Abstract

Quantitative determination of fluorophore content from fluorescence measurements in turbid media, such as tissue, is complicated by the influence of scattering properties on the collected signal. This study utilizes a Monte Carlo model to characterize the relationship between the fluorescence intensity collected by a single fiber optic probe (FSF) and the scattering properties. Simulations investigate a wide range of biologically relevant scattering properties specified independently at excitation (λx) and emission (λm) wavelengths, including reduced scattering coefficients in the range μs(λx) ∈ [0.1 – 8]mm−1 and μs(λm) ∈ [0.25 – 1] × μs(λx). Investigated scattering phase functions (P(θ)) include both Henyey-Greenstein and Modified Henyey-Greenstein forms, and a wide range of fiber diameters (df ∈ [0.2 – 1.0] mm) was simulated. A semi-empirical model is developed to estimate the collected FSF as the product of an effective sampling volume, and the effective excitation fluence and the effective escape probability within the effective sampling volume. The model accurately estimates FSF intensities (r=0.999) over the investigated range of μs(λx) and μs(λm), is insensitive to the form of the P(θ), and provides novel insight into a dimensionless relationship linking FSF measured by different df.

© 2011 OSA

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2011

2010

V. Ntziachristos, “Going deeper than microscopy: the optical imaging frontier in biology,” Nat. Methods.7:603–614 (2010).
[CrossRef] [PubMed]

D. J Robinson, M. B. Karakulluku, B. Kruijt, S. C. Kanick, R. L. P. van Veen, A. Amelink, H. J. C. M. Sterenborg, M. J. H. Witjes, and I. B. Tan, “Optical spectroscopy to guide photodynamic therapy of head and neck tumors,” IEEE J. Sel. Top. Quantum Electron.16:854–862 (2010).
[CrossRef]

A. Kim, M. Khurana, Y. Moriyama, and B. C. Wilson, “Quantification of in vivo fluorescence decoupled from the effects of tissue optical properties using fiber-optic spectroscopy measurements,” J. Biomed. Opt.15:067006 (2010).
[CrossRef]

2009

G. M. Palmer, R. J. Viola, T. Schroeder, P. S. Yarmolenko, M. W. Dewhirst, and N. Ramanujam, “Quantitative diffuse reflectance and fluorescence spectroscopy: tool to monitor tumor physiology in vivo,” J. Biomed. Opt.14:024010 (2009).
[CrossRef] [PubMed]

S.L. Gibbs-Strauss, J.A. O’Hara, S. Srinivasan, P.J. Hoopes, T. Hasan, and B.W. Pogue, “Diagnostic detection of diffuse glioma tumors in vivo with molecular fluorescent probe-based transmission spectroscopy,” Med. Phys.36:974–983 (2009).
[CrossRef] [PubMed]

R. H. Wilson, M. Chandra, J. Scheiman, D. Simeone, B. McKenna, J. Purdy, and M. A. Mycek, “Optical spectroscopy detects histological hallmarks of pancreatic cancer,” Opt. Express17:17502–17516 (2009).
[CrossRef] [PubMed]

2008

G. M. Palmer and N. Ramanujam, “Monte-carlo-based model for the extraction of intrinsic fluorescence from turbid media,” J. Biomed. Opt.13:024017 (2008).
[CrossRef] [PubMed]

A. Amelink, B. Kruijt, D. J. Robinson, and H. J. C. M. Sterenborg, “Quantitative fluorescence spectroscopy in turbid media using fluorescence differential path length spectroscopy,” J. Biomed. Opt.13:054051 (2008).
[CrossRef] [PubMed]

A. Amelink, D. J. Robinson, and H. J. C. M. Sterenborg, “Confidence intervals on fit parameters derived from optical reflectance spectroscopy measurements,” J. Biomed. Opt.13:05040144 (2008).
[CrossRef]

2007

H. Stepp, T. Beck, W. Beyer, C. Pfaller, M. Schuppler, R. Sroka, and R. Baumgartner, “Measurement of fluorophore concentration in turbid media by a single optical fiber,” Medical Laser Application22:23–34 (2007).
[CrossRef]

2006

J. C. Finlay, T. C. Zhu, A. Dimofte, D. Stripp, S. B. Malkowicz, T. M. Busch, and S. M. Hahn, “Interstitial fluorescence spectroscopy in the human prostate during motexafin lutetium-mediated photodynamic therapy,” Photochem. Photobiol.82:1270–1278 (2006).
[CrossRef] [PubMed]

2005

2003

2001

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

A. Kienle, F. Forster, and R. Hibst, “Influence of the phase function on determination of the optical properties of biological tissue by spatially resolved reflectance,” Opt. Lett.26:1571–1573 (2001).
[CrossRef]

R. Weersink, M. S. Patterson, K. Diamond, S. Silver, and N. Padgett, “Noninvasive measurement of fluorophore concentration in turbid media with a simple fluorescence /reflectance ratio technique,” Appl. Opt.40:6389–6395 (2001).
[CrossRef]

C. C. Lee, B. W. Pogue, R. R. Strawbridge, K. L. Moodie, L. R. Bartholomew, G. C. Burke, and P. J. Hoopes, “Comparison of photosensitizer (AIPcS2) quantification techniques: in situ fluorescence microsampling versus tissue chemical extraction,” Photochem. Photobiol.74:453–460 (2001).
[CrossRef] [PubMed]

T. J. Pfefer, K. T. Schomacker, M. N. Ediger, and N. S. Nishioka, “Light propagation in tissue during fluorescence spectroscopy with single-fiber probes,” IEEE J. Sel. Top. Quantum Electron.7:1004–1012 (2001).
[CrossRef]

2000

1999

1998

1997

A. J. Welch, C. Gardner, R. Richards-Kortum, E. Chan, G. Criswell, J. Pfefer, and S. Warren, “Propagation of fluorescent light,” Lasers Surg. Med.21:166–178 (1997).
[CrossRef] [PubMed]

1996

1995

L. Wang, S. Jacques, and L. Zheng, “MCML–Monte Carlo modeling of light transport in multi-layered tissues,” Comp. Meth. Prog. Biomed.47:131–146 (1995).
[CrossRef]

1994

E. J. Hudson, M. R. Stringer, F. Cairnduff, D. V. Ash, and M. A. Smith, “The optical properties of skin tumours measured during superficial photodynamic therapy,” Laser. Med. Sci.9:99–103 (1994).
[CrossRef]

1993

1990

W. Cheong, S. A. Prahl, and A. J. Welch, “A review of the optical properties of biological tissues,” IEEE J. Quant. Electron.26:2166–2185 (1990).
[CrossRef]

Amelink, A.

S. C. Kanick, U. A. Gamm, M. Schouten, H. J. C. M. Sterenborg, D. J. Robinson, and A. Amelink, “Measurement of the reduced scattering coefficient of turbid media using single fiber reflectance spectroscopy: fiber diameter and phase function dependence,” Biomed. Opt. Express2:1687–1702 (2011).
[CrossRef] [PubMed]

S. C. Kanick, U. A. Gamm, H. J. C. M. Sterenborg, D. J. Robinson, and A. Amelink, “Method to quantitatively estimate wavelength-dependent scattering properties from multi-diameter single fiber reflectance spectra measured in a turbid medium,” Opt. Lett.36:2997–2999 (2011).
[CrossRef] [PubMed]

U. A. Gamm, S. C. Kanick, H. J. C. M. Sterenborg, D. J. Robinson, and A. Amelink, “Measurement of tissue scattering properties using multi-diameter single fiber reflectance spectroscopy: in silico sensitivity analysis,” Biomed. Opt. Express2:3150–3166 (2011).
[CrossRef] [PubMed]

D. J Robinson, M. B. Karakulluku, B. Kruijt, S. C. Kanick, R. L. P. van Veen, A. Amelink, H. J. C. M. Sterenborg, M. J. H. Witjes, and I. B. Tan, “Optical spectroscopy to guide photodynamic therapy of head and neck tumors,” IEEE J. Sel. Top. Quantum Electron.16:854–862 (2010).
[CrossRef]

A. Amelink, B. Kruijt, D. J. Robinson, and H. J. C. M. Sterenborg, “Quantitative fluorescence spectroscopy in turbid media using fluorescence differential path length spectroscopy,” J. Biomed. Opt.13:054051 (2008).
[CrossRef] [PubMed]

A. Amelink, D. J. Robinson, and H. J. C. M. Sterenborg, “Confidence intervals on fit parameters derived from optical reflectance spectroscopy measurements,” J. Biomed. Opt.13:05040144 (2008).
[CrossRef]

Anandasabapathy, S.

N. Thekkek, S. Anandasabapathy, and R. Richards-Kortum, “Optical molecular imaging for detection of Barrett’s-associated neoplasia,” World J. Gastroenterol.17:53–62 (2011).
[CrossRef] [PubMed]

Ash, D. V.

E. J. Hudson, M. R. Stringer, F. Cairnduff, D. V. Ash, and M. A. Smith, “The optical properties of skin tumours measured during superficial photodynamic therapy,” Laser. Med. Sci.9:99–103 (1994).
[CrossRef]

Bartholomew, L. R.

C. C. Lee, B. W. Pogue, R. R. Strawbridge, K. L. Moodie, L. R. Bartholomew, G. C. Burke, and P. J. Hoopes, “Comparison of photosensitizer (AIPcS2) quantification techniques: in situ fluorescence microsampling versus tissue chemical extraction,” Photochem. Photobiol.74:453–460 (2001).
[CrossRef] [PubMed]

Baumgartner, R.

H. Stepp, T. Beck, W. Beyer, C. Pfaller, M. Schuppler, R. Sroka, and R. Baumgartner, “Measurement of fluorophore concentration in turbid media by a single optical fiber,” Medical Laser Application22:23–34 (2007).
[CrossRef]

Beck, T.

H. Stepp, T. Beck, W. Beyer, C. Pfaller, M. Schuppler, R. Sroka, and R. Baumgartner, “Measurement of fluorophore concentration in turbid media by a single optical fiber,” Medical Laser Application22:23–34 (2007).
[CrossRef]

Bevilacqua, F.

Beyer, W.

H. Stepp, T. Beck, W. Beyer, C. Pfaller, M. Schuppler, R. Sroka, and R. Baumgartner, “Measurement of fluorophore concentration in turbid media by a single optical fiber,” Medical Laser Application22:23–34 (2007).
[CrossRef]

Burke, G.

Burke, G. C.

C. C. Lee, B. W. Pogue, R. R. Strawbridge, K. L. Moodie, L. R. Bartholomew, G. C. Burke, and P. J. Hoopes, “Comparison of photosensitizer (AIPcS2) quantification techniques: in situ fluorescence microsampling versus tissue chemical extraction,” Photochem. Photobiol.74:453–460 (2001).
[CrossRef] [PubMed]

Busch, T. M.

J. C. Finlay, T. C. Zhu, A. Dimofte, D. Stripp, S. B. Malkowicz, T. M. Busch, and S. M. Hahn, “Interstitial fluorescence spectroscopy in the human prostate during motexafin lutetium-mediated photodynamic therapy,” Photochem. Photobiol.82:1270–1278 (2006).
[CrossRef] [PubMed]

Cairnduff, F.

E. J. Hudson, M. R. Stringer, F. Cairnduff, D. V. Ash, and M. A. Smith, “The optical properties of skin tumours measured during superficial photodynamic therapy,” Laser. Med. Sci.9:99–103 (1994).
[CrossRef]

Chan, E.

A. J. Welch, C. Gardner, R. Richards-Kortum, E. Chan, G. Criswell, J. Pfefer, and S. Warren, “Propagation of fluorescent light,” Lasers Surg. Med.21:166–178 (1997).
[CrossRef] [PubMed]

Chandra, M.

Cheong, W.

W. Cheong, S. A. Prahl, and A. J. Welch, “A review of the optical properties of biological tissues,” IEEE J. Quant. Electron.26:2166–2185 (1990).
[CrossRef]

Criswell, G.

A. J. Welch, C. Gardner, R. Richards-Kortum, E. Chan, G. Criswell, J. Pfefer, and S. Warren, “Propagation of fluorescent light,” Lasers Surg. Med.21:166–178 (1997).
[CrossRef] [PubMed]

Depeursinge, C.

Dewhirst, M. W.

G. M. Palmer, R. J. Viola, T. Schroeder, P. S. Yarmolenko, M. W. Dewhirst, and N. Ramanujam, “Quantitative diffuse reflectance and fluorescence spectroscopy: tool to monitor tumor physiology in vivo,” J. Biomed. Opt.14:024010 (2009).
[CrossRef] [PubMed]

Diamond, K.

Diamond, K. R.

Dimofte, A.

J. C. Finlay, T. C. Zhu, A. Dimofte, D. Stripp, S. B. Malkowicz, T. M. Busch, and S. M. Hahn, “Interstitial fluorescence spectroscopy in the human prostate during motexafin lutetium-mediated photodynamic therapy,” Photochem. Photobiol.82:1270–1278 (2006).
[CrossRef] [PubMed]

Ediger, M. N.

T. J. Pfefer, K. T. Schomacker, M. N. Ediger, and N. S. Nishioka, “Light propagation in tissue during fluorescence spectroscopy with single-fiber probes,” IEEE J. Sel. Top. Quantum Electron.7:1004–1012 (2001).
[CrossRef]

Farrell, T. J.

Feld, M. S.

Finlay, J. C.

J. C. Finlay, T. C. Zhu, A. Dimofte, D. Stripp, S. B. Malkowicz, T. M. Busch, and S. M. Hahn, “Interstitial fluorescence spectroscopy in the human prostate during motexafin lutetium-mediated photodynamic therapy,” Photochem. Photobiol.82:1270–1278 (2006).
[CrossRef] [PubMed]

J. C. Finlay and T. H. Foster, “Recovery of hemoglobin oxygen saturation and intrinsic fluorescence with a forward-adjoint model,” Appl. Opt.44:1917–1933 (2005).
[CrossRef] [PubMed]

Forster, F.

Foster, T. H.

Gamm, U. A.

Gardner, C.

A. J. Welch, C. Gardner, R. Richards-Kortum, E. Chan, G. Criswell, J. Pfefer, and S. Warren, “Propagation of fluorescent light,” Lasers Surg. Med.21:166–178 (1997).
[CrossRef] [PubMed]

Gardner, C. M.

Georgakoudi, I.

Gibbs-Strauss, S.L.

S.L. Gibbs-Strauss, J.A. O’Hara, S. Srinivasan, P.J. Hoopes, T. Hasan, and B.W. Pogue, “Diagnostic detection of diffuse glioma tumors in vivo with molecular fluorescent probe-based transmission spectroscopy,” Med. Phys.36:974–983 (2009).
[CrossRef] [PubMed]

Hahn, S. M.

J. C. Finlay, T. C. Zhu, A. Dimofte, D. Stripp, S. B. Malkowicz, T. M. Busch, and S. M. Hahn, “Interstitial fluorescence spectroscopy in the human prostate during motexafin lutetium-mediated photodynamic therapy,” Photochem. Photobiol.82:1270–1278 (2006).
[CrossRef] [PubMed]

Hasan, T.

S.L. Gibbs-Strauss, J.A. O’Hara, S. Srinivasan, P.J. Hoopes, T. Hasan, and B.W. Pogue, “Diagnostic detection of diffuse glioma tumors in vivo with molecular fluorescent probe-based transmission spectroscopy,” Med. Phys.36:974–983 (2009).
[CrossRef] [PubMed]

Hibst, R.

Hoopes, P. J.

C. C. Lee, B. W. Pogue, R. R. Strawbridge, K. L. Moodie, L. R. Bartholomew, G. C. Burke, and P. J. Hoopes, “Comparison of photosensitizer (AIPcS2) quantification techniques: in situ fluorescence microsampling versus tissue chemical extraction,” Photochem. Photobiol.74:453–460 (2001).
[CrossRef] [PubMed]

Hoopes, P.J.

S.L. Gibbs-Strauss, J.A. O’Hara, S. Srinivasan, P.J. Hoopes, T. Hasan, and B.W. Pogue, “Diagnostic detection of diffuse glioma tumors in vivo with molecular fluorescent probe-based transmission spectroscopy,” Med. Phys.36:974–983 (2009).
[CrossRef] [PubMed]

Hudson, E. J.

E. J. Hudson, M. R. Stringer, F. Cairnduff, D. V. Ash, and M. A. Smith, “The optical properties of skin tumours measured during superficial photodynamic therapy,” Laser. Med. Sci.9:99–103 (1994).
[CrossRef]

Jacques, S.

L. Wang, S. Jacques, and L. Zheng, “MCML–Monte Carlo modeling of light transport in multi-layered tissues,” Comp. Meth. Prog. Biomed.47:131–146 (1995).
[CrossRef]

Jacques, S. L.

Kanick, S. C.

Karakulluku, M. B.

D. J Robinson, M. B. Karakulluku, B. Kruijt, S. C. Kanick, R. L. P. van Veen, A. Amelink, H. J. C. M. Sterenborg, M. J. H. Witjes, and I. B. Tan, “Optical spectroscopy to guide photodynamic therapy of head and neck tumors,” IEEE J. Sel. Top. Quantum Electron.16:854–862 (2010).
[CrossRef]

Khurana, M.

A. Kim, M. Khurana, Y. Moriyama, and B. C. Wilson, “Quantification of in vivo fluorescence decoupled from the effects of tissue optical properties using fiber-optic spectroscopy measurements,” J. Biomed. Opt.15:067006 (2010).
[CrossRef]

Kienle, A.

Kim, A.

A. Kim, M. Khurana, Y. Moriyama, and B. C. Wilson, “Quantification of in vivo fluorescence decoupled from the effects of tissue optical properties using fiber-optic spectroscopy measurements,” J. Biomed. Opt.15:067006 (2010).
[CrossRef]

Kruijt, B.

D. J Robinson, M. B. Karakulluku, B. Kruijt, S. C. Kanick, R. L. P. van Veen, A. Amelink, H. J. C. M. Sterenborg, M. J. H. Witjes, and I. B. Tan, “Optical spectroscopy to guide photodynamic therapy of head and neck tumors,” IEEE J. Sel. Top. Quantum Electron.16:854–862 (2010).
[CrossRef]

A. Amelink, B. Kruijt, D. J. Robinson, and H. J. C. M. Sterenborg, “Quantitative fluorescence spectroscopy in turbid media using fluorescence differential path length spectroscopy,” J. Biomed. Opt.13:054051 (2008).
[CrossRef] [PubMed]

Lee, C. C.

C. C. Lee, B. W. Pogue, R. R. Strawbridge, K. L. Moodie, L. R. Bartholomew, G. C. Burke, and P. J. Hoopes, “Comparison of photosensitizer (AIPcS2) quantification techniques: in situ fluorescence microsampling versus tissue chemical extraction,” Photochem. Photobiol.74:453–460 (2001).
[CrossRef] [PubMed]

Malkowicz, S. B.

J. C. Finlay, T. C. Zhu, A. Dimofte, D. Stripp, S. B. Malkowicz, T. M. Busch, and S. M. Hahn, “Interstitial fluorescence spectroscopy in the human prostate during motexafin lutetium-mediated photodynamic therapy,” Photochem. Photobiol.82:1270–1278 (2006).
[CrossRef] [PubMed]

McKenna, B.

Moodie, K. L.

C. C. Lee, B. W. Pogue, R. R. Strawbridge, K. L. Moodie, L. R. Bartholomew, G. C. Burke, and P. J. Hoopes, “Comparison of photosensitizer (AIPcS2) quantification techniques: in situ fluorescence microsampling versus tissue chemical extraction,” Photochem. Photobiol.74:453–460 (2001).
[CrossRef] [PubMed]

Moriyama, Y.

A. Kim, M. Khurana, Y. Moriyama, and B. C. Wilson, “Quantification of in vivo fluorescence decoupled from the effects of tissue optical properties using fiber-optic spectroscopy measurements,” J. Biomed. Opt.15:067006 (2010).
[CrossRef]

Müller, M. G.

Mycek, M. A.

Nishioka, N. S.

T. J. Pfefer, K. T. Schomacker, M. N. Ediger, and N. S. Nishioka, “Light propagation in tissue during fluorescence spectroscopy with single-fiber probes,” IEEE J. Sel. Top. Quantum Electron.7:1004–1012 (2001).
[CrossRef]

Ntziachristos, V.

V. Ntziachristos, “Going deeper than microscopy: the optical imaging frontier in biology,” Nat. Methods.7:603–614 (2010).
[CrossRef] [PubMed]

O’Hara, J.A.

S.L. Gibbs-Strauss, J.A. O’Hara, S. Srinivasan, P.J. Hoopes, T. Hasan, and B.W. Pogue, “Diagnostic detection of diffuse glioma tumors in vivo with molecular fluorescent probe-based transmission spectroscopy,” Med. Phys.36:974–983 (2009).
[CrossRef] [PubMed]

Padgett, N.

Palmer, G. M.

G. M. Palmer, R. J. Viola, T. Schroeder, P. S. Yarmolenko, M. W. Dewhirst, and N. Ramanujam, “Quantitative diffuse reflectance and fluorescence spectroscopy: tool to monitor tumor physiology in vivo,” J. Biomed. Opt.14:024010 (2009).
[CrossRef] [PubMed]

G. M. Palmer and N. Ramanujam, “Monte-carlo-based model for the extraction of intrinsic fluorescence from turbid media,” J. Biomed. Opt.13:024017 (2008).
[CrossRef] [PubMed]

Patterson, M. S.

Pfaller, C.

H. Stepp, T. Beck, W. Beyer, C. Pfaller, M. Schuppler, R. Sroka, and R. Baumgartner, “Measurement of fluorophore concentration in turbid media by a single optical fiber,” Medical Laser Application22:23–34 (2007).
[CrossRef]

Pfefer, J.

A. J. Welch, C. Gardner, R. Richards-Kortum, E. Chan, G. Criswell, J. Pfefer, and S. Warren, “Propagation of fluorescent light,” Lasers Surg. Med.21:166–178 (1997).
[CrossRef] [PubMed]

Pfefer, T. J.

T. J. Pfefer, K. T. Schomacker, M. N. Ediger, and N. S. Nishioka, “Light propagation in tissue during fluorescence spectroscopy with single-fiber probes,” IEEE J. Sel. Top. Quantum Electron.7:1004–1012 (2001).
[CrossRef]

Pogue, B. W.

C. C. Lee, B. W. Pogue, R. R. Strawbridge, K. L. Moodie, L. R. Bartholomew, G. C. Burke, and P. J. Hoopes, “Comparison of photosensitizer (AIPcS2) quantification techniques: in situ fluorescence microsampling versus tissue chemical extraction,” Photochem. Photobiol.74:453–460 (2001).
[CrossRef] [PubMed]

B. W. Pogue and G. Burke, “Fiber-optic bundle design for quantitative fluorescence measurement from tissue,” Appl. Opt.37: 7429–7436 (1998).
[CrossRef]

Pogue, B.W.

S.L. Gibbs-Strauss, J.A. O’Hara, S. Srinivasan, P.J. Hoopes, T. Hasan, and B.W. Pogue, “Diagnostic detection of diffuse glioma tumors in vivo with molecular fluorescent probe-based transmission spectroscopy,” Med. Phys.36:974–983 (2009).
[CrossRef] [PubMed]

Prahl, S. A.

W. Cheong, S. A. Prahl, and A. J. Welch, “A review of the optical properties of biological tissues,” IEEE J. Quant. Electron.26:2166–2185 (1990).
[CrossRef]

Purdy, J.

Ramanujam, N.

G. M. Palmer, R. J. Viola, T. Schroeder, P. S. Yarmolenko, M. W. Dewhirst, and N. Ramanujam, “Quantitative diffuse reflectance and fluorescence spectroscopy: tool to monitor tumor physiology in vivo,” J. Biomed. Opt.14:024010 (2009).
[CrossRef] [PubMed]

G. M. Palmer and N. Ramanujam, “Monte-carlo-based model for the extraction of intrinsic fluorescence from turbid media,” J. Biomed. Opt.13:024017 (2008).
[CrossRef] [PubMed]

Rava, R. P

Richards-Kortum, R.

N. Thekkek, S. Anandasabapathy, and R. Richards-Kortum, “Optical molecular imaging for detection of Barrett’s-associated neoplasia,” World J. Gastroenterol.17:53–62 (2011).
[CrossRef] [PubMed]

A. J. Welch, C. Gardner, R. Richards-Kortum, E. Chan, G. Criswell, J. Pfefer, and S. Warren, “Propagation of fluorescent light,” Lasers Surg. Med.21:166–178 (1997).
[CrossRef] [PubMed]

Robinson, D. J

D. J Robinson, M. B. Karakulluku, B. Kruijt, S. C. Kanick, R. L. P. van Veen, A. Amelink, H. J. C. M. Sterenborg, M. J. H. Witjes, and I. B. Tan, “Optical spectroscopy to guide photodynamic therapy of head and neck tumors,” IEEE J. Sel. Top. Quantum Electron.16:854–862 (2010).
[CrossRef]

Robinson, D. J.

Scheiman, J.

Schomacker, K. T.

T. J. Pfefer, K. T. Schomacker, M. N. Ediger, and N. S. Nishioka, “Light propagation in tissue during fluorescence spectroscopy with single-fiber probes,” IEEE J. Sel. Top. Quantum Electron.7:1004–1012 (2001).
[CrossRef]

Schouten, M.

Schroeder, T.

G. M. Palmer, R. J. Viola, T. Schroeder, P. S. Yarmolenko, M. W. Dewhirst, and N. Ramanujam, “Quantitative diffuse reflectance and fluorescence spectroscopy: tool to monitor tumor physiology in vivo,” J. Biomed. Opt.14:024010 (2009).
[CrossRef] [PubMed]

Schuppler, M.

H. Stepp, T. Beck, W. Beyer, C. Pfaller, M. Schuppler, R. Sroka, and R. Baumgartner, “Measurement of fluorophore concentration in turbid media by a single optical fiber,” Medical Laser Application22:23–34 (2007).
[CrossRef]

Silver, S.

Simeone, D.

Sinaasappel, M.

Smith, M. A.

E. J. Hudson, M. R. Stringer, F. Cairnduff, D. V. Ash, and M. A. Smith, “The optical properties of skin tumours measured during superficial photodynamic therapy,” Laser. Med. Sci.9:99–103 (1994).
[CrossRef]

Srinivasan, S.

S.L. Gibbs-Strauss, J.A. O’Hara, S. Srinivasan, P.J. Hoopes, T. Hasan, and B.W. Pogue, “Diagnostic detection of diffuse glioma tumors in vivo with molecular fluorescent probe-based transmission spectroscopy,” Med. Phys.36:974–983 (2009).
[CrossRef] [PubMed]

Sroka, R.

H. Stepp, T. Beck, W. Beyer, C. Pfaller, M. Schuppler, R. Sroka, and R. Baumgartner, “Measurement of fluorophore concentration in turbid media by a single optical fiber,” Medical Laser Application22:23–34 (2007).
[CrossRef]

Stepp, H.

H. Stepp, T. Beck, W. Beyer, C. Pfaller, M. Schuppler, R. Sroka, and R. Baumgartner, “Measurement of fluorophore concentration in turbid media by a single optical fiber,” Medical Laser Application22:23–34 (2007).
[CrossRef]

Sterenborg, H. J. C. M.

S. C. Kanick, U. A. Gamm, M. Schouten, H. J. C. M. Sterenborg, D. J. Robinson, and A. Amelink, “Measurement of the reduced scattering coefficient of turbid media using single fiber reflectance spectroscopy: fiber diameter and phase function dependence,” Biomed. Opt. Express2:1687–1702 (2011).
[CrossRef] [PubMed]

U. A. Gamm, S. C. Kanick, H. J. C. M. Sterenborg, D. J. Robinson, and A. Amelink, “Measurement of tissue scattering properties using multi-diameter single fiber reflectance spectroscopy: in silico sensitivity analysis,” Biomed. Opt. Express2:3150–3166 (2011).
[CrossRef] [PubMed]

S. C. Kanick, U. A. Gamm, H. J. C. M. Sterenborg, D. J. Robinson, and A. Amelink, “Method to quantitatively estimate wavelength-dependent scattering properties from multi-diameter single fiber reflectance spectra measured in a turbid medium,” Opt. Lett.36:2997–2999 (2011).
[CrossRef] [PubMed]

D. J Robinson, M. B. Karakulluku, B. Kruijt, S. C. Kanick, R. L. P. van Veen, A. Amelink, H. J. C. M. Sterenborg, M. J. H. Witjes, and I. B. Tan, “Optical spectroscopy to guide photodynamic therapy of head and neck tumors,” IEEE J. Sel. Top. Quantum Electron.16:854–862 (2010).
[CrossRef]

A. Amelink, B. Kruijt, D. J. Robinson, and H. J. C. M. Sterenborg, “Quantitative fluorescence spectroscopy in turbid media using fluorescence differential path length spectroscopy,” J. Biomed. Opt.13:054051 (2008).
[CrossRef] [PubMed]

A. Amelink, D. J. Robinson, and H. J. C. M. Sterenborg, “Confidence intervals on fit parameters derived from optical reflectance spectroscopy measurements,” J. Biomed. Opt.13:05040144 (2008).
[CrossRef]

M. Sinaasappel and H. J. C. M. Sterenborg, “Quantification of the hematoporphyrin derivative by fluorescence measurement using dual-wavelength excitation and dual-wavelength detection,” Appl. Opt.32:541–548 (1993).
[CrossRef] [PubMed]

Strawbridge, R. R.

C. C. Lee, B. W. Pogue, R. R. Strawbridge, K. L. Moodie, L. R. Bartholomew, G. C. Burke, and P. J. Hoopes, “Comparison of photosensitizer (AIPcS2) quantification techniques: in situ fluorescence microsampling versus tissue chemical extraction,” Photochem. Photobiol.74:453–460 (2001).
[CrossRef] [PubMed]

Stringer, M. R.

E. J. Hudson, M. R. Stringer, F. Cairnduff, D. V. Ash, and M. A. Smith, “The optical properties of skin tumours measured during superficial photodynamic therapy,” Laser. Med. Sci.9:99–103 (1994).
[CrossRef]

Stripp, D.

J. C. Finlay, T. C. Zhu, A. Dimofte, D. Stripp, S. B. Malkowicz, T. M. Busch, and S. M. Hahn, “Interstitial fluorescence spectroscopy in the human prostate during motexafin lutetium-mediated photodynamic therapy,” Photochem. Photobiol.82:1270–1278 (2006).
[CrossRef] [PubMed]

Tan, I. B.

D. J Robinson, M. B. Karakulluku, B. Kruijt, S. C. Kanick, R. L. P. van Veen, A. Amelink, H. J. C. M. Sterenborg, M. J. H. Witjes, and I. B. Tan, “Optical spectroscopy to guide photodynamic therapy of head and neck tumors,” IEEE J. Sel. Top. Quantum Electron.16:854–862 (2010).
[CrossRef]

Thekkek, N.

N. Thekkek, S. Anandasabapathy, and R. Richards-Kortum, “Optical molecular imaging for detection of Barrett’s-associated neoplasia,” World J. Gastroenterol.17:53–62 (2011).
[CrossRef] [PubMed]

van Veen, R. L. P.

D. J Robinson, M. B. Karakulluku, B. Kruijt, S. C. Kanick, R. L. P. van Veen, A. Amelink, H. J. C. M. Sterenborg, M. J. H. Witjes, and I. B. Tan, “Optical spectroscopy to guide photodynamic therapy of head and neck tumors,” IEEE J. Sel. Top. Quantum Electron.16:854–862 (2010).
[CrossRef]

Viola, R. J.

G. M. Palmer, R. J. Viola, T. Schroeder, P. S. Yarmolenko, M. W. Dewhirst, and N. Ramanujam, “Quantitative diffuse reflectance and fluorescence spectroscopy: tool to monitor tumor physiology in vivo,” J. Biomed. Opt.14:024010 (2009).
[CrossRef] [PubMed]

Wang, L.

L. Wang, S. Jacques, and L. Zheng, “MCML–Monte Carlo modeling of light transport in multi-layered tissues,” Comp. Meth. Prog. Biomed.47:131–146 (1995).
[CrossRef]

Warren, S.

A. J. Welch, C. Gardner, R. Richards-Kortum, E. Chan, G. Criswell, J. Pfefer, and S. Warren, “Propagation of fluorescent light,” Lasers Surg. Med.21:166–178 (1997).
[CrossRef] [PubMed]

Weersink, R.

Welch, A. J.

A. J. Welch, C. Gardner, R. Richards-Kortum, E. Chan, G. Criswell, J. Pfefer, and S. Warren, “Propagation of fluorescent light,” Lasers Surg. Med.21:166–178 (1997).
[CrossRef] [PubMed]

C. M. Gardner, S. L. Jacques, and A. J. Welch, “Fluorescence spectroscopy of tissue: recovery of intrinsic fluorescence from measured fluorescence,” Appl. Opt.35:1780–1792 (1996).
[CrossRef] [PubMed]

W. Cheong, S. A. Prahl, and A. J. Welch, “A review of the optical properties of biological tissues,” IEEE J. Quant. Electron.26:2166–2185 (1990).
[CrossRef]

Wilson, B. C.

A. Kim, M. Khurana, Y. Moriyama, and B. C. Wilson, “Quantification of in vivo fluorescence decoupled from the effects of tissue optical properties using fiber-optic spectroscopy measurements,” J. Biomed. Opt.15:067006 (2010).
[CrossRef]

Wilson, R. H.

Witjes, M. J. H.

D. J Robinson, M. B. Karakulluku, B. Kruijt, S. C. Kanick, R. L. P. van Veen, A. Amelink, H. J. C. M. Sterenborg, M. J. H. Witjes, and I. B. Tan, “Optical spectroscopy to guide photodynamic therapy of head and neck tumors,” IEEE J. Sel. Top. Quantum Electron.16:854–862 (2010).
[CrossRef]

Wu, J.

Yarmolenko, P. S.

G. M. Palmer, R. J. Viola, T. Schroeder, P. S. Yarmolenko, M. W. Dewhirst, and N. Ramanujam, “Quantitative diffuse reflectance and fluorescence spectroscopy: tool to monitor tumor physiology in vivo,” J. Biomed. Opt.14:024010 (2009).
[CrossRef] [PubMed]

Zhang, Q.

Zheng, L.

L. Wang, S. Jacques, and L. Zheng, “MCML–Monte Carlo modeling of light transport in multi-layered tissues,” Comp. Meth. Prog. Biomed.47:131–146 (1995).
[CrossRef]

Zhu, T. C.

J. C. Finlay, T. C. Zhu, A. Dimofte, D. Stripp, S. B. Malkowicz, T. M. Busch, and S. M. Hahn, “Interstitial fluorescence spectroscopy in the human prostate during motexafin lutetium-mediated photodynamic therapy,” Photochem. Photobiol.82:1270–1278 (2006).
[CrossRef] [PubMed]

Appl. Opt.

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

M. Sinaasappel and H. J. C. M. Sterenborg, “Quantification of the hematoporphyrin derivative by fluorescence measurement using dual-wavelength excitation and dual-wavelength detection,” Appl. Opt.32:541–548 (1993).
[CrossRef] [PubMed]

B. W. Pogue and G. Burke, “Fiber-optic bundle design for quantitative fluorescence measurement from tissue,” Appl. Opt.37: 7429–7436 (1998).
[CrossRef]

C. M. Gardner, S. L. Jacques, and A. J. Welch, “Fluorescence spectroscopy of tissue: recovery of intrinsic fluorescence from measured fluorescence,” Appl. Opt.35:1780–1792 (1996).
[CrossRef] [PubMed]

R. Weersink, M. S. Patterson, K. Diamond, S. Silver, and N. Padgett, “Noninvasive measurement of fluorophore concentration in turbid media with a simple fluorescence /reflectance ratio technique,” Appl. Opt.40:6389–6395 (2001).
[CrossRef]

K. R. Diamond, M. S. Patterson, and T. J. Farrell, “Quantification of fluorophore concentration in tissue-simulating media by fluorescence measurements with a single optical fiber,” Appl. Opt.42:2436–2442 (2003).
[CrossRef] [PubMed]

J. C. Finlay and T. H. Foster, “Recovery of hemoglobin oxygen saturation and intrinsic fluorescence with a forward-adjoint model,” Appl. Opt.44:1917–1933 (2005).
[CrossRef] [PubMed]

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

Biomed. Opt. Express

Comp. Meth. Prog. Biomed.

L. Wang, S. Jacques, and L. Zheng, “MCML–Monte Carlo modeling of light transport in multi-layered tissues,” Comp. Meth. Prog. Biomed.47:131–146 (1995).
[CrossRef]

IEEE J. Quant. Electron.

W. Cheong, S. A. Prahl, and A. J. Welch, “A review of the optical properties of biological tissues,” IEEE J. Quant. Electron.26:2166–2185 (1990).
[CrossRef]

IEEE J. Sel. Top. Quantum Electron.

T. J. Pfefer, K. T. Schomacker, M. N. Ediger, and N. S. Nishioka, “Light propagation in tissue during fluorescence spectroscopy with single-fiber probes,” IEEE J. Sel. Top. Quantum Electron.7:1004–1012 (2001).
[CrossRef]

D. J Robinson, M. B. Karakulluku, B. Kruijt, S. C. Kanick, R. L. P. van Veen, A. Amelink, H. J. C. M. Sterenborg, M. J. H. Witjes, and I. B. Tan, “Optical spectroscopy to guide photodynamic therapy of head and neck tumors,” IEEE J. Sel. Top. Quantum Electron.16:854–862 (2010).
[CrossRef]

J. Biomed. Opt.

G. M. Palmer and N. Ramanujam, “Monte-carlo-based model for the extraction of intrinsic fluorescence from turbid media,” J. Biomed. Opt.13:024017 (2008).
[CrossRef] [PubMed]

G. M. Palmer, R. J. Viola, T. Schroeder, P. S. Yarmolenko, M. W. Dewhirst, and N. Ramanujam, “Quantitative diffuse reflectance and fluorescence spectroscopy: tool to monitor tumor physiology in vivo,” J. Biomed. Opt.14:024010 (2009).
[CrossRef] [PubMed]

A. Kim, M. Khurana, Y. Moriyama, and B. C. Wilson, “Quantification of in vivo fluorescence decoupled from the effects of tissue optical properties using fiber-optic spectroscopy measurements,” J. Biomed. Opt.15:067006 (2010).
[CrossRef]

A. Amelink, B. Kruijt, D. J. Robinson, and H. J. C. M. Sterenborg, “Quantitative fluorescence spectroscopy in turbid media using fluorescence differential path length spectroscopy,” J. Biomed. Opt.13:054051 (2008).
[CrossRef] [PubMed]

A. Amelink, D. J. Robinson, and H. J. C. M. Sterenborg, “Confidence intervals on fit parameters derived from optical reflectance spectroscopy measurements,” J. Biomed. Opt.13:05040144 (2008).
[CrossRef]

J. Opt. Soc. Am. A

Laser. Med. Sci.

E. J. Hudson, M. R. Stringer, F. Cairnduff, D. V. Ash, and M. A. Smith, “The optical properties of skin tumours measured during superficial photodynamic therapy,” Laser. Med. Sci.9:99–103 (1994).
[CrossRef]

Lasers Surg. Med.

A. J. Welch, C. Gardner, R. Richards-Kortum, E. Chan, G. Criswell, J. Pfefer, and S. Warren, “Propagation of fluorescent light,” Lasers Surg. Med.21:166–178 (1997).
[CrossRef] [PubMed]

Med. Phys.

S.L. Gibbs-Strauss, J.A. O’Hara, S. Srinivasan, P.J. Hoopes, T. Hasan, and B.W. Pogue, “Diagnostic detection of diffuse glioma tumors in vivo with molecular fluorescent probe-based transmission spectroscopy,” Med. Phys.36:974–983 (2009).
[CrossRef] [PubMed]

Medical Laser Application

H. Stepp, T. Beck, W. Beyer, C. Pfaller, M. Schuppler, R. Sroka, and R. Baumgartner, “Measurement of fluorophore concentration in turbid media by a single optical fiber,” Medical Laser Application22:23–34 (2007).
[CrossRef]

Nat. Methods.

V. Ntziachristos, “Going deeper than microscopy: the optical imaging frontier in biology,” Nat. Methods.7:603–614 (2010).
[CrossRef] [PubMed]

Opt. Express

Opt. Lett.

Photochem. Photobiol.

C. C. Lee, B. W. Pogue, R. R. Strawbridge, K. L. Moodie, L. R. Bartholomew, G. C. Burke, and P. J. Hoopes, “Comparison of photosensitizer (AIPcS2) quantification techniques: in situ fluorescence microsampling versus tissue chemical extraction,” Photochem. Photobiol.74:453–460 (2001).
[CrossRef] [PubMed]

J. C. Finlay, T. C. Zhu, A. Dimofte, D. Stripp, S. B. Malkowicz, T. M. Busch, and S. M. Hahn, “Interstitial fluorescence spectroscopy in the human prostate during motexafin lutetium-mediated photodynamic therapy,” Photochem. Photobiol.82:1270–1278 (2006).
[CrossRef] [PubMed]

World J. Gastroenterol.

N. Thekkek, S. Anandasabapathy, and R. Richards-Kortum, “Optical molecular imaging for detection of Barrett’s-associated neoplasia,” World J. Gastroenterol.17:53–62 (2011).
[CrossRef] [PubMed]

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Figures (6)

Fig. 1
Fig. 1

Effect of reduced scattering coefficient (equivalent at λx, λm) on single fiber fluorescence intensity. Linear and log scales of the data are presented in the following panel pairings: A and B show collected F S F sim vs. μs. C and D shift the x-axis to dimensionless reduced scattering μsdf. E and F shift the y-axis to a dimensionless form of fluorescence, as F S F ratio M C / d f.

Fig. 2
Fig. 2

Effect of independent variation of μs(λx) and μs(λm) on dimensionless single fiber fluorescence intensity, F S F sim / d f plotted vs μs(λx)df ; vertical stratification is due to influence of μs(λm) variation. Linear and log plots given on A and B, respectively.

Fig. 3
Fig. 3

A) Dimensionless sampling depth 〈ZMC〉/df vs. the product of average of reduced scattering coefficients at excitation and emission wavelengths, μs,avg and df. B) Excitation fluence within the sampled volume, Φ x M C d f 2 vs. dimensionless reduced scattering at the excitation wavelength, μs(λx)df. C) Escape probability of emission photons, H m M C vs. dimensionless reduced scattering at the emission wavelength, μs(λm)df. Fitted model estimates visualized by solid black lines.

Fig. 4
Fig. 4

Dimensionless single fiber fluorescence intensity estimated by fitted model vs. MC simulated values. Data include variations of μs(λx) and μs(λm). Line of unity included for comparative purposes.

Fig. 5
Fig. 5

Dimensionless single fiber fluorescence intensity estimated by fitted model (× marks) and returned by MC simulations (○ marks). Data include independent variation of μs(λx) and μs(λm), and are plotted vs. μs(λx)df. Linear and log plots given on A and B, respectively.

Fig. 6
Fig. 6

Dimensionless single fiber fluorescence intensity plotted vs. dimensionless reduced scattering calculated as A) mean of μs(λx) and μs(λm) and B) harmonic average expression including μs(λx) and μs(λm), given in Eqn 16. Smooth dependence of fluorescence intensity vs. these respective scattering parameters suggests region μsdf < 0.5 is dominated by volume effects, region μsdf > 0.5 is dominated by excitation fluence and emission probability within sampled volume.

Equations (16)

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

F S F ratio M C = TMPC TXPL
Z M C = i = 1 n z z i ( j = 1 n r F col ( r j , z i ) Δ a j ) Δ z i = 1 n z ( j = 1 n r F col ( r j , z i ) Δ a j ) Δ z
Φ x M C = i = 1 n z ( j = 1 n r Φ x ( r j , z i ) F col ( r j , z i ) Δ a j ) Δ z i = 1 n z ( j = 1 n r F col ( r j , z i ) Δ a j ) Δ z
H m M C = i = 1 n z ( j = 1 n r H m ( r j , z i ) F col ( r j , z i ) Δ a j ) Δ z i = 1 n z ( j = 1 n r F col ( r j , z i ) Δ a j ) Δ z
F = ( λ x / λ m ) μ a f Q f V Φ x ( r ) H m ( r ) d 3 r
F S F μ a f Q f V Φ x V H m V
V A 1 Z M C d f 2
Φ x V = P x Φ x M C
H m V = H m M C
F S F ratio M C = T M P C T X P L A 1 μ a f Q f Z M C d f 2 ϕ x M C H m M C
Z M C = d f A 2 ( μ s , avg d f ) A 3
Φ x M C = d f 2 B 1 e 1 B 2 ( μ s ( λ x ) d f ) + 1
H m M C = C 1 e C 3 C 2 ( μ s ( λ m ) d f ) + 1
F S F ratio M C μ a f Q f d f ν n = ζ 1 ( μ s , avg d f ) ζ 2 e ( 1 ζ 2 ( μ s ( λ x ) d f ) + 1 ζ 3 ζ 2 ( μ s ( λ m ) d f ) + 1 )
F S F sim = F S F ratio M C μ a f Q f ν n
μ s , h avg = 1 + ζ 3 1 μ s + ζ 3 μ s

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