Abstract

There is potential clinical significance in identifying cellular responses in the anterior chamber (AC) of the eye, which can indicate hyphema (an accumulation of red blood cells [RBCs]) or aberrant intraocular inflammation (an accumulation of white blood cells [WBCs]). In this work, we developed a spectroscopic OCT analysis method to differentiate between populations of RBCs and subtypes of WBCs, including granulocytes, lymphocytes and monocytes, both in vitro and in ACs of porcine eyes. We developed an algorithm to track single cells within OCT data sets, and extracted the backscatter reflectance spectrum of each single cell from the detected interferograms using the short-time Fourier transform (STFT). A look-up table of Mie back-scattering spectra was generated and used to correlate the backscatter spectral features of single cells to their characteristic sizes. The extracted size distributions based on the best Mie spectra fit were significantly different between each cell type. We also studied theoretical backscattering models of single RBCs to further validate our experimental results. The described work is a promising step towards clinically differentiating and quantifying AC blood cell types.

© 2019 Optical Society of America under the terms of the OSA Open Access Publishing Agreement

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2018 (2)

N. Biophysical JournalDis Model MechDave P. Chevour, P. Mahendradas, A. Venkatesh, A. Kawali, R. Shetty, A. Ghosh, and S. Sethu, “Increased Aqueous Humor CD4+/CD8+ Lymphocyte Ratio in Sarcoid Uveitis,” Ocul. Immunol. Inflamm. 2018, 1–8 (2018).

W. J. Choi, K. L. Pepple, and R. K. Wang, “Automated three-dimensional cell counting method for grading uveitis of rodent eye in vivo with optical coherence tomography,” J. Biophotonics 11(9), e201800140 (2018).
[Crossref] [PubMed]

2017 (2)

R. Liu, G. Spicer, S. Chen, H. F. Zhang, J. Yi, and V. Backman, “Theoretical model for optical oximetry at the capillary level: exploring hemoglobin oxygen saturation through backscattering of single red blood cells,” J. Biomed. Opt. 22(2), 025002 (2017).
[Crossref] [PubMed]

Y. K. Li, J. Hu, W. F. Huang, Z. P. Nie, and Q. H. Liu, “A Spectral Integral Method for Smooth Multilayered Bodies of Revolution,” IEEE Trans. Antenn. Propag. 65(8), 4146–4154 (2017).
[Crossref]

2016 (5)

M. Habaza, M. Kirschbaum, C. Guernth-Marschner, G. Dardikman, I. Barnea, R. Korenstein, C. Duschl, and N. T. Shaked, “Rapid 3D Refractive-Index Imaging of Live Cells in Suspension without Labeling Using Dielectrophoretic Cell Rotation,” Adv. Sci. (Weinh.) 4(2), 1600205 (2016).
[Crossref] [PubMed]

M. Edmond, A. Yuan, B. A. Bell, A. Sharma, R. M. DiCicco, L. Tucker, J. Bena, Y. K. Tao, and S. K. Srivastava, “The Feasibility of Spectral-Domain Optical Coherence Tomography Grading of Anterior Chamber Inflammation in a Rabbit Model of Anterior Uveitis,” Invest. Ophthalmol. Vis. Sci. 57(9), OCT184 (2016).
[Crossref] [PubMed]

A. Baltmr, S. Lightman, and O. Tomkins-Netzer, “Vogt-Koyanagi-Harada syndrome - current perspectives,” Clin. Ophthalmol. 10, 2345–2361 (2016).
[Crossref] [PubMed]

C. J. Chu, P. J. Gardner, D. A. Copland, S. E. Liyanage, A. Gonzalez-Cordero, S. M. Kleine Holthaus, U. F. Luhmann, A. J. Smith, R. R. Ali, and A. D. Dick, “Multimodal analysis of ocular inflammation using the endotoxin-induced uveitis mouse model,” Dis. Model. Mech. 9(4), 473–481 (2016).
[Crossref] [PubMed]

O. M. Carrasco-Zevallos, D. Nankivil, C. Viehland, B. Keller, and J. A. Izatt, “Pupil Tracking for Real-Time Motion Corrected Anterior Segment Optical Coherence Tomography,” PLoS One 11(8), e0162015 (2016).
[Crossref] [PubMed]

2015 (4)

2014 (1)

A. O. Igbre, M. C. Rico, and S. J. Garg, “High-Speed Optical Coherence Tomography as a Reliable Adjuvant Tool to Grade Ocular Anterior Chamber Inflammation,” Retina 34(3), 504–508 (2014).
[Crossref] [PubMed]

2013 (3)

Y. Li, C. Lowder, X. Zhang, and D. Huang, “Anterior chamber cell grading by optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 54(1), 258–265 (2013).
[Crossref] [PubMed]

I. Grulkowski, J. J. Liu, J. Y. Zhang, B. Potsaid, V. Jayaraman, A. E. Cable, J. S. Duker, and J. G. Fujimoto, “Reproducibility of a Long-Range Swept-Source Optical Coherence Tomography Ocular Biometry System and Comparison with Clinical Biometers,” Ophthalmology 120(11), 2184–2190 (2013).
[Crossref] [PubMed]

J. Yi, Q. Wei, W. Liu, V. Backman, and H. F. Zhang, “Visible-light optical coherence tomography for retinal oximetry,” Opt. Lett. 38(11), 1796–1798 (2013).
[Crossref] [PubMed]

2012 (1)

2011 (3)

J. Lim, H. Ding, M. Mir, R. Zhu, K. Tangella, and G. Popescu, “Born approximation model for light scattering by red blood cells,” Biomed. Opt. Express 2(10), 2784–2791 (2011).
[Crossref] [PubMed]

A. Hsiao, M. Hunter, C. Greiner, S. Gupta, and I. Georgakoudi, “Noninvasive identification of subcellular organization and nuclear morphology features associated with leukemic cells using light-scattering spectroscopy,” J. Biomed. Opt. 16(3), 037007 (2011).
[Crossref] [PubMed]

F. E. Robles, C. Wilson, G. Grant, and A. Wax, “Molecular imaging true-colour spectroscopic optical coherence tomography,” Nat. Photonics 5(12), 744–747 (2011).
[Crossref] [PubMed]

2010 (4)

M. Diez-Silva, M. Dao, J. Han, C. T. Lim, and S. Suresh, “Shape and Biomechanical Characteristics of Human Red Blood Cells in Health and Disease,” MRS Bull. 35(5), 382–388 (2010).
[Crossref] [PubMed]

M. Goel, R. G. Picciani, R. K. Lee, and S. K. Bhattacharya, “Aqueous humor dynamics: a review,” Open Ophthalmol. J. 4(1), 52–59 (2010).
[Crossref] [PubMed]

Y. K. Chan, M. H. Tsai, D. C. Huang, Z. H. Zheng, and K. D. Hung, “Leukocyte nucleus segmentation and nucleus lobe counting,” BMC Bioinformatics 11(1), 558 (2010).
[Crossref] [PubMed]

D. A. Fedosov, B. Caswell, and G. E. Karniadakis, “A Multiscale Red Blood Cell Model with Accurate Mechanics, Rheology, and Dynamics,” Biophys. J. 98(10), 2215–2225 (2010).
[Crossref] [PubMed]

2009 (1)

A. Agarwal, D. Ashokkumar, S. Jacob, A. Agarwal, and Y. Saravanan, “High-speed Optical Coherence Tomography for Imaging Anterior Chamber Inflammatory Reaction in Uveitis: Clinical Correlation and Grading,” Am. J. Ophthalmol. 147(3), 413–416 (2009).
[Crossref] [PubMed]

2008 (2)

T. H. Flynn, N. A. Mitchison, S. J. Ono, and D. F. P. Larkin, “Aqueous humor alloreactive cell phenotypes, cytokines and chemokines in corneal allograft rejection,” Am. J. Transplant. 8(7), 1537–1543 (2008).
[Crossref] [PubMed]

H. Shankar, D. Taranath, C. T. Santhirathelagan, and K. Pesudovs, “Anterior segment biometry with the Pentacam: comprehensive assessment of repeatability of automated measurements,” J. Cataract Refract. Surg. 34(1), 103–113 (2008).
[Crossref] [PubMed]

2007 (2)

G. I. Ruban, S. M. Kosmacheva, N. V. Goncharova, D. Van Bockstaele, and V. A. Loiko, “Investigation of morphometric parameters for granulocytes and lymphocytes as applied to a solution of direct and inverse light-scattering problems,” J. Biomed. Opt. 12(4), 044017 (2007).
[Crossref] [PubMed]

A. L. Oldenburg, C. Y. Xu, and S. A. Boppart, “Spectroscopic optical coherence tomography and microscopy,” IEEE J. Sel. Top. Quantum Electron. 13(6), 1629–1640 (2007).
[Crossref]

2006 (1)

2005 (5)

C. Xu, P. Carney, and S. Boppart, “Wavelength-dependent scattering in spectroscopic optical coherence tomography,” Opt. Express 13(14), 5450–5462 (2005).
[Crossref] [PubMed]

M. A. Yurkin, K. A. Semyanov, P. A. Tarasov, A. V. Chernyshev, A. G. Hoekstra, and V. P. Maltsev, “Experimental and theoretical study of light scattering by individual mature red blood cells by use of scanning flow cytometry and a discrete dipole approximation,” Appl. Opt. 44(25), 5249–5256 (2005).
[Crossref] [PubMed]

J. H. Chang, P. J. McCluskey, and D. Wakefield, “Acute anterior uveitis and HLA-B27,” Surv. Ophthalmol. 50(4), 364–388 (2005).
[Crossref] [PubMed]

C. Liu, C. Capjack, and W. Rozmus, “3-D simulation of light scattering from biological cells and cell differentiation,” J. Biomed. Opt. 10(1), 14007 (2005).
[Crossref] [PubMed]

J. Q. Lu, P. Yang, and X. H. Hu, “Simulations of light scattering from a biconcave red blood cell using the finite-difference time-domain method,” J. Biomed. Opt. 10(2), 024022 (2005).
[Crossref] [PubMed]

2002 (1)

W. Walton, S. Von Hagen, R. Grigorian, and M. Zarbin, “Management of traumatic hyphema,” Surv. Ophthalmol. 47(4), 297–334 (2002).
[Crossref] [PubMed]

2000 (2)

1998 (1)

1997 (1)

A. Van der Lelij and A. Rothova, “Diagnostic anterior chamber paracentesis in uveitis: a safe procedure?” Br. J. Ophthalmol. 81(11), 976–979 (1997).
[Crossref] [PubMed]

1994 (1)

J. A. Izatt, M. R. Hee, E. A. Swanson, C. P. Lin, D. Huang, J. S. Schuman, C. A. Puliafito, and J. G. Fujimoto, “Micrometer-Scale Resolution Imaging of the Anterior Eye in Vivo with Optical Coherence Tomography,” Arch. Ophthalmol. 112(12), 1584–1589 (1994).
[Crossref] [PubMed]

1981 (1)

Y. C. Fung, W. C. Tsang, and P. Patitucci, “High-resolution data on the geometry of red blood cells,” Biorheology 18(3-6), 369–385 (1981).
[Crossref] [PubMed]

1959 (1)

M. J. Hogan, S. J. Kimura, and P. Thygeson, “Signs and Symptoms of Uveitis*. I. Anterior Uveitis,” Am. J. Ophthalmol. 47(5 Pt 2), 155–170 (1959).
[Crossref] [PubMed]

Agarwal, A.

A. Agarwal, D. Ashokkumar, S. Jacob, A. Agarwal, and Y. Saravanan, “High-speed Optical Coherence Tomography for Imaging Anterior Chamber Inflammatory Reaction in Uveitis: Clinical Correlation and Grading,” Am. J. Ophthalmol. 147(3), 413–416 (2009).
[Crossref] [PubMed]

A. Agarwal, D. Ashokkumar, S. Jacob, A. Agarwal, and Y. Saravanan, “High-speed Optical Coherence Tomography for Imaging Anterior Chamber Inflammatory Reaction in Uveitis: Clinical Correlation and Grading,” Am. J. Ophthalmol. 147(3), 413–416 (2009).
[Crossref] [PubMed]

Ali, R. R.

C. J. Chu, P. J. Gardner, D. A. Copland, S. E. Liyanage, A. Gonzalez-Cordero, S. M. Kleine Holthaus, U. F. Luhmann, A. J. Smith, R. R. Ali, and A. D. Dick, “Multimodal analysis of ocular inflammation using the endotoxin-induced uveitis mouse model,” Dis. Model. Mech. 9(4), 473–481 (2016).
[Crossref] [PubMed]

Alsholm, P.

Andersson-Engels, S.

Arathorn, D. W.

Ashokkumar, D.

A. Agarwal, D. Ashokkumar, S. Jacob, A. Agarwal, and Y. Saravanan, “High-speed Optical Coherence Tomography for Imaging Anterior Chamber Inflammatory Reaction in Uveitis: Clinical Correlation and Grading,” Am. J. Ophthalmol. 147(3), 413–416 (2009).
[Crossref] [PubMed]

Asquith, M.

J. Rose-Nussbaumer, Y. Li, P. Lin, E. Suhler, M. Asquith, J. T. Rosenbaum, and D. Huang, “Aqueous Cell Differentiation in Anterior Uveitis Using Fourier-Domain Optical Coherence Tomography,” Invest. Ophthalmol. Vis. Sci. 56(3), 1430–1436 (2015).
[Crossref] [PubMed]

Backman, V.

R. Liu, G. Spicer, S. Chen, H. F. Zhang, J. Yi, and V. Backman, “Theoretical model for optical oximetry at the capillary level: exploring hemoglobin oxygen saturation through backscattering of single red blood cells,” J. Biomed. Opt. 22(2), 025002 (2017).
[Crossref] [PubMed]

J. Yi, Q. Wei, W. Liu, V. Backman, and H. F. Zhang, “Visible-light optical coherence tomography for retinal oximetry,” Opt. Lett. 38(11), 1796–1798 (2013).
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Baltmr, A.

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A. O. Igbre, M. C. Rico, and S. J. Garg, “High-Speed Optical Coherence Tomography as a Reliable Adjuvant Tool to Grade Ocular Anterior Chamber Inflammation,” Retina 34(3), 504–508 (2014).
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Kim, K.

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[Crossref] [PubMed]

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Y. K. Li, J. Hu, W. F. Huang, Z. P. Nie, and Q. H. Liu, “A Spectral Integral Method for Smooth Multilayered Bodies of Revolution,” IEEE Trans. Antenn. Propag. 65(8), 4146–4154 (2017).
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A. Baltmr, S. Lightman, and O. Tomkins-Netzer, “Vogt-Koyanagi-Harada syndrome - current perspectives,” Clin. Ophthalmol. 10, 2345–2361 (2016).
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M. Diez-Silva, M. Dao, J. Han, C. T. Lim, and S. Suresh, “Shape and Biomechanical Characteristics of Human Red Blood Cells in Health and Disease,” MRS Bull. 35(5), 382–388 (2010).
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Lin, C. P.

J. A. Izatt, M. R. Hee, E. A. Swanson, C. P. Lin, D. Huang, J. S. Schuman, C. A. Puliafito, and J. G. Fujimoto, “Micrometer-Scale Resolution Imaging of the Anterior Eye in Vivo with Optical Coherence Tomography,” Arch. Ophthalmol. 112(12), 1584–1589 (1994).
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J. Rose-Nussbaumer, Y. Li, P. Lin, E. Suhler, M. Asquith, J. T. Rosenbaum, and D. Huang, “Aqueous Cell Differentiation in Anterior Uveitis Using Fourier-Domain Optical Coherence Tomography,” Invest. Ophthalmol. Vis. Sci. 56(3), 1430–1436 (2015).
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Liu, C.

C. Liu, C. Capjack, and W. Rozmus, “3-D simulation of light scattering from biological cells and cell differentiation,” J. Biomed. Opt. 10(1), 14007 (2005).
[Crossref] [PubMed]

Liu, J. J.

I. Grulkowski, J. J. Liu, J. Y. Zhang, B. Potsaid, V. Jayaraman, A. E. Cable, J. S. Duker, and J. G. Fujimoto, “Reproducibility of a Long-Range Swept-Source Optical Coherence Tomography Ocular Biometry System and Comparison with Clinical Biometers,” Ophthalmology 120(11), 2184–2190 (2013).
[Crossref] [PubMed]

Liu, Q. H.

Y. K. Li, J. Hu, W. F. Huang, Z. P. Nie, and Q. H. Liu, “A Spectral Integral Method for Smooth Multilayered Bodies of Revolution,” IEEE Trans. Antenn. Propag. 65(8), 4146–4154 (2017).
[Crossref]

Liu, R.

R. Liu, G. Spicer, S. Chen, H. F. Zhang, J. Yi, and V. Backman, “Theoretical model for optical oximetry at the capillary level: exploring hemoglobin oxygen saturation through backscattering of single red blood cells,” J. Biomed. Opt. 22(2), 025002 (2017).
[Crossref] [PubMed]

Liu, W.

Liyanage, S. E.

C. J. Chu, P. J. Gardner, D. A. Copland, S. E. Liyanage, A. Gonzalez-Cordero, S. M. Kleine Holthaus, U. F. Luhmann, A. J. Smith, R. R. Ali, and A. D. Dick, “Multimodal analysis of ocular inflammation using the endotoxin-induced uveitis mouse model,” Dis. Model. Mech. 9(4), 473–481 (2016).
[Crossref] [PubMed]

Loiko, V. A.

G. I. Ruban, S. M. Kosmacheva, N. V. Goncharova, D. Van Bockstaele, and V. A. Loiko, “Investigation of morphometric parameters for granulocytes and lymphocytes as applied to a solution of direct and inverse light-scattering problems,” J. Biomed. Opt. 12(4), 044017 (2007).
[Crossref] [PubMed]

Lowder, C.

Y. Li, C. Lowder, X. Zhang, and D. Huang, “Anterior chamber cell grading by optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 54(1), 258–265 (2013).
[Crossref] [PubMed]

Lu, J. Q.

J. Q. Lu, P. Yang, and X. H. Hu, “Simulations of light scattering from a biconcave red blood cell using the finite-difference time-domain method,” J. Biomed. Opt. 10(2), 024022 (2005).
[Crossref] [PubMed]

Luhmann, U. F.

C. J. Chu, P. J. Gardner, D. A. Copland, S. E. Liyanage, A. Gonzalez-Cordero, S. M. Kleine Holthaus, U. F. Luhmann, A. J. Smith, R. R. Ali, and A. D. Dick, “Multimodal analysis of ocular inflammation using the endotoxin-induced uveitis mouse model,” Dis. Model. Mech. 9(4), 473–481 (2016).
[Crossref] [PubMed]

Luo, W.

Mahendradas, P.

N. Biophysical JournalDis Model MechDave P. Chevour, P. Mahendradas, A. Venkatesh, A. Kawali, R. Shetty, A. Ghosh, and S. Sethu, “Increased Aqueous Humor CD4+/CD8+ Lymphocyte Ratio in Sarcoid Uveitis,” Ocul. Immunol. Inflamm. 2018, 1–8 (2018).

Maher, J. R.

Maltsev, V. P.

McCluskey, P. J.

J. H. Chang, P. J. McCluskey, and D. Wakefield, “Acute anterior uveitis and HLA-B27,” Surv. Ophthalmol. 50(4), 364–388 (2005).
[Crossref] [PubMed]

Mir, M.

Mitchison, N. A.

T. H. Flynn, N. A. Mitchison, S. J. Ono, and D. F. P. Larkin, “Aqueous humor alloreactive cell phenotypes, cytokines and chemokines in corneal allograft rejection,” Am. J. Transplant. 8(7), 1537–1543 (2008).
[Crossref] [PubMed]

Morgner, U.

Nankivil, D.

O. M. Carrasco-Zevallos, D. Nankivil, C. Viehland, B. Keller, and J. A. Izatt, “Pupil Tracking for Real-Time Motion Corrected Anterior Segment Optical Coherence Tomography,” PLoS One 11(8), e0162015 (2016).
[Crossref] [PubMed]

Nie, Z. P.

Y. K. Li, J. Hu, W. F. Huang, Z. P. Nie, and Q. H. Liu, “A Spectral Integral Method for Smooth Multilayered Bodies of Revolution,” IEEE Trans. Antenn. Propag. 65(8), 4146–4154 (2017).
[Crossref]

Nilsson, A. M. K.

Oldenburg, A. L.

A. L. Oldenburg, C. Y. Xu, and S. A. Boppart, “Spectroscopic optical coherence tomography and microscopy,” IEEE J. Sel. Top. Quantum Electron. 13(6), 1629–1640 (2007).
[Crossref]

Ono, S. J.

T. H. Flynn, N. A. Mitchison, S. J. Ono, and D. F. P. Larkin, “Aqueous humor alloreactive cell phenotypes, cytokines and chemokines in corneal allograft rejection,” Am. J. Transplant. 8(7), 1537–1543 (2008).
[Crossref] [PubMed]

Ossowski, P.

Park, H.

Park, Y.

Patitucci, P.

Y. C. Fung, W. C. Tsang, and P. Patitucci, “High-resolution data on the geometry of red blood cells,” Biorheology 18(3-6), 369–385 (1981).
[Crossref] [PubMed]

Pepple, K. L.

W. J. Choi, K. L. Pepple, and R. K. Wang, “Automated three-dimensional cell counting method for grading uveitis of rodent eye in vivo with optical coherence tomography,” J. Biophotonics 11(9), e201800140 (2018).
[Crossref] [PubMed]

Pesudovs, K.

H. Shankar, D. Taranath, C. T. Santhirathelagan, and K. Pesudovs, “Anterior segment biometry with the Pentacam: comprehensive assessment of repeatability of automated measurements,” J. Cataract Refract. Surg. 34(1), 103–113 (2008).
[Crossref] [PubMed]

Picciani, R. G.

M. Goel, R. G. Picciani, R. K. Lee, and S. K. Bhattacharya, “Aqueous humor dynamics: a review,” Open Ophthalmol. J. 4(1), 52–59 (2010).
[Crossref] [PubMed]

Pitris, C.

Popescu, G.

Potsaid, B.

I. Grulkowski, J. J. Liu, J. Y. Zhang, B. Potsaid, V. Jayaraman, A. E. Cable, J. S. Duker, and J. G. Fujimoto, “Reproducibility of a Long-Range Swept-Source Optical Coherence Tomography Ocular Biometry System and Comparison with Clinical Biometers,” Ophthalmology 120(11), 2184–2190 (2013).
[Crossref] [PubMed]

Puliafito, C. A.

J. A. Izatt, M. R. Hee, E. A. Swanson, C. P. Lin, D. Huang, J. S. Schuman, C. A. Puliafito, and J. G. Fujimoto, “Micrometer-Scale Resolution Imaging of the Anterior Eye in Vivo with Optical Coherence Tomography,” Arch. Ophthalmol. 112(12), 1584–1589 (1994).
[Crossref] [PubMed]

Raiter-Smiljanic, A.

Ralston, T. S.

Rico, M. C.

A. O. Igbre, M. C. Rico, and S. J. Garg, “High-Speed Optical Coherence Tomography as a Reliable Adjuvant Tool to Grade Ocular Anterior Chamber Inflammation,” Retina 34(3), 504–508 (2014).
[Crossref] [PubMed]

Robles, F. E.

F. E. Robles, C. Wilson, G. Grant, and A. Wax, “Molecular imaging true-colour spectroscopic optical coherence tomography,” Nat. Photonics 5(12), 744–747 (2011).
[Crossref] [PubMed]

Roorda, A.

Rosenbaum, J. T.

J. Rose-Nussbaumer, Y. Li, P. Lin, E. Suhler, M. Asquith, J. T. Rosenbaum, and D. Huang, “Aqueous Cell Differentiation in Anterior Uveitis Using Fourier-Domain Optical Coherence Tomography,” Invest. Ophthalmol. Vis. Sci. 56(3), 1430–1436 (2015).
[Crossref] [PubMed]

Rose-Nussbaumer, J.

J. Rose-Nussbaumer, Y. Li, P. Lin, E. Suhler, M. Asquith, J. T. Rosenbaum, and D. Huang, “Aqueous Cell Differentiation in Anterior Uveitis Using Fourier-Domain Optical Coherence Tomography,” Invest. Ophthalmol. Vis. Sci. 56(3), 1430–1436 (2015).
[Crossref] [PubMed]

Rothova, A.

A. Van der Lelij and A. Rothova, “Diagnostic anterior chamber paracentesis in uveitis: a safe procedure?” Br. J. Ophthalmol. 81(11), 976–979 (1997).
[Crossref] [PubMed]

Rozmus, W.

C. Liu, C. Capjack, and W. Rozmus, “3-D simulation of light scattering from biological cells and cell differentiation,” J. Biomed. Opt. 10(1), 14007 (2005).
[Crossref] [PubMed]

Ruban, G. I.

G. I. Ruban, S. M. Kosmacheva, N. V. Goncharova, D. Van Bockstaele, and V. A. Loiko, “Investigation of morphometric parameters for granulocytes and lymphocytes as applied to a solution of direct and inverse light-scattering problems,” J. Biomed. Opt. 12(4), 044017 (2007).
[Crossref] [PubMed]

Santhirathelagan, C. T.

H. Shankar, D. Taranath, C. T. Santhirathelagan, and K. Pesudovs, “Anterior segment biometry with the Pentacam: comprehensive assessment of repeatability of automated measurements,” J. Cataract Refract. Surg. 34(1), 103–113 (2008).
[Crossref] [PubMed]

Saravanan, Y.

A. Agarwal, D. Ashokkumar, S. Jacob, A. Agarwal, and Y. Saravanan, “High-speed Optical Coherence Tomography for Imaging Anterior Chamber Inflammatory Reaction in Uveitis: Clinical Correlation and Grading,” Am. J. Ophthalmol. 147(3), 413–416 (2009).
[Crossref] [PubMed]

Schuman, J. S.

J. A. Izatt, M. R. Hee, E. A. Swanson, C. P. Lin, D. Huang, J. S. Schuman, C. A. Puliafito, and J. G. Fujimoto, “Micrometer-Scale Resolution Imaging of the Anterior Eye in Vivo with Optical Coherence Tomography,” Arch. Ophthalmol. 112(12), 1584–1589 (1994).
[Crossref] [PubMed]

Selim, M. A.

Semyanov, K. A.

Sethu, S.

N. Biophysical JournalDis Model MechDave P. Chevour, P. Mahendradas, A. Venkatesh, A. Kawali, R. Shetty, A. Ghosh, and S. Sethu, “Increased Aqueous Humor CD4+/CD8+ Lymphocyte Ratio in Sarcoid Uveitis,” Ocul. Immunol. Inflamm. 2018, 1–8 (2018).

Shaked, N. T.

M. Habaza, M. Kirschbaum, C. Guernth-Marschner, G. Dardikman, I. Barnea, R. Korenstein, C. Duschl, and N. T. Shaked, “Rapid 3D Refractive-Index Imaging of Live Cells in Suspension without Labeling Using Dielectrophoretic Cell Rotation,” Adv. Sci. (Weinh.) 4(2), 1600205 (2016).
[Crossref] [PubMed]

Shankar, H.

H. Shankar, D. Taranath, C. T. Santhirathelagan, and K. Pesudovs, “Anterior segment biometry with the Pentacam: comprehensive assessment of repeatability of automated measurements,” J. Cataract Refract. Surg. 34(1), 103–113 (2008).
[Crossref] [PubMed]

Sharma, A.

M. Edmond, A. Yuan, B. A. Bell, A. Sharma, R. M. DiCicco, L. Tucker, J. Bena, Y. K. Tao, and S. K. Srivastava, “The Feasibility of Spectral-Domain Optical Coherence Tomography Grading of Anterior Chamber Inflammation in a Rabbit Model of Anterior Uveitis,” Invest. Ophthalmol. Vis. Sci. 57(9), OCT184 (2016).
[Crossref] [PubMed]

Sheehy, C. K.

Shetty, R.

N. Biophysical JournalDis Model MechDave P. Chevour, P. Mahendradas, A. Venkatesh, A. Kawali, R. Shetty, A. Ghosh, and S. Sethu, “Increased Aqueous Humor CD4+/CD8+ Lymphocyte Ratio in Sarcoid Uveitis,” Ocul. Immunol. Inflamm. 2018, 1–8 (2018).

Smith, A. J.

C. J. Chu, P. J. Gardner, D. A. Copland, S. E. Liyanage, A. Gonzalez-Cordero, S. M. Kleine Holthaus, U. F. Luhmann, A. J. Smith, R. R. Ali, and A. D. Dick, “Multimodal analysis of ocular inflammation using the endotoxin-induced uveitis mouse model,” Dis. Model. Mech. 9(4), 473–481 (2016).
[Crossref] [PubMed]

Spicer, G.

R. Liu, G. Spicer, S. Chen, H. F. Zhang, J. Yi, and V. Backman, “Theoretical model for optical oximetry at the capillary level: exploring hemoglobin oxygen saturation through backscattering of single red blood cells,” J. Biomed. Opt. 22(2), 025002 (2017).
[Crossref] [PubMed]

Srivastava, S. K.

M. Edmond, A. Yuan, B. A. Bell, A. Sharma, R. M. DiCicco, L. Tucker, J. Bena, Y. K. Tao, and S. K. Srivastava, “The Feasibility of Spectral-Domain Optical Coherence Tomography Grading of Anterior Chamber Inflammation in a Rabbit Model of Anterior Uveitis,” Invest. Ophthalmol. Vis. Sci. 57(9), OCT184 (2016).
[Crossref] [PubMed]

Sticker, M.

Suhler, E.

J. Rose-Nussbaumer, Y. Li, P. Lin, E. Suhler, M. Asquith, J. T. Rosenbaum, and D. Huang, “Aqueous Cell Differentiation in Anterior Uveitis Using Fourier-Domain Optical Coherence Tomography,” Invest. Ophthalmol. Vis. Sci. 56(3), 1430–1436 (2015).
[Crossref] [PubMed]

Suresh, S.

M. Diez-Silva, M. Dao, J. Han, C. T. Lim, and S. Suresh, “Shape and Biomechanical Characteristics of Human Red Blood Cells in Health and Disease,” MRS Bull. 35(5), 382–388 (2010).
[Crossref] [PubMed]

Swanson, E. A.

J. A. Izatt, M. R. Hee, E. A. Swanson, C. P. Lin, D. Huang, J. S. Schuman, C. A. Puliafito, and J. G. Fujimoto, “Micrometer-Scale Resolution Imaging of the Anterior Eye in Vivo with Optical Coherence Tomography,” Arch. Ophthalmol. 112(12), 1584–1589 (1994).
[Crossref] [PubMed]

Szkulmowska, A.

Tan, W.

Tangella, K.

Tao, Y. K.

M. Edmond, A. Yuan, B. A. Bell, A. Sharma, R. M. DiCicco, L. Tucker, J. Bena, Y. K. Tao, and S. K. Srivastava, “The Feasibility of Spectral-Domain Optical Coherence Tomography Grading of Anterior Chamber Inflammation in a Rabbit Model of Anterior Uveitis,” Invest. Ophthalmol. Vis. Sci. 57(9), OCT184 (2016).
[Crossref] [PubMed]

Taranath, D.

H. Shankar, D. Taranath, C. T. Santhirathelagan, and K. Pesudovs, “Anterior segment biometry with the Pentacam: comprehensive assessment of repeatability of automated measurements,” J. Cataract Refract. Surg. 34(1), 103–113 (2008).
[Crossref] [PubMed]

Tarasov, P. A.

Thygeson, P.

M. J. Hogan, S. J. Kimura, and P. Thygeson, “Signs and Symptoms of Uveitis*. I. Anterior Uveitis,” Am. J. Ophthalmol. 47(5 Pt 2), 155–170 (1959).
[Crossref] [PubMed]

Tiruveedhula, P.

Tomkins-Netzer, O.

A. Baltmr, S. Lightman, and O. Tomkins-Netzer, “Vogt-Koyanagi-Harada syndrome - current perspectives,” Clin. Ophthalmol. 10, 2345–2361 (2016).
[Crossref] [PubMed]

Tsai, M. H.

Y. K. Chan, M. H. Tsai, D. C. Huang, Z. H. Zheng, and K. D. Hung, “Leukocyte nucleus segmentation and nucleus lobe counting,” BMC Bioinformatics 11(1), 558 (2010).
[Crossref] [PubMed]

Tsang, W. C.

Y. C. Fung, W. C. Tsang, and P. Patitucci, “High-resolution data on the geometry of red blood cells,” Biorheology 18(3-6), 369–385 (1981).
[Crossref] [PubMed]

Tucker, L.

M. Edmond, A. Yuan, B. A. Bell, A. Sharma, R. M. DiCicco, L. Tucker, J. Bena, Y. K. Tao, and S. K. Srivastava, “The Feasibility of Spectral-Domain Optical Coherence Tomography Grading of Anterior Chamber Inflammation in a Rabbit Model of Anterior Uveitis,” Invest. Ophthalmol. Vis. Sci. 57(9), OCT184 (2016).
[Crossref] [PubMed]

Van Bockstaele, D.

G. I. Ruban, S. M. Kosmacheva, N. V. Goncharova, D. Van Bockstaele, and V. A. Loiko, “Investigation of morphometric parameters for granulocytes and lymphocytes as applied to a solution of direct and inverse light-scattering problems,” J. Biomed. Opt. 12(4), 044017 (2007).
[Crossref] [PubMed]

Van der Lelij, A.

A. Van der Lelij and A. Rothova, “Diagnostic anterior chamber paracentesis in uveitis: a safe procedure?” Br. J. Ophthalmol. 81(11), 976–979 (1997).
[Crossref] [PubMed]

Venkatesh, A.

N. Biophysical JournalDis Model MechDave P. Chevour, P. Mahendradas, A. Venkatesh, A. Kawali, R. Shetty, A. Ghosh, and S. Sethu, “Increased Aqueous Humor CD4+/CD8+ Lymphocyte Ratio in Sarcoid Uveitis,” Ocul. Immunol. Inflamm. 2018, 1–8 (2018).

Viehland, C.

O. M. Carrasco-Zevallos, D. Nankivil, C. Viehland, B. Keller, and J. A. Izatt, “Pupil Tracking for Real-Time Motion Corrected Anterior Segment Optical Coherence Tomography,” PLoS One 11(8), e0162015 (2016).
[Crossref] [PubMed]

Vienola, K. V.

Vinegoni, C.

Von Hagen, S.

W. Walton, S. Von Hagen, R. Grigorian, and M. Zarbin, “Management of traumatic hyphema,” Surv. Ophthalmol. 47(4), 297–334 (2002).
[Crossref] [PubMed]

Wakefield, D.

J. H. Chang, P. J. McCluskey, and D. Wakefield, “Acute anterior uveitis and HLA-B27,” Surv. Ophthalmol. 50(4), 364–388 (2005).
[Crossref] [PubMed]

Walton, W.

W. Walton, S. Von Hagen, R. Grigorian, and M. Zarbin, “Management of traumatic hyphema,” Surv. Ophthalmol. 47(4), 297–334 (2002).
[Crossref] [PubMed]

Wang, R. K.

W. J. Choi, K. L. Pepple, and R. K. Wang, “Automated three-dimensional cell counting method for grading uveitis of rodent eye in vivo with optical coherence tomography,” J. Biophotonics 11(9), e201800140 (2018).
[Crossref] [PubMed]

Wax, A.

Wei, Q.

Wiese, M.

Wilson, C.

F. E. Robles, C. Wilson, G. Grant, and A. Wax, “Molecular imaging true-colour spectroscopic optical coherence tomography,” Nat. Photonics 5(12), 744–747 (2011).
[Crossref] [PubMed]

Wojtkowski, M.

Xu, C.

Xu, C. Y.

A. L. Oldenburg, C. Y. Xu, and S. A. Boppart, “Spectroscopic optical coherence tomography and microscopy,” IEEE J. Sel. Top. Quantum Electron. 13(6), 1629–1640 (2007).
[Crossref]

Yang, P.

J. Q. Lu, P. Yang, and X. H. Hu, “Simulations of light scattering from a biconcave red blood cell using the finite-difference time-domain method,” J. Biomed. Opt. 10(2), 024022 (2005).
[Crossref] [PubMed]

Yang, Q.

Yi, J.

R. Liu, G. Spicer, S. Chen, H. F. Zhang, J. Yi, and V. Backman, “Theoretical model for optical oximetry at the capillary level: exploring hemoglobin oxygen saturation through backscattering of single red blood cells,” J. Biomed. Opt. 22(2), 025002 (2017).
[Crossref] [PubMed]

J. Yi, Q. Wei, W. Liu, V. Backman, and H. F. Zhang, “Visible-light optical coherence tomography for retinal oximetry,” Opt. Lett. 38(11), 1796–1798 (2013).
[Crossref] [PubMed]

Yoon, J.

Yuan, A.

M. Edmond, A. Yuan, B. A. Bell, A. Sharma, R. M. DiCicco, L. Tucker, J. Bena, Y. K. Tao, and S. K. Srivastava, “The Feasibility of Spectral-Domain Optical Coherence Tomography Grading of Anterior Chamber Inflammation in a Rabbit Model of Anterior Uveitis,” Invest. Ophthalmol. Vis. Sci. 57(9), OCT184 (2016).
[Crossref] [PubMed]

Yurkin, M. A.

Zarbin, M.

W. Walton, S. Von Hagen, R. Grigorian, and M. Zarbin, “Management of traumatic hyphema,” Surv. Ophthalmol. 47(4), 297–334 (2002).
[Crossref] [PubMed]

Zhang, H. F.

R. Liu, G. Spicer, S. Chen, H. F. Zhang, J. Yi, and V. Backman, “Theoretical model for optical oximetry at the capillary level: exploring hemoglobin oxygen saturation through backscattering of single red blood cells,” J. Biomed. Opt. 22(2), 025002 (2017).
[Crossref] [PubMed]

J. Yi, Q. Wei, W. Liu, V. Backman, and H. F. Zhang, “Visible-light optical coherence tomography for retinal oximetry,” Opt. Lett. 38(11), 1796–1798 (2013).
[Crossref] [PubMed]

Zhang, J. Y.

I. Grulkowski, J. J. Liu, J. Y. Zhang, B. Potsaid, V. Jayaraman, A. E. Cable, J. S. Duker, and J. G. Fujimoto, “Reproducibility of a Long-Range Swept-Source Optical Coherence Tomography Ocular Biometry System and Comparison with Clinical Biometers,” Ophthalmology 120(11), 2184–2190 (2013).
[Crossref] [PubMed]

Zhang, X.

Y. Li, C. Lowder, X. Zhang, and D. Huang, “Anterior chamber cell grading by optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 54(1), 258–265 (2013).
[Crossref] [PubMed]

Zhao, Y.

Zheng, Z. H.

Y. K. Chan, M. H. Tsai, D. C. Huang, Z. H. Zheng, and K. D. Hung, “Leukocyte nucleus segmentation and nucleus lobe counting,” BMC Bioinformatics 11(1), 558 (2010).
[Crossref] [PubMed]

Zhu, R.

Adv. Sci. (Weinh.) (1)

M. Habaza, M. Kirschbaum, C. Guernth-Marschner, G. Dardikman, I. Barnea, R. Korenstein, C. Duschl, and N. T. Shaked, “Rapid 3D Refractive-Index Imaging of Live Cells in Suspension without Labeling Using Dielectrophoretic Cell Rotation,” Adv. Sci. (Weinh.) 4(2), 1600205 (2016).
[Crossref] [PubMed]

Am. J. Ophthalmol. (2)

A. Agarwal, D. Ashokkumar, S. Jacob, A. Agarwal, and Y. Saravanan, “High-speed Optical Coherence Tomography for Imaging Anterior Chamber Inflammatory Reaction in Uveitis: Clinical Correlation and Grading,” Am. J. Ophthalmol. 147(3), 413–416 (2009).
[Crossref] [PubMed]

M. J. Hogan, S. J. Kimura, and P. Thygeson, “Signs and Symptoms of Uveitis*. I. Anterior Uveitis,” Am. J. Ophthalmol. 47(5 Pt 2), 155–170 (1959).
[Crossref] [PubMed]

Am. J. Transplant. (1)

T. H. Flynn, N. A. Mitchison, S. J. Ono, and D. F. P. Larkin, “Aqueous humor alloreactive cell phenotypes, cytokines and chemokines in corneal allograft rejection,” Am. J. Transplant. 8(7), 1537–1543 (2008).
[Crossref] [PubMed]

Appl. Opt. (2)

Arch. Ophthalmol. (1)

J. A. Izatt, M. R. Hee, E. A. Swanson, C. P. Lin, D. Huang, J. S. Schuman, C. A. Puliafito, and J. G. Fujimoto, “Micrometer-Scale Resolution Imaging of the Anterior Eye in Vivo with Optical Coherence Tomography,” Arch. Ophthalmol. 112(12), 1584–1589 (1994).
[Crossref] [PubMed]

Biomed. Opt. Express (4)

Biophys. J. (1)

D. A. Fedosov, B. Caswell, and G. E. Karniadakis, “A Multiscale Red Blood Cell Model with Accurate Mechanics, Rheology, and Dynamics,” Biophys. J. 98(10), 2215–2225 (2010).
[Crossref] [PubMed]

Biorheology (1)

Y. C. Fung, W. C. Tsang, and P. Patitucci, “High-resolution data on the geometry of red blood cells,” Biorheology 18(3-6), 369–385 (1981).
[Crossref] [PubMed]

BMC Bioinformatics (1)

Y. K. Chan, M. H. Tsai, D. C. Huang, Z. H. Zheng, and K. D. Hung, “Leukocyte nucleus segmentation and nucleus lobe counting,” BMC Bioinformatics 11(1), 558 (2010).
[Crossref] [PubMed]

Br. J. Ophthalmol. (1)

A. Van der Lelij and A. Rothova, “Diagnostic anterior chamber paracentesis in uveitis: a safe procedure?” Br. J. Ophthalmol. 81(11), 976–979 (1997).
[Crossref] [PubMed]

Clin. Ophthalmol. (1)

A. Baltmr, S. Lightman, and O. Tomkins-Netzer, “Vogt-Koyanagi-Harada syndrome - current perspectives,” Clin. Ophthalmol. 10, 2345–2361 (2016).
[Crossref] [PubMed]

Dis. Model. Mech. (1)

C. J. Chu, P. J. Gardner, D. A. Copland, S. E. Liyanage, A. Gonzalez-Cordero, S. M. Kleine Holthaus, U. F. Luhmann, A. J. Smith, R. R. Ali, and A. D. Dick, “Multimodal analysis of ocular inflammation using the endotoxin-induced uveitis mouse model,” Dis. Model. Mech. 9(4), 473–481 (2016).
[Crossref] [PubMed]

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

A. L. Oldenburg, C. Y. Xu, and S. A. Boppart, “Spectroscopic optical coherence tomography and microscopy,” IEEE J. Sel. Top. Quantum Electron. 13(6), 1629–1640 (2007).
[Crossref]

IEEE Trans. Antenn. Propag. (1)

Y. K. Li, J. Hu, W. F. Huang, Z. P. Nie, and Q. H. Liu, “A Spectral Integral Method for Smooth Multilayered Bodies of Revolution,” IEEE Trans. Antenn. Propag. 65(8), 4146–4154 (2017).
[Crossref]

Invest. Ophthalmol. Vis. Sci. (3)

Y. Li, C. Lowder, X. Zhang, and D. Huang, “Anterior chamber cell grading by optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 54(1), 258–265 (2013).
[Crossref] [PubMed]

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Figures (12)

Fig. 1
Fig. 1 (a) Schematic diagram of the custom swept-source OCT system. L, L1, L2: lenses, G: galvanometer scanner, M: mirror, BD: beam dump, UP: unused port, BR: balanced receiver (b) fall off sensitivity performance and axial resolution of the system across an imaging range of 5.5mm
Fig. 2
Fig. 2 (a) Representative B-scan of lymphocytes suspended in the cuvette; (b) Binary B-scan image after intensity thresholding; (c) Individual cell localization using 8-connected component labeling, with each cell assigned a different overlay color; (d) Same B-scan as (a) with the centers of cells labeled.
Fig.3
Fig.3 (a) Representative OCT B-scan of a lymphocyte suspension with individual cells (white), their localized and tracked centers (blue), and an example A-scan used for spectroscopic analysys (red line); (b) STFT analysis of the red A-scan in (a) from a localized cell; (c) single and (d) 30 averaged spectroscopic data extracted from a localized lymphocyte.
Fig. 4
Fig. 4 The (a) cross section and (b) 3D rendered shape of the RBC model. In (b), illustrative angles are shown of the incident field α (blue arrows), at two orthogonal linear polarizations, horizontal θ (green arrow) and vertical Φ (yellow arrow).
Fig. 5
Fig. 5 Results of ex vivo polystyrene microspheres experiment. (a) A single B-scan of 10um polystyrene microspheres injected into the AC of a porcine eye; (b) Five averaged STFT spectra obtained from a single microsphere (red circle in (a)) and its best Mie spectra fit. The best fit Mie spectra was for a 10.02µm diameter sphere; (c) Extracted microsphere thickness histogram from 121 microsphere measurements.
Fig. 6
Fig. 6 Results of in vitro studies of each cell type. (a,b,g,h) Histogram plots of characteristic cell sizes extracted from the best Mie spectra fit with mean and standard deviation; (c,d,i,j) Representative spectrum of a single cell from each blood cell type, and its best Mie spectra fit; (e,f,k,l) OCT B-scan image of each cell sample with color-coded overlay of the characteristic best-fit sizes of individual cells observed (see color bar for best-fit cell size scale). Distance scale bar (white): 100µm.
Fig. 7
Fig. 7 Boxplot of the characteristic size distributions of RBCs, granulocytes, lymphocytes and monocytes observed in the in vitro cell study. The box plot represents the range of characteristic sizes, with the red line corresponding to the median size of each cell type, the blue box corresponding to the interquartile distribution, the whiskers corresponding to the sizes within 1.5 times the interquartile range and the red plus signs representing outliers that are located outside the whiskers.
Fig. 8
Fig. 8 The ROC curves between the characteristic sizes of each pairs of cell types, along with the corresponding AUC values.
Fig. 9
Fig. 9 Results of ex vivo porcine eye studies of each cell type. (a) Representative OCT volume of granulocytes suspended in the AC of a porcine eye; (b,c,f,g) Histogram plots of characteristic cell sizes extracted from the best Mie spectra fit with means and standard deviations; (d,e,h,i) Boxplot of the characteristic size distributions of all four types of cells in vitro and ex vivo, and the corresponding p-values calculated using the Wilcoxon rank sum test.
Fig. 10
Fig. 10 The backscattering spectra of an RBC with different incident angles of light at two orthogonal linear polarizations. (a) 0°, perpendicular to the long axis of the RBC; (b) 30°; (c) 60°; (d) 90°, parallel to the long axis of the RBC. (e) The total backscattering cross-sectional intensity across the entire spectrum as a function of incident angle from 0° to 90° with a step size of 2.5°.
Fig. 11
Fig. 11 (a) Normalized backscattering spectra and their best Mie fits at difference incident angles of light; (b) Characteristic sizes extracted from the best Mie fit as a function of incident angles of light ( 0°90° with a step size of 2.5°); (c) Backscattering cross-section as a function of characteristic size at all the incident angles ( 0°90° with a step size of 2.5°)
Fig. 12
Fig. 12 (a) The intensity of individual RBCs in the OCT volume vs. their characteristic sizes. (b)-(c) Two representative spectra from RBCs with small and large characteristic sizes.

Equations (6)

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I( k o ,z )=| FT( I D ( k )W( k k o ) ) |,
I( k o ,z )| FT( S( k ) R s ( k ) cos( 2k z i )W( k k o ) ) |.
I( k o ,z>0 ) R s ( k o ) | FT( S( k )W( k k o ) )*δ( z z i ) |       R s ( k o ) | PSF( k o ,z )*δ( z z i ) |      R s ( k o ) | PSF( k o ,z z i ) |.
I norm ( k o , z i )= I( k o , z i ) | PSF( k o ,0 ) | R s ( k o ) .
T( x )=0.65d 1 x 2 ( 0.1583+1.5262 x 2 0.8579 x 4 ).
f( x )= a 1 e (x μ 1 ) 2 2 σ 1 2 + a 2 e (x μ 2 ) 2 2 σ 2 2 .

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