Abstract

In vitro experiments have demonstrated the ability of Raman spectroscopy to diagnose a wide variety of diseases. Recent in vivo investigations performed with optical fiber probes were promising but generally limited to easily accessible organs, often requiring relatively long collection times. We have implemented an optical design strategy to utilize system throughput fully by characterizing the Raman distribution from tissue. This scheme optimizes collection efficiency, minimizes noise, and has resulted in small-diameter, highly efficient Raman probes that are capable of collecting high-quality data in 1 s. Performance has been tested through simulations and experiments with tissue models and several in vitro tissue types, demonstrating that this new design can advance Raman spectroscopy as a clinically practical technique.

© 2004 Optical Society of America

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    [CrossRef]
  33. K. E. Shafer-Peltier, A. S. Haka, M. Fitzmaurice, J. Crowe, J. Myles, R. R. Dasari, and M. S. Feld, “Raman microspectroscopic model of human breast tissue: implications for breast cancer diagnosis in vivo,” J. Raman Spectrosc. 33, 552–563 (2002).
    [CrossRef]
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2003 (1)

U. Utzinger and R. Richards-Kortum, “Fiber optic probes for biomedical spectroscopy,” J. Biomed. Opt. 8, 121–147 (2003).
[CrossRef] [PubMed]

2002 (3)

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, 5375–5380 (2002).
[PubMed]

T. C. Bakker Schut, R. Wolthuis, P. J. Caspers, and G. J. Puppels, “Real-time tissue characterization on the basis of in vivo Raman spectra,” J. Raman Spectrosc. 33, 580–585 (2002).
[CrossRef]

K. E. Shafer-Peltier, A. S. Haka, M. Fitzmaurice, J. Crowe, J. Myles, R. R. Dasari, and M. S. Feld, “Raman microspectroscopic model of human breast tissue: implications for breast cancer diagnosis in vivo,” J. Raman Spectrosc. 33, 552–563 (2002).
[CrossRef]

2001 (4)

H. P. J. Buschman, G. Deinum, J. T. Motz, M. Fitzmaurice, J. R. Kramer, A. van der Laarse, A. V. G. Bruschke, and M. S. Feld, “Raman microspectroscopy of human coronary atherosclerosis: biochemical assessment of cellular and extracellular morphologic structures in situ,” Cardiovasc. Pathol. 10, 69–82 (2001).
[CrossRef] [PubMed]

T.-W. Koo, “Measurement of blood analytes in turbid biological tissue using near-infrared Raman spectroscopy,” Ph.D. dissertation (Massachusetts Institute of Technology, Cambridge, Mass., 2001).

U. Utzinger, D. L. Heintzelman, A. Mahadevan-Jansen, A. Malpica, M. Follen, and R. Richards-Kortum, “Near-infrared Raman spectroscopy for in vivo detection of cervical precancers,” Appl. Spectrosc. 55, 955–959 (2001).
[CrossRef]

H. P. Buschman, J. T. Motz, G. Deinum, T. J. Römer, M. Fitzmaurice, J. R. Kramer, A. van der Laarse, A. V. Bruschke, and M. S. Feld, “Diagnosis of human coronary atherosclerosis by morphology-based Raman spectroscopy,” Cardiovasc. Pathol. 10, 59–68 (2001).
[CrossRef] [PubMed]

2000 (7)

E. B. Hanlon, R. Manoharan, T.-W. Koo, K. E. Shafer, J. T. Motz, M. Fitzmaurice, J. R. Kramer, I. Itzkan, R. R. Dasari, and M. S. Feld, “Prospects for in vivo Raman spectroscopy,” Phys. Med. Biol. 45, R1–R59 (2000).
[CrossRef] [PubMed]

M. G. Shim, L.-M. W. K. Song, N. E. Marcon, and B. C. Wilson, “In vivo near-infrared Raman spectroscopy: demonstration of feasibility during clinical gastrointestinal endoscopy,” Photochem. Photobiol. 72, 146–150 (2000).
[PubMed]

P. J. Caspers, G. W. Lucassen, H. A. Bruining, and G. J. Puppels, “Automated depth-scanning confocal Raman microspectrometer for rapid in vivo determination of water concentration profiles in human skin,” J. Raman Spectrosc. 31, 813–818 (2000).
[CrossRef]

T. R. Hata, T. A. Scholz, I. V. Ermakov, R. W. McClane, F. Khachik, W. Gellermann, and L. K. Pershing, “Non-invasive Raman spectroscopic detection of carotenoids in human skin,” J. Invest. Dermatol. 115, 441–448 (2000).
[CrossRef] [PubMed]

H. P. Buschman, E. T. Marple, M. L. Wach, B. Bennett, T. C. B. Schut, H. A. Bruining, A. V. Bruschke, A. van der Laarse, and G. J. Puppels, “In vivo determination of the molecular composition of artery wall by intravascular Raman spectroscopy,” Anal. Chem. 72, 3771–3775 (2000).
[CrossRef] [PubMed]

S. W. E. van de Poll, H. P. J. Buschman, M. J. Visser, J. H. van Bockel, A. van der Laarse, A. V. G. Bruschke, and G. J. Puppels, “Raman spectroscopy provides characterization of human atherosclerotic plaque composition in vivo,” J. Am. Coll. Cardiol. 35, 52A (2000).

R. L. McCreery, Raman Spectroscopy for Chemical Analysis (Wiley, New York, 2000).
[CrossRef]

1999 (1)

1998 (4)

P. J. Caspers, G. W. Lucassen, R. Wolthuis, H. A. Bruining, and G. J. Puppels, “In vitro and in vivo Raman spectroscopy of human skin,” Biospectroscopy 4, S31–S39 (1998).
[CrossRef]

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

T. J. Römer, J. F. B. Brennan, M. Fitzmaurice, M. L. Feldstein, G. Deinum, J. L. Myles, J. R. Kramer, R. S. Lees, and M. S. Feld, “Histopathology of human coronary atherosclerosis by quantifying its chemical composition with Raman spectroscopy,” Circulation 97, 878–885 (1998).
[CrossRef] [PubMed]

G. Puppels, T. van Aken, R. Wolthuis, P. Caspers, T. Bakker Schutt, H. Bruining, T. Römer, H. Buschman, M. Wach, and J. Robinson, Jr., “In vivo tissue characterization by Raman spectroscopy,” in Infrared Spectroscopy: New Tool in Medicine, H. Mantsch and M. Jackson, eds., Proc. SPIE 3257, 78–83 (1998).

1997 (3)

M. Shim and B. Wilson, “Development of an in vivo Raman spectroscopic system for diagnostic applications,” J. Raman Spectrosc. 28, 131–142 (1997).
[CrossRef]

G. Zhang, S. Demos, and R. Alfano, “Raman spectra of biomedical samples using optical fiber probes,” in Biomedical Sensing, Imaging, and Tracking Technologies II, T. Vo-Dinh, R. Lieberman, and G. Vurek, eds., Proc. SPIE 2976, 2–9 (1997).
[CrossRef]

J. F. Brennan, Y. Wang, R. R. Dasari, and M. S. Feld, “Near-infrared Raman spectrometer systems for human tissue studies,” Appl. Spectrosc. 51, 201–208 (1997).
[CrossRef]

1996 (5)

1995 (1)

P. Libby, “Molecular bases of the acute coronary syndromes,” Circulation 91, 2844–2850 (1995).
[CrossRef] [PubMed]

1994 (1)

1993 (1)

M. Diem, Introduction to Modern Vibrational Spectroscopy (Wiley, New York, 1993).

1985 (1)

J. M. C. van Gemert, R. M. Verdaasdonk, E. G. Stassen, G. A. C. M. Schets, G. H. M. Gijsbers, and J. J. Bonnier, “Optical properties of human blood vessel wall and plaque,” Lasers Surg. Med. 5, 235–237 (1985).
[CrossRef] [PubMed]

1983 (2)

C. F. Bohren and D. R. Huffman, Absorption and Scattering of Light by Small Particles (Wiley, New York, 1983).

R. W. Boyd, Radiometry and the Detection of Optical Radiation (Wiley, New York, 1983).

Alfano, R.

G. Zhang, S. Demos, and R. Alfano, “Raman spectra of biomedical samples using optical fiber probes,” in Biomedical Sensing, Imaging, and Tracking Technologies II, T. Vo-Dinh, R. Lieberman, and G. Vurek, eds., Proc. SPIE 2976, 2–9 (1997).
[CrossRef]

Angel, S. M.

Bakker Schut, T. C.

T. C. Bakker Schut, R. Wolthuis, P. J. Caspers, and G. J. Puppels, “Real-time tissue characterization on the basis of in vivo Raman spectra,” J. Raman Spectrosc. 33, 580–585 (2002).
[CrossRef]

Bakker Schutt, T.

G. Puppels, T. van Aken, R. Wolthuis, P. Caspers, T. Bakker Schutt, H. Bruining, T. Römer, H. Buschman, M. Wach, and J. Robinson, Jr., “In vivo tissue characterization by Raman spectroscopy,” in Infrared Spectroscopy: New Tool in Medicine, H. Mantsch and M. Jackson, eds., Proc. SPIE 3257, 78–83 (1998).

Bennett, B.

H. P. Buschman, E. T. Marple, M. L. Wach, B. Bennett, T. C. B. Schut, H. A. Bruining, A. V. Bruschke, A. van der Laarse, and G. J. Puppels, “In vivo determination of the molecular composition of artery wall by intravascular Raman spectroscopy,” Anal. Chem. 72, 3771–3775 (2000).
[CrossRef] [PubMed]

Bohren, C. F.

C. F. Bohren and D. R. Huffman, Absorption and Scattering of Light by Small Particles (Wiley, New York, 1983).

Bonnier, J. J.

J. M. C. van Gemert, R. M. Verdaasdonk, E. G. Stassen, G. A. C. M. Schets, G. H. M. Gijsbers, and J. J. Bonnier, “Optical properties of human blood vessel wall and plaque,” Lasers Surg. Med. 5, 235–237 (1985).
[CrossRef] [PubMed]

Boyd, R. W.

R. W. Boyd, Radiometry and the Detection of Optical Radiation (Wiley, New York, 1983).

Brennan, J. F.

Brennan, J. F. B.

T. J. Römer, J. F. B. Brennan, M. Fitzmaurice, M. L. Feldstein, G. Deinum, J. L. Myles, J. R. Kramer, R. S. Lees, and M. S. Feld, “Histopathology of human coronary atherosclerosis by quantifying its chemical composition with Raman spectroscopy,” Circulation 97, 878–885 (1998).
[CrossRef] [PubMed]

Bruining, H.

G. Puppels, T. van Aken, R. Wolthuis, P. Caspers, T. Bakker Schutt, H. Bruining, T. Römer, H. Buschman, M. Wach, and J. Robinson, Jr., “In vivo tissue characterization by Raman spectroscopy,” in Infrared Spectroscopy: New Tool in Medicine, H. Mantsch and M. Jackson, eds., Proc. SPIE 3257, 78–83 (1998).

Bruining, H. A.

P. J. Caspers, G. W. Lucassen, H. A. Bruining, and G. J. Puppels, “Automated depth-scanning confocal Raman microspectrometer for rapid in vivo determination of water concentration profiles in human skin,” J. Raman Spectrosc. 31, 813–818 (2000).
[CrossRef]

H. P. Buschman, E. T. Marple, M. L. Wach, B. Bennett, T. C. B. Schut, H. A. Bruining, A. V. Bruschke, A. van der Laarse, and G. J. Puppels, “In vivo determination of the molecular composition of artery wall by intravascular Raman spectroscopy,” Anal. Chem. 72, 3771–3775 (2000).
[CrossRef] [PubMed]

P. J. Caspers, G. W. Lucassen, R. Wolthuis, H. A. Bruining, and G. J. Puppels, “In vitro and in vivo Raman spectroscopy of human skin,” Biospectroscopy 4, S31–S39 (1998).
[CrossRef]

Bruschke, A. V.

H. P. Buschman, J. T. Motz, G. Deinum, T. J. Römer, M. Fitzmaurice, J. R. Kramer, A. van der Laarse, A. V. Bruschke, and M. S. Feld, “Diagnosis of human coronary atherosclerosis by morphology-based Raman spectroscopy,” Cardiovasc. Pathol. 10, 59–68 (2001).
[CrossRef] [PubMed]

H. P. Buschman, E. T. Marple, M. L. Wach, B. Bennett, T. C. B. Schut, H. A. Bruining, A. V. Bruschke, A. van der Laarse, and G. J. Puppels, “In vivo determination of the molecular composition of artery wall by intravascular Raman spectroscopy,” Anal. Chem. 72, 3771–3775 (2000).
[CrossRef] [PubMed]

Bruschke, A. V. G.

H. P. J. Buschman, G. Deinum, J. T. Motz, M. Fitzmaurice, J. R. Kramer, A. van der Laarse, A. V. G. Bruschke, and M. S. Feld, “Raman microspectroscopy of human coronary atherosclerosis: biochemical assessment of cellular and extracellular morphologic structures in situ,” Cardiovasc. Pathol. 10, 69–82 (2001).
[CrossRef] [PubMed]

S. W. E. van de Poll, H. P. J. Buschman, M. J. Visser, J. H. van Bockel, A. van der Laarse, A. V. G. Bruschke, and G. J. Puppels, “Raman spectroscopy provides characterization of human atherosclerotic plaque composition in vivo,” J. Am. Coll. Cardiol. 35, 52A (2000).

Buschman, H.

G. Puppels, T. van Aken, R. Wolthuis, P. Caspers, T. Bakker Schutt, H. Bruining, T. Römer, H. Buschman, M. Wach, and J. Robinson, Jr., “In vivo tissue characterization by Raman spectroscopy,” in Infrared Spectroscopy: New Tool in Medicine, H. Mantsch and M. Jackson, eds., Proc. SPIE 3257, 78–83 (1998).

Buschman, H. P.

H. P. Buschman, J. T. Motz, G. Deinum, T. J. Römer, M. Fitzmaurice, J. R. Kramer, A. van der Laarse, A. V. Bruschke, and M. S. Feld, “Diagnosis of human coronary atherosclerosis by morphology-based Raman spectroscopy,” Cardiovasc. Pathol. 10, 59–68 (2001).
[CrossRef] [PubMed]

H. P. Buschman, E. T. Marple, M. L. Wach, B. Bennett, T. C. B. Schut, H. A. Bruining, A. V. Bruschke, A. van der Laarse, and G. J. Puppels, “In vivo determination of the molecular composition of artery wall by intravascular Raman spectroscopy,” Anal. Chem. 72, 3771–3775 (2000).
[CrossRef] [PubMed]

Buschman, H. P. J.

H. P. J. Buschman, G. Deinum, J. T. Motz, M. Fitzmaurice, J. R. Kramer, A. van der Laarse, A. V. G. Bruschke, and M. S. Feld, “Raman microspectroscopy of human coronary atherosclerosis: biochemical assessment of cellular and extracellular morphologic structures in situ,” Cardiovasc. Pathol. 10, 69–82 (2001).
[CrossRef] [PubMed]

S. W. E. van de Poll, H. P. J. Buschman, M. J. Visser, J. H. van Bockel, A. van der Laarse, A. V. G. Bruschke, and G. J. Puppels, “Raman spectroscopy provides characterization of human atherosclerotic plaque composition in vivo,” J. Am. Coll. Cardiol. 35, 52A (2000).

Caspers, P.

G. Puppels, T. van Aken, R. Wolthuis, P. Caspers, T. Bakker Schutt, H. Bruining, T. Römer, H. Buschman, M. Wach, and J. Robinson, Jr., “In vivo tissue characterization by Raman spectroscopy,” in Infrared Spectroscopy: New Tool in Medicine, H. Mantsch and M. Jackson, eds., Proc. SPIE 3257, 78–83 (1998).

Caspers, P. J.

T. C. Bakker Schut, R. Wolthuis, P. J. Caspers, and G. J. Puppels, “Real-time tissue characterization on the basis of in vivo Raman spectra,” J. Raman Spectrosc. 33, 580–585 (2002).
[CrossRef]

P. J. Caspers, G. W. Lucassen, H. A. Bruining, and G. J. Puppels, “Automated depth-scanning confocal Raman microspectrometer for rapid in vivo determination of water concentration profiles in human skin,” J. Raman Spectrosc. 31, 813–818 (2000).
[CrossRef]

P. J. Caspers, G. W. Lucassen, R. Wolthuis, H. A. Bruining, and G. J. Puppels, “In vitro and in vivo Raman spectroscopy of human skin,” Biospectroscopy 4, S31–S39 (1998).
[CrossRef]

Chen, K.

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

Cooney, T. F.

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, 5375–5380 (2002).
[PubMed]

K. E. Shafer-Peltier, A. S. Haka, M. Fitzmaurice, J. Crowe, J. Myles, R. R. Dasari, and M. S. Feld, “Raman microspectroscopic model of human breast tissue: implications for breast cancer diagnosis in vivo,” J. Raman Spectrosc. 33, 552–563 (2002).
[CrossRef]

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

Dasari, R.

R. Manoharan, K. Shafer, L. Perelman, J. Wu, K. Chen, G. Deinum, M. Fitzmaurice, J. Myles, J. Crowe, R. Dasari, and M. Feld, “Raman spectroscopy and fluorescence photon migration for breast cancer diagnosis and imaging,” Photochem. Photobiol. 67, 15–22 (1998).
[CrossRef] [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, 5375–5380 (2002).
[PubMed]

K. E. Shafer-Peltier, A. S. Haka, M. Fitzmaurice, J. Crowe, J. Myles, R. R. Dasari, and M. S. Feld, “Raman microspectroscopic model of human breast tissue: implications for breast cancer diagnosis in vivo,” J. Raman Spectrosc. 33, 552–563 (2002).
[CrossRef]

E. B. Hanlon, R. Manoharan, T.-W. Koo, K. E. Shafer, J. T. Motz, M. Fitzmaurice, J. R. Kramer, I. Itzkan, R. R. Dasari, and M. S. Feld, “Prospects for in vivo Raman spectroscopy,” Phys. Med. Biol. 45, R1–R59 (2000).
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J. M. Mann and M. J. Davies, “Vulnerable plaque: relation of characteristics to degree of stenosis in human coronary arteries,” Circulation 94, 928–931 (1996).
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H. P. Buschman, J. T. Motz, G. Deinum, T. J. Römer, M. Fitzmaurice, J. R. Kramer, A. van der Laarse, A. V. Bruschke, and M. S. Feld, “Diagnosis of human coronary atherosclerosis by morphology-based Raman spectroscopy,” Cardiovasc. Pathol. 10, 59–68 (2001).
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H. P. J. Buschman, G. Deinum, J. T. Motz, M. Fitzmaurice, J. R. Kramer, A. van der Laarse, A. V. G. Bruschke, and M. S. Feld, “Raman microspectroscopy of human coronary atherosclerosis: biochemical assessment of cellular and extracellular morphologic structures in situ,” Cardiovasc. Pathol. 10, 69–82 (2001).
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R. Manoharan, K. Shafer, L. Perelman, J. Wu, K. Chen, G. Deinum, M. Fitzmaurice, J. Myles, J. Crowe, R. Dasari, and M. Feld, “Raman spectroscopy and fluorescence photon migration for breast cancer diagnosis and imaging,” Photochem. Photobiol. 67, 15–22 (1998).
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[CrossRef] [PubMed]

Feld, M.

R. Manoharan, K. Shafer, L. Perelman, J. Wu, K. Chen, G. Deinum, M. Fitzmaurice, J. Myles, J. Crowe, R. Dasari, and M. Feld, “Raman spectroscopy and fluorescence photon migration for breast cancer diagnosis and imaging,” Photochem. Photobiol. 67, 15–22 (1998).
[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, 5375–5380 (2002).
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H. P. J. Buschman, G. Deinum, J. T. Motz, M. Fitzmaurice, J. R. Kramer, A. van der Laarse, A. V. G. Bruschke, and M. S. Feld, “Raman microspectroscopy of human coronary atherosclerosis: biochemical assessment of cellular and extracellular morphologic structures in situ,” Cardiovasc. Pathol. 10, 69–82 (2001).
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H. P. Buschman, J. T. Motz, G. Deinum, T. J. Römer, M. Fitzmaurice, J. R. Kramer, A. van der Laarse, A. V. Bruschke, and M. S. Feld, “Diagnosis of human coronary atherosclerosis by morphology-based Raman spectroscopy,” Cardiovasc. Pathol. 10, 59–68 (2001).
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E. B. Hanlon, R. Manoharan, T.-W. Koo, K. E. Shafer, J. T. Motz, M. Fitzmaurice, J. R. Kramer, I. Itzkan, R. R. Dasari, and M. S. Feld, “Prospects for in vivo Raman spectroscopy,” Phys. Med. Biol. 45, R1–R59 (2000).
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T. J. Römer, J. F. B. Brennan, M. Fitzmaurice, M. L. Feldstein, G. Deinum, J. L. Myles, J. R. Kramer, R. S. Lees, and M. S. Feld, “Histopathology of human coronary atherosclerosis by quantifying its chemical composition with Raman spectroscopy,” Circulation 97, 878–885 (1998).
[CrossRef] [PubMed]

J. F. Brennan, Y. Wang, R. R. Dasari, and M. S. Feld, “Near-infrared Raman spectrometer systems for human tissue studies,” Appl. Spectrosc. 51, 201–208 (1997).
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T. J. Römer, J. F. B. Brennan, M. Fitzmaurice, M. L. Feldstein, G. Deinum, J. L. Myles, J. R. Kramer, R. S. Lees, and M. S. Feld, “Histopathology of human coronary atherosclerosis by quantifying its chemical composition with Raman spectroscopy,” Circulation 97, 878–885 (1998).
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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, 5375–5380 (2002).
[PubMed]

K. E. Shafer-Peltier, A. S. Haka, M. Fitzmaurice, J. Crowe, J. Myles, R. R. Dasari, and M. S. Feld, “Raman microspectroscopic model of human breast tissue: implications for breast cancer diagnosis in vivo,” J. Raman Spectrosc. 33, 552–563 (2002).
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H. P. J. Buschman, G. Deinum, J. T. Motz, M. Fitzmaurice, J. R. Kramer, A. van der Laarse, A. V. G. Bruschke, and M. S. Feld, “Raman microspectroscopy of human coronary atherosclerosis: biochemical assessment of cellular and extracellular morphologic structures in situ,” Cardiovasc. Pathol. 10, 69–82 (2001).
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H. P. Buschman, J. T. Motz, G. Deinum, T. J. Römer, M. Fitzmaurice, J. R. Kramer, A. van der Laarse, A. V. Bruschke, and M. S. Feld, “Diagnosis of human coronary atherosclerosis by morphology-based Raman spectroscopy,” Cardiovasc. Pathol. 10, 59–68 (2001).
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E. B. Hanlon, R. Manoharan, T.-W. Koo, K. E. Shafer, J. T. Motz, M. Fitzmaurice, J. R. Kramer, I. Itzkan, R. R. Dasari, and M. S. Feld, “Prospects for in vivo Raman spectroscopy,” Phys. Med. Biol. 45, R1–R59 (2000).
[CrossRef] [PubMed]

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

T. J. Römer, J. F. B. Brennan, M. Fitzmaurice, M. L. Feldstein, G. Deinum, J. L. Myles, J. R. Kramer, R. S. Lees, and M. S. Feld, “Histopathology of human coronary atherosclerosis by quantifying its chemical composition with Raman spectroscopy,” Circulation 97, 878–885 (1998).
[CrossRef] [PubMed]

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Gellermann, W.

T. R. Hata, T. A. Scholz, I. V. Ermakov, R. W. McClane, F. Khachik, W. Gellermann, and L. K. Pershing, “Non-invasive Raman spectroscopic detection of carotenoids in human skin,” J. Invest. Dermatol. 115, 441–448 (2000).
[CrossRef] [PubMed]

Gijsbers, G. H. M.

J. M. C. van Gemert, R. M. Verdaasdonk, E. G. Stassen, G. A. C. M. Schets, G. H. M. Gijsbers, and J. J. Bonnier, “Optical properties of human blood vessel wall and plaque,” Lasers Surg. Med. 5, 235–237 (1985).
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K. E. Shafer-Peltier, A. S. Haka, M. Fitzmaurice, J. Crowe, J. Myles, R. R. Dasari, and M. S. Feld, “Raman microspectroscopic model of human breast tissue: implications for breast cancer diagnosis in vivo,” J. Raman Spectrosc. 33, 552–563 (2002).
[CrossRef]

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, 5375–5380 (2002).
[PubMed]

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E. B. Hanlon, R. Manoharan, T.-W. Koo, K. E. Shafer, J. T. Motz, M. Fitzmaurice, J. R. Kramer, I. Itzkan, R. R. Dasari, and M. S. Feld, “Prospects for in vivo Raman spectroscopy,” Phys. Med. Biol. 45, R1–R59 (2000).
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T. R. Hata, T. A. Scholz, I. V. Ermakov, R. W. McClane, F. Khachik, W. Gellermann, and L. K. Pershing, “Non-invasive Raman spectroscopic detection of carotenoids in human skin,” J. Invest. Dermatol. 115, 441–448 (2000).
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E. B. Hanlon, R. Manoharan, T.-W. Koo, K. E. Shafer, J. T. Motz, M. Fitzmaurice, J. R. Kramer, I. Itzkan, R. R. Dasari, and M. S. Feld, “Prospects for in vivo Raman spectroscopy,” Phys. Med. Biol. 45, R1–R59 (2000).
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Khachik, F.

T. R. Hata, T. A. Scholz, I. V. Ermakov, R. W. McClane, F. Khachik, W. Gellermann, and L. K. Pershing, “Non-invasive Raman spectroscopic detection of carotenoids in human skin,” J. Invest. Dermatol. 115, 441–448 (2000).
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H. P. Buschman, J. T. Motz, G. Deinum, T. J. Römer, M. Fitzmaurice, J. R. Kramer, A. van der Laarse, A. V. Bruschke, and M. S. Feld, “Diagnosis of human coronary atherosclerosis by morphology-based Raman spectroscopy,” Cardiovasc. Pathol. 10, 59–68 (2001).
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H. P. J. Buschman, G. Deinum, J. T. Motz, M. Fitzmaurice, J. R. Kramer, A. van der Laarse, A. V. G. Bruschke, and M. S. Feld, “Raman microspectroscopy of human coronary atherosclerosis: biochemical assessment of cellular and extracellular morphologic structures in situ,” Cardiovasc. Pathol. 10, 69–82 (2001).
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E. B. Hanlon, R. Manoharan, T.-W. Koo, K. E. Shafer, J. T. Motz, M. Fitzmaurice, J. R. Kramer, I. Itzkan, R. R. Dasari, and M. S. Feld, “Prospects for in vivo Raman spectroscopy,” Phys. Med. Biol. 45, R1–R59 (2000).
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T. J. Römer, J. F. B. Brennan, M. Fitzmaurice, M. L. Feldstein, G. Deinum, J. L. Myles, J. R. Kramer, R. S. Lees, and M. S. Feld, “Histopathology of human coronary atherosclerosis by quantifying its chemical composition with Raman spectroscopy,” Circulation 97, 878–885 (1998).
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Lees, R. S.

T. J. Römer, J. F. B. Brennan, M. Fitzmaurice, M. L. Feldstein, G. Deinum, J. L. Myles, J. R. Kramer, R. S. Lees, and M. S. Feld, “Histopathology of human coronary atherosclerosis by quantifying its chemical composition with Raman spectroscopy,” Circulation 97, 878–885 (1998).
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P. J. Caspers, G. W. Lucassen, R. Wolthuis, H. A. Bruining, and G. J. Puppels, “In vitro and in vivo Raman spectroscopy of human skin,” Biospectroscopy 4, S31–S39 (1998).
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Ma, J.

Ma, J. Y.

Mahadevan-Jansen, A.

Malpica, A.

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J. M. Mann and M. J. Davies, “Vulnerable plaque: relation of characteristics to degree of stenosis in human coronary arteries,” Circulation 94, 928–931 (1996).
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Manoharan, R.

E. B. Hanlon, R. Manoharan, T.-W. Koo, K. E. Shafer, J. T. Motz, M. Fitzmaurice, J. R. Kramer, I. Itzkan, R. R. Dasari, and M. S. Feld, “Prospects for in vivo Raman spectroscopy,” Phys. Med. Biol. 45, R1–R59 (2000).
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R. Manoharan, K. Shafer, L. Perelman, J. Wu, K. Chen, G. Deinum, M. Fitzmaurice, J. Myles, J. Crowe, R. Dasari, and M. Feld, “Raman spectroscopy and fluorescence photon migration for breast cancer diagnosis and imaging,” Photochem. Photobiol. 67, 15–22 (1998).
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Marcon, N. E.

M. G. Shim, L.-M. W. K. Song, N. E. Marcon, and B. C. Wilson, “In vivo near-infrared Raman spectroscopy: demonstration of feasibility during clinical gastrointestinal endoscopy,” Photochem. Photobiol. 72, 146–150 (2000).
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Marple, E. T.

H. P. Buschman, E. T. Marple, M. L. Wach, B. Bennett, T. C. B. Schut, H. A. Bruining, A. V. Bruschke, A. van der Laarse, and G. J. Puppels, “In vivo determination of the molecular composition of artery wall by intravascular Raman spectroscopy,” Anal. Chem. 72, 3771–3775 (2000).
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T. R. Hata, T. A. Scholz, I. V. Ermakov, R. W. McClane, F. Khachik, W. Gellermann, and L. K. Pershing, “Non-invasive Raman spectroscopic detection of carotenoids in human skin,” J. Invest. Dermatol. 115, 441–448 (2000).
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H. P. J. Buschman, G. Deinum, J. T. Motz, M. Fitzmaurice, J. R. Kramer, A. van der Laarse, A. V. G. Bruschke, and M. S. Feld, “Raman microspectroscopy of human coronary atherosclerosis: biochemical assessment of cellular and extracellular morphologic structures in situ,” Cardiovasc. Pathol. 10, 69–82 (2001).
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H. P. Buschman, J. T. Motz, G. Deinum, T. J. Römer, M. Fitzmaurice, J. R. Kramer, A. van der Laarse, A. V. Bruschke, and M. S. Feld, “Diagnosis of human coronary atherosclerosis by morphology-based Raman spectroscopy,” Cardiovasc. Pathol. 10, 59–68 (2001).
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E. B. Hanlon, R. Manoharan, T.-W. Koo, K. E. Shafer, J. T. Motz, M. Fitzmaurice, J. R. Kramer, I. Itzkan, R. R. Dasari, and M. S. Feld, “Prospects for in vivo Raman spectroscopy,” Phys. Med. Biol. 45, R1–R59 (2000).
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Myles, J.

K. E. Shafer-Peltier, A. S. Haka, M. Fitzmaurice, J. Crowe, J. Myles, R. R. Dasari, and M. S. Feld, “Raman microspectroscopic model of human breast tissue: implications for breast cancer diagnosis in vivo,” J. Raman Spectrosc. 33, 552–563 (2002).
[CrossRef]

R. Manoharan, K. Shafer, L. Perelman, J. Wu, K. Chen, G. Deinum, M. Fitzmaurice, J. Myles, J. Crowe, R. Dasari, and M. Feld, “Raman spectroscopy and fluorescence photon migration for breast cancer diagnosis and imaging,” Photochem. Photobiol. 67, 15–22 (1998).
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Myles, J. L.

T. J. Römer, J. F. B. Brennan, M. Fitzmaurice, M. L. Feldstein, G. Deinum, J. L. Myles, J. R. Kramer, R. S. Lees, and M. S. Feld, “Histopathology of human coronary atherosclerosis by quantifying its chemical composition with Raman spectroscopy,” Circulation 97, 878–885 (1998).
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Perelman, L.

R. Manoharan, K. Shafer, L. Perelman, J. Wu, K. Chen, G. Deinum, M. Fitzmaurice, J. Myles, J. Crowe, R. Dasari, and M. Feld, “Raman spectroscopy and fluorescence photon migration for breast cancer diagnosis and imaging,” Photochem. Photobiol. 67, 15–22 (1998).
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T. R. Hata, T. A. Scholz, I. V. Ermakov, R. W. McClane, F. Khachik, W. Gellermann, and L. K. Pershing, “Non-invasive Raman spectroscopic detection of carotenoids in human skin,” J. Invest. Dermatol. 115, 441–448 (2000).
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Puppels, G. J.

T. C. Bakker Schut, R. Wolthuis, P. J. Caspers, and G. J. Puppels, “Real-time tissue characterization on the basis of in vivo Raman spectra,” J. Raman Spectrosc. 33, 580–585 (2002).
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P. J. Caspers, G. W. Lucassen, H. A. Bruining, and G. J. Puppels, “Automated depth-scanning confocal Raman microspectrometer for rapid in vivo determination of water concentration profiles in human skin,” J. Raman Spectrosc. 31, 813–818 (2000).
[CrossRef]

H. P. Buschman, E. T. Marple, M. L. Wach, B. Bennett, T. C. B. Schut, H. A. Bruining, A. V. Bruschke, A. van der Laarse, and G. J. Puppels, “In vivo determination of the molecular composition of artery wall by intravascular Raman spectroscopy,” Anal. Chem. 72, 3771–3775 (2000).
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P. J. Caspers, G. W. Lucassen, R. Wolthuis, H. A. Bruining, and G. J. Puppels, “In vitro and in vivo Raman spectroscopy of human skin,” Biospectroscopy 4, S31–S39 (1998).
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G. Puppels, T. van Aken, R. Wolthuis, P. Caspers, T. Bakker Schutt, H. Bruining, T. Römer, H. Buschman, M. Wach, and J. Robinson, Jr., “In vivo tissue characterization by Raman spectroscopy,” in Infrared Spectroscopy: New Tool in Medicine, H. Mantsch and M. Jackson, eds., Proc. SPIE 3257, 78–83 (1998).

Römer, T.

G. Puppels, T. van Aken, R. Wolthuis, P. Caspers, T. Bakker Schutt, H. Bruining, T. Römer, H. Buschman, M. Wach, and J. Robinson, Jr., “In vivo tissue characterization by Raman spectroscopy,” in Infrared Spectroscopy: New Tool in Medicine, H. Mantsch and M. Jackson, eds., Proc. SPIE 3257, 78–83 (1998).

Römer, T. J.

H. P. Buschman, J. T. Motz, G. Deinum, T. J. Römer, M. Fitzmaurice, J. R. Kramer, A. van der Laarse, A. V. Bruschke, and M. S. Feld, “Diagnosis of human coronary atherosclerosis by morphology-based Raman spectroscopy,” Cardiovasc. Pathol. 10, 59–68 (2001).
[CrossRef] [PubMed]

T. J. Römer, J. F. B. Brennan, M. Fitzmaurice, M. L. Feldstein, G. Deinum, J. L. Myles, J. R. Kramer, R. S. Lees, and M. S. Feld, “Histopathology of human coronary atherosclerosis by quantifying its chemical composition with Raman spectroscopy,” Circulation 97, 878–885 (1998).
[CrossRef] [PubMed]

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J. M. C. van Gemert, R. M. Verdaasdonk, E. G. Stassen, G. A. C. M. Schets, G. H. M. Gijsbers, and J. J. Bonnier, “Optical properties of human blood vessel wall and plaque,” Lasers Surg. Med. 5, 235–237 (1985).
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T. R. Hata, T. A. Scholz, I. V. Ermakov, R. W. McClane, F. Khachik, W. Gellermann, and L. K. Pershing, “Non-invasive Raman spectroscopic detection of carotenoids in human skin,” J. Invest. Dermatol. 115, 441–448 (2000).
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H. P. Buschman, E. T. Marple, M. L. Wach, B. Bennett, T. C. B. Schut, H. A. Bruining, A. V. Bruschke, A. van der Laarse, and G. J. Puppels, “In vivo determination of the molecular composition of artery wall by intravascular Raman spectroscopy,” Anal. Chem. 72, 3771–3775 (2000).
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R. Manoharan, K. Shafer, L. Perelman, J. Wu, K. Chen, G. Deinum, M. Fitzmaurice, J. Myles, J. Crowe, R. Dasari, and M. Feld, “Raman spectroscopy and fluorescence photon migration for breast cancer diagnosis and imaging,” Photochem. Photobiol. 67, 15–22 (1998).
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E. B. Hanlon, R. Manoharan, T.-W. Koo, K. E. Shafer, J. T. Motz, M. Fitzmaurice, J. R. Kramer, I. Itzkan, R. R. Dasari, and M. S. Feld, “Prospects for in vivo Raman spectroscopy,” Phys. Med. Biol. 45, R1–R59 (2000).
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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, 5375–5380 (2002).
[PubMed]

K. E. Shafer-Peltier, A. S. Haka, M. Fitzmaurice, J. Crowe, J. Myles, R. R. Dasari, and M. S. Feld, “Raman microspectroscopic model of human breast tissue: implications for breast cancer diagnosis in vivo,” J. Raman Spectrosc. 33, 552–563 (2002).
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[PubMed]

Skinner, H. T.

Song, L.-M. W. K.

M. G. Shim, L.-M. W. K. Song, N. E. Marcon, and B. C. Wilson, “In vivo near-infrared Raman spectroscopy: demonstration of feasibility during clinical gastrointestinal endoscopy,” Photochem. Photobiol. 72, 146–150 (2000).
[PubMed]

Stassen, E. G.

J. M. C. van Gemert, R. M. Verdaasdonk, E. G. Stassen, G. A. C. M. Schets, G. H. M. Gijsbers, and J. J. Bonnier, “Optical properties of human blood vessel wall and plaque,” Lasers Surg. Med. 5, 235–237 (1985).
[CrossRef] [PubMed]

Utzinger, U.

van Aken, T.

G. Puppels, T. van Aken, R. Wolthuis, P. Caspers, T. Bakker Schutt, H. Bruining, T. Römer, H. Buschman, M. Wach, and J. Robinson, Jr., “In vivo tissue characterization by Raman spectroscopy,” in Infrared Spectroscopy: New Tool in Medicine, H. Mantsch and M. Jackson, eds., Proc. SPIE 3257, 78–83 (1998).

van Bockel, J. H.

S. W. E. van de Poll, H. P. J. Buschman, M. J. Visser, J. H. van Bockel, A. van der Laarse, A. V. G. Bruschke, and G. J. Puppels, “Raman spectroscopy provides characterization of human atherosclerotic plaque composition in vivo,” J. Am. Coll. Cardiol. 35, 52A (2000).

van de Poll, S. W. E.

S. W. E. van de Poll, H. P. J. Buschman, M. J. Visser, J. H. van Bockel, A. van der Laarse, A. V. G. Bruschke, and G. J. Puppels, “Raman spectroscopy provides characterization of human atherosclerotic plaque composition in vivo,” J. Am. Coll. Cardiol. 35, 52A (2000).

van der Laarse, A.

H. P. Buschman, J. T. Motz, G. Deinum, T. J. Römer, M. Fitzmaurice, J. R. Kramer, A. van der Laarse, A. V. Bruschke, and M. S. Feld, “Diagnosis of human coronary atherosclerosis by morphology-based Raman spectroscopy,” Cardiovasc. Pathol. 10, 59–68 (2001).
[CrossRef] [PubMed]

H. P. J. Buschman, G. Deinum, J. T. Motz, M. Fitzmaurice, J. R. Kramer, A. van der Laarse, A. V. G. Bruschke, and M. S. Feld, “Raman microspectroscopy of human coronary atherosclerosis: biochemical assessment of cellular and extracellular morphologic structures in situ,” Cardiovasc. Pathol. 10, 69–82 (2001).
[CrossRef] [PubMed]

H. P. Buschman, E. T. Marple, M. L. Wach, B. Bennett, T. C. B. Schut, H. A. Bruining, A. V. Bruschke, A. van der Laarse, and G. J. Puppels, “In vivo determination of the molecular composition of artery wall by intravascular Raman spectroscopy,” Anal. Chem. 72, 3771–3775 (2000).
[CrossRef] [PubMed]

S. W. E. van de Poll, H. P. J. Buschman, M. J. Visser, J. H. van Bockel, A. van der Laarse, A. V. G. Bruschke, and G. J. Puppels, “Raman spectroscopy provides characterization of human atherosclerotic plaque composition in vivo,” J. Am. Coll. Cardiol. 35, 52A (2000).

van Gemert, J. M. C.

J. M. C. van Gemert, R. M. Verdaasdonk, E. G. Stassen, G. A. C. M. Schets, G. H. M. Gijsbers, and J. J. Bonnier, “Optical properties of human blood vessel wall and plaque,” Lasers Surg. Med. 5, 235–237 (1985).
[CrossRef] [PubMed]

Verdaasdonk, R. M.

J. M. C. van Gemert, R. M. Verdaasdonk, E. G. Stassen, G. A. C. M. Schets, G. H. M. Gijsbers, and J. J. Bonnier, “Optical properties of human blood vessel wall and plaque,” Lasers Surg. Med. 5, 235–237 (1985).
[CrossRef] [PubMed]

Visser, M. J.

S. W. E. van de Poll, H. P. J. Buschman, M. J. Visser, J. H. van Bockel, A. van der Laarse, A. V. G. Bruschke, and G. J. Puppels, “Raman spectroscopy provides characterization of human atherosclerotic plaque composition in vivo,” J. Am. Coll. Cardiol. 35, 52A (2000).

Wach, M.

M. Shim, B. Wilson, E. Marple, and M. Wach, “Study of fiber-optic probes for in vivo medical Raman spectroscopy,” Appl. Spectrosc. 53, 619–627 (1999).
[CrossRef]

G. Puppels, T. van Aken, R. Wolthuis, P. Caspers, T. Bakker Schutt, H. Bruining, T. Römer, H. Buschman, M. Wach, and J. Robinson, Jr., “In vivo tissue characterization by Raman spectroscopy,” in Infrared Spectroscopy: New Tool in Medicine, H. Mantsch and M. Jackson, eds., Proc. SPIE 3257, 78–83 (1998).

Wach, M. L.

H. P. Buschman, E. T. Marple, M. L. Wach, B. Bennett, T. C. B. Schut, H. A. Bruining, A. V. Bruschke, A. van der Laarse, and G. J. Puppels, “In vivo determination of the molecular composition of artery wall by intravascular Raman spectroscopy,” Anal. Chem. 72, 3771–3775 (2000).
[CrossRef] [PubMed]

Wang, Y.

Wilson, B.

M. Shim, B. Wilson, E. Marple, and M. Wach, “Study of fiber-optic probes for in vivo medical Raman spectroscopy,” Appl. Spectrosc. 53, 619–627 (1999).
[CrossRef]

M. Shim and B. Wilson, “Development of an in vivo Raman spectroscopic system for diagnostic applications,” J. Raman Spectrosc. 28, 131–142 (1997).
[CrossRef]

Wilson, B. C.

M. G. Shim, L.-M. W. K. Song, N. E. Marcon, and B. C. Wilson, “In vivo near-infrared Raman spectroscopy: demonstration of feasibility during clinical gastrointestinal endoscopy,” Photochem. Photobiol. 72, 146–150 (2000).
[PubMed]

Wolthuis, R.

T. C. Bakker Schut, R. Wolthuis, P. J. Caspers, and G. J. Puppels, “Real-time tissue characterization on the basis of in vivo Raman spectra,” J. Raman Spectrosc. 33, 580–585 (2002).
[CrossRef]

P. J. Caspers, G. W. Lucassen, R. Wolthuis, H. A. Bruining, and G. J. Puppels, “In vitro and in vivo Raman spectroscopy of human skin,” Biospectroscopy 4, S31–S39 (1998).
[CrossRef]

G. Puppels, T. van Aken, R. Wolthuis, P. Caspers, T. Bakker Schutt, H. Bruining, T. Römer, H. Buschman, M. Wach, and J. Robinson, Jr., “In vivo tissue characterization by Raman spectroscopy,” in Infrared Spectroscopy: New Tool in Medicine, H. Mantsch and M. Jackson, eds., Proc. SPIE 3257, 78–83 (1998).

Wu, J.

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

Zhang, G.

G. Zhang, S. Demos, and R. Alfano, “Raman spectra of biomedical samples using optical fiber probes,” in Biomedical Sensing, Imaging, and Tracking Technologies II, T. Vo-Dinh, R. Lieberman, and G. Vurek, eds., Proc. SPIE 2976, 2–9 (1997).
[CrossRef]

Anal. Chem. (1)

H. P. Buschman, E. T. Marple, M. L. Wach, B. Bennett, T. C. B. Schut, H. A. Bruining, A. V. Bruschke, A. van der Laarse, and G. J. Puppels, “In vivo determination of the molecular composition of artery wall by intravascular Raman spectroscopy,” Anal. Chem. 72, 3771–3775 (2000).
[CrossRef] [PubMed]

Appl. Opt. (1)

Appl. Spectrosc. (6)

Biospectroscopy (1)

P. J. Caspers, G. W. Lucassen, R. Wolthuis, H. A. Bruining, and G. J. Puppels, “In vitro and in vivo Raman spectroscopy of human skin,” Biospectroscopy 4, S31–S39 (1998).
[CrossRef]

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, 5375–5380 (2002).
[PubMed]

Cardiovasc. Pathol. (2)

H. P. Buschman, J. T. Motz, G. Deinum, T. J. Römer, M. Fitzmaurice, J. R. Kramer, A. van der Laarse, A. V. Bruschke, and M. S. Feld, “Diagnosis of human coronary atherosclerosis by morphology-based Raman spectroscopy,” Cardiovasc. Pathol. 10, 59–68 (2001).
[CrossRef] [PubMed]

H. P. J. Buschman, G. Deinum, J. T. Motz, M. Fitzmaurice, J. R. Kramer, A. van der Laarse, A. V. G. Bruschke, and M. S. Feld, “Raman microspectroscopy of human coronary atherosclerosis: biochemical assessment of cellular and extracellular morphologic structures in situ,” Cardiovasc. Pathol. 10, 69–82 (2001).
[CrossRef] [PubMed]

Circulation (3)

T. J. Römer, J. F. B. Brennan, M. Fitzmaurice, M. L. Feldstein, G. Deinum, J. L. Myles, J. R. Kramer, R. S. Lees, and M. S. Feld, “Histopathology of human coronary atherosclerosis by quantifying its chemical composition with Raman spectroscopy,” Circulation 97, 878–885 (1998).
[CrossRef] [PubMed]

P. Libby, “Molecular bases of the acute coronary syndromes,” Circulation 91, 2844–2850 (1995).
[CrossRef] [PubMed]

J. M. Mann and M. J. Davies, “Vulnerable plaque: relation of characteristics to degree of stenosis in human coronary arteries,” Circulation 94, 928–931 (1996).
[CrossRef] [PubMed]

J. Am. Coll. Cardiol. (1)

S. W. E. van de Poll, H. P. J. Buschman, M. J. Visser, J. H. van Bockel, A. van der Laarse, A. V. G. Bruschke, and G. J. Puppels, “Raman spectroscopy provides characterization of human atherosclerotic plaque composition in vivo,” J. Am. Coll. Cardiol. 35, 52A (2000).

J. Biomed. Opt. (2)

A. Mahadevan-Jansen and R. Richards-Kortum, “Raman spectroscopy for the detection of cancers and precancers,” J. Biomed. Opt. 1, 31–70 (1996).
[CrossRef] [PubMed]

U. Utzinger and R. Richards-Kortum, “Fiber optic probes for biomedical spectroscopy,” J. Biomed. Opt. 8, 121–147 (2003).
[CrossRef] [PubMed]

J. Invest. Dermatol. (1)

T. R. Hata, T. A. Scholz, I. V. Ermakov, R. W. McClane, F. Khachik, W. Gellermann, and L. K. Pershing, “Non-invasive Raman spectroscopic detection of carotenoids in human skin,” J. Invest. Dermatol. 115, 441–448 (2000).
[CrossRef] [PubMed]

J. Raman Spectrosc. (4)

P. J. Caspers, G. W. Lucassen, H. A. Bruining, and G. J. Puppels, “Automated depth-scanning confocal Raman microspectrometer for rapid in vivo determination of water concentration profiles in human skin,” J. Raman Spectrosc. 31, 813–818 (2000).
[CrossRef]

M. Shim and B. Wilson, “Development of an in vivo Raman spectroscopic system for diagnostic applications,” J. Raman Spectrosc. 28, 131–142 (1997).
[CrossRef]

T. C. Bakker Schut, R. Wolthuis, P. J. Caspers, and G. J. Puppels, “Real-time tissue characterization on the basis of in vivo Raman spectra,” J. Raman Spectrosc. 33, 580–585 (2002).
[CrossRef]

K. E. Shafer-Peltier, A. S. Haka, M. Fitzmaurice, J. Crowe, J. Myles, R. R. Dasari, and M. S. Feld, “Raman microspectroscopic model of human breast tissue: implications for breast cancer diagnosis in vivo,” J. Raman Spectrosc. 33, 552–563 (2002).
[CrossRef]

Lasers Surg. Med. (1)

J. M. C. van Gemert, R. M. Verdaasdonk, E. G. Stassen, G. A. C. M. Schets, G. H. M. Gijsbers, and J. J. Bonnier, “Optical properties of human blood vessel wall and plaque,” Lasers Surg. Med. 5, 235–237 (1985).
[CrossRef] [PubMed]

Photochem. Photobiol. (2)

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

M. G. Shim, L.-M. W. K. Song, N. E. Marcon, and B. C. Wilson, “In vivo near-infrared Raman spectroscopy: demonstration of feasibility during clinical gastrointestinal endoscopy,” Photochem. Photobiol. 72, 146–150 (2000).
[PubMed]

Phys. Med. Biol. (1)

E. B. Hanlon, R. Manoharan, T.-W. Koo, K. E. Shafer, J. T. Motz, M. Fitzmaurice, J. R. Kramer, I. Itzkan, R. R. Dasari, and M. S. Feld, “Prospects for in vivo Raman spectroscopy,” Phys. Med. Biol. 45, R1–R59 (2000).
[CrossRef] [PubMed]

Other (8)

C. F. Bohren and D. R. Huffman, Absorption and Scattering of Light by Small Particles (Wiley, New York, 1983).

T.-W. Koo, “Measurement of blood analytes in turbid biological tissue using near-infrared Raman spectroscopy,” Ph.D. dissertation (Massachusetts Institute of Technology, Cambridge, Mass., 2001).

T.-W. Koo, M. Hunter, A. M. K. Enejder, J. Oh, S. Sasic, R. R. Dasari, and M. S. Feld, George R. Harrison Spectroscopy Laboratory, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Mass. 02139, are preparing a manuscript to be called “Development of a high sensitivity Raman spectroscopy system for biological studies.”

M. Diem, Introduction to Modern Vibrational Spectroscopy (Wiley, New York, 1993).

R. L. McCreery, Raman Spectroscopy for Chemical Analysis (Wiley, New York, 2000).
[CrossRef]

R. W. Boyd, Radiometry and the Detection of Optical Radiation (Wiley, New York, 1983).

G. Zhang, S. Demos, and R. Alfano, “Raman spectra of biomedical samples using optical fiber probes,” in Biomedical Sensing, Imaging, and Tracking Technologies II, T. Vo-Dinh, R. Lieberman, and G. Vurek, eds., Proc. SPIE 2976, 2–9 (1997).
[CrossRef]

G. Puppels, T. van Aken, R. Wolthuis, P. Caspers, T. Bakker Schutt, H. Bruining, T. Römer, H. Buschman, M. Wach, and J. Robinson, Jr., “In vivo tissue characterization by Raman spectroscopy,” in Infrared Spectroscopy: New Tool in Medicine, H. Mantsch and M. Jackson, eds., Proc. SPIE 3257, 78–83 (1998).

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Figures (13)

Fig. 1
Fig. 1

Transmission of the long-pass filter (peaked beyond 500 cm-1) for collection and the short-pass filter (peaked at 0 cm) for excitation, used in the Raman probe filter module, where 0 cm-1 = 830 nm.

Fig. 2
Fig. 2

Spatial distribution of Raman light emitted from normal aorta. (a) Measured (circles) discrete radial distribution β1(r) and a multi-Gaussian fit (solid curve) to the data shown as functions of distance from the excitation beam. The radial collection efficiency [η1(r c ), circles] is plotted in (b) along with a least-squares fit (solid curve) demonstrating a Gaussian profile.

Fig. 3
Fig. 3

Integrated angular distribution [η2 c ), circles] and the theoretical sin2(θ) distribution for a Lambertian source (solid curve). Theory and experiment agree well for the range of angles measured, which was limited to 20° by the collection optics. The dotted curve extends the theoretical curve to 90°.

Fig. 4
Fig. 4

Angular (dashed curve) and radial (thinner solid curve) collection efficiencies from Figs. 2(b) and 3 as a function of collection radius. The product is the total collection efficiency η T (r c ) (thicker solid curve).

Fig. 5
Fig. 5

Schematic of the Raman probe tip, showing a longitudinal view at the left and a transverse cross section at the fiber-filter interface at the right (see text for details). Ball lens B is in contact with the filter module that couples to the fiber bundle.

Fig. 6
Fig. 6

Results of simulation of the Raman probe excitation spot diameter. Slight focusing occurs 1 mm from the ball lens with no scattering (circles with solid curve), but an immediate divergence occurs when the probe is in contact with a scattering medium (squares with dashed curve). The curves represent least-squares fits with a second-order polynomial.

Fig. 7
Fig. 7

Simulated Raman probe collection efficiency as a function of Raman source radius, showing significant increases with smaller sources. Results with the probe-sample interface in air (circles with solid curve) are ∼1.75 times greater than that with a scattering medium (squares with dashed curve).

Fig. 8
Fig. 8

Schematic of the Raman spectroscopy system used for experimental testing of the Raman probe (see text for details). Details of the probe tip are presented in Fig. 5. 10 × MO, MO, microscopic objective.

Fig. 9
Fig. 9

Raman spectrum of BaSO4 collected with the single-ring probe, demonstrating the efficiency of the filter module. There is minimal evidence of fiber background in this spectrum.

Fig. 10
Fig. 10

Results of the tissue phantom studies showing signal collection as a function of the reduced transport coefficient. Intensities of the perchlorate signal of interest (circles and solid curves) are plotted along with the fiber background (squares with dashed curves). Lines connecting points of constant absorption were drawn to demonstrate the effects of signal collection with increased scattering.

Fig. 11
Fig. 11

Comparison of traditional open-air optics Raman system with optical fiber probes. Raw data are shown in (a), demonstrating intense background in an unfiltered probe (upper spectrum) but only a slightly increased background in the Raman probe (middle spectrum) compared with the open-air data (lower spectrum). The slightly increased collection efficiency from the Raman probe (b, upper spectrum) compared with that of the open air optics spectrum (b, lower spectrum) offsets the noise associated with the remaining fiber background. Removal of fiber background from the Raman probe spectrum (c, upper) and tissue fluorescence from the probe and open-air optics (c, lower) data results in identical spectra, except for the peaks at 750 and just below 1600 cm-1 that are due to probe tip components.

Fig. 12
Fig. 12

Raman spectra of (a) normal aorta, (b) noncalcified atherosclerotic plaque, and (c) calcified atherosclerotic plaque. Data are shown as filled circles with the corresponding model fit (solid curves). The residual (data fit) is plotted below on the same scale.

Fig. 13
Fig. 13

Raman spectra of (a) normal breast tissue and (b) a malignant breast tumor. Data are shown as filled circles with the corresponding model fit (solid curves). The residual is plotted below on the same scale.

Equations (5)

Equations on this page are rendered with MathJax. Learn more.

Ω=π sin2θ
PRaman=ASΩS Br, θdAdΩ,
PRamanAS β1rdA ΩS β2θdΩ=PrPθ,
ηTrc, θcη1rcη2θc=r=0rc rβ1rdrr=0 rβ1rdrθ=0θcsinθβ2θdθθ=0π/2sinθβ2θdθ,
β1r=0.348 exp-r2/0.025+0.113 exp-r2/0.200+0.557 exp-r2,

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