Abstract

The measurement of optical scattering as a function of angle, goniometry, can provide a wealth of information about tissue. The goniometry technique described here measures the intensity profile at the pupil planes of two microscope objectives with a scattering sample between them. The maximum observable scattering angle is extended by employing off-axis illumination. This configuration permits several advantages including: i) rapid measurement of scattering into 4π sr to characterize the entire scattering phase function in isotropic tissue, ii) sensitivity to axially asymmetric scattering from anisotropic fibrous tissue, iii) selective interrogation of small regions within spatially inhomogenous tissue, iv) concurrent measurement of scattering coefficient μs, and v) measurement of wavelength dependent scattering properties via spectrally tunable source. The instrument is validated by comparing measurements of microsphere suspensions to the Mie scattering solution. Instrument capabilities are demonstrated with samples of rat brain and mouse eye tissues.

© 2017 Optical Society of America

Full Article  |  PDF Article
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2016 (1)

2015 (4)

J. A. Kurvits, M. Jiang, and R. Zia, “Comparative analysis of imaging configurations and objectives for Fourier microscopy,” J. Opt. Soc. Am. A 32, 2082–2092 (2015).
[Crossref]

Y. Liu, S. L. Jacques, M. Azimipour, J. D. Rogers, R. Pashaie, and K. W. Eliceiri, “OptogenSIM: a 3D Monte Carlo simulation platform for light delivery design in optogenetics,” Biomed. Opt. Express 6, 4859–4870 (2015).
[Crossref] [PubMed]

N. N. Mutyal, A. J. Radosevich, S. Bajaj, V. Konda, U. D. Siddiqui, I. Waxman, M. J. Goldberg, J. D. Rogers, B. Gould, A. Eshein, and et al., “In vivo risk analysis of pancreatic cancer through optical characterization of duodenal mucosa,” Pancreas 44, 735–741 (2015).
[Crossref] [PubMed]

A. J. Radosevich, N. N. Mutyal, A. Eshein, B. Gould, J. D. Rogers, M. J. Goldberg, L. K. Bianchi, E. F. Yen, V. Konda, D. K. Rex, and et al., “Rectal optical markers for in vivo risk stratification of premalignant colorectal lesions,” Clinical Cancer Research 21, 4347–4355 (2015).
[Crossref] [PubMed]

2014 (5)

A. J. Radosevich, N. N. Mutyal, J. D. Rogers, B. Gould, T. A. Hensing, D. Ray, V. Backman, and H. K. Roy, “Buccal spectral markers for lung cancer risk stratification,” PLoS ONE 9, e110157 (2014).
[Crossref]

L. Cherkezyan, Y. Stypula-Cyrus, H. Subramanian, C. White, M. Dela Cruz, R. K. Wali, M. J. Goldberg, L. K. Bianchi, H. K. Roy, and V. Backman, “Nanoscale changes in chromatin organization represent the initial steps of tumorigenesis: a transmission electron microscopy study,” BMC Cancer 14, 189 (2014).
[Crossref]

J. D. Rogers, A. J. Radosevich, J. Yi, and V. Backman, “Modeling light scattering in tissue as continuous random media using a versatile refractive index correlation function,” IEEE J. Sel. Top.n Quantum Electron. 20, 173 (2014).

Y. N. Sulai, D. Scoles, Z. Harvey, and A. Dubra, “Visualization of retinal vascular structure and perfusion with a nonconfocal adaptive optics scanning light ophthalmoscope,” J. Opt. Soc. Am. A 31, 569–579 (2014).
[Crossref]

S. C. Kanick, D. M. McClatchy, V. Krishnaswamy, J. T. Elliott, K. D. Paulsen, and B. W. Pogue, “Sub-diffusive scattering parameter maps recovered using wide-field high-frequency structured light imaging,” Biomed. Opt. Express 5, 3376–3390 (2014).
[Crossref] [PubMed]

2013 (4)

G. Zheng, R. Horstmeyer, and C. Yang, “Wide-field, high-resolution Fourier ptychographic microscopy,” Nature Photonics 7, 739–745 (2013).
[Crossref]

C. Zhu and Q. Liu, “Review of Monte Carlo modeling of light transport in tissues,” J. Biomed. Opt. 18, 050902 (2013).
[Crossref]

F. Foschum and A. Kienle, “Optimized goniometer for determination of the scattering phase function of suspended particles: simulations and measurements,” J. Biomed. Opt. 18, 85002 (2013).
[Crossref] [PubMed]

A. J. Radosevich, N. N. Mutyal, J. Yi, Y. Stypula-Cyrus, J. D. Rogers, M. J. Goldberg, L. K. Bianchi, S. Bajaj, H. K. Roy, and V. Backman, “Ultrastructural alterations in field carcinogenesis measured by enhanced backscattering spectroscopy,” J. Biomed. Opt. 18, 097002 (2013).
[Crossref] [PubMed]

2012 (2)

B. G. Yust, L. C. Mimun, and D. K. Sardar, “Optical absorption and scattering of bovine cornea, lens, and retina in the near-infrared region,” Lasers in Medical Science 27, 413–422 (2012).
[Crossref]

G. Hall, S. L. Jacques, K. W. Eliceiri, and P. J. Campagnola, “Goniometric measurements of thick tissue using Monte Carlo simulations to obtain the single scattering anisotropy coefficient,” Biomed. Opt. Express 3, 2707–2719 (2012).
[Crossref] [PubMed]

2011 (1)

A. Wax, N. G. Terry, E. S. Dellon, and N. J. Shaheen, “Angle-resolved low coherence interferometry for detection of dysplasia in Barrett’s esophagus,” Gastroenterology 141, 443–447 (2011).
[Crossref]

2010 (1)

D. Levitz, M. T. Hinds, A. Ardeshiri, S. R. Hanson, and S. L. Jacques, “Non-destructive label-free monitoring of collagen gel remodeling using optical coherence tomography,” Biomaterials 31, 8210–8217 (2010).
[Crossref] [PubMed]

2009 (2)

2007 (1)

2005 (3)

M. Xu and R. R. Alfano, “Fractal mechanisms of light scattering in biological tissue and cells,” Opt. Lett. 30, 3051–3053 (2005).
[Crossref]

D. K. Sardar, R. M. Yow, A. T. C. Tsin, and R. Sardar, “Optical scattering, absorption, and polarization of healthy and neovascularized human retinal tissues,” J. Biomed. Opt. 10, 051501 (2005).
[Crossref] [PubMed]

A. L. Mattheyses and D. Axelrod, “Fluorescence emission patterns near glass and metal-coated surfaces investigated with back focal plane imaging,” J. Biomed. Opt. 10, 054007 (2005).
[Crossref] [PubMed]

2004 (1)

2003 (2)

R. Drezek, M. Guillaud, T. Collier, I. Boiko, A. Malpica, C. Macaulay, M. Follen, and R. Richards-Kortum, “Light scattering from cervical cells throughout neoplastic progression: influence of nuclear morphology, DNA content, and chromatin texture,” J. Biomed. Opt. 8, 7–16 (2003).
[Crossref] [PubMed]

P. Thueler, I. Charvet, F. Bevilacqua, M. St Ghislain, G. Ory, P. Marquet, P. Meda, B. Vermeulen, and C. Depeursinge, “In vivo endoscopic tissue diagnostics based on spectroscopic absorption, scattering, and phase function properties,” J. Biomed. Opt. 8, 495–503 (2003).
[Crossref]

2002 (1)

A. Yaroslavsky, P. C. Schulze, I. V. Yaroslavsky, R. Schober, F. Ulrich, and H.-J. Schwarzmaier, “Optical properties of selected native and coagulated human brain tissues in vitro in the visible and near infrared spectral range,” Phys. Med. Biol. 47, 2059–2073 (2002).
[Crossref] [PubMed]

2001 (2)

1998 (1)

1996 (2)

J. Schmitt and G. Kumar, “Turbulent nature of refractive-index variations in biological tissue,” Opt. Lett. 21, 1310–1312 (1996).
[Crossref] [PubMed]

J. R. Mourant, J. Boyer, a. H. Hielscher, and I. J. Bigio, “Influence of the scattering phase function on light transport measurements in turbid media performed with small source-detector separations,” Optics Letters 21, 546–548 (1996).
[Crossref]

1995 (1)

M. Hammer, A. Roggan, D. Schweitzer, and G. Muller, “Optical properties of ocular fundus tissues-an in vitro study using the double-integrating-sphere technique and inverse Monte Carlo simulation,” Phys. Med. Biol. 40, 963–978 (1995).
[Crossref] [PubMed]

1987 (1)

S. L. Jacques, C. A. Alter, and S. A. Prahl, “Angular dependence of HeNe laser light scattering by human dermis,” Lasers in the Life Sciences 1, 309–333 (1987).

1982 (1)

D. E. Burger, J. H. Jett, and P. F. Mullaney, “Extraction of morphological features from biological models and cells by fourier analysis of static light scatter measurements,” Cytometry 2, 327–336 (1982).
[Crossref] [PubMed]

1966 (1)

W. Lukosz, “Optical Systems with Resolving Powers Exceeding the Classical Limit,” Journal of the Optical Society of America 56, 1463–1472 (1966).
[Crossref]

1941 (1)

L. C. Henyey and J. L. Greenstein, “Diffuse radiation in the Galaxy,” The Astrophysical Journal 93, 70–83 (1941).
[Crossref]

Ajtai, K.

T. P. Burghardt and K. Ajtai, “Mapping microscope object polarized emission to the back focal plane pattern,” J. Biomed. Opt. 14, 34036 (2009).
[Crossref]

Alfano, R. R.

Alter, C. A.

S. L. Jacques, C. A. Alter, and S. A. Prahl, “Angular dependence of HeNe laser light scattering by human dermis,” Lasers in the Life Sciences 1, 309–333 (1987).

Ardeshiri, A.

D. Levitz, M. T. Hinds, A. Ardeshiri, S. R. Hanson, and S. L. Jacques, “Non-destructive label-free monitoring of collagen gel remodeling using optical coherence tomography,” Biomaterials 31, 8210–8217 (2010).
[Crossref] [PubMed]

Axelrod, D.

A. L. Mattheyses and D. Axelrod, “Fluorescence emission patterns near glass and metal-coated surfaces investigated with back focal plane imaging,” J. Biomed. Opt. 10, 054007 (2005).
[Crossref] [PubMed]

Azimipour, M.

Backman, V.

A. J. Radosevich, N. N. Mutyal, J. D. Rogers, B. Gould, T. A. Hensing, D. Ray, V. Backman, and H. K. Roy, “Buccal spectral markers for lung cancer risk stratification,” PLoS ONE 9, e110157 (2014).
[Crossref]

J. D. Rogers, A. J. Radosevich, J. Yi, and V. Backman, “Modeling light scattering in tissue as continuous random media using a versatile refractive index correlation function,” IEEE J. Sel. Top.n Quantum Electron. 20, 173 (2014).

L. Cherkezyan, Y. Stypula-Cyrus, H. Subramanian, C. White, M. Dela Cruz, R. K. Wali, M. J. Goldberg, L. K. Bianchi, H. K. Roy, and V. Backman, “Nanoscale changes in chromatin organization represent the initial steps of tumorigenesis: a transmission electron microscopy study,” BMC Cancer 14, 189 (2014).
[Crossref]

A. J. Radosevich, N. N. Mutyal, J. Yi, Y. Stypula-Cyrus, J. D. Rogers, M. J. Goldberg, L. K. Bianchi, S. Bajaj, H. K. Roy, and V. Backman, “Ultrastructural alterations in field carcinogenesis measured by enhanced backscattering spectroscopy,” J. Biomed. Opt. 18, 097002 (2013).
[Crossref] [PubMed]

H. Subramanian, P. Pradhan, Y. Liu, I. R. Capoglu, J. D. Rogers, H. K. Roy, R. E. Brand, and V. Backman, “Partial-wave microscopic spectroscopy detects subwavelength refractive index fluctuations: an application to cancer diagnosis,” Opt. Lett. 34, 518–520 (2009).
[Crossref] [PubMed]

Bajaj, S.

N. N. Mutyal, A. J. Radosevich, S. Bajaj, V. Konda, U. D. Siddiqui, I. Waxman, M. J. Goldberg, J. D. Rogers, B. Gould, A. Eshein, and et al., “In vivo risk analysis of pancreatic cancer through optical characterization of duodenal mucosa,” Pancreas 44, 735–741 (2015).
[Crossref] [PubMed]

A. J. Radosevich, N. N. Mutyal, J. Yi, Y. Stypula-Cyrus, J. D. Rogers, M. J. Goldberg, L. K. Bianchi, S. Bajaj, H. K. Roy, and V. Backman, “Ultrastructural alterations in field carcinogenesis measured by enhanced backscattering spectroscopy,” J. Biomed. Opt. 18, 097002 (2013).
[Crossref] [PubMed]

Bevilacqua, F.

P. Thueler, I. Charvet, F. Bevilacqua, M. St Ghislain, G. Ory, P. Marquet, P. Meda, B. Vermeulen, and C. Depeursinge, “In vivo endoscopic tissue diagnostics based on spectroscopic absorption, scattering, and phase function properties,” J. Biomed. Opt. 8, 495–503 (2003).
[Crossref]

Bianchi, L. K.

A. J. Radosevich, N. N. Mutyal, A. Eshein, B. Gould, J. D. Rogers, M. J. Goldberg, L. K. Bianchi, E. F. Yen, V. Konda, D. K. Rex, and et al., “Rectal optical markers for in vivo risk stratification of premalignant colorectal lesions,” Clinical Cancer Research 21, 4347–4355 (2015).
[Crossref] [PubMed]

L. Cherkezyan, Y. Stypula-Cyrus, H. Subramanian, C. White, M. Dela Cruz, R. K. Wali, M. J. Goldberg, L. K. Bianchi, H. K. Roy, and V. Backman, “Nanoscale changes in chromatin organization represent the initial steps of tumorigenesis: a transmission electron microscopy study,” BMC Cancer 14, 189 (2014).
[Crossref]

A. J. Radosevich, N. N. Mutyal, J. Yi, Y. Stypula-Cyrus, J. D. Rogers, M. J. Goldberg, L. K. Bianchi, S. Bajaj, H. K. Roy, and V. Backman, “Ultrastructural alterations in field carcinogenesis measured by enhanced backscattering spectroscopy,” J. Biomed. Opt. 18, 097002 (2013).
[Crossref] [PubMed]

Bigio, I. J.

J. R. Mourant, J. Boyer, a. H. Hielscher, and I. J. Bigio, “Influence of the scattering phase function on light transport measurements in turbid media performed with small source-detector separations,” Optics Letters 21, 546–548 (1996).
[Crossref]

Bohren, C. F.

C. F. Bohren and D. Huffman, Absorption and Scattering of Light by Small Particles, Wiley science paperback series (Wiley, 1983).

Boiko, I.

R. Drezek, M. Guillaud, T. Collier, I. Boiko, A. Malpica, C. Macaulay, M. Follen, and R. Richards-Kortum, “Light scattering from cervical cells throughout neoplastic progression: influence of nuclear morphology, DNA content, and chromatin texture,” J. Biomed. Opt. 8, 7–16 (2003).
[Crossref] [PubMed]

Boustany, N. N.

Boyer, J.

J. R. Mourant, J. Boyer, a. H. Hielscher, and I. J. Bigio, “Influence of the scattering phase function on light transport measurements in turbid media performed with small source-detector separations,” Optics Letters 21, 546–548 (1996).
[Crossref]

Brand, R. E.

Burger, D. E.

D. E. Burger, J. H. Jett, and P. F. Mullaney, “Extraction of morphological features from biological models and cells by fourier analysis of static light scatter measurements,” Cytometry 2, 327–336 (1982).
[Crossref] [PubMed]

Burghardt, T. P.

T. P. Burghardt and K. Ajtai, “Mapping microscope object polarized emission to the back focal plane pattern,” J. Biomed. Opt. 14, 34036 (2009).
[Crossref]

Campagnola, P. J.

Capoglu, I. R.

Charvet, I.

P. Thueler, I. Charvet, F. Bevilacqua, M. St Ghislain, G. Ory, P. Marquet, P. Meda, B. Vermeulen, and C. Depeursinge, “In vivo endoscopic tissue diagnostics based on spectroscopic absorption, scattering, and phase function properties,” J. Biomed. Opt. 8, 495–503 (2003).
[Crossref]

Cherkezyan, L.

L. Cherkezyan, Y. Stypula-Cyrus, H. Subramanian, C. White, M. Dela Cruz, R. K. Wali, M. J. Goldberg, L. K. Bianchi, H. K. Roy, and V. Backman, “Nanoscale changes in chromatin organization represent the initial steps of tumorigenesis: a transmission electron microscopy study,” BMC Cancer 14, 189 (2014).
[Crossref]

Collier, T.

R. Drezek, M. Guillaud, T. Collier, I. Boiko, A. Malpica, C. Macaulay, M. Follen, and R. Richards-Kortum, “Light scattering from cervical cells throughout neoplastic progression: influence of nuclear morphology, DNA content, and chromatin texture,” J. Biomed. Opt. 8, 7–16 (2003).
[Crossref] [PubMed]

Dela Cruz, M.

L. Cherkezyan, Y. Stypula-Cyrus, H. Subramanian, C. White, M. Dela Cruz, R. K. Wali, M. J. Goldberg, L. K. Bianchi, H. K. Roy, and V. Backman, “Nanoscale changes in chromatin organization represent the initial steps of tumorigenesis: a transmission electron microscopy study,” BMC Cancer 14, 189 (2014).
[Crossref]

Dellon, E. S.

A. Wax, N. G. Terry, E. S. Dellon, and N. J. Shaheen, “Angle-resolved low coherence interferometry for detection of dysplasia in Barrett’s esophagus,” Gastroenterology 141, 443–447 (2011).
[Crossref]

Depeursinge, C.

P. Thueler, I. Charvet, F. Bevilacqua, M. St Ghislain, G. Ory, P. Marquet, P. Meda, B. Vermeulen, and C. Depeursinge, “In vivo endoscopic tissue diagnostics based on spectroscopic absorption, scattering, and phase function properties,” J. Biomed. Opt. 8, 495–503 (2003).
[Crossref]

Drezek, R.

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A. J. Radosevich, N. N. Mutyal, A. Eshein, B. Gould, J. D. Rogers, M. J. Goldberg, L. K. Bianchi, E. F. Yen, V. Konda, D. K. Rex, and et al., “Rectal optical markers for in vivo risk stratification of premalignant colorectal lesions,” Clinical Cancer Research 21, 4347–4355 (2015).
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R. Drezek, M. Guillaud, T. Collier, I. Boiko, A. Malpica, C. Macaulay, M. Follen, and R. Richards-Kortum, “Light scattering from cervical cells throughout neoplastic progression: influence of nuclear morphology, DNA content, and chromatin texture,” J. Biomed. Opt. 8, 7–16 (2003).
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N. N. Mutyal, A. J. Radosevich, S. Bajaj, V. Konda, U. D. Siddiqui, I. Waxman, M. J. Goldberg, J. D. Rogers, B. Gould, A. Eshein, and et al., “In vivo risk analysis of pancreatic cancer through optical characterization of duodenal mucosa,” Pancreas 44, 735–741 (2015).
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A. J. Radosevich, N. N. Mutyal, J. Yi, Y. Stypula-Cyrus, J. D. Rogers, M. J. Goldberg, L. K. Bianchi, S. Bajaj, H. K. Roy, and V. Backman, “Ultrastructural alterations in field carcinogenesis measured by enhanced backscattering spectroscopy,” J. Biomed. Opt. 18, 097002 (2013).
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N. N. Mutyal, A. J. Radosevich, S. Bajaj, V. Konda, U. D. Siddiqui, I. Waxman, M. J. Goldberg, J. D. Rogers, B. Gould, A. Eshein, and et al., “In vivo risk analysis of pancreatic cancer through optical characterization of duodenal mucosa,” Pancreas 44, 735–741 (2015).
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A. J. Radosevich, N. N. Mutyal, A. Eshein, B. Gould, J. D. Rogers, M. J. Goldberg, L. K. Bianchi, E. F. Yen, V. Konda, D. K. Rex, and et al., “Rectal optical markers for in vivo risk stratification of premalignant colorectal lesions,” Clinical Cancer Research 21, 4347–4355 (2015).
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A. J. Radosevich, N. N. Mutyal, J. D. Rogers, B. Gould, T. A. Hensing, D. Ray, V. Backman, and H. K. Roy, “Buccal spectral markers for lung cancer risk stratification,” PLoS ONE 9, e110157 (2014).
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M. Hammer, A. Roggan, D. Schweitzer, and G. Muller, “Optical properties of ocular fundus tissues-an in vitro study using the double-integrating-sphere technique and inverse Monte Carlo simulation,” Phys. Med. Biol. 40, 963–978 (1995).
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A. J. Radosevich, N. N. Mutyal, J. D. Rogers, B. Gould, T. A. Hensing, D. Ray, V. Backman, and H. K. Roy, “Buccal spectral markers for lung cancer risk stratification,” PLoS ONE 9, e110157 (2014).
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D. Levitz, M. T. Hinds, A. Ardeshiri, S. R. Hanson, and S. L. Jacques, “Non-destructive label-free monitoring of collagen gel remodeling using optical coherence tomography,” Biomaterials 31, 8210–8217 (2010).
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F. Foschum and A. Kienle, “Optimized goniometer for determination of the scattering phase function of suspended particles: simulations and measurements,” J. Biomed. Opt. 18, 85002 (2013).
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N. N. Mutyal, A. J. Radosevich, S. Bajaj, V. Konda, U. D. Siddiqui, I. Waxman, M. J. Goldberg, J. D. Rogers, B. Gould, A. Eshein, and et al., “In vivo risk analysis of pancreatic cancer through optical characterization of duodenal mucosa,” Pancreas 44, 735–741 (2015).
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A. J. Radosevich, N. N. Mutyal, A. Eshein, B. Gould, J. D. Rogers, M. J. Goldberg, L. K. Bianchi, E. F. Yen, V. Konda, D. K. Rex, and et al., “Rectal optical markers for in vivo risk stratification of premalignant colorectal lesions,” Clinical Cancer Research 21, 4347–4355 (2015).
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D. Levitz, M. T. Hinds, A. Ardeshiri, S. R. Hanson, and S. L. Jacques, “Non-destructive label-free monitoring of collagen gel remodeling using optical coherence tomography,” Biomaterials 31, 8210–8217 (2010).
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R. Drezek, M. Guillaud, T. Collier, I. Boiko, A. Malpica, C. Macaulay, M. Follen, and R. Richards-Kortum, “Light scattering from cervical cells throughout neoplastic progression: influence of nuclear morphology, DNA content, and chromatin texture,” J. Biomed. Opt. 8, 7–16 (2003).
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P. Thueler, I. Charvet, F. Bevilacqua, M. St Ghislain, G. Ory, P. Marquet, P. Meda, B. Vermeulen, and C. Depeursinge, “In vivo endoscopic tissue diagnostics based on spectroscopic absorption, scattering, and phase function properties,” J. Biomed. Opt. 8, 495–503 (2003).
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B. G. Yust, L. C. Mimun, and D. K. Sardar, “Optical absorption and scattering of bovine cornea, lens, and retina in the near-infrared region,” Lasers in Medical Science 27, 413–422 (2012).
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J. R. Mourant, J. P. Freyer, a. H. Hielscher, a. a. Eick, D. Shen, and T. M. Johnson, “Mechanisms of light scattering from biological cells relevant to noninvasive optical-tissue diagnostics,” Appl. Opt. 37, 3586–3593 (1998).
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J. R. Mourant, J. Boyer, a. H. Hielscher, and I. J. Bigio, “Influence of the scattering phase function on light transport measurements in turbid media performed with small source-detector separations,” Optics Letters 21, 546–548 (1996).
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Mullaney, P. F.

D. E. Burger, J. H. Jett, and P. F. Mullaney, “Extraction of morphological features from biological models and cells by fourier analysis of static light scatter measurements,” Cytometry 2, 327–336 (1982).
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M. Hammer, A. Roggan, D. Schweitzer, and G. Muller, “Optical properties of ocular fundus tissues-an in vitro study using the double-integrating-sphere technique and inverse Monte Carlo simulation,” Phys. Med. Biol. 40, 963–978 (1995).
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N. N. Mutyal, A. J. Radosevich, S. Bajaj, V. Konda, U. D. Siddiqui, I. Waxman, M. J. Goldberg, J. D. Rogers, B. Gould, A. Eshein, and et al., “In vivo risk analysis of pancreatic cancer through optical characterization of duodenal mucosa,” Pancreas 44, 735–741 (2015).
[Crossref] [PubMed]

A. J. Radosevich, N. N. Mutyal, A. Eshein, B. Gould, J. D. Rogers, M. J. Goldberg, L. K. Bianchi, E. F. Yen, V. Konda, D. K. Rex, and et al., “Rectal optical markers for in vivo risk stratification of premalignant colorectal lesions,” Clinical Cancer Research 21, 4347–4355 (2015).
[Crossref] [PubMed]

A. J. Radosevich, N. N. Mutyal, J. D. Rogers, B. Gould, T. A. Hensing, D. Ray, V. Backman, and H. K. Roy, “Buccal spectral markers for lung cancer risk stratification,” PLoS ONE 9, e110157 (2014).
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A. J. Radosevich, N. N. Mutyal, J. Yi, Y. Stypula-Cyrus, J. D. Rogers, M. J. Goldberg, L. K. Bianchi, S. Bajaj, H. K. Roy, and V. Backman, “Ultrastructural alterations in field carcinogenesis measured by enhanced backscattering spectroscopy,” J. Biomed. Opt. 18, 097002 (2013).
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A. J. Radosevich, N. N. Mutyal, A. Eshein, B. Gould, J. D. Rogers, M. J. Goldberg, L. K. Bianchi, E. F. Yen, V. Konda, D. K. Rex, and et al., “Rectal optical markers for in vivo risk stratification of premalignant colorectal lesions,” Clinical Cancer Research 21, 4347–4355 (2015).
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N. N. Mutyal, A. J. Radosevich, S. Bajaj, V. Konda, U. D. Siddiqui, I. Waxman, M. J. Goldberg, J. D. Rogers, B. Gould, A. Eshein, and et al., “In vivo risk analysis of pancreatic cancer through optical characterization of duodenal mucosa,” Pancreas 44, 735–741 (2015).
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J. D. Rogers, A. J. Radosevich, J. Yi, and V. Backman, “Modeling light scattering in tissue as continuous random media using a versatile refractive index correlation function,” IEEE J. Sel. Top.n Quantum Electron. 20, 173 (2014).

A. J. Radosevich, N. N. Mutyal, J. D. Rogers, B. Gould, T. A. Hensing, D. Ray, V. Backman, and H. K. Roy, “Buccal spectral markers for lung cancer risk stratification,” PLoS ONE 9, e110157 (2014).
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A. J. Radosevich, N. N. Mutyal, J. Yi, Y. Stypula-Cyrus, J. D. Rogers, M. J. Goldberg, L. K. Bianchi, S. Bajaj, H. K. Roy, and V. Backman, “Ultrastructural alterations in field carcinogenesis measured by enhanced backscattering spectroscopy,” J. Biomed. Opt. 18, 097002 (2013).
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A. J. Radosevich, N. N. Mutyal, J. D. Rogers, B. Gould, T. A. Hensing, D. Ray, V. Backman, and H. K. Roy, “Buccal spectral markers for lung cancer risk stratification,” PLoS ONE 9, e110157 (2014).
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A. J. Radosevich, N. N. Mutyal, A. Eshein, B. Gould, J. D. Rogers, M. J. Goldberg, L. K. Bianchi, E. F. Yen, V. Konda, D. K. Rex, and et al., “Rectal optical markers for in vivo risk stratification of premalignant colorectal lesions,” Clinical Cancer Research 21, 4347–4355 (2015).
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R. Drezek, M. Guillaud, T. Collier, I. Boiko, A. Malpica, C. Macaulay, M. Follen, and R. Richards-Kortum, “Light scattering from cervical cells throughout neoplastic progression: influence of nuclear morphology, DNA content, and chromatin texture,” J. Biomed. Opt. 8, 7–16 (2003).
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N. N. Mutyal, A. J. Radosevich, S. Bajaj, V. Konda, U. D. Siddiqui, I. Waxman, M. J. Goldberg, J. D. Rogers, B. Gould, A. Eshein, and et al., “In vivo risk analysis of pancreatic cancer through optical characterization of duodenal mucosa,” Pancreas 44, 735–741 (2015).
[Crossref] [PubMed]

A. J. Radosevich, N. N. Mutyal, A. Eshein, B. Gould, J. D. Rogers, M. J. Goldberg, L. K. Bianchi, E. F. Yen, V. Konda, D. K. Rex, and et al., “Rectal optical markers for in vivo risk stratification of premalignant colorectal lesions,” Clinical Cancer Research 21, 4347–4355 (2015).
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A. J. Radosevich, N. N. Mutyal, J. D. Rogers, B. Gould, T. A. Hensing, D. Ray, V. Backman, and H. K. Roy, “Buccal spectral markers for lung cancer risk stratification,” PLoS ONE 9, e110157 (2014).
[Crossref]

J. D. Rogers, A. J. Radosevich, J. Yi, and V. Backman, “Modeling light scattering in tissue as continuous random media using a versatile refractive index correlation function,” IEEE J. Sel. Top.n Quantum Electron. 20, 173 (2014).

A. J. Radosevich, N. N. Mutyal, J. Yi, Y. Stypula-Cyrus, J. D. Rogers, M. J. Goldberg, L. K. Bianchi, S. Bajaj, H. K. Roy, and V. Backman, “Ultrastructural alterations in field carcinogenesis measured by enhanced backscattering spectroscopy,” J. Biomed. Opt. 18, 097002 (2013).
[Crossref] [PubMed]

H. Subramanian, P. Pradhan, Y. Liu, I. R. Capoglu, J. D. Rogers, H. K. Roy, R. E. Brand, and V. Backman, “Partial-wave microscopic spectroscopy detects subwavelength refractive index fluctuations: an application to cancer diagnosis,” Opt. Lett. 34, 518–520 (2009).
[Crossref] [PubMed]

Roggan, A.

M. Hammer, A. Roggan, D. Schweitzer, and G. Muller, “Optical properties of ocular fundus tissues-an in vitro study using the double-integrating-sphere technique and inverse Monte Carlo simulation,” Phys. Med. Biol. 40, 963–978 (1995).
[Crossref] [PubMed]

Rossi, V. M.

Roy, H. K.

A. J. Radosevich, N. N. Mutyal, J. D. Rogers, B. Gould, T. A. Hensing, D. Ray, V. Backman, and H. K. Roy, “Buccal spectral markers for lung cancer risk stratification,” PLoS ONE 9, e110157 (2014).
[Crossref]

L. Cherkezyan, Y. Stypula-Cyrus, H. Subramanian, C. White, M. Dela Cruz, R. K. Wali, M. J. Goldberg, L. K. Bianchi, H. K. Roy, and V. Backman, “Nanoscale changes in chromatin organization represent the initial steps of tumorigenesis: a transmission electron microscopy study,” BMC Cancer 14, 189 (2014).
[Crossref]

A. J. Radosevich, N. N. Mutyal, J. Yi, Y. Stypula-Cyrus, J. D. Rogers, M. J. Goldberg, L. K. Bianchi, S. Bajaj, H. K. Roy, and V. Backman, “Ultrastructural alterations in field carcinogenesis measured by enhanced backscattering spectroscopy,” J. Biomed. Opt. 18, 097002 (2013).
[Crossref] [PubMed]

H. Subramanian, P. Pradhan, Y. Liu, I. R. Capoglu, J. D. Rogers, H. K. Roy, R. E. Brand, and V. Backman, “Partial-wave microscopic spectroscopy detects subwavelength refractive index fluctuations: an application to cancer diagnosis,” Opt. Lett. 34, 518–520 (2009).
[Crossref] [PubMed]

Sardar, D. K.

B. G. Yust, L. C. Mimun, and D. K. Sardar, “Optical absorption and scattering of bovine cornea, lens, and retina in the near-infrared region,” Lasers in Medical Science 27, 413–422 (2012).
[Crossref]

D. K. Sardar, R. M. Yow, A. T. C. Tsin, and R. Sardar, “Optical scattering, absorption, and polarization of healthy and neovascularized human retinal tissues,” J. Biomed. Opt. 10, 051501 (2005).
[Crossref] [PubMed]

Sardar, R.

D. K. Sardar, R. M. Yow, A. T. C. Tsin, and R. Sardar, “Optical scattering, absorption, and polarization of healthy and neovascularized human retinal tissues,” J. Biomed. Opt. 10, 051501 (2005).
[Crossref] [PubMed]

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Schober, R.

A. Yaroslavsky, P. C. Schulze, I. V. Yaroslavsky, R. Schober, F. Ulrich, and H.-J. Schwarzmaier, “Optical properties of selected native and coagulated human brain tissues in vitro in the visible and near infrared spectral range,” Phys. Med. Biol. 47, 2059–2073 (2002).
[Crossref] [PubMed]

Schulze, P. C.

A. Yaroslavsky, P. C. Schulze, I. V. Yaroslavsky, R. Schober, F. Ulrich, and H.-J. Schwarzmaier, “Optical properties of selected native and coagulated human brain tissues in vitro in the visible and near infrared spectral range,” Phys. Med. Biol. 47, 2059–2073 (2002).
[Crossref] [PubMed]

Schwarzmaier, H.-J.

A. Yaroslavsky, P. C. Schulze, I. V. Yaroslavsky, R. Schober, F. Ulrich, and H.-J. Schwarzmaier, “Optical properties of selected native and coagulated human brain tissues in vitro in the visible and near infrared spectral range,” Phys. Med. Biol. 47, 2059–2073 (2002).
[Crossref] [PubMed]

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M. Hammer, A. Roggan, D. Schweitzer, and G. Muller, “Optical properties of ocular fundus tissues-an in vitro study using the double-integrating-sphere technique and inverse Monte Carlo simulation,” Phys. Med. Biol. 40, 963–978 (1995).
[Crossref] [PubMed]

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Shaheen, N. J.

A. Wax, N. G. Terry, E. S. Dellon, and N. J. Shaheen, “Angle-resolved low coherence interferometry for detection of dysplasia in Barrett’s esophagus,” Gastroenterology 141, 443–447 (2011).
[Crossref]

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Sheppard, C. J.

Siddiqui, U. D.

N. N. Mutyal, A. J. Radosevich, S. Bajaj, V. Konda, U. D. Siddiqui, I. Waxman, M. J. Goldberg, J. D. Rogers, B. Gould, A. Eshein, and et al., “In vivo risk analysis of pancreatic cancer through optical characterization of duodenal mucosa,” Pancreas 44, 735–741 (2015).
[Crossref] [PubMed]

St Ghislain, M.

P. Thueler, I. Charvet, F. Bevilacqua, M. St Ghislain, G. Ory, P. Marquet, P. Meda, B. Vermeulen, and C. Depeursinge, “In vivo endoscopic tissue diagnostics based on spectroscopic absorption, scattering, and phase function properties,” J. Biomed. Opt. 8, 495–503 (2003).
[Crossref]

Stypula-Cyrus, Y.

L. Cherkezyan, Y. Stypula-Cyrus, H. Subramanian, C. White, M. Dela Cruz, R. K. Wali, M. J. Goldberg, L. K. Bianchi, H. K. Roy, and V. Backman, “Nanoscale changes in chromatin organization represent the initial steps of tumorigenesis: a transmission electron microscopy study,” BMC Cancer 14, 189 (2014).
[Crossref]

A. J. Radosevich, N. N. Mutyal, J. Yi, Y. Stypula-Cyrus, J. D. Rogers, M. J. Goldberg, L. K. Bianchi, S. Bajaj, H. K. Roy, and V. Backman, “Ultrastructural alterations in field carcinogenesis measured by enhanced backscattering spectroscopy,” J. Biomed. Opt. 18, 097002 (2013).
[Crossref] [PubMed]

Subramanian, H.

L. Cherkezyan, Y. Stypula-Cyrus, H. Subramanian, C. White, M. Dela Cruz, R. K. Wali, M. J. Goldberg, L. K. Bianchi, H. K. Roy, and V. Backman, “Nanoscale changes in chromatin organization represent the initial steps of tumorigenesis: a transmission electron microscopy study,” BMC Cancer 14, 189 (2014).
[Crossref]

H. Subramanian, P. Pradhan, Y. Liu, I. R. Capoglu, J. D. Rogers, H. K. Roy, R. E. Brand, and V. Backman, “Partial-wave microscopic spectroscopy detects subwavelength refractive index fluctuations: an application to cancer diagnosis,” Opt. Lett. 34, 518–520 (2009).
[Crossref] [PubMed]

Sulai, Y. N.

Terry, N. G.

A. Wax, N. G. Terry, E. S. Dellon, and N. J. Shaheen, “Angle-resolved low coherence interferometry for detection of dysplasia in Barrett’s esophagus,” Gastroenterology 141, 443–447 (2011).
[Crossref]

Thakor, N. V.

Thueler, P.

P. Thueler, I. Charvet, F. Bevilacqua, M. St Ghislain, G. Ory, P. Marquet, P. Meda, B. Vermeulen, and C. Depeursinge, “In vivo endoscopic tissue diagnostics based on spectroscopic absorption, scattering, and phase function properties,” J. Biomed. Opt. 8, 495–503 (2003).
[Crossref]

Tsin, A. T. C.

D. K. Sardar, R. M. Yow, A. T. C. Tsin, and R. Sardar, “Optical scattering, absorption, and polarization of healthy and neovascularized human retinal tissues,” J. Biomed. Opt. 10, 051501 (2005).
[Crossref] [PubMed]

Ulrich, F.

A. Yaroslavsky, P. C. Schulze, I. V. Yaroslavsky, R. Schober, F. Ulrich, and H.-J. Schwarzmaier, “Optical properties of selected native and coagulated human brain tissues in vitro in the visible and near infrared spectral range,” Phys. Med. Biol. 47, 2059–2073 (2002).
[Crossref] [PubMed]

Valentine, M. T.

Vermeulen, B.

P. Thueler, I. Charvet, F. Bevilacqua, M. St Ghislain, G. Ory, P. Marquet, P. Meda, B. Vermeulen, and C. Depeursinge, “In vivo endoscopic tissue diagnostics based on spectroscopic absorption, scattering, and phase function properties,” J. Biomed. Opt. 8, 495–503 (2003).
[Crossref]

Wali, R. K.

L. Cherkezyan, Y. Stypula-Cyrus, H. Subramanian, C. White, M. Dela Cruz, R. K. Wali, M. J. Goldberg, L. K. Bianchi, H. K. Roy, and V. Backman, “Nanoscale changes in chromatin organization represent the initial steps of tumorigenesis: a transmission electron microscopy study,” BMC Cancer 14, 189 (2014).
[Crossref]

Wax, A.

A. Wax, N. G. Terry, E. S. Dellon, and N. J. Shaheen, “Angle-resolved low coherence interferometry for detection of dysplasia in Barrett’s esophagus,” Gastroenterology 141, 443–447 (2011).
[Crossref]

Waxman, I.

N. N. Mutyal, A. J. Radosevich, S. Bajaj, V. Konda, U. D. Siddiqui, I. Waxman, M. J. Goldberg, J. D. Rogers, B. Gould, A. Eshein, and et al., “In vivo risk analysis of pancreatic cancer through optical characterization of duodenal mucosa,” Pancreas 44, 735–741 (2015).
[Crossref] [PubMed]

Weitz, D. A.

White, C.

L. Cherkezyan, Y. Stypula-Cyrus, H. Subramanian, C. White, M. Dela Cruz, R. K. Wali, M. J. Goldberg, L. K. Bianchi, H. K. Roy, and V. Backman, “Nanoscale changes in chromatin organization represent the initial steps of tumorigenesis: a transmission electron microscopy study,” BMC Cancer 14, 189 (2014).
[Crossref]

Xu, M.

Yang, C.

G. Zheng, R. Horstmeyer, and C. Yang, “Wide-field, high-resolution Fourier ptychographic microscopy,” Nature Photonics 7, 739–745 (2013).
[Crossref]

Yaroslavsky, A.

A. Yaroslavsky, P. C. Schulze, I. V. Yaroslavsky, R. Schober, F. Ulrich, and H.-J. Schwarzmaier, “Optical properties of selected native and coagulated human brain tissues in vitro in the visible and near infrared spectral range,” Phys. Med. Biol. 47, 2059–2073 (2002).
[Crossref] [PubMed]

Yaroslavsky, I. V.

A. Yaroslavsky, P. C. Schulze, I. V. Yaroslavsky, R. Schober, F. Ulrich, and H.-J. Schwarzmaier, “Optical properties of selected native and coagulated human brain tissues in vitro in the visible and near infrared spectral range,” Phys. Med. Biol. 47, 2059–2073 (2002).
[Crossref] [PubMed]

Yen, E. F.

A. J. Radosevich, N. N. Mutyal, A. Eshein, B. Gould, J. D. Rogers, M. J. Goldberg, L. K. Bianchi, E. F. Yen, V. Konda, D. K. Rex, and et al., “Rectal optical markers for in vivo risk stratification of premalignant colorectal lesions,” Clinical Cancer Research 21, 4347–4355 (2015).
[Crossref] [PubMed]

Yi, J.

J. D. Rogers, A. J. Radosevich, J. Yi, and V. Backman, “Modeling light scattering in tissue as continuous random media using a versatile refractive index correlation function,” IEEE J. Sel. Top.n Quantum Electron. 20, 173 (2014).

A. J. Radosevich, N. N. Mutyal, J. Yi, Y. Stypula-Cyrus, J. D. Rogers, M. J. Goldberg, L. K. Bianchi, S. Bajaj, H. K. Roy, and V. Backman, “Ultrastructural alterations in field carcinogenesis measured by enhanced backscattering spectroscopy,” J. Biomed. Opt. 18, 097002 (2013).
[Crossref] [PubMed]

Yow, R. M.

D. K. Sardar, R. M. Yow, A. T. C. Tsin, and R. Sardar, “Optical scattering, absorption, and polarization of healthy and neovascularized human retinal tissues,” J. Biomed. Opt. 10, 051501 (2005).
[Crossref] [PubMed]

Yust, B. G.

B. G. Yust, L. C. Mimun, and D. K. Sardar, “Optical absorption and scattering of bovine cornea, lens, and retina in the near-infrared region,” Lasers in Medical Science 27, 413–422 (2012).
[Crossref]

Zavislan, J. M.

Zheng, G.

G. Zheng, R. Horstmeyer, and C. Yang, “Wide-field, high-resolution Fourier ptychographic microscopy,” Nature Photonics 7, 739–745 (2013).
[Crossref]

Zhu, C.

C. Zhu and Q. Liu, “Review of Monte Carlo modeling of light transport in tissues,” J. Biomed. Opt. 18, 050902 (2013).
[Crossref]

Zia, R.

Appl. Opt. (1)

Biomaterials (1)

D. Levitz, M. T. Hinds, A. Ardeshiri, S. R. Hanson, and S. L. Jacques, “Non-destructive label-free monitoring of collagen gel remodeling using optical coherence tomography,” Biomaterials 31, 8210–8217 (2010).
[Crossref] [PubMed]

Biomed. Opt. Express (3)

BMC Cancer (1)

L. Cherkezyan, Y. Stypula-Cyrus, H. Subramanian, C. White, M. Dela Cruz, R. K. Wali, M. J. Goldberg, L. K. Bianchi, H. K. Roy, and V. Backman, “Nanoscale changes in chromatin organization represent the initial steps of tumorigenesis: a transmission electron microscopy study,” BMC Cancer 14, 189 (2014).
[Crossref]

Clinical Cancer Research (1)

A. J. Radosevich, N. N. Mutyal, A. Eshein, B. Gould, J. D. Rogers, M. J. Goldberg, L. K. Bianchi, E. F. Yen, V. Konda, D. K. Rex, and et al., “Rectal optical markers for in vivo risk stratification of premalignant colorectal lesions,” Clinical Cancer Research 21, 4347–4355 (2015).
[Crossref] [PubMed]

Cytometry (1)

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Gastroenterology (1)

A. Wax, N. G. Terry, E. S. Dellon, and N. J. Shaheen, “Angle-resolved low coherence interferometry for detection of dysplasia in Barrett’s esophagus,” Gastroenterology 141, 443–447 (2011).
[Crossref]

IEEE J. Sel. Top.n Quantum Electron. (1)

J. D. Rogers, A. J. Radosevich, J. Yi, and V. Backman, “Modeling light scattering in tissue as continuous random media using a versatile refractive index correlation function,” IEEE J. Sel. Top.n Quantum Electron. 20, 173 (2014).

J. Biomed. Opt. (8)

C. Zhu and Q. Liu, “Review of Monte Carlo modeling of light transport in tissues,” J. Biomed. Opt. 18, 050902 (2013).
[Crossref]

R. Drezek, M. Guillaud, T. Collier, I. Boiko, A. Malpica, C. Macaulay, M. Follen, and R. Richards-Kortum, “Light scattering from cervical cells throughout neoplastic progression: influence of nuclear morphology, DNA content, and chromatin texture,” J. Biomed. Opt. 8, 7–16 (2003).
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A. J. Radosevich, N. N. Mutyal, J. Yi, Y. Stypula-Cyrus, J. D. Rogers, M. J. Goldberg, L. K. Bianchi, S. Bajaj, H. K. Roy, and V. Backman, “Ultrastructural alterations in field carcinogenesis measured by enhanced backscattering spectroscopy,” J. Biomed. Opt. 18, 097002 (2013).
[Crossref] [PubMed]

D. K. Sardar, R. M. Yow, A. T. C. Tsin, and R. Sardar, “Optical scattering, absorption, and polarization of healthy and neovascularized human retinal tissues,” J. Biomed. Opt. 10, 051501 (2005).
[Crossref] [PubMed]

F. Foschum and A. Kienle, “Optimized goniometer for determination of the scattering phase function of suspended particles: simulations and measurements,” J. Biomed. Opt. 18, 85002 (2013).
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A. L. Mattheyses and D. Axelrod, “Fluorescence emission patterns near glass and metal-coated surfaces investigated with back focal plane imaging,” J. Biomed. Opt. 10, 054007 (2005).
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T. P. Burghardt and K. Ajtai, “Mapping microscope object polarized emission to the back focal plane pattern,” J. Biomed. Opt. 14, 34036 (2009).
[Crossref]

P. Thueler, I. Charvet, F. Bevilacqua, M. St Ghislain, G. Ory, P. Marquet, P. Meda, B. Vermeulen, and C. Depeursinge, “In vivo endoscopic tissue diagnostics based on spectroscopic absorption, scattering, and phase function properties,” J. Biomed. Opt. 8, 495–503 (2003).
[Crossref]

J. Opt. Soc. Am. A (2)

J. Opt. Soc. Am. B (1)

Journal of the Optical Society of America (1)

W. Lukosz, “Optical Systems with Resolving Powers Exceeding the Classical Limit,” Journal of the Optical Society of America 56, 1463–1472 (1966).
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Lasers in Medical Science (1)

B. G. Yust, L. C. Mimun, and D. K. Sardar, “Optical absorption and scattering of bovine cornea, lens, and retina in the near-infrared region,” Lasers in Medical Science 27, 413–422 (2012).
[Crossref]

Lasers in the Life Sciences (1)

S. L. Jacques, C. A. Alter, and S. A. Prahl, “Angular dependence of HeNe laser light scattering by human dermis,” Lasers in the Life Sciences 1, 309–333 (1987).

Nature Photonics (1)

G. Zheng, R. Horstmeyer, and C. Yang, “Wide-field, high-resolution Fourier ptychographic microscopy,” Nature Photonics 7, 739–745 (2013).
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Opt. Express (1)

Opt. Lett. (6)

Optics Letters (1)

J. R. Mourant, J. Boyer, a. H. Hielscher, and I. J. Bigio, “Influence of the scattering phase function on light transport measurements in turbid media performed with small source-detector separations,” Optics Letters 21, 546–548 (1996).
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Pancreas (1)

N. N. Mutyal, A. J. Radosevich, S. Bajaj, V. Konda, U. D. Siddiqui, I. Waxman, M. J. Goldberg, J. D. Rogers, B. Gould, A. Eshein, and et al., “In vivo risk analysis of pancreatic cancer through optical characterization of duodenal mucosa,” Pancreas 44, 735–741 (2015).
[Crossref] [PubMed]

Phys. Med. Biol. (2)

A. Yaroslavsky, P. C. Schulze, I. V. Yaroslavsky, R. Schober, F. Ulrich, and H.-J. Schwarzmaier, “Optical properties of selected native and coagulated human brain tissues in vitro in the visible and near infrared spectral range,” Phys. Med. Biol. 47, 2059–2073 (2002).
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PLoS ONE (1)

A. J. Radosevich, N. N. Mutyal, J. D. Rogers, B. Gould, T. A. Hensing, D. Ray, V. Backman, and H. K. Roy, “Buccal spectral markers for lung cancer risk stratification,” PLoS ONE 9, e110157 (2014).
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Figures (6)

Fig. 1
Fig. 1

Off-axis objective goniometry: (a) Incident light is focused into the back focal plane of an objective, creating a collimated beam through the sample plane. Angle space is only observable up to the objective NA, as indicated by the dashed lines. (b) By moving the location of the input focus, the angle at the sample plane is changed. As a result, angles up to 2NA are observable. Utilizing high-NA objectives, this allows observation of scattering angles beyond 90°. Demonstration of the off-axis approach: (c) forward scattering of circularly polarized 525 nm light by polystyrene spheres in water (azimuthally equidistant projection of the BFP, normalized log intensity scale.) (d) two off-axis scattering acquisitions from opposite sides of the BFP over-layed on (c). While (c) allows observation of scattering out to the objective NA, (d) demonstrates measurement to 2NA. The additional images demonstrate observation of forward scattering past θ = 90°. Color bar shows intensity spanning three orders of magnitude.

Fig. 2
Fig. 2

Experimental set-up and instrument modes: (a) Focused light is directed by galvos into the back focal plane (BFP) of the input objective. Scattered light is collected by an objective in the forward direction as well as by the input objective. Combining patterns from forward and backward channels for different angles allows observation of 4π sr of scattering. Removing the Bertrand lens allows for forward imaging for navigating the sample. Instrument modes: (b) imaging: 1.54 μm polystyrene spheres in water used for scattering calibration. The area illuminated in imaging mode is adjustable from ∼ 25 − 300 μm; scale-bar = 50 μm. Although not optimized for image quality, 1.54μm spheres are easily seen and this functionality allows for navigation of the sample. (c) goniometry: forward Mie scattering pattern observed from area illuminated in (b).

Fig. 3
Fig. 3

Mie calibration: Expected Mie phase function and experimentally observed phase function for scattering of 525 nm light from 1.54 um PS spheres in water. This trace is derived from azimuthal average of Fig. 1(d) and the corresponding backward channel. The Mie pattern angular structure functions as a ‘ruler’ to verify that accounting for refraction, distortion, rotations, and stitching is correctly implemented.

Fig. 4
Fig. 4

Optical scattering properties of fixed rat brain tissue: Left panel: Scattering coefficient (μs). Scattering is larger for white matter than grey matter, as expected. Error bars indicate standard deviation of measurements from 10 tissue locations. Right panel: Anisotropy (g) for scattering from isotropic tissue, grey matter. This technique gives access to the entire scattering phase function, 4π sr of scattering angle space. Values of g are derived from analysis of an experimental scattering curve (an example is shown in the inset). The dashed/dotted trace comes from fitting the Henyey-Greenstein phase function, while the dotted trace is the anisotropy computed directly via integration. Error bars indicate standard deviation from 3 different tissue locations.

Fig. 5
Fig. 5

Anisotropic tissue such as rat brain white-matter shows a scattering pattern that is not axially symmetric. As a result, intensity curves at different ϕ angles have broader or narrower scattering profiles. Inset: raw BFP image showing the asymmetrical pattern with approximate location of corresponding intensity curves.

Fig. 6
Fig. 6

Measurement of μs and g in mouse eye tissue. The small size of the ∼100 μm diameter interrogation spot enables measurements of distinct layers in ocular tissue. (a) Scattering coefficient, μs, decrease with wavelength as expected. The sclera is the most scattering, followed by photoreceptor (PR) layer and outer nuclear layer (ONL). Although both part of the retina, the ONL is much less scattering than the PR layer. (b) Anisotropy, g, is computed via integration, see equation 6. g increases with wavelength as expected. Error bars indicate the standard deviation from 3 spots for each tissue type. Although sclera and the photoreceptor layers exhibit similar g, the ONL has significantly higher g. (c) A dark-field image from a commercial microscope shows consistent results with higher scattering from sclera and PR, but lower scattering from the ONL: Dashed circles indicate representative relative locations and interrogation beam spot size. (d) Goniometer in ‘imaging’ mode showing the view of the sample used for navigation by removing the Bertrand lens. A wide-field image is obtained by illuminating a diffuser in the optical and the green overlay is an image of the spot used during a measurement of the PR layer.

Equations (6)

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p ( θ ) = 1 4 π 1 g 2 ( 1 + g 2 2 g cos ( θ ) ) 3 / 2
R x = [ 1 0 0 0 cos α sin α 0 sin α cos α ] R y = [ cos β 0 sin β 0 1 0 sin β 0 cos β ]
β = arctan ( tan θ cos ϕ ) α = arccos ( cos θ cos β )
μ s p ( θ , ϕ ) = d σ d Ω ( θ , ϕ ) / V
d σ d Ω ( θ / ϕ ) / V = I s ( θ , ϕ ) r 2 I i V exp
g = 2 π p ( θ ) cos ( θ ) sin ( θ ) d θ

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