossRef] [PubMed]

Chen, K.

R. Manoharan, K. Shafer, L. Perelman, J. Wu, K. Chen, G. Deinum, M. Fitzmaurice, J. Myles, J. Crowe, R. R. Dasari and M. S. Feld, "Raman spectroscopy and fluorescence photon migration for breast cancer diagnosis and imaging," Photochem. Photobiol. 67,15-22 (1998).
[CrossRef] [PubMed]

Chicken, D. W.

D. W. Chicken, A. C. Lee, G. M. Briggs, M. R. S. Keshtgar, K. S. Johnson, D. D. O. Pickard, I. J. Bigio and S. G. Bown, "Optical biopsy: A novel intraoperative diagnostic tool to determine sentinel lymph node status instantly in breast cancer," Breast Cancer Res. Treat. 82,S172-S174 (2003).

Crowe, J.

A. S. Haka, K. E. Shafer-Peltier, M. Fitzmaurice, J. Crowe, R. R. Dasari and M. S. Feld, "Identifying microcalcifications in benign and malignant breast lesions by probing differences in their chemical composition using Raman spectroscopy," Cancer Res. 62,5375-80 (2002).
[PubMed]

R. Manoharan, K. Shafer, L. Perelman, J. Wu, K. Chen, G. Deinum, M. Fitzmaurice, J. Myles, J. Crowe, R. R. Dasari and M. S. Feld, "Raman spectroscopy and fluorescence photon migration for breast cancer diagnosis and imaging," Photochem. Photobiol. 67,15-22 (1998).
[CrossRef] [PubMed]

Cutler, M.

M. Cutler, "Transillumination as an aid in the diagnosis of breast lesions.," Surg. Gynecol. Obstet. 48,721-729 (1929).

Daldrup, H.

H. Daldrup, D. M. Shames, M. Wendland, Y. Okuhata, T. M. Link, W. Rosenau, Y. Lu and R. C. Brasch, "Correlation of dynamic contrast-enhanced MR imaging with histologic tumor grade: comparison of macromolecular and small-molecular contrast media," AJR Am. J. Roentgenol. 171,941-9. (1998).
[PubMed]

Dasari, R. R.

A. S. Haka, K. E. Shafer-Peltier, M. Fitzmaurice, J. Crowe, R. R. Dasari and M. S. Feld, "Identifying microcalcifications in benign and malignant breast lesions by probing differences in their chemical composition using Raman spectroscopy," Cancer Res. 62,5375-80 (2002).
[PubMed]

R. Manoharan, K. Shafer, L. Perelman, J. Wu, K. Chen, G. Deinum, M. Fitzmaurice, J. Myles, J. Crowe, R. R. Dasari and M. S. Feld, "Raman spectroscopy and fluorescence photon migration for breast cancer diagnosis and imaging," Photochem. Photobiol. 67,15-22 (1998).
[CrossRef] [PubMed]

Deinum, G.

R. Manoharan, K. Shafer, L. Perelman, J. Wu, K. Chen, G. Deinum, M. Fitzmaurice, J. Myles, J. Crowe, R. R. Dasari and M. S. Feld, "Raman spectroscopy and fluorescence photon migration for breast cancer diagnosis and imaging," Photochem. Photobiol. 67,15-22 (1998).
[CrossRef] [PubMed]

Demos,

Demos, S. G. , R. Gandour-Edwards, R. Ramsamooj and R. DeVere White, "Spectroscopic detection of bladder cancer using near-infrared imaging techniques," J. Biomed. Opt. 9, 767-71 (2004).
[CrossRef] [PubMed]

Demos, S. G.

S. G. Demos, R. Gandour-Edwards, R. Ramsamooj and R. White, "Near-infrared autofluorescence imaging for detection of cancer," J. Biomed. Opt. 9,587-92 (2004).
[CrossRef] [PubMed]

G. Zhang, S. G. Demos and R. R. Alfano, "Far-red and NIR spectral wing emission from tissues under 532-nm and 632-nm photo-excitation," Lasers Life Sci. 9,1-16 (1999).

S. G. Demos, H. Savage, A. S. Heerdt, S. Schantz and R. R. Alfano, "Time Resolved Degree of Polarization for Human Breast Tissue," Optics Commun. 124,439 (1996).
[CrossRef]

DeVere White, R.

Demos, S. G. , R. Gandour-Edwards, R. Ramsamooj and R. DeVere White, "Spectroscopic detection of bladder cancer using near-infrared imaging techniques," J. Biomed. Opt. 9, 767-71 (2004).
[CrossRef] [PubMed]

Drago, G. W.

L. Rasetti, G. F. Rubino, L. Tettinatti and G. W. Drago, "Porphyrin porphobilinogen and amino ketone levels in tumor tissue," Panminerva Med. 7,105-110 (1965).

el-Sharabasy, M. M.

M. M. el-Sharabasy, A. M. el-Waseef, M. M. Hafez and S. A. Salim, "Porphyrin metabolism in some malignant diseases," Br. J. Cancer 65,409-12. (1992).
[CrossRef] [PubMed]

el-Waseef, A. M.

M. M. el-Sharabasy, A. M. el-Waseef, M. M. Hafez and S. A. Salim, "Porphyrin metabolism in some malignant diseases," Br. J. Cancer 65,409-12. (1992).
[CrossRef] [PubMed]

Fajardo, L. L.

X. Gu, Q. Zhang, M. Bartlett, L. Schutz, L. L. Fajardo and H. Jiang, "Differentiation of cysts from solid tumors in the breast with diffuse optical tomography," Acad. Radiol. 11,53-60 (2004).
[CrossRef] [PubMed]

Feld, M. S.

A. S. Haka, K. E. Shafer-Peltier, M. Fitzmaurice, J. Crowe, R. R. Dasari and M. S. Feld, "Identifying microcalcifications in benign and malignant breast lesions by probing differences in their chemical composition using Raman spectroscopy," Cancer Res. 62,5375-80 (2002).
[PubMed]

R. Manoharan, K. Shafer, L. Perelman, J. Wu, K. Chen, G. Deinum, M. Fitzmaurice, J. Myles, J. Crowe, R. R. Dasari and M. S. Feld, "Raman spectroscopy and fluorescence photon migration for breast cancer diagnosis and imaging," Photochem. Photobiol. 67,15-22 (1998).
[CrossRef] [PubMed]

Fitzmaurice, M.

A. S. Haka, K. E. Shafer-Peltier, M. Fitzmaurice, J. Crowe, R. R. Dasari and M. S. Feld, "Identifying microcalcifications in benign and malignant breast lesions by probing differences in their chemical composition using Raman spectroscopy," Cancer Res. 62,5375-80 (2002).
[PubMed]

R. Manoharan, K. Shafer, L. Perelman, J. Wu, K. Chen, G. Deinum, M. Fitzmaurice, J. Myles, J. Crowe, R. R. Dasari and M. S. Feld, "Raman spectroscopy and fluorescence photon migration for breast cancer diagnosis and imaging," Photochem. Photobiol. 67,15-22 (1998).
[CrossRef] [PubMed]

Frank, C. J.

C. J. Frank, D. C. Redd, T. S. Gansler and R. L. McCreery, "Characterization of human breast biopsy specimens with near-IR Raman spectroscopy," Anal. Chem. 66,319-26 (1994).
[CrossRef] [PubMed]

Gandour-Edwards, R.

S. G. Demos, R. Gandour-Edwards, R. Ramsamooj and R. White, "Near-infrared autofluorescence imaging for detection of cancer," J. Biomed. Opt. 9,587-92 (2004).
[CrossRef] [PubMed]

Demos, S. G. , R. Gandour-Edwards, R. Ramsamooj and R. DeVere White, "Spectroscopic detection of bladder cancer using near-infrared imaging techniques," J. Biomed. Opt. 9, 767-71 (2004).
[CrossRef] [PubMed]

Gansler, T. S.

C. J. Frank, D. C. Redd, T. S. Gansler and R. L. McCreery, "Characterization of human breast biopsy specimens with near-IR Raman spectroscopy," Anal. Chem. 66,319-26 (1994).
[CrossRef] [PubMed]

Gu, X.

X. Gu, Q. Zhang, M. Bartlett, L. Schutz, L. L. Fajardo and H. Jiang, "Differentiation of cysts from solid tumors in the breast with diffuse optical tomography," Acad. Radiol. 11,53-60 (2004).
[CrossRef] [PubMed]

Hafez, M. M.

M. M. el-Sharabasy, A. M. el-Waseef, M. M. Hafez and S. A. Salim, "Porphyrin metabolism in some malignant diseases," Br. J. Cancer 65,409-12. (1992).
[CrossRef] [PubMed]

Haka, A. S.

A. S. Haka, K. E. Shafer-Peltier, M. Fitzmaurice, J. Crowe, R. R. Dasari and M. S. Feld, "Identifying microcalcifications in benign and malignant breast lesions by probing differences in their chemical composition using Raman spectroscopy," Cancer Res. 62,5375-80 (2002).
[PubMed]

Harris, D. M.

D. M. Harris and J. Werkhaven, "Endogenous porphyrin fluorescence in tumors," Lasers Surg. Med. 7,467-72. (1987).
[CrossRef] [PubMed]

Hashimoto, K.

M. Inaguma and K. Hashimoto, "Porphyrin-like fluorescence in oral cancer: In vivo fluorescence spectral characterization of lesions by use of a near-ultraviolet excited autofluorescence diagnosis system and separation of fluorescent extracts by capillary electrophoresis," Cancer 86,2201-11. (1999).
[CrossRef] [PubMed]

Heerdt, A. S.

S. G. Demos, H. Savage, A. S. Heerdt, S. Schantz and R. R. Alfano, "Time Resolved Degree of Polarization for Human Breast Tissue," Optics Commun. 124,439 (1996).
[CrossRef]

Hsiang, D.

D. B. Jakubowski, A. E. Cerussi, F. Bevilacqua, N. Shah, D. Hsiang, J. Butler and B. J. Tromberg, "Monitoring neoadjuvant chemotherapy in breast cancer using quantitative diffuse optical spectroscopy: a case study," J. Biomed. Opt. 9,230-8 (2004).
[CrossRef] [PubMed]

Inaguma, M.

M. Inaguma and K. Hashimoto, "Porphyrin-like fluorescence in oral cancer: In vivo fluorescence spectral characterization of lesions by use of a near-ultraviolet excited autofluorescence diagnosis system and separation of fluorescent extracts by capillary electrophoresis," Cancer 86,2201-11. (1999).
[CrossRef] [PubMed]

Jakubowski, D. B.

D. B. Jakubowski, A. E. Cerussi, F. Bevilacqua, N. Shah, D. Hsiang, J. Butler and B. J. Tromberg, "Monitoring neoadjuvant chemotherapy in breast cancer using quantitative diffuse optical spectroscopy: a case study," J. Biomed. Opt. 9,230-8 (2004).
[CrossRef] [PubMed]

Jiang, H.

X. Gu, Q. Zhang, M. Bartlett, L. Schutz, L. L. Fajardo and H. Jiang, "Differentiation of cysts from solid tumors in the breast with diffuse optical tomography," Acad. Radiol. 11,53-60 (2004).
[CrossRef] [PubMed]

Johnson, K. S.

D. W. Chicken, A. C. Lee, G. M. Briggs, M. R. S. Keshtgar, K. S. Johnson, D. D. O. Pickard, I. J. Bigio and S. G. Bown, "Optical biopsy: A novel intraoperative diagnostic tool to determine sentinel lymph node status instantly in breast cancer," Breast Cancer Res. Treat. 82,S172-S174 (2003).

Keshtgar, M. R. S.

D. W. Chicken, A. C. Lee, G. M. Briggs, M. R. S. Keshtgar, K. S. Johnson, D. D. O. Pickard, I. J. Bigio and S. G. Bown, "Optical biopsy: A novel intraoperative diagnostic tool to determine sentinel lymph node status instantly in breast cancer," Breast Cancer Res. Treat. 82,S172-S174 (2003).

Koestner, A.

G. Stoica and A. Koestner, "Diverse spectrum of tumors in male Sprague-Dawley rats following single high doses of N-ethyl-N-nitrosourea (ENU)," Am. J. Pathol. 116,319-26 (1984).
[PubMed]

Kolb, T. M.

T. M. Kolb, J. Lichy and J. H. Newhouse, "Comparison of the performance of screening mammography, physical examination, and breast US and evaluation of factors that influence them: an analysis of 27,825 patient evaluations," Radiology 225, 165-75 (2002).
[CrossRef] [PubMed]

Lao, X.

M. Y. Su, Z. Wang, P. M. Carpenter, X. Lao, A. Muhler and O. Nalcioglu, "Characterization of N-ethyl-N-nitrosourea-induced malignant and benign breast tumors in rats by using three MR contrast agents," J. Magn. Reson. 9,177-86 (1999).
[CrossRef]

Lee, A. C.

D. W. Chicken, A. C. Lee, G. M. Briggs, M. R. S. Keshtgar, K. S. Johnson, D. D. O. Pickard, I. J. Bigio and S. G. Bown, "Optical biopsy: A novel intraoperative diagnostic tool to determine sentinel lymph node status instantly in breast cancer," Breast Cancer Res. Treat. 82,S172-S174 (2003).

Lichy, J.

T. M. Kolb, J. Lichy and J. H. Newhouse, "Comparison of the performance of screening mammography, physical examination, and breast US and evaluation of factors that influence them: an analysis of 27,825 patient evaluations," Radiology 225, 165-75 (2002).
[CrossRef] [PubMed]

Link, T. M.

H. Daldrup, D. M. Shames, M. Wendland, Y. Okuhata, T. M. Link, W. Rosenau, Y. Lu and R. C. Brasch, "Correlation of dynamic contrast-enhanced MR imaging with histologic tumor grade: comparison of macromolecular and small-molecular contrast media," AJR Am. J. Roentgenol. 171,941-9. (1998).
[PubMed]

Lu, Y.

H. Daldrup, D. M. Shames, M. Wendland, Y. Okuhata, T. M. Link, W. Rosenau, Y. Lu and R. C. Brasch, "Correlation of dynamic contrast-enhanced MR imaging with histologic tumor grade: comparison of macromolecular and small-molecular contrast media," AJR Am. J. Roentgenol. 171,941-9. (1998).
[PubMed]

MacRobert, A. J.

T. Theodossiou and A. J. MacRobert, "Comparison of the photodynamic effect of exogenous photoprotoporphyrin and protoporphyrin IX on PAM 212 murine keratocytes.," Photochem. Photobiol. 76,530-537 (2002).
[CrossRef] [PubMed]

Manoharan, R.

R. Manoharan, K. Shafer, L. Perelman, J. Wu, K. Chen, G. Deinum, M. Fitzmaurice, J. Myles, J. Crowe, R. R. Dasari and M. S. Feld, "Raman spectroscopy and fluorescence photon migration for breast cancer diagnosis and imaging," Photochem. Photobiol. 67,15-22 (1998).
[CrossRef] [PubMed]

McCreery, R. L.

C. J. Frank, D. C. Redd, T. S. Gansler and R. L. McCreery, "Characterization of human breast biopsy specimens with near-IR Raman spectroscopy," Anal. Chem. 66,319-26 (1994).
[CrossRef] [PubMed]

Muhler, A.

M. Y. Su, Z. Wang, P. M. Carpenter, X. Lao, A. Muhler and O. Nalcioglu, "Characterization of N-ethyl-N-nitrosourea-induced malignant and benign breast tumors in rats by using three MR contrast agents," J. Magn. Reson. 9,177-86 (1999).
[CrossRef]

Myles, J.

R. Manoharan, K. Shafer, L. Perelman, J. Wu, K. Chen, G. Deinum, M. Fitzmaurice, J. Myles, J. Crowe, R. R. Dasari and M. S. Feld, "Raman spectroscopy and fluorescence photon migration for breast cancer diagnosis and imaging," Photochem. Photobiol. 67,15-22 (1998).
[CrossRef] [PubMed]

Nalcioglu, O.

M. Y. Su, Z. Wang, P. M. Carpenter, X. Lao, A. Muhler and O. Nalcioglu, "Characterization of N-ethyl-N-nitrosourea-induced malignant and benign breast tumors in rats by using three MR contrast agents," J. Magn. Reson. 9,177-86 (1999).
[CrossRef]

Newhouse, J. H.

T. M. Kolb, J. Lichy and J. H. Newhouse, "Comparison of the performance of screening mammography, physical examination, and breast US and evaluation of factors that influence them: an analysis of 27,825 patient evaluations," Radiology 225, 165-75 (2002).
[CrossRef] [PubMed]

Ntziachristos, V.

V. Ntziachristos, A. G. Yodh, M. Schnall and B. Chance, "Concurrent MRI and diffuse optical tomography of breast after indocyanine green enhancement," Proc. Natl. Acad. Sci. U. S. A. 97,2767-72. (2000).
[CrossRef] [PubMed]

Okuhata, Y.

H. Daldrup, D. M. Shames, M. Wendland, Y. Okuhata, T. M. Link, W. Rosenau, Y. Lu and R. C. Brasch, "Correlation of dynamic contrast-enhanced MR imaging with histologic tumor grade: comparison of macromolecular and small-molecular contrast media," AJR Am. J. Roentgenol. 171,941-9. (1998).
[PubMed]

Perelman, L.

R. Manoharan, K. Shafer, L. Perelman, J. Wu, K. Chen, G. Deinum, M. Fitzmaurice, J. Myles, J. Crowe, R. R. Dasari and M. S. Feld, "Raman spectroscopy and fluorescence photon migration for breast cancer diagnosis and imaging," Photochem. Photobiol. 67,15-22 (1998).
[CrossRef] [PubMed]

Pickard, D. D. O.

D. W. Chicken, A. C. Lee, G. M. Briggs, M. R. S. Keshtgar, K. S. Johnson, D. D. O. Pickard, I. J. Bigio and S. G. Bown, "Optical biopsy: A novel intraoperative diagnostic tool to determine sentinel lymph node status instantly in breast cancer," Breast Cancer Res. Treat. 82,S172-S174 (2003).

Ramsamooj, R.

Demos, S. G. , R. Gandour-Edwards, R. Ramsamooj and R. DeVere White, "Spectroscopic detection of bladder cancer using near-infrared imaging techniques," J. Biomed. Opt. 9, 767-71 (2004).
[CrossRef] [PubMed]

S. G. Demos, R. Gandour-Edwards, R. Ramsamooj and R. White, "Near-infrared autofluorescence imaging for detection of cancer," J. Biomed. Opt. 9,587-92 (2004).
[CrossRef] [PubMed]

Rasetti, L.

L. Rasetti, G. F. Rubino, L. Tettinatti and G. W. Drago, "Porphyrin porphobilinogen and amino ketone levels in tumor tissue," Panminerva Med. 7,105-110 (1965).

Redd, D. C.

C. J. Frank, D. C. Redd, T. S. Gansler and R. L. McCreery, "Characterization of human breast biopsy specimens with near-IR Raman spectroscopy," Anal. Chem. 66,319-26 (1994).
[CrossRef] [PubMed]

Rosenau, W.

H. Daldrup, D. M. Shames, M. Wendland, Y. Okuhata, T. M. Link, W. Rosenau, Y. Lu and R. C. Brasch, "Correlation of dynamic contrast-enhanced MR imaging with histologic tumor grade: comparison of macromolecular and small-molecular contrast media," AJR Am. J. Roentgenol. 171,941-9. (1998).
[PubMed]

Rubino, G. F.

L. Rasetti, G. F. Rubino, L. Tettinatti and G. W. Drago, "Porphyrin porphobilinogen and amino ketone levels in tumor tissue," Panminerva Med. 7,105-110 (1965).

Salim, S. A.

M. M. el-Sharabasy, A. M. el-Waseef, M. M. Hafez and S. A. Salim, "Porphyrin metabolism in some malignant diseases," Br. J. Cancer 65,409-12. (1992).
[CrossRef] [PubMed]

Savage, H.

S. G. Demos, H. Savage, A. S. Heerdt, S. Schantz and R. R. Alfano, "Time Resolved Degree of Polarization for Human Breast Tissue," Optics Commun. 124,439 (1996).
[CrossRef]

Schantz, S.

S. G. Demos, H. Savage, A. S. Heerdt, S. Schantz and R. R. Alfano, "Time Resolved Degree of Polarization for Human Breast Tissue," Optics Commun. 124,439 (1996).
[CrossRef]

Schnall, M.

V. Ntziachristos, A. G. Yodh, M. Schnall and B. Chance, "Concurrent MRI and diffuse optical tomography of breast after indocyanine green enhancement," Proc. Natl. Acad. Sci. U. S. A. 97,2767-72. (2000).
[CrossRef] [PubMed]

Schutz, L.

X. Gu, Q. Zhang, M. Bartlett, L. Schutz, L. L. Fajardo and H. Jiang, "Differentiation of cysts from solid tumors in the breast with diffuse optical tomography," Acad. Radiol. 11,53-60 (2004).
[CrossRef] [PubMed]

Shafer, K.

R. Manoharan, K. Shafer, L. Perelman, J. Wu, K. Chen, G. Deinum, M. Fitzmaurice, J. Myles, J. Crowe, R. R. Dasari and M. S. Feld, "Raman spectroscopy and fluorescence photon migration for breast cancer diagnosis and imaging," Photochem. Photobiol. 67,15-22 (1998).
[CrossRef] [PubMed]

Shafer-Peltier, K. E.

A. S. Haka, K. E. Shafer-Peltier, M. Fitzmaurice, J. Crowe, R. R. Dasari and M. S. Feld, "Identifying microcalcifications in benign and malignant breast lesions by probing differences in their chemical composition using Raman spectroscopy," Cancer Res. 62,5375-80 (2002).
[PubMed]

Shah, N.

D. B. Jakubowski, A. E. Cerussi, F. Bevilacqua, N. Shah, D. Hsiang, J. Butler and B. J. Tromberg, "Monitoring neoadjuvant chemotherapy in breast cancer using quantitative diffuse optical spectroscopy: a case study," J. Biomed. Opt. 9,230-8 (2004).
[CrossRef] [PubMed]

Shames, D. M.

H. Daldrup, D. M. Shames, M. Wendland, Y. Okuhata, T. M. Link, W. Rosenau, Y. Lu and R. C. Brasch, "Correlation of dynamic contrast-enhanced MR imaging with histologic tumor grade: comparison of macromolecular and small-molecular contrast media," AJR Am. J. Roentgenol. 171,941-9. (1998).
[PubMed]

Star, W. M.

G. A. Wagnieres, W. M. Star and B. C. Wilson, "In vivo fluorescence spectroscopy and imaging for oncological applications," Photochem. Photobiol. 68,603-32. (1998).
[PubMed]

Stoica, G.

G. Stoica and A. Koestner, "Diverse spectrum of tumors in male Sprague-Dawley rats following single high doses of N-ethyl-N-nitrosourea (ENU)," Am. J. Pathol. 116,319-26 (1984).
[PubMed]

Su, M. Y.

M. Y. Su, Z. Wang, P. M. Carpenter, X. Lao, A. Muhler and O. Nalcioglu, "Characterization of N-ethyl-N-nitrosourea-induced malignant and benign breast tumors in rats by using three MR contrast agents," J. Magn. Reson. 9,177-86 (1999).
[CrossRef]

Tettinatti, L.

L. Rasetti, G. F. Rubino, L. Tettinatti and G. W. Drago, "Porphyrin porphobilinogen and amino ketone levels in tumor tissue," Panminerva Med. 7,105-110 (1965).

Theodossiou, T.

T. Theodossiou and A. J. MacRobert, "Comparison of the photodynamic effect of exogenous photoprotoporphyrin and protoporphyrin IX on PAM 212 murine keratocytes.," Photochem. Photobiol. 76,530-537 (2002).
[CrossRef] [PubMed]

Tromberg, B. J.

D. B. Jakubowski, A. E. Cerussi, F. Bevilacqua, N. Shah, D. Hsiang, J. Butler and B. J. Tromberg, "Monitoring neoadjuvant chemotherapy in breast cancer using quantitative diffuse optical spectroscopy: a case study," J. Biomed. Opt. 9,230-8 (2004).
[CrossRef] [PubMed]

Wagnieres, G. A.

G. A. Wagnieres, W. M. Star and B. C. Wilson, "In vivo fluorescence spectroscopy and imaging for oncological applications," Photochem. Photobiol. 68,603-32. (1998).
[PubMed]

Wang, Z.

M. Y. Su, Z. Wang, P. M. Carpenter, X. Lao, A. Muhler and O. Nalcioglu, "Characterization of N-ethyl-N-nitrosourea-induced malignant and benign breast tumors in rats by using three MR contrast agents," J. Magn. Reson. 9,177-86 (1999).
[CrossRef]

Wendland, M.

H. Daldrup, D. M. Shames, M. Wendland, Y. Okuhata, T. M. Link, W. Rosenau, Y. Lu and R. C. Brasch, "Correlation of dynamic contrast-enhanced MR imaging with histologic tumor grade: comparison of macromolecular and small-molecular contrast media," AJR Am. J. Roentgenol. 171,941-9. (1998).
[PubMed]

Werkhaven, J.

D. M. Harris and J. Werkhaven, "Endogenous porphyrin fluorescence in tumors," Lasers Surg. Med. 7,467-72. (1987).
[CrossRef] [PubMed]

White, R.

S. G. Demos, R. Gandour-Edwards, R. Ramsamooj and R. White, "Near-infrared autofluorescence imaging for detection of cancer," J. Biomed. Opt. 9,587-92 (2004).
[CrossRef] [PubMed]

Wilson, B. C.

G. A. Wagnieres, W. M. Star and B. C. Wilson, "In vivo fluorescence spectroscopy and imaging for oncological applications," Photochem. Photobiol. 68,603-32. (1998).
[PubMed]

Wu, J.

R. Manoharan, K. Shafer, L. Perelman, J. Wu, K. Chen, G. Deinum, M. Fitzmaurice, J. Myles, J. Crowe, R. R. Dasari and M. S. Feld, "Raman spectroscopy and fluorescence photon migration for breast cancer diagnosis and imaging," Photochem. Photobiol. 67,15-22 (1998).
[CrossRef] [PubMed]

Yodh, A. G.

V. Ntziachristos, A. G. Yodh, M. Schnall and B. Chance, "Concurrent MRI and diffuse optical tomography of breast after indocyanine green enhancement," Proc. Natl. Acad. Sci. U. S. A. 97,2767-72. (2000).
[CrossRef] [PubMed]

Zawirska, B.

B. Zawirska, "Comparative porphyrin content in tumors with contiguous non-neoplastic tissues," Neoplasma 26,223-9. (1979).
[PubMed]

Zhang, G.

G. Zhang, S. G. Demos and R. R. Alfano, "Far-red and NIR spectral wing emission from tissues under 532-nm and 632-nm photo-excitation," Lasers Life Sci. 9,1-16 (1999).

Zhang, Q.

X. Gu, Q. Zhang, M. Bartlett, L. Schutz, L. L. Fajardo and H. Jiang, "Differentiation of cysts from solid tumors in the breast with diffuse optical tomography," Acad. Radiol. 11,53-60 (2004).
[CrossRef] [PubMed]

Acad. Radiol. (1)

X. Gu, Q. Zhang, M. Bartlett, L. Schutz, L. L. Fajardo and H. Jiang, "Differentiation of cysts from solid tumors in the breast with diffuse optical tomography," Acad. Radiol. 11,53-60 (2004).
[CrossRef] [PubMed]

AJR Am. J. Roentgenol. (1)

H. Daldrup, D. M. Shames, M. Wendland, Y. Okuhata, T. M. Link, W. Rosenau, Y. Lu and R. C. Brasch, "Correlation of dynamic contrast-enhanced MR imaging with histologic tumor grade: comparison of macromolecular and small-molecular contrast media," AJR Am. J. Roentgenol. 171,941-9. (1998).
[PubMed]

Am. J. Pathol. (1)

G. Stoica and A. Koestner, "Diverse spectrum of tumors in male Sprague-Dawley rats following single high doses of N-ethyl-N-nitrosourea (ENU)," Am. J. Pathol. 116,319-26 (1984).
[PubMed]

Anal. Chem. (1)

C. J. Frank, D. C. Redd, T. S. Gansler and R. L. McCreery, "Characterization of human breast biopsy specimens with near-IR Raman spectroscopy," Anal. Chem. 66,319-26 (1994).
[CrossRef] [PubMed]

Br. J. Cancer (1)

M. M. el-Sharabasy, A. M. el-Waseef, M. M. Hafez and S. A. Salim, "Porphyrin metabolism in some malignant diseases," Br. J. Cancer 65,409-12. (1992).
[CrossRef] [PubMed]

Breast Cancer Res. Treat. (1)

D. W. Chicken, A. C. Lee, G. M. Briggs, M. R. S. Keshtgar, K. S. Johnson, D. D. O. Pickard, I. J. Bigio and S. G. Bown, "Optical biopsy: A novel intraoperative diagnostic tool to determine sentinel lymph node status instantly in breast cancer," Breast Cancer Res. Treat. 82,S172-S174 (2003).

Cancer (1)

M. Inaguma and K. Hashimoto, "Porphyrin-like fluorescence in oral cancer: In vivo fluorescence spectral characterization of lesions by use of a near-ultraviolet excited autofluorescence diagnosis system and separation of fluorescent extracts by capillary electrophoresis," Cancer 86,2201-11. (1999).
[CrossRef] [PubMed]

Cancer Res. (1)

A. S. Haka, K. E. Shafer-Peltier, M. Fitzmaurice, J. Crowe, R. R. Dasari and M. S. Feld, "Identifying microcalcifications in benign and malignant breast lesions by probing differences in their chemical composition using Raman spectroscopy," Cancer Res. 62,5375-80 (2002).
[PubMed]

J. Biomed. Opt. (3)

D. B. Jakubowski, A. E. Cerussi, F. Bevilacqua, N. Shah, D. Hsiang, J. Butler and B. J. Tromberg, "Monitoring neoadjuvant chemotherapy in breast cancer using quantitative diffuse optical spectroscopy: a case study," J. Biomed. Opt. 9,230-8 (2004).
[CrossRef] [PubMed]

Demos, S. G. , R. Gandour-Edwards, R. Ramsamooj and R. DeVere White, "Spectroscopic detection of bladder cancer using near-infrared imaging techniques," J. Biomed. Opt. 9, 767-71 (2004).
[CrossRef] [PubMed]

S. G. Demos, R. Gandour-Edwards, R. Ramsamooj and R. White, "Near-infrared autofluorescence imaging for detection of cancer," J. Biomed. Opt. 9,587-92 (2004).
[CrossRef] [PubMed]

J. Magn. Reson. (1)

M. Y. Su, Z. Wang, P. M. Carpenter, X. Lao, A. Muhler and O. Nalcioglu, "Characterization of N-ethyl-N-nitrosourea-induced malignant and benign breast tumors in rats by using three MR contrast agents," J. Magn. Reson. 9,177-86 (1999).
[CrossRef]

Lasers Life Sci. (1)

G. Zhang, S. G. Demos and R. R. Alfano, "Far-red and NIR spectral wing emission from tissues under 532-nm and 632-nm photo-excitation," Lasers Life Sci. 9,1-16 (1999).

Lasers Surg. Med. (1)

D. M. Harris and J. Werkhaven, "Endogenous porphyrin fluorescence in tumors," Lasers Surg. Med. 7,467-72. (1987).
[CrossRef] [PubMed]

Neoplasma (1)

B. Zawirska, "Comparative porphyrin content in tumors with contiguous non-neoplastic tissues," Neoplasma 26,223-9. (1979).
[PubMed]

Optics Commun. (1)

S. G. Demos, H. Savage, A. S. Heerdt, S. Schantz and R. R. Alfano, "Time Resolved Degree of Polarization for Human Breast Tissue," Optics Commun. 124,439 (1996).
[CrossRef]

Panminerva Med. (1)

L. Rasetti, G. F. Rubino, L. Tettinatti and G. W. Drago, "Porphyrin porphobilinogen and amino ketone levels in tumor tissue," Panminerva Med. 7,105-110 (1965).

Photochem. Photobiol. (3)

T. Theodossiou and A. J. MacRobert, "Comparison of the photodynamic effect of exogenous photoprotoporphyrin and protoporphyrin IX on PAM 212 murine keratocytes.," Photochem. Photobiol. 76,530-537 (2002).
[CrossRef] [PubMed]

G. A. Wagnieres, W. M. Star and B. C. Wilson, "In vivo fluorescence spectroscopy and imaging for oncological applications," Photochem. Photobiol. 68,603-32. (1998).
[PubMed]

R. Manoharan, K. Shafer, L. Perelman, J. Wu, K. Chen, G. Deinum, M. Fitzmaurice, J. Myles, J. Crowe, R. R. Dasari and M. S. Feld, "Raman spectroscopy and fluorescence photon migration for breast cancer diagnosis and imaging," Photochem. Photobiol. 67,15-22 (1998).
[CrossRef] [PubMed]

Proc. Natl. Acad. Sci. U. S. A. (1)

V. Ntziachristos, A. G. Yodh, M. Schnall and B. Chance, "Concurrent MRI and diffuse optical tomography of breast after indocyanine green enhancement," Proc. Natl. Acad. Sci. U. S. A. 97,2767-72. (2000).
[CrossRef] [PubMed]

Radiology (1)

T. M. Kolb, J. Lichy and J. H. Newhouse, "Comparison of the performance of screening mammography, physical examination, and breast US and evaluation of factors that influence them: an analysis of 27,825 patient evaluations," Radiology 225, 165-75 (2002).
[CrossRef] [PubMed]

Surg. Gynecol. Obstet. (1)

M. Cutler, "Transillumination as an aid in the diagnosis of breast lesions.," Surg. Gynecol. Obstet. 48,721-729 (1929).

Other (3)

National Cancer Institute, "Cancernet resource" (National Cancer Institute, 2003), http://cis.nci.nih.gov/fact/5_6.htm.

National Cancer Institute, "Surveillance, Epidemiology, and End Results: Estimated new cancer cases and deaths for 2004" (National Cancer Institute, 2004), http://seer.cancer.gov/cgi-bin/csr/1975_2001/search.pl#results

R. Scarff and H. Torloni, "Histological typing of breast tumors," in World Health Organization, (Geneva, 1968), pp. 13-20.

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Figures (4)

Fig. 1.
Fig. 1.

Schematic layout of the key components of the optical imaging system.

Fig. 2.
Fig. 2.

(a) Light scattering image under ambient light and (b) corresponding autofluorescence image under 670-nm excitation showing a rat containing malignant tumors in supine position (tumors #2 and 3). The spectral window for image formation was at 800-nm in both images. The hair represents the very bright regions visible on the fluorescence image outside the area of interest. On the fluorescence image (b), the tumor (indicated by the black arrow), spontaneously emits more fluorescence than adjacent normal mammary tissue (white arrow).

Fig. 3.
Fig. 3.

(a) Light scattering image under ambient light and (b) corresponding autofluorescence image under 670-nm excitation and detection at 800-nm showing a rat containing a benign tumor in supine position (tumor #7). In the fluorescence image (b), the tumor (white arrow) is on the contrary to Fig. 2, much less fluorescent than the adjacent normal mammary tissue (black arrow). This tumor was shown to be a benign fibroadenoma on pathology. The signal intensity ratio T/N was in this case 0.22. Note the visibility of a blood vessel, absorbing light (black arrowheads), outlined by the brighter normal tissue. Small variation in the autofluorescence intensity in the normal tissue area is attributed to the presence of various organs of the animal located below the surface that exhibit different autofluorescence intensities under the deeply propagating excitation light.

Fig. 4.
Fig. 4.

Tumor-to-normal signal intensity ratio plotted according to size for benign (엯) and malignant (Δ) tumors.

Tables (3)

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Table 1. Tumor-to-normal average signal intensity ratios at different laser excitation and detection spectral bands, for benign and malignant tumors.

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Table 2. Tumor-to-normal autofluorescence intensity ratios measured using laser excitation at 670 nm and detection spectral window of 750±20 nm 800±20 nm.

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Table 3. Diagnostic value of NIR autofluorescence imaging under 670-nm excitation and 800-nm detection for the differentiation of benign and malignant breast tumors.

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