Abstract

We report the development of a combined confocal Raman spectroscopy (CRS) and optical coherence tomography (OCT) instrument (CRS-OCT) capable of measuring analytes in targeted biological tissues with sub-100-micron spatial resolution. The OCT subsystem was used to measure depth-resolved tissue morphology and guide the acquisition of chemically-specific Raman spectra. To demonstrate its utility, the instrument was used to accurately measure depth-resolved, physiologically-relevant concentrations of Tenofovir, a microbicide drug used to prevent the sexual transmission of HIV, in ex vivo tissue samples.

© 2015 Optical Society of America

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References

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  1. Y. Gao and D. F. Katz, “Multicompartmental pharmacokinetic model of tenofovir delivery by a vaginal gel,” PLoS ONE 8(9), e74404 (2013).
    [Crossref] [PubMed]
  2. S. O. Choi, N. Rezk, J. S. Kim, and A. D. M. Kashuba, “Development of an LC-MS method for measuring TNF in human vaginal tissue,” J. Chromatogr. Sci. 48(3), 219–223 (2010).
    [Crossref] [PubMed]
  3. D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
    [Crossref] [PubMed]
  4. J. R. Maher, V. Jaedicke, M. Medina, H. Levinson, M. A. Selim, W. J. Brown, and A. Wax, “In vivo analysis of burns in a mouse model using spectroscopic optical coherence tomography,” Opt. Lett. 39(19), 5594–5597 (2014).
    [PubMed]
  5. J. R. Maher and A. J. Berger, “Determination of ideal offset for spatially offset Raman spectroscopy,” Appl. Spectrosc. 64(1), 61–65 (2010).
    [Crossref] [PubMed]
  6. J. R. Maher, J. A. Inzana, H. A. Awad, and A. J. Berger, “Overconstrained library-based fitting method reveals age- and disease-related differences in transcutaneous Raman spectra of murine bones,” J. Biomed. Opt. 18(7), 077001 (2013).
    [Crossref] [PubMed]
  7. J. R. Maher, M. Takahata, H. A. Awad, and A. J. Berger, “Raman spectroscopy detects deterioration in biomechanical properties of bone in a glucocorticoid-treated mouse model of rheumatoid arthritis,” J. Biomed. Opt. 16(8), 087012 (2011).
    [Crossref] [PubMed]
  8. J. R. Maher, T. E. Matthews, A. K. Reid, D. F. Katz, and A. Wax, “Sensitivity of coded aperture Raman spectroscopy to analytes beneath turbid biological tissue and tissue-simulating phantoms,” J. Biomed. Opt. 19(11), 117001 (2014).
    [Crossref] [PubMed]
  9. J. A. Inzana, J. R. Maher, M. Takahata, E. M. Schwarz, A. J. Berger, and H. A. Awad, “Bone fragility beyond strength and mineral density: Raman spectroscopy predicts femoral fracture toughness in a murine model of rheumatoid arthritis,” J. Biomech. 46(4), 723–730 (2013).
    [Crossref] [PubMed]
  10. M. Takahata, J. R. Maher, S. C. Juneja, J. Inzana, L. Xing, E. M. Schwarz, A. J. Berger, and H. A. Awad, “Mechanisms of bone fragility in a mouse model of glucocorticoid-treated rheumatoid arthritis: implications for insufficiency fracture risk,” Arthritis Rheum. 64(11), 3649–3659 (2012).
    [Crossref] [PubMed]
  11. E. E. Beier, J. R. Maher, T. J. Sheu, D. A. Cory-Slechta, A. J. Berger, M. J. Zuscik, and J. E. Puzas, “Heavy metal lead exposure, osteoporotic-like phenotype in an animal model, and depression of Wnt signaling,” Environ. Health Perspect. 121(1), 97–104 (2013).
    [PubMed]
  12. P. J. Caspers, G. W. Lucassen, E. A. Carter, H. A. Bruining, and G. J. Puppels, “In vivo confocal Raman microspectroscopy of the skin: noninvasive determination of molecular concentration profiles,” J. Invest. Dermatol. 116(3), 434–442 (2001).
    [Crossref] [PubMed]
  13. O. Chuchuen, M. H. Henderson, C. Sykes, M. S. Kim, A. D. M. Kashuba, and D. F. Katz, “Quantitative analysis of microbicide concentrations in fluids, gels and tissues using confocal Raman spectroscopy,” PLoS ONE 8(12), e85124 (2013).
    [Crossref] [PubMed]
  14. C. A. Patil, N. Bosschaart, M. D. Keller, T. G. van Leeuwen, and A. Mahadevan-Jansen, “Combined Raman spectroscopy and optical coherence tomography device for tissue characterization,” Opt. Lett. 33(10), 1135–1137 (2008).
    [Crossref] [PubMed]
  15. J. W. Evans, R. J. Zawadzki, R. Liu, J. W. Chan, S. M. Lane, and J. S. Werner, “Optical coherence tomography and Raman spectroscopy of the ex-vivo retina,” J. Biophotonics 2(6-7), 398–406 (2009).
    [Crossref] [PubMed]
  16. C. A. Patil, J. Kalkman, D. J. Faber, J. S. Nyman, T. G. van Leeuwen, and A. Mahadevan-Jansen, “Integrated system for combined Raman spectroscopy-spectral domain optical coherence tomography,” J. Biomed. Opt. 16(1), 011007 (2011).
    [Crossref] [PubMed]
  17. C. A. Patil, H. Kirshnamoorthi, D. L. Ellis, T. G. van Leeuwen, and A. Mahadevan-Jansen, “A clinical instrument for combined Raman spectroscopy-optical coherence tomography of skin cancers,” Lasers Surg. Med. 43(2), 143–151 (2011).
    [Crossref] [PubMed]
  18. K. M. Khan, H. Krishna, S. K. Majumder, K. D. Rao, and P. K. Gupta, “Depth-sensitive Raman spectroscopy combined with optical coherence tomography for layered tissue analysis,” J. Biophotonics 7(1-2), 77–85 (2014).
    [Crossref] [PubMed]
  19. American National Standard for the Safe Use of Lasers Z136. 1-2007,” (Laser Institute of America, Orlando, FL, 2007).
  20. A. F. Fercher, W. Drexler, C. K. Hitzenberger, and T. Lasser, “Optical coherence tomography - principles and applications,” Rep. Prog. Phys. 66(2), 239–303 (2003).
    [Crossref]
  21. C. Akcay, P. Parrein, and J. P. Rolland, “Estimation of longitudinal resolution in optical coherence imaging,” Appl. Opt. 41(25), 5256–5262 (2002).
    [Crossref] [PubMed]
  22. A. Fercher, C. Hitzenberger, M. Sticker, R. Zawadzki, B. Karamata, and T. Lasser, “Numerical dispersion compensation for partial coherence interferometry and optical coherence tomography,” Opt. Express 9(12), 610–615 (2001).
    [Crossref] [PubMed]
  23. Y. Zhu, N. G. Terry, J. T. Woosley, N. J. Shaheen, and A. Wax, “Design and validation of an angle-resolved low-coherence interferometry fiber probe for in vivo clinical measurements of depth-resolved nuclear morphology,” J. Biomed. Opt. 16(1), 011003 (2011).
    [Crossref] [PubMed]
  24. A. Hanna, J. C. Marshall, and T. L. Isenhour, “A GC/FT-IR compound identification system,” J. Chromatogr. Sci. 17(8), 434–440 (1979).
    [Crossref]
  25. C. A. Lieber and A. Mahadevan-Jansen, “Automated method for subtraction of fluorescence from biological Raman spectra,” Appl. Spectrosc. 57(11), 1363–1367 (2003).
    [Crossref] [PubMed]
  26. A. Savitzky and M. J. E. Golay, “Smoothing + differentiation of data by simplified least squares procedures,” Anal. Chem. 36(8), 1627–1639 (1964).
    [Crossref]
  27. N. J. Everall, “Confocal Raman microscopy: common errors and artefacts,” Analyst (Lond.) 135(10), 2512–2522 (2010).
    [Crossref] [PubMed]
  28. B. W. Pogue and M. S. Patterson, “Review of tissue simulating phantoms for optical spectroscopy, imaging and dosimetry,” J. Biomed. Opt. 11(4), 041102 (2006).
    [Crossref] [PubMed]
  29. G. J. Tearney, M. E. Brezinski, J. F. Southern, B. E. Bouma, M. R. Hee, and J. G. Fujimoto, “Determination of the refractive index of highly scattering human tissue by optical coherence tomography,” Opt. Lett. 20(21), 2258–2260 (1995).
    [Crossref] [PubMed]
  30. W. F. Cheong, S. A. Prahl, and A. J. Welch, “A review of the optical-properties of biological tissues,” IEEE J. Quantum Electron. 26(12), 2166–2185 (1990).
    [Crossref]
  31. A. N. Bashkatov, E. A. Genina, and V. V. Tuchin, “Optical properties of skin, subcutaneous, and muscle tissues: a review,” J. Innov. Opt. Health Sci. 4(1), 9–38 (2011).
    [Crossref]
  32. S. L. Jacques, “Optical properties of biological tissues: a review,” Phys. Med. Biol. 58(11), R37–R61 (2013).
    [Crossref] [PubMed]
  33. A. N. Bashkatov, E. A. Genina, V. I. Kochubey, and V. V. Tuchin, “Optical properties of human skin, subcutaneous and mucous tissues in the wavelength range from 400 to 2000 nm,” J. Phys. D Appl. Phys. 38(15), 2543–2555 (2005).
    [Crossref]
  34. D. M. Haaland and E. V. Thomas, “Partial least-squares methods for spectral analyses. 1. relation to other quantitative calibration methods and the extraction of qualitative information,” Anal. Chem. 60(11), 1193–1202 (1988).
    [Crossref]
  35. A. J. Berger, T. W. Koo, I. Itzkan, and M. S. Feld, “An enhanced algorithm for linear multivariate calibration,” Anal. Chem. 70(3), 623–627 (1998).
    [Crossref] [PubMed]
  36. A. J. Berger and M. S. Feld, “Analytical method of estimating chemometric prediction error,” Appl. Spectrosc. 51(5), 725–732 (1997).
    [Crossref]
  37. T. T. Nguyen, C. Gobinet, J. Feru, S. Brassart-Pasco, M. Manfait, and O. Piot, “Characterization of Type I and IV collagens by Raman microspectroscopy: identification of spectral markers of the dermo-epidermal junction,” Spectrosc. Int. J. 27, 421–427 (2012).
    [Crossref]
  38. A. C. S. Talari, Z. Movasaghi, S. Rehman, and I. U. Rehman, “Raman Spectroscopy of Biological Tissues,” Appl. Spectrosc. Rev. 50(1), 46–111 (2015).
    [Crossref]

2015 (1)

A. C. S. Talari, Z. Movasaghi, S. Rehman, and I. U. Rehman, “Raman Spectroscopy of Biological Tissues,” Appl. Spectrosc. Rev. 50(1), 46–111 (2015).
[Crossref]

2014 (3)

J. R. Maher, V. Jaedicke, M. Medina, H. Levinson, M. A. Selim, W. J. Brown, and A. Wax, “In vivo analysis of burns in a mouse model using spectroscopic optical coherence tomography,” Opt. Lett. 39(19), 5594–5597 (2014).
[PubMed]

J. R. Maher, T. E. Matthews, A. K. Reid, D. F. Katz, and A. Wax, “Sensitivity of coded aperture Raman spectroscopy to analytes beneath turbid biological tissue and tissue-simulating phantoms,” J. Biomed. Opt. 19(11), 117001 (2014).
[Crossref] [PubMed]

K. M. Khan, H. Krishna, S. K. Majumder, K. D. Rao, and P. K. Gupta, “Depth-sensitive Raman spectroscopy combined with optical coherence tomography for layered tissue analysis,” J. Biophotonics 7(1-2), 77–85 (2014).
[Crossref] [PubMed]

2013 (6)

E. E. Beier, J. R. Maher, T. J. Sheu, D. A. Cory-Slechta, A. J. Berger, M. J. Zuscik, and J. E. Puzas, “Heavy metal lead exposure, osteoporotic-like phenotype in an animal model, and depression of Wnt signaling,” Environ. Health Perspect. 121(1), 97–104 (2013).
[PubMed]

O. Chuchuen, M. H. Henderson, C. Sykes, M. S. Kim, A. D. M. Kashuba, and D. F. Katz, “Quantitative analysis of microbicide concentrations in fluids, gels and tissues using confocal Raman spectroscopy,” PLoS ONE 8(12), e85124 (2013).
[Crossref] [PubMed]

J. A. Inzana, J. R. Maher, M. Takahata, E. M. Schwarz, A. J. Berger, and H. A. Awad, “Bone fragility beyond strength and mineral density: Raman spectroscopy predicts femoral fracture toughness in a murine model of rheumatoid arthritis,” J. Biomech. 46(4), 723–730 (2013).
[Crossref] [PubMed]

J. R. Maher, J. A. Inzana, H. A. Awad, and A. J. Berger, “Overconstrained library-based fitting method reveals age- and disease-related differences in transcutaneous Raman spectra of murine bones,” J. Biomed. Opt. 18(7), 077001 (2013).
[Crossref] [PubMed]

Y. Gao and D. F. Katz, “Multicompartmental pharmacokinetic model of tenofovir delivery by a vaginal gel,” PLoS ONE 8(9), e74404 (2013).
[Crossref] [PubMed]

S. L. Jacques, “Optical properties of biological tissues: a review,” Phys. Med. Biol. 58(11), R37–R61 (2013).
[Crossref] [PubMed]

2012 (2)

M. Takahata, J. R. Maher, S. C. Juneja, J. Inzana, L. Xing, E. M. Schwarz, A. J. Berger, and H. A. Awad, “Mechanisms of bone fragility in a mouse model of glucocorticoid-treated rheumatoid arthritis: implications for insufficiency fracture risk,” Arthritis Rheum. 64(11), 3649–3659 (2012).
[Crossref] [PubMed]

T. T. Nguyen, C. Gobinet, J. Feru, S. Brassart-Pasco, M. Manfait, and O. Piot, “Characterization of Type I and IV collagens by Raman microspectroscopy: identification of spectral markers of the dermo-epidermal junction,” Spectrosc. Int. J. 27, 421–427 (2012).
[Crossref]

2011 (5)

J. R. Maher, M. Takahata, H. A. Awad, and A. J. Berger, “Raman spectroscopy detects deterioration in biomechanical properties of bone in a glucocorticoid-treated mouse model of rheumatoid arthritis,” J. Biomed. Opt. 16(8), 087012 (2011).
[Crossref] [PubMed]

A. N. Bashkatov, E. A. Genina, and V. V. Tuchin, “Optical properties of skin, subcutaneous, and muscle tissues: a review,” J. Innov. Opt. Health Sci. 4(1), 9–38 (2011).
[Crossref]

C. A. Patil, J. Kalkman, D. J. Faber, J. S. Nyman, T. G. van Leeuwen, and A. Mahadevan-Jansen, “Integrated system for combined Raman spectroscopy-spectral domain optical coherence tomography,” J. Biomed. Opt. 16(1), 011007 (2011).
[Crossref] [PubMed]

C. A. Patil, H. Kirshnamoorthi, D. L. Ellis, T. G. van Leeuwen, and A. Mahadevan-Jansen, “A clinical instrument for combined Raman spectroscopy-optical coherence tomography of skin cancers,” Lasers Surg. Med. 43(2), 143–151 (2011).
[Crossref] [PubMed]

Y. Zhu, N. G. Terry, J. T. Woosley, N. J. Shaheen, and A. Wax, “Design and validation of an angle-resolved low-coherence interferometry fiber probe for in vivo clinical measurements of depth-resolved nuclear morphology,” J. Biomed. Opt. 16(1), 011003 (2011).
[Crossref] [PubMed]

2010 (3)

N. J. Everall, “Confocal Raman microscopy: common errors and artefacts,” Analyst (Lond.) 135(10), 2512–2522 (2010).
[Crossref] [PubMed]

S. O. Choi, N. Rezk, J. S. Kim, and A. D. M. Kashuba, “Development of an LC-MS method for measuring TNF in human vaginal tissue,” J. Chromatogr. Sci. 48(3), 219–223 (2010).
[Crossref] [PubMed]

J. R. Maher and A. J. Berger, “Determination of ideal offset for spatially offset Raman spectroscopy,” Appl. Spectrosc. 64(1), 61–65 (2010).
[Crossref] [PubMed]

2009 (1)

J. W. Evans, R. J. Zawadzki, R. Liu, J. W. Chan, S. M. Lane, and J. S. Werner, “Optical coherence tomography and Raman spectroscopy of the ex-vivo retina,” J. Biophotonics 2(6-7), 398–406 (2009).
[Crossref] [PubMed]

2008 (1)

2006 (1)

B. W. Pogue and M. S. Patterson, “Review of tissue simulating phantoms for optical spectroscopy, imaging and dosimetry,” J. Biomed. Opt. 11(4), 041102 (2006).
[Crossref] [PubMed]

2005 (1)

A. N. Bashkatov, E. A. Genina, V. I. Kochubey, and V. V. Tuchin, “Optical properties of human skin, subcutaneous and mucous tissues in the wavelength range from 400 to 2000 nm,” J. Phys. D Appl. Phys. 38(15), 2543–2555 (2005).
[Crossref]

2003 (2)

C. A. Lieber and A. Mahadevan-Jansen, “Automated method for subtraction of fluorescence from biological Raman spectra,” Appl. Spectrosc. 57(11), 1363–1367 (2003).
[Crossref] [PubMed]

A. F. Fercher, W. Drexler, C. K. Hitzenberger, and T. Lasser, “Optical coherence tomography - principles and applications,” Rep. Prog. Phys. 66(2), 239–303 (2003).
[Crossref]

2002 (1)

2001 (2)

A. Fercher, C. Hitzenberger, M. Sticker, R. Zawadzki, B. Karamata, and T. Lasser, “Numerical dispersion compensation for partial coherence interferometry and optical coherence tomography,” Opt. Express 9(12), 610–615 (2001).
[Crossref] [PubMed]

P. J. Caspers, G. W. Lucassen, E. A. Carter, H. A. Bruining, and G. J. Puppels, “In vivo confocal Raman microspectroscopy of the skin: noninvasive determination of molecular concentration profiles,” J. Invest. Dermatol. 116(3), 434–442 (2001).
[Crossref] [PubMed]

1998 (1)

A. J. Berger, T. W. Koo, I. Itzkan, and M. S. Feld, “An enhanced algorithm for linear multivariate calibration,” Anal. Chem. 70(3), 623–627 (1998).
[Crossref] [PubMed]

1997 (1)

1995 (1)

1991 (1)

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[Crossref] [PubMed]

1990 (1)

W. F. Cheong, S. A. Prahl, and A. J. Welch, “A review of the optical-properties of biological tissues,” IEEE J. Quantum Electron. 26(12), 2166–2185 (1990).
[Crossref]

1988 (1)

D. M. Haaland and E. V. Thomas, “Partial least-squares methods for spectral analyses. 1. relation to other quantitative calibration methods and the extraction of qualitative information,” Anal. Chem. 60(11), 1193–1202 (1988).
[Crossref]

1979 (1)

A. Hanna, J. C. Marshall, and T. L. Isenhour, “A GC/FT-IR compound identification system,” J. Chromatogr. Sci. 17(8), 434–440 (1979).
[Crossref]

1964 (1)

A. Savitzky and M. J. E. Golay, “Smoothing + differentiation of data by simplified least squares procedures,” Anal. Chem. 36(8), 1627–1639 (1964).
[Crossref]

Akcay, C.

Awad, H. A.

J. R. Maher, J. A. Inzana, H. A. Awad, and A. J. Berger, “Overconstrained library-based fitting method reveals age- and disease-related differences in transcutaneous Raman spectra of murine bones,” J. Biomed. Opt. 18(7), 077001 (2013).
[Crossref] [PubMed]

J. A. Inzana, J. R. Maher, M. Takahata, E. M. Schwarz, A. J. Berger, and H. A. Awad, “Bone fragility beyond strength and mineral density: Raman spectroscopy predicts femoral fracture toughness in a murine model of rheumatoid arthritis,” J. Biomech. 46(4), 723–730 (2013).
[Crossref] [PubMed]

M. Takahata, J. R. Maher, S. C. Juneja, J. Inzana, L. Xing, E. M. Schwarz, A. J. Berger, and H. A. Awad, “Mechanisms of bone fragility in a mouse model of glucocorticoid-treated rheumatoid arthritis: implications for insufficiency fracture risk,” Arthritis Rheum. 64(11), 3649–3659 (2012).
[Crossref] [PubMed]

J. R. Maher, M. Takahata, H. A. Awad, and A. J. Berger, “Raman spectroscopy detects deterioration in biomechanical properties of bone in a glucocorticoid-treated mouse model of rheumatoid arthritis,” J. Biomed. Opt. 16(8), 087012 (2011).
[Crossref] [PubMed]

Bashkatov, A. N.

A. N. Bashkatov, E. A. Genina, and V. V. Tuchin, “Optical properties of skin, subcutaneous, and muscle tissues: a review,” J. Innov. Opt. Health Sci. 4(1), 9–38 (2011).
[Crossref]

A. N. Bashkatov, E. A. Genina, V. I. Kochubey, and V. V. Tuchin, “Optical properties of human skin, subcutaneous and mucous tissues in the wavelength range from 400 to 2000 nm,” J. Phys. D Appl. Phys. 38(15), 2543–2555 (2005).
[Crossref]

Beier, E. E.

E. E. Beier, J. R. Maher, T. J. Sheu, D. A. Cory-Slechta, A. J. Berger, M. J. Zuscik, and J. E. Puzas, “Heavy metal lead exposure, osteoporotic-like phenotype in an animal model, and depression of Wnt signaling,” Environ. Health Perspect. 121(1), 97–104 (2013).
[PubMed]

Berger, A. J.

E. E. Beier, J. R. Maher, T. J. Sheu, D. A. Cory-Slechta, A. J. Berger, M. J. Zuscik, and J. E. Puzas, “Heavy metal lead exposure, osteoporotic-like phenotype in an animal model, and depression of Wnt signaling,” Environ. Health Perspect. 121(1), 97–104 (2013).
[PubMed]

J. R. Maher, J. A. Inzana, H. A. Awad, and A. J. Berger, “Overconstrained library-based fitting method reveals age- and disease-related differences in transcutaneous Raman spectra of murine bones,” J. Biomed. Opt. 18(7), 077001 (2013).
[Crossref] [PubMed]

J. A. Inzana, J. R. Maher, M. Takahata, E. M. Schwarz, A. J. Berger, and H. A. Awad, “Bone fragility beyond strength and mineral density: Raman spectroscopy predicts femoral fracture toughness in a murine model of rheumatoid arthritis,” J. Biomech. 46(4), 723–730 (2013).
[Crossref] [PubMed]

M. Takahata, J. R. Maher, S. C. Juneja, J. Inzana, L. Xing, E. M. Schwarz, A. J. Berger, and H. A. Awad, “Mechanisms of bone fragility in a mouse model of glucocorticoid-treated rheumatoid arthritis: implications for insufficiency fracture risk,” Arthritis Rheum. 64(11), 3649–3659 (2012).
[Crossref] [PubMed]

J. R. Maher, M. Takahata, H. A. Awad, and A. J. Berger, “Raman spectroscopy detects deterioration in biomechanical properties of bone in a glucocorticoid-treated mouse model of rheumatoid arthritis,” J. Biomed. Opt. 16(8), 087012 (2011).
[Crossref] [PubMed]

J. R. Maher and A. J. Berger, “Determination of ideal offset for spatially offset Raman spectroscopy,” Appl. Spectrosc. 64(1), 61–65 (2010).
[Crossref] [PubMed]

A. J. Berger, T. W. Koo, I. Itzkan, and M. S. Feld, “An enhanced algorithm for linear multivariate calibration,” Anal. Chem. 70(3), 623–627 (1998).
[Crossref] [PubMed]

A. J. Berger and M. S. Feld, “Analytical method of estimating chemometric prediction error,” Appl. Spectrosc. 51(5), 725–732 (1997).
[Crossref]

Bosschaart, N.

Bouma, B. E.

Brassart-Pasco, S.

T. T. Nguyen, C. Gobinet, J. Feru, S. Brassart-Pasco, M. Manfait, and O. Piot, “Characterization of Type I and IV collagens by Raman microspectroscopy: identification of spectral markers of the dermo-epidermal junction,” Spectrosc. Int. J. 27, 421–427 (2012).
[Crossref]

Brezinski, M. E.

Brown, W. J.

Bruining, H. A.

P. J. Caspers, G. W. Lucassen, E. A. Carter, H. A. Bruining, and G. J. Puppels, “In vivo confocal Raman microspectroscopy of the skin: noninvasive determination of molecular concentration profiles,” J. Invest. Dermatol. 116(3), 434–442 (2001).
[Crossref] [PubMed]

Carter, E. A.

P. J. Caspers, G. W. Lucassen, E. A. Carter, H. A. Bruining, and G. J. Puppels, “In vivo confocal Raman microspectroscopy of the skin: noninvasive determination of molecular concentration profiles,” J. Invest. Dermatol. 116(3), 434–442 (2001).
[Crossref] [PubMed]

Caspers, P. J.

P. J. Caspers, G. W. Lucassen, E. A. Carter, H. A. Bruining, and G. J. Puppels, “In vivo confocal Raman microspectroscopy of the skin: noninvasive determination of molecular concentration profiles,” J. Invest. Dermatol. 116(3), 434–442 (2001).
[Crossref] [PubMed]

Chan, J. W.

J. W. Evans, R. J. Zawadzki, R. Liu, J. W. Chan, S. M. Lane, and J. S. Werner, “Optical coherence tomography and Raman spectroscopy of the ex-vivo retina,” J. Biophotonics 2(6-7), 398–406 (2009).
[Crossref] [PubMed]

Chang, W.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[Crossref] [PubMed]

Cheong, W. F.

W. F. Cheong, S. A. Prahl, and A. J. Welch, “A review of the optical-properties of biological tissues,” IEEE J. Quantum Electron. 26(12), 2166–2185 (1990).
[Crossref]

Choi, S. O.

S. O. Choi, N. Rezk, J. S. Kim, and A. D. M. Kashuba, “Development of an LC-MS method for measuring TNF in human vaginal tissue,” J. Chromatogr. Sci. 48(3), 219–223 (2010).
[Crossref] [PubMed]

Chuchuen, O.

O. Chuchuen, M. H. Henderson, C. Sykes, M. S. Kim, A. D. M. Kashuba, and D. F. Katz, “Quantitative analysis of microbicide concentrations in fluids, gels and tissues using confocal Raman spectroscopy,” PLoS ONE 8(12), e85124 (2013).
[Crossref] [PubMed]

Cory-Slechta, D. A.

E. E. Beier, J. R. Maher, T. J. Sheu, D. A. Cory-Slechta, A. J. Berger, M. J. Zuscik, and J. E. Puzas, “Heavy metal lead exposure, osteoporotic-like phenotype in an animal model, and depression of Wnt signaling,” Environ. Health Perspect. 121(1), 97–104 (2013).
[PubMed]

Drexler, W.

A. F. Fercher, W. Drexler, C. K. Hitzenberger, and T. Lasser, “Optical coherence tomography - principles and applications,” Rep. Prog. Phys. 66(2), 239–303 (2003).
[Crossref]

Ellis, D. L.

C. A. Patil, H. Kirshnamoorthi, D. L. Ellis, T. G. van Leeuwen, and A. Mahadevan-Jansen, “A clinical instrument for combined Raman spectroscopy-optical coherence tomography of skin cancers,” Lasers Surg. Med. 43(2), 143–151 (2011).
[Crossref] [PubMed]

Evans, J. W.

J. W. Evans, R. J. Zawadzki, R. Liu, J. W. Chan, S. M. Lane, and J. S. Werner, “Optical coherence tomography and Raman spectroscopy of the ex-vivo retina,” J. Biophotonics 2(6-7), 398–406 (2009).
[Crossref] [PubMed]

Everall, N. J.

N. J. Everall, “Confocal Raman microscopy: common errors and artefacts,” Analyst (Lond.) 135(10), 2512–2522 (2010).
[Crossref] [PubMed]

Faber, D. J.

C. A. Patil, J. Kalkman, D. J. Faber, J. S. Nyman, T. G. van Leeuwen, and A. Mahadevan-Jansen, “Integrated system for combined Raman spectroscopy-spectral domain optical coherence tomography,” J. Biomed. Opt. 16(1), 011007 (2011).
[Crossref] [PubMed]

Feld, M. S.

A. J. Berger, T. W. Koo, I. Itzkan, and M. S. Feld, “An enhanced algorithm for linear multivariate calibration,” Anal. Chem. 70(3), 623–627 (1998).
[Crossref] [PubMed]

A. J. Berger and M. S. Feld, “Analytical method of estimating chemometric prediction error,” Appl. Spectrosc. 51(5), 725–732 (1997).
[Crossref]

Fercher, A.

Fercher, A. F.

A. F. Fercher, W. Drexler, C. K. Hitzenberger, and T. Lasser, “Optical coherence tomography - principles and applications,” Rep. Prog. Phys. 66(2), 239–303 (2003).
[Crossref]

Feru, J.

T. T. Nguyen, C. Gobinet, J. Feru, S. Brassart-Pasco, M. Manfait, and O. Piot, “Characterization of Type I and IV collagens by Raman microspectroscopy: identification of spectral markers of the dermo-epidermal junction,” Spectrosc. Int. J. 27, 421–427 (2012).
[Crossref]

Flotte, T.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[Crossref] [PubMed]

Fujimoto, J. G.

G. J. Tearney, M. E. Brezinski, J. F. Southern, B. E. Bouma, M. R. Hee, and J. G. Fujimoto, “Determination of the refractive index of highly scattering human tissue by optical coherence tomography,” Opt. Lett. 20(21), 2258–2260 (1995).
[Crossref] [PubMed]

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[Crossref] [PubMed]

Gao, Y.

Y. Gao and D. F. Katz, “Multicompartmental pharmacokinetic model of tenofovir delivery by a vaginal gel,” PLoS ONE 8(9), e74404 (2013).
[Crossref] [PubMed]

Genina, E. A.

A. N. Bashkatov, E. A. Genina, and V. V. Tuchin, “Optical properties of skin, subcutaneous, and muscle tissues: a review,” J. Innov. Opt. Health Sci. 4(1), 9–38 (2011).
[Crossref]

A. N. Bashkatov, E. A. Genina, V. I. Kochubey, and V. V. Tuchin, “Optical properties of human skin, subcutaneous and mucous tissues in the wavelength range from 400 to 2000 nm,” J. Phys. D Appl. Phys. 38(15), 2543–2555 (2005).
[Crossref]

Gobinet, C.

T. T. Nguyen, C. Gobinet, J. Feru, S. Brassart-Pasco, M. Manfait, and O. Piot, “Characterization of Type I and IV collagens by Raman microspectroscopy: identification of spectral markers of the dermo-epidermal junction,” Spectrosc. Int. J. 27, 421–427 (2012).
[Crossref]

Golay, M. J. E.

A. Savitzky and M. J. E. Golay, “Smoothing + differentiation of data by simplified least squares procedures,” Anal. Chem. 36(8), 1627–1639 (1964).
[Crossref]

Gregory, K.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[Crossref] [PubMed]

Gupta, P. K.

K. M. Khan, H. Krishna, S. K. Majumder, K. D. Rao, and P. K. Gupta, “Depth-sensitive Raman spectroscopy combined with optical coherence tomography for layered tissue analysis,” J. Biophotonics 7(1-2), 77–85 (2014).
[Crossref] [PubMed]

Haaland, D. M.

D. M. Haaland and E. V. Thomas, “Partial least-squares methods for spectral analyses. 1. relation to other quantitative calibration methods and the extraction of qualitative information,” Anal. Chem. 60(11), 1193–1202 (1988).
[Crossref]

Hanna, A.

A. Hanna, J. C. Marshall, and T. L. Isenhour, “A GC/FT-IR compound identification system,” J. Chromatogr. Sci. 17(8), 434–440 (1979).
[Crossref]

Hee, M. R.

G. J. Tearney, M. E. Brezinski, J. F. Southern, B. E. Bouma, M. R. Hee, and J. G. Fujimoto, “Determination of the refractive index of highly scattering human tissue by optical coherence tomography,” Opt. Lett. 20(21), 2258–2260 (1995).
[Crossref] [PubMed]

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[Crossref] [PubMed]

Henderson, M. H.

O. Chuchuen, M. H. Henderson, C. Sykes, M. S. Kim, A. D. M. Kashuba, and D. F. Katz, “Quantitative analysis of microbicide concentrations in fluids, gels and tissues using confocal Raman spectroscopy,” PLoS ONE 8(12), e85124 (2013).
[Crossref] [PubMed]

Hitzenberger, C.

Hitzenberger, C. K.

A. F. Fercher, W. Drexler, C. K. Hitzenberger, and T. Lasser, “Optical coherence tomography - principles and applications,” Rep. Prog. Phys. 66(2), 239–303 (2003).
[Crossref]

Huang, D.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[Crossref] [PubMed]

Inzana, J.

M. Takahata, J. R. Maher, S. C. Juneja, J. Inzana, L. Xing, E. M. Schwarz, A. J. Berger, and H. A. Awad, “Mechanisms of bone fragility in a mouse model of glucocorticoid-treated rheumatoid arthritis: implications for insufficiency fracture risk,” Arthritis Rheum. 64(11), 3649–3659 (2012).
[Crossref] [PubMed]

Inzana, J. A.

J. A. Inzana, J. R. Maher, M. Takahata, E. M. Schwarz, A. J. Berger, and H. A. Awad, “Bone fragility beyond strength and mineral density: Raman spectroscopy predicts femoral fracture toughness in a murine model of rheumatoid arthritis,” J. Biomech. 46(4), 723–730 (2013).
[Crossref] [PubMed]

J. R. Maher, J. A. Inzana, H. A. Awad, and A. J. Berger, “Overconstrained library-based fitting method reveals age- and disease-related differences in transcutaneous Raman spectra of murine bones,” J. Biomed. Opt. 18(7), 077001 (2013).
[Crossref] [PubMed]

Isenhour, T. L.

A. Hanna, J. C. Marshall, and T. L. Isenhour, “A GC/FT-IR compound identification system,” J. Chromatogr. Sci. 17(8), 434–440 (1979).
[Crossref]

Itzkan, I.

A. J. Berger, T. W. Koo, I. Itzkan, and M. S. Feld, “An enhanced algorithm for linear multivariate calibration,” Anal. Chem. 70(3), 623–627 (1998).
[Crossref] [PubMed]

Jacques, S. L.

S. L. Jacques, “Optical properties of biological tissues: a review,” Phys. Med. Biol. 58(11), R37–R61 (2013).
[Crossref] [PubMed]

Jaedicke, V.

Juneja, S. C.

M. Takahata, J. R. Maher, S. C. Juneja, J. Inzana, L. Xing, E. M. Schwarz, A. J. Berger, and H. A. Awad, “Mechanisms of bone fragility in a mouse model of glucocorticoid-treated rheumatoid arthritis: implications for insufficiency fracture risk,” Arthritis Rheum. 64(11), 3649–3659 (2012).
[Crossref] [PubMed]

Kalkman, J.

C. A. Patil, J. Kalkman, D. J. Faber, J. S. Nyman, T. G. van Leeuwen, and A. Mahadevan-Jansen, “Integrated system for combined Raman spectroscopy-spectral domain optical coherence tomography,” J. Biomed. Opt. 16(1), 011007 (2011).
[Crossref] [PubMed]

Karamata, B.

Kashuba, A. D. M.

O. Chuchuen, M. H. Henderson, C. Sykes, M. S. Kim, A. D. M. Kashuba, and D. F. Katz, “Quantitative analysis of microbicide concentrations in fluids, gels and tissues using confocal Raman spectroscopy,” PLoS ONE 8(12), e85124 (2013).
[Crossref] [PubMed]

S. O. Choi, N. Rezk, J. S. Kim, and A. D. M. Kashuba, “Development of an LC-MS method for measuring TNF in human vaginal tissue,” J. Chromatogr. Sci. 48(3), 219–223 (2010).
[Crossref] [PubMed]

Katz, D. F.

J. R. Maher, T. E. Matthews, A. K. Reid, D. F. Katz, and A. Wax, “Sensitivity of coded aperture Raman spectroscopy to analytes beneath turbid biological tissue and tissue-simulating phantoms,” J. Biomed. Opt. 19(11), 117001 (2014).
[Crossref] [PubMed]

O. Chuchuen, M. H. Henderson, C. Sykes, M. S. Kim, A. D. M. Kashuba, and D. F. Katz, “Quantitative analysis of microbicide concentrations in fluids, gels and tissues using confocal Raman spectroscopy,” PLoS ONE 8(12), e85124 (2013).
[Crossref] [PubMed]

Y. Gao and D. F. Katz, “Multicompartmental pharmacokinetic model of tenofovir delivery by a vaginal gel,” PLoS ONE 8(9), e74404 (2013).
[Crossref] [PubMed]

Keller, M. D.

Khan, K. M.

K. M. Khan, H. Krishna, S. K. Majumder, K. D. Rao, and P. K. Gupta, “Depth-sensitive Raman spectroscopy combined with optical coherence tomography for layered tissue analysis,” J. Biophotonics 7(1-2), 77–85 (2014).
[Crossref] [PubMed]

Kim, J. S.

S. O. Choi, N. Rezk, J. S. Kim, and A. D. M. Kashuba, “Development of an LC-MS method for measuring TNF in human vaginal tissue,” J. Chromatogr. Sci. 48(3), 219–223 (2010).
[Crossref] [PubMed]

Kim, M. S.

O. Chuchuen, M. H. Henderson, C. Sykes, M. S. Kim, A. D. M. Kashuba, and D. F. Katz, “Quantitative analysis of microbicide concentrations in fluids, gels and tissues using confocal Raman spectroscopy,” PLoS ONE 8(12), e85124 (2013).
[Crossref] [PubMed]

Kirshnamoorthi, H.

C. A. Patil, H. Kirshnamoorthi, D. L. Ellis, T. G. van Leeuwen, and A. Mahadevan-Jansen, “A clinical instrument for combined Raman spectroscopy-optical coherence tomography of skin cancers,” Lasers Surg. Med. 43(2), 143–151 (2011).
[Crossref] [PubMed]

Kochubey, V. I.

A. N. Bashkatov, E. A. Genina, V. I. Kochubey, and V. V. Tuchin, “Optical properties of human skin, subcutaneous and mucous tissues in the wavelength range from 400 to 2000 nm,” J. Phys. D Appl. Phys. 38(15), 2543–2555 (2005).
[Crossref]

Koo, T. W.

A. J. Berger, T. W. Koo, I. Itzkan, and M. S. Feld, “An enhanced algorithm for linear multivariate calibration,” Anal. Chem. 70(3), 623–627 (1998).
[Crossref] [PubMed]

Krishna, H.

K. M. Khan, H. Krishna, S. K. Majumder, K. D. Rao, and P. K. Gupta, “Depth-sensitive Raman spectroscopy combined with optical coherence tomography for layered tissue analysis,” J. Biophotonics 7(1-2), 77–85 (2014).
[Crossref] [PubMed]

Lane, S. M.

J. W. Evans, R. J. Zawadzki, R. Liu, J. W. Chan, S. M. Lane, and J. S. Werner, “Optical coherence tomography and Raman spectroscopy of the ex-vivo retina,” J. Biophotonics 2(6-7), 398–406 (2009).
[Crossref] [PubMed]

Lasser, T.

Levinson, H.

Lieber, C. A.

Lin, C. P.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[Crossref] [PubMed]

Liu, R.

J. W. Evans, R. J. Zawadzki, R. Liu, J. W. Chan, S. M. Lane, and J. S. Werner, “Optical coherence tomography and Raman spectroscopy of the ex-vivo retina,” J. Biophotonics 2(6-7), 398–406 (2009).
[Crossref] [PubMed]

Lucassen, G. W.

P. J. Caspers, G. W. Lucassen, E. A. Carter, H. A. Bruining, and G. J. Puppels, “In vivo confocal Raman microspectroscopy of the skin: noninvasive determination of molecular concentration profiles,” J. Invest. Dermatol. 116(3), 434–442 (2001).
[Crossref] [PubMed]

Mahadevan-Jansen, A.

C. A. Patil, H. Kirshnamoorthi, D. L. Ellis, T. G. van Leeuwen, and A. Mahadevan-Jansen, “A clinical instrument for combined Raman spectroscopy-optical coherence tomography of skin cancers,” Lasers Surg. Med. 43(2), 143–151 (2011).
[Crossref] [PubMed]

C. A. Patil, J. Kalkman, D. J. Faber, J. S. Nyman, T. G. van Leeuwen, and A. Mahadevan-Jansen, “Integrated system for combined Raman spectroscopy-spectral domain optical coherence tomography,” J. Biomed. Opt. 16(1), 011007 (2011).
[Crossref] [PubMed]

C. A. Patil, N. Bosschaart, M. D. Keller, T. G. van Leeuwen, and A. Mahadevan-Jansen, “Combined Raman spectroscopy and optical coherence tomography device for tissue characterization,” Opt. Lett. 33(10), 1135–1137 (2008).
[Crossref] [PubMed]

C. A. Lieber and A. Mahadevan-Jansen, “Automated method for subtraction of fluorescence from biological Raman spectra,” Appl. Spectrosc. 57(11), 1363–1367 (2003).
[Crossref] [PubMed]

Maher, J. R.

J. R. Maher, V. Jaedicke, M. Medina, H. Levinson, M. A. Selim, W. J. Brown, and A. Wax, “In vivo analysis of burns in a mouse model using spectroscopic optical coherence tomography,” Opt. Lett. 39(19), 5594–5597 (2014).
[PubMed]

J. R. Maher, T. E. Matthews, A. K. Reid, D. F. Katz, and A. Wax, “Sensitivity of coded aperture Raman spectroscopy to analytes beneath turbid biological tissue and tissue-simulating phantoms,” J. Biomed. Opt. 19(11), 117001 (2014).
[Crossref] [PubMed]

J. R. Maher, J. A. Inzana, H. A. Awad, and A. J. Berger, “Overconstrained library-based fitting method reveals age- and disease-related differences in transcutaneous Raman spectra of murine bones,” J. Biomed. Opt. 18(7), 077001 (2013).
[Crossref] [PubMed]

J. A. Inzana, J. R. Maher, M. Takahata, E. M. Schwarz, A. J. Berger, and H. A. Awad, “Bone fragility beyond strength and mineral density: Raman spectroscopy predicts femoral fracture toughness in a murine model of rheumatoid arthritis,” J. Biomech. 46(4), 723–730 (2013).
[Crossref] [PubMed]

E. E. Beier, J. R. Maher, T. J. Sheu, D. A. Cory-Slechta, A. J. Berger, M. J. Zuscik, and J. E. Puzas, “Heavy metal lead exposure, osteoporotic-like phenotype in an animal model, and depression of Wnt signaling,” Environ. Health Perspect. 121(1), 97–104 (2013).
[PubMed]

M. Takahata, J. R. Maher, S. C. Juneja, J. Inzana, L. Xing, E. M. Schwarz, A. J. Berger, and H. A. Awad, “Mechanisms of bone fragility in a mouse model of glucocorticoid-treated rheumatoid arthritis: implications for insufficiency fracture risk,” Arthritis Rheum. 64(11), 3649–3659 (2012).
[Crossref] [PubMed]

J. R. Maher, M. Takahata, H. A. Awad, and A. J. Berger, “Raman spectroscopy detects deterioration in biomechanical properties of bone in a glucocorticoid-treated mouse model of rheumatoid arthritis,” J. Biomed. Opt. 16(8), 087012 (2011).
[Crossref] [PubMed]

J. R. Maher and A. J. Berger, “Determination of ideal offset for spatially offset Raman spectroscopy,” Appl. Spectrosc. 64(1), 61–65 (2010).
[Crossref] [PubMed]

Majumder, S. K.

K. M. Khan, H. Krishna, S. K. Majumder, K. D. Rao, and P. K. Gupta, “Depth-sensitive Raman spectroscopy combined with optical coherence tomography for layered tissue analysis,” J. Biophotonics 7(1-2), 77–85 (2014).
[Crossref] [PubMed]

Manfait, M.

T. T. Nguyen, C. Gobinet, J. Feru, S. Brassart-Pasco, M. Manfait, and O. Piot, “Characterization of Type I and IV collagens by Raman microspectroscopy: identification of spectral markers of the dermo-epidermal junction,” Spectrosc. Int. J. 27, 421–427 (2012).
[Crossref]

Marshall, J. C.

A. Hanna, J. C. Marshall, and T. L. Isenhour, “A GC/FT-IR compound identification system,” J. Chromatogr. Sci. 17(8), 434–440 (1979).
[Crossref]

Matthews, T. E.

J. R. Maher, T. E. Matthews, A. K. Reid, D. F. Katz, and A. Wax, “Sensitivity of coded aperture Raman spectroscopy to analytes beneath turbid biological tissue and tissue-simulating phantoms,” J. Biomed. Opt. 19(11), 117001 (2014).
[Crossref] [PubMed]

Medina, M.

Movasaghi, Z.

A. C. S. Talari, Z. Movasaghi, S. Rehman, and I. U. Rehman, “Raman Spectroscopy of Biological Tissues,” Appl. Spectrosc. Rev. 50(1), 46–111 (2015).
[Crossref]

Nguyen, T. T.

T. T. Nguyen, C. Gobinet, J. Feru, S. Brassart-Pasco, M. Manfait, and O. Piot, “Characterization of Type I and IV collagens by Raman microspectroscopy: identification of spectral markers of the dermo-epidermal junction,” Spectrosc. Int. J. 27, 421–427 (2012).
[Crossref]

Nyman, J. S.

C. A. Patil, J. Kalkman, D. J. Faber, J. S. Nyman, T. G. van Leeuwen, and A. Mahadevan-Jansen, “Integrated system for combined Raman spectroscopy-spectral domain optical coherence tomography,” J. Biomed. Opt. 16(1), 011007 (2011).
[Crossref] [PubMed]

Parrein, P.

Patil, C. A.

C. A. Patil, H. Kirshnamoorthi, D. L. Ellis, T. G. van Leeuwen, and A. Mahadevan-Jansen, “A clinical instrument for combined Raman spectroscopy-optical coherence tomography of skin cancers,” Lasers Surg. Med. 43(2), 143–151 (2011).
[Crossref] [PubMed]

C. A. Patil, J. Kalkman, D. J. Faber, J. S. Nyman, T. G. van Leeuwen, and A. Mahadevan-Jansen, “Integrated system for combined Raman spectroscopy-spectral domain optical coherence tomography,” J. Biomed. Opt. 16(1), 011007 (2011).
[Crossref] [PubMed]

C. A. Patil, N. Bosschaart, M. D. Keller, T. G. van Leeuwen, and A. Mahadevan-Jansen, “Combined Raman spectroscopy and optical coherence tomography device for tissue characterization,” Opt. Lett. 33(10), 1135–1137 (2008).
[Crossref] [PubMed]

Patterson, M. S.

B. W. Pogue and M. S. Patterson, “Review of tissue simulating phantoms for optical spectroscopy, imaging and dosimetry,” J. Biomed. Opt. 11(4), 041102 (2006).
[Crossref] [PubMed]

Piot, O.

T. T. Nguyen, C. Gobinet, J. Feru, S. Brassart-Pasco, M. Manfait, and O. Piot, “Characterization of Type I and IV collagens by Raman microspectroscopy: identification of spectral markers of the dermo-epidermal junction,” Spectrosc. Int. J. 27, 421–427 (2012).
[Crossref]

Pogue, B. W.

B. W. Pogue and M. S. Patterson, “Review of tissue simulating phantoms for optical spectroscopy, imaging and dosimetry,” J. Biomed. Opt. 11(4), 041102 (2006).
[Crossref] [PubMed]

Prahl, S. A.

W. F. Cheong, S. A. Prahl, and A. J. Welch, “A review of the optical-properties of biological tissues,” IEEE J. Quantum Electron. 26(12), 2166–2185 (1990).
[Crossref]

Puliafito, C. A.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[Crossref] [PubMed]

Puppels, G. J.

P. J. Caspers, G. W. Lucassen, E. A. Carter, H. A. Bruining, and G. J. Puppels, “In vivo confocal Raman microspectroscopy of the skin: noninvasive determination of molecular concentration profiles,” J. Invest. Dermatol. 116(3), 434–442 (2001).
[Crossref] [PubMed]

Puzas, J. E.

E. E. Beier, J. R. Maher, T. J. Sheu, D. A. Cory-Slechta, A. J. Berger, M. J. Zuscik, and J. E. Puzas, “Heavy metal lead exposure, osteoporotic-like phenotype in an animal model, and depression of Wnt signaling,” Environ. Health Perspect. 121(1), 97–104 (2013).
[PubMed]

Rao, K. D.

K. M. Khan, H. Krishna, S. K. Majumder, K. D. Rao, and P. K. Gupta, “Depth-sensitive Raman spectroscopy combined with optical coherence tomography for layered tissue analysis,” J. Biophotonics 7(1-2), 77–85 (2014).
[Crossref] [PubMed]

Rehman, I. U.

A. C. S. Talari, Z. Movasaghi, S. Rehman, and I. U. Rehman, “Raman Spectroscopy of Biological Tissues,” Appl. Spectrosc. Rev. 50(1), 46–111 (2015).
[Crossref]

Rehman, S.

A. C. S. Talari, Z. Movasaghi, S. Rehman, and I. U. Rehman, “Raman Spectroscopy of Biological Tissues,” Appl. Spectrosc. Rev. 50(1), 46–111 (2015).
[Crossref]

Reid, A. K.

J. R. Maher, T. E. Matthews, A. K. Reid, D. F. Katz, and A. Wax, “Sensitivity of coded aperture Raman spectroscopy to analytes beneath turbid biological tissue and tissue-simulating phantoms,” J. Biomed. Opt. 19(11), 117001 (2014).
[Crossref] [PubMed]

Rezk, N.

S. O. Choi, N. Rezk, J. S. Kim, and A. D. M. Kashuba, “Development of an LC-MS method for measuring TNF in human vaginal tissue,” J. Chromatogr. Sci. 48(3), 219–223 (2010).
[Crossref] [PubMed]

Rolland, J. P.

Savitzky, A.

A. Savitzky and M. J. E. Golay, “Smoothing + differentiation of data by simplified least squares procedures,” Anal. Chem. 36(8), 1627–1639 (1964).
[Crossref]

Schuman, J. S.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[Crossref] [PubMed]

Schwarz, E. M.

J. A. Inzana, J. R. Maher, M. Takahata, E. M. Schwarz, A. J. Berger, and H. A. Awad, “Bone fragility beyond strength and mineral density: Raman spectroscopy predicts femoral fracture toughness in a murine model of rheumatoid arthritis,” J. Biomech. 46(4), 723–730 (2013).
[Crossref] [PubMed]

M. Takahata, J. R. Maher, S. C. Juneja, J. Inzana, L. Xing, E. M. Schwarz, A. J. Berger, and H. A. Awad, “Mechanisms of bone fragility in a mouse model of glucocorticoid-treated rheumatoid arthritis: implications for insufficiency fracture risk,” Arthritis Rheum. 64(11), 3649–3659 (2012).
[Crossref] [PubMed]

Selim, M. A.

Shaheen, N. J.

Y. Zhu, N. G. Terry, J. T. Woosley, N. J. Shaheen, and A. Wax, “Design and validation of an angle-resolved low-coherence interferometry fiber probe for in vivo clinical measurements of depth-resolved nuclear morphology,” J. Biomed. Opt. 16(1), 011003 (2011).
[Crossref] [PubMed]

Sheu, T. J.

E. E. Beier, J. R. Maher, T. J. Sheu, D. A. Cory-Slechta, A. J. Berger, M. J. Zuscik, and J. E. Puzas, “Heavy metal lead exposure, osteoporotic-like phenotype in an animal model, and depression of Wnt signaling,” Environ. Health Perspect. 121(1), 97–104 (2013).
[PubMed]

Southern, J. F.

Sticker, M.

Stinson, W. G.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[Crossref] [PubMed]

Swanson, E. A.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[Crossref] [PubMed]

Sykes, C.

O. Chuchuen, M. H. Henderson, C. Sykes, M. S. Kim, A. D. M. Kashuba, and D. F. Katz, “Quantitative analysis of microbicide concentrations in fluids, gels and tissues using confocal Raman spectroscopy,” PLoS ONE 8(12), e85124 (2013).
[Crossref] [PubMed]

Takahata, M.

J. A. Inzana, J. R. Maher, M. Takahata, E. M. Schwarz, A. J. Berger, and H. A. Awad, “Bone fragility beyond strength and mineral density: Raman spectroscopy predicts femoral fracture toughness in a murine model of rheumatoid arthritis,” J. Biomech. 46(4), 723–730 (2013).
[Crossref] [PubMed]

M. Takahata, J. R. Maher, S. C. Juneja, J. Inzana, L. Xing, E. M. Schwarz, A. J. Berger, and H. A. Awad, “Mechanisms of bone fragility in a mouse model of glucocorticoid-treated rheumatoid arthritis: implications for insufficiency fracture risk,” Arthritis Rheum. 64(11), 3649–3659 (2012).
[Crossref] [PubMed]

J. R. Maher, M. Takahata, H. A. Awad, and A. J. Berger, “Raman spectroscopy detects deterioration in biomechanical properties of bone in a glucocorticoid-treated mouse model of rheumatoid arthritis,” J. Biomed. Opt. 16(8), 087012 (2011).
[Crossref] [PubMed]

Talari, A. C. S.

A. C. S. Talari, Z. Movasaghi, S. Rehman, and I. U. Rehman, “Raman Spectroscopy of Biological Tissues,” Appl. Spectrosc. Rev. 50(1), 46–111 (2015).
[Crossref]

Tearney, G. J.

Terry, N. G.

Y. Zhu, N. G. Terry, J. T. Woosley, N. J. Shaheen, and A. Wax, “Design and validation of an angle-resolved low-coherence interferometry fiber probe for in vivo clinical measurements of depth-resolved nuclear morphology,” J. Biomed. Opt. 16(1), 011003 (2011).
[Crossref] [PubMed]

Thomas, E. V.

D. M. Haaland and E. V. Thomas, “Partial least-squares methods for spectral analyses. 1. relation to other quantitative calibration methods and the extraction of qualitative information,” Anal. Chem. 60(11), 1193–1202 (1988).
[Crossref]

Tuchin, V. V.

A. N. Bashkatov, E. A. Genina, and V. V. Tuchin, “Optical properties of skin, subcutaneous, and muscle tissues: a review,” J. Innov. Opt. Health Sci. 4(1), 9–38 (2011).
[Crossref]

A. N. Bashkatov, E. A. Genina, V. I. Kochubey, and V. V. Tuchin, “Optical properties of human skin, subcutaneous and mucous tissues in the wavelength range from 400 to 2000 nm,” J. Phys. D Appl. Phys. 38(15), 2543–2555 (2005).
[Crossref]

van Leeuwen, T. G.

C. A. Patil, J. Kalkman, D. J. Faber, J. S. Nyman, T. G. van Leeuwen, and A. Mahadevan-Jansen, “Integrated system for combined Raman spectroscopy-spectral domain optical coherence tomography,” J. Biomed. Opt. 16(1), 011007 (2011).
[Crossref] [PubMed]

C. A. Patil, H. Kirshnamoorthi, D. L. Ellis, T. G. van Leeuwen, and A. Mahadevan-Jansen, “A clinical instrument for combined Raman spectroscopy-optical coherence tomography of skin cancers,” Lasers Surg. Med. 43(2), 143–151 (2011).
[Crossref] [PubMed]

C. A. Patil, N. Bosschaart, M. D. Keller, T. G. van Leeuwen, and A. Mahadevan-Jansen, “Combined Raman spectroscopy and optical coherence tomography device for tissue characterization,” Opt. Lett. 33(10), 1135–1137 (2008).
[Crossref] [PubMed]

Wax, A.

J. R. Maher, V. Jaedicke, M. Medina, H. Levinson, M. A. Selim, W. J. Brown, and A. Wax, “In vivo analysis of burns in a mouse model using spectroscopic optical coherence tomography,” Opt. Lett. 39(19), 5594–5597 (2014).
[PubMed]

J. R. Maher, T. E. Matthews, A. K. Reid, D. F. Katz, and A. Wax, “Sensitivity of coded aperture Raman spectroscopy to analytes beneath turbid biological tissue and tissue-simulating phantoms,” J. Biomed. Opt. 19(11), 117001 (2014).
[Crossref] [PubMed]

Y. Zhu, N. G. Terry, J. T. Woosley, N. J. Shaheen, and A. Wax, “Design and validation of an angle-resolved low-coherence interferometry fiber probe for in vivo clinical measurements of depth-resolved nuclear morphology,” J. Biomed. Opt. 16(1), 011003 (2011).
[Crossref] [PubMed]

Welch, A. J.

W. F. Cheong, S. A. Prahl, and A. J. Welch, “A review of the optical-properties of biological tissues,” IEEE J. Quantum Electron. 26(12), 2166–2185 (1990).
[Crossref]

Werner, J. S.

J. W. Evans, R. J. Zawadzki, R. Liu, J. W. Chan, S. M. Lane, and J. S. Werner, “Optical coherence tomography and Raman spectroscopy of the ex-vivo retina,” J. Biophotonics 2(6-7), 398–406 (2009).
[Crossref] [PubMed]

Woosley, J. T.

Y. Zhu, N. G. Terry, J. T. Woosley, N. J. Shaheen, and A. Wax, “Design and validation of an angle-resolved low-coherence interferometry fiber probe for in vivo clinical measurements of depth-resolved nuclear morphology,” J. Biomed. Opt. 16(1), 011003 (2011).
[Crossref] [PubMed]

Xing, L.

M. Takahata, J. R. Maher, S. C. Juneja, J. Inzana, L. Xing, E. M. Schwarz, A. J. Berger, and H. A. Awad, “Mechanisms of bone fragility in a mouse model of glucocorticoid-treated rheumatoid arthritis: implications for insufficiency fracture risk,” Arthritis Rheum. 64(11), 3649–3659 (2012).
[Crossref] [PubMed]

Zawadzki, R.

Zawadzki, R. J.

J. W. Evans, R. J. Zawadzki, R. Liu, J. W. Chan, S. M. Lane, and J. S. Werner, “Optical coherence tomography and Raman spectroscopy of the ex-vivo retina,” J. Biophotonics 2(6-7), 398–406 (2009).
[Crossref] [PubMed]

Zhu, Y.

Y. Zhu, N. G. Terry, J. T. Woosley, N. J. Shaheen, and A. Wax, “Design and validation of an angle-resolved low-coherence interferometry fiber probe for in vivo clinical measurements of depth-resolved nuclear morphology,” J. Biomed. Opt. 16(1), 011003 (2011).
[Crossref] [PubMed]

Zuscik, M. J.

E. E. Beier, J. R. Maher, T. J. Sheu, D. A. Cory-Slechta, A. J. Berger, M. J. Zuscik, and J. E. Puzas, “Heavy metal lead exposure, osteoporotic-like phenotype in an animal model, and depression of Wnt signaling,” Environ. Health Perspect. 121(1), 97–104 (2013).
[PubMed]

Anal. Chem. (3)

A. Savitzky and M. J. E. Golay, “Smoothing + differentiation of data by simplified least squares procedures,” Anal. Chem. 36(8), 1627–1639 (1964).
[Crossref]

D. M. Haaland and E. V. Thomas, “Partial least-squares methods for spectral analyses. 1. relation to other quantitative calibration methods and the extraction of qualitative information,” Anal. Chem. 60(11), 1193–1202 (1988).
[Crossref]

A. J. Berger, T. W. Koo, I. Itzkan, and M. S. Feld, “An enhanced algorithm for linear multivariate calibration,” Anal. Chem. 70(3), 623–627 (1998).
[Crossref] [PubMed]

Analyst (Lond.) (1)

N. J. Everall, “Confocal Raman microscopy: common errors and artefacts,” Analyst (Lond.) 135(10), 2512–2522 (2010).
[Crossref] [PubMed]

Appl. Opt. (1)

Appl. Spectrosc. (3)

Appl. Spectrosc. Rev. (1)

A. C. S. Talari, Z. Movasaghi, S. Rehman, and I. U. Rehman, “Raman Spectroscopy of Biological Tissues,” Appl. Spectrosc. Rev. 50(1), 46–111 (2015).
[Crossref]

Arthritis Rheum. (1)

M. Takahata, J. R. Maher, S. C. Juneja, J. Inzana, L. Xing, E. M. Schwarz, A. J. Berger, and H. A. Awad, “Mechanisms of bone fragility in a mouse model of glucocorticoid-treated rheumatoid arthritis: implications for insufficiency fracture risk,” Arthritis Rheum. 64(11), 3649–3659 (2012).
[Crossref] [PubMed]

Environ. Health Perspect. (1)

E. E. Beier, J. R. Maher, T. J. Sheu, D. A. Cory-Slechta, A. J. Berger, M. J. Zuscik, and J. E. Puzas, “Heavy metal lead exposure, osteoporotic-like phenotype in an animal model, and depression of Wnt signaling,” Environ. Health Perspect. 121(1), 97–104 (2013).
[PubMed]

IEEE J. Quantum Electron. (1)

W. F. Cheong, S. A. Prahl, and A. J. Welch, “A review of the optical-properties of biological tissues,” IEEE J. Quantum Electron. 26(12), 2166–2185 (1990).
[Crossref]

J. Biomech. (1)

J. A. Inzana, J. R. Maher, M. Takahata, E. M. Schwarz, A. J. Berger, and H. A. Awad, “Bone fragility beyond strength and mineral density: Raman spectroscopy predicts femoral fracture toughness in a murine model of rheumatoid arthritis,” J. Biomech. 46(4), 723–730 (2013).
[Crossref] [PubMed]

J. Biomed. Opt. (6)

C. A. Patil, J. Kalkman, D. J. Faber, J. S. Nyman, T. G. van Leeuwen, and A. Mahadevan-Jansen, “Integrated system for combined Raman spectroscopy-spectral domain optical coherence tomography,” J. Biomed. Opt. 16(1), 011007 (2011).
[Crossref] [PubMed]

J. R. Maher, J. A. Inzana, H. A. Awad, and A. J. Berger, “Overconstrained library-based fitting method reveals age- and disease-related differences in transcutaneous Raman spectra of murine bones,” J. Biomed. Opt. 18(7), 077001 (2013).
[Crossref] [PubMed]

J. R. Maher, M. Takahata, H. A. Awad, and A. J. Berger, “Raman spectroscopy detects deterioration in biomechanical properties of bone in a glucocorticoid-treated mouse model of rheumatoid arthritis,” J. Biomed. Opt. 16(8), 087012 (2011).
[Crossref] [PubMed]

J. R. Maher, T. E. Matthews, A. K. Reid, D. F. Katz, and A. Wax, “Sensitivity of coded aperture Raman spectroscopy to analytes beneath turbid biological tissue and tissue-simulating phantoms,” J. Biomed. Opt. 19(11), 117001 (2014).
[Crossref] [PubMed]

B. W. Pogue and M. S. Patterson, “Review of tissue simulating phantoms for optical spectroscopy, imaging and dosimetry,” J. Biomed. Opt. 11(4), 041102 (2006).
[Crossref] [PubMed]

Y. Zhu, N. G. Terry, J. T. Woosley, N. J. Shaheen, and A. Wax, “Design and validation of an angle-resolved low-coherence interferometry fiber probe for in vivo clinical measurements of depth-resolved nuclear morphology,” J. Biomed. Opt. 16(1), 011003 (2011).
[Crossref] [PubMed]

J. Biophotonics (2)

K. M. Khan, H. Krishna, S. K. Majumder, K. D. Rao, and P. K. Gupta, “Depth-sensitive Raman spectroscopy combined with optical coherence tomography for layered tissue analysis,” J. Biophotonics 7(1-2), 77–85 (2014).
[Crossref] [PubMed]

J. W. Evans, R. J. Zawadzki, R. Liu, J. W. Chan, S. M. Lane, and J. S. Werner, “Optical coherence tomography and Raman spectroscopy of the ex-vivo retina,” J. Biophotonics 2(6-7), 398–406 (2009).
[Crossref] [PubMed]

J. Chromatogr. Sci. (2)

A. Hanna, J. C. Marshall, and T. L. Isenhour, “A GC/FT-IR compound identification system,” J. Chromatogr. Sci. 17(8), 434–440 (1979).
[Crossref]

S. O. Choi, N. Rezk, J. S. Kim, and A. D. M. Kashuba, “Development of an LC-MS method for measuring TNF in human vaginal tissue,” J. Chromatogr. Sci. 48(3), 219–223 (2010).
[Crossref] [PubMed]

J. Innov. Opt. Health Sci. (1)

A. N. Bashkatov, E. A. Genina, and V. V. Tuchin, “Optical properties of skin, subcutaneous, and muscle tissues: a review,” J. Innov. Opt. Health Sci. 4(1), 9–38 (2011).
[Crossref]

J. Invest. Dermatol. (1)

P. J. Caspers, G. W. Lucassen, E. A. Carter, H. A. Bruining, and G. J. Puppels, “In vivo confocal Raman microspectroscopy of the skin: noninvasive determination of molecular concentration profiles,” J. Invest. Dermatol. 116(3), 434–442 (2001).
[Crossref] [PubMed]

J. Phys. D Appl. Phys. (1)

A. N. Bashkatov, E. A. Genina, V. I. Kochubey, and V. V. Tuchin, “Optical properties of human skin, subcutaneous and mucous tissues in the wavelength range from 400 to 2000 nm,” J. Phys. D Appl. Phys. 38(15), 2543–2555 (2005).
[Crossref]

Lasers Surg. Med. (1)

C. A. Patil, H. Kirshnamoorthi, D. L. Ellis, T. G. van Leeuwen, and A. Mahadevan-Jansen, “A clinical instrument for combined Raman spectroscopy-optical coherence tomography of skin cancers,” Lasers Surg. Med. 43(2), 143–151 (2011).
[Crossref] [PubMed]

Opt. Express (1)

Opt. Lett. (3)

Phys. Med. Biol. (1)

S. L. Jacques, “Optical properties of biological tissues: a review,” Phys. Med. Biol. 58(11), R37–R61 (2013).
[Crossref] [PubMed]

PLoS ONE (2)

Y. Gao and D. F. Katz, “Multicompartmental pharmacokinetic model of tenofovir delivery by a vaginal gel,” PLoS ONE 8(9), e74404 (2013).
[Crossref] [PubMed]

O. Chuchuen, M. H. Henderson, C. Sykes, M. S. Kim, A. D. M. Kashuba, and D. F. Katz, “Quantitative analysis of microbicide concentrations in fluids, gels and tissues using confocal Raman spectroscopy,” PLoS ONE 8(12), e85124 (2013).
[Crossref] [PubMed]

Rep. Prog. Phys. (1)

A. F. Fercher, W. Drexler, C. K. Hitzenberger, and T. Lasser, “Optical coherence tomography - principles and applications,” Rep. Prog. Phys. 66(2), 239–303 (2003).
[Crossref]

Science (1)

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[Crossref] [PubMed]

Spectrosc. Int. J. (1)

T. T. Nguyen, C. Gobinet, J. Feru, S. Brassart-Pasco, M. Manfait, and O. Piot, “Characterization of Type I and IV collagens by Raman microspectroscopy: identification of spectral markers of the dermo-epidermal junction,” Spectrosc. Int. J. 27, 421–427 (2012).
[Crossref]

Other (1)

American National Standard for the Safe Use of Lasers Z136. 1-2007,” (Laser Institute of America, Orlando, FL, 2007).

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Figures (7)

Fig. 1
Fig. 1 Diagram of the instrument used to acquire cross-sectional OCT images and co-localized Raman spectra through a common objective lens. Abbreviations: SLD, superluminescent diode; FI, faraday isolator; FC, fiber coupler; REF, reference arm; PC, polarization controller; GM, galvanometer mirror; 4F, 4F lens system; spec1, spectrometer #1; LD, laser diode; BSO, beam shaping optics; BP, bandpass filter; DBS, dichroic beamsplitter; NF, notch filter; MMF, multimode fiber; spec2, spectrometer #2; FM, flip mirror; OBJ, objective lens; MTS, motorized translation stage.
Fig. 2
Fig. 2 Procedure used to measure the axial resolution of the CRS subsystem as a function of sampling depth in tissue phantoms. (a)-(c) Scattering or absorption coefficient of phantom constituents versus concentration, C, along with least-squares linear fits. Error bars represent the standard deviation of each measurement. (d) Diagram depicting the optical properties (determined with 785-nm illumination) and physical dimensions of the two-layer tissue phantoms. The top layer was a mixture of Intralipid and India ink while the bottom layer was a mixture of PM, PDMS, and India ink. (e) Representative, cross-sectional OCT image of a tissue phantom with a top-layer thickness of 140 µm. (f) Representative Raman spectrum of a tissue phantom acquired near the boundary between the layers along with the corresponding least-squares fit showing the underlying spectral components (offset for clarity). (g) Normalized signal intensity of the bottom-layer spectrum versus focal position (z) for varying top-layer thicknesses, d. Each data set was fit with a Gaussian cumulative distribution function (black lines).
Fig. 3
Fig. 3 (a) Relationship between the height of the motorized translation stage, z stage , and the CRS focal position or sampling depth, z. (b) Relationship between the axial resolution (FWHM) of CRS measurements and z. Least-squares fits suggest that both relationships are approximately linear over this range.
Fig. 4
Fig. 4 Representative Raman spectra of porcine vaginal tissue, pure tenofovir (TFV), and tissue homogenized with 0.64% w/w TFV (offset for clarity). The vertical bar highlights the spectral location of the adenine ring breathing mode near 730 cm−1.
Fig. 5
Fig. 5 (a) Cross-validated, Raman-based predictions of Tenofovir concentration in homogenized, porcine vaginal tissue versus gold-standard measurements acquired with LC-MS/MS. The root mean squared error of cross-validation (RMSECV) was 0.03% w/w for an integration time of 10 minutes per sample. (b) RMSECV versus total integration time in minutes (t) per sample. The solid lines represent a power-law fit and the 95% confidence interval of the fit.
Fig. 6
Fig. 6 (a) Representative cross-sectional OCT image of intact, ex vivo porcine vaginal tissue. The arrow highlights the thickness of the superficial epithelium. The colorbar shows the axial locations where Raman spectra were acquired. (b) Co-localized, depth-resolved Raman spectra acquired from the same tissue sample (offset for clarity). Spectroscopic differences due to natural biochemical variation (e.g., collagen content) in the epithelium versus the stroma are highlighted by the pale-colored columns. The highlighted spectral regions include hydroxyproline and proline bands (800 – 1000 cm−1) and the amide III protein band (1200 – 1400 cm−1). Note that the Raman data were cropped to the 800 – 1800 cm−1 spectral range for display purposes only; the full spectral range was retained for quantitative analyses.
Fig. 7
Fig. 7 Depth-resolved concentrations of Tenofovir in tissue. A standard-formulation gel loaded with 0% (control) or 1% Tenofovir was applied to the tissue surface in a Transwell assay and the concentration of the drug in the tissue was measured at 5, 60, or 120 minutes (min) post-application. Error bars and the limit of detection (LOD), both defined as the RMSECV calculated with homogenized tissue samples (Fig. 5), are also displayed. Co-localized OCT images were acquired and used to determine the average depth of the interface between the epithelium and stroma.

Tables (1)

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Table 1 Detailed instrument properties

Equations (3)

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SNR=20×[ log 10 ( E M / E N )+ND ]
I(k)= I S (k)+ I R (k)+2 I S (k) I R (k) ×cos( 2Δzk ),
F( z )= 1 2 [ 1+erf( zd σ 2 ) ],

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