Abstract

Biological functions rely on local microvasculature to deliver oxygen and nutrients and carry away metabolic waste. Alterations to local oxygenation levels are manifested in diseases including cancer, diabetes mellitus, etc. The ability to quantify oxygen saturation (sO2) within microvasculature in vivo to assess local tissue oxygenation and metabolic function is highly sought after. Visible light optical coherence tomography (vis-OCT) angiography has shown promise in reaching this goal. However, achieving reliable measurements in small vessels can be challenging due to the reduced contrast and requires data averaging to improve the spectral data quality. Therefore, a method for quality-control of the vis-OCT data from small vessels becomes essential to reject unreliable readings. In this work, we present a quantitative metrics to evaluate the spectral data for a reliable measurement of sO2, including angiography signal to noise ratio (SNR), spectral anomaly detection and discard, and theory-experiment correlation analysis. The thresholds for each quantity can be flexibly adjusted according to different applications and system performance. We used these metrics to measure sO2 of C57BL/6J mouse lower extremity microvasculature and validated it by introducing hyperoxia for expected sO2 changes. After validation, we applied this protocol on C57BL/6J mouse ear microvasculature to conduct in vivo small blood vessel OCT oximetry. This work seeks to standardize the data processing method for in vivo oximetry in small vessels by vis-OCT.

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

Full Article  |  PDF Article
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2018 (2)

R. Liu, J. A. Winkelmann, G. Spicer, Y. Zhu, A. Eid, G. A. Ameer, V. Backman, and J. Yi, “Single capillary oximetry and tissue ultrastructural sensing by dual-band dual-scan inverse spectroscopic optical coherence tomography,” Light Sci. Appl. 7(1), 57 (2018).
[Crossref]

W. Song, L. Zhou, S. Zhang, S. Ness, D. Manishi, and Y. Ji, “Fiber-based visible and near infrared optical coherence tomography (vnOCT) enables quantitative elastic light scattering spectroscopy in human retina,” Biomed. Opt. Express 9(7), 3464–3480 (2018).
[Crossref]

2017 (3)

X. Shu, L. Beckmann, and H. Zhang, “Visible-light optical coherence tomography: a review,” J. Biomed. Opt. 22(12), 1–14 (2017).
[Crossref] [PubMed]

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]

L. Zhang, W. Song, D. Shao, S. Zhang, M. Desai, S. Ness, S. Roy, and J. Yi, “Volumetric fluorescence retinal imaging in vivo over a 30-degree field of view by oblique scanning laser ophthalmoscopy (oSLO),” Biomed. Opt. Express 9(1), 25–40 (2017).
[Crossref] [PubMed]

2015 (2)

2014 (1)

2013 (4)

2012 (3)

Y. Jia, O. Tan, J. Tokayer, B. Potsaid, Y. Wang, J. Jonathan, M. F. Kraus, H. Subhash, J. G. Fujimoto, J. Hornegger, and D. Huang, “Split-spectrum amplitude-decorrelation angiography with optical coherence tomography,” Opt. Express 20(4), 3116–3121 (2012).
[Crossref]

T. Y. P. Chui, D. A. Vannasdale, and S. A. Burns, “The use of forward scatter to improve retinal vascular imaging with an adaptive optics scanning laser ophthalmoscope,” Biomed. Opt. Express 3(10), 2537–2549 (2012).
[Crossref] [PubMed]

L. Scolaro, R. A. Mclaughlin, B. R. Klyen, B. A. Wood, P. D. Robbins, C. M. Saunders, S. L. Jacques, and D. D. Sampson, “Parametric imaging of the local attenuation coefficient in human axillary lymph nodes assessed using optical coherence tomography,” Biomed. Opt. Express 3 (2), 1122–1128 (2012).
[Crossref]

2011 (2)

2010 (3)

2009 (1)

R. N. Kalaria, “Neurodegenerative disease: Diabetes, microvascular pathology and Alzheimer disease,” Nat. Rev. Neurol. 5(6), 305–306 (2009).
[Crossref] [PubMed]

2008 (2)

B. I. Levy, E. L. Schiffrin, J. Mourad, D. Agostini, E. Vicaut, M. E. Safar, and H. A. J. Struijker-boudier, “Impaired Tissue Perfusion A Pathology Common to Hypertension, Obesity, and Diabetes Mellitus,” Circulation 118(9), 968–976 (2008).

Y. Wang, H. Song, K. Maslov, Z. Yu, X. Younan, and W. Lihong V., “In vivo integrated photoacoustic and confocal microscopy of hemoglobin oxygen saturation and oxygen partial pressure,” Opt. Lett. 141(4), 520–529 (2008).

2007 (1)

L. Kagemann, G. Wollstein, M. Wojtkowski, H. Ishikawa, K. A. Townsend, M. L. Gabriele, V. J. Srinivasan, J. G. Fujimoto, and J. S. Schuman, “Spectral oximetry assessed with high-speed ultra-high-resolution optical coherence tomography,” J. Biomed. Opt. 12(4), 041212 (2007).
[Crossref] [PubMed]

2006 (1)

E. Stefansson, “Ocular Oxygenation and the Treatment of Diabetic Retinopathy,” Surv. Ophyhalmology 51(4), 364–380 (2006).

2003 (1)

2001 (1)

G. Zonios, J. Bykowski, and N. Kollias, “Skin melanin, hemoglobin, and light scattering properties can be quantitatively assessed in vivo using diffuse reflectance spectroscopy,” J. Invest. Dermatol. 117(6), 1452–1457 (2001).
[Crossref] [PubMed]

2000 (1)

P. Vajkoczy, A. Ullrich, and M. D. Menger, “Intravital Fluorescence Videomicroscopy to Study Tumor Angiogenesis and Microcirculation,” Neoplasia 2(1-2), 53–61 (2000).
[Crossref] [PubMed]

Aalders, M. C. G.

Abitbol, C. L.

A. Edwards-richards, M. Defreitas, C. P. Katsou, W. Seeherunvong, N. Sasaki, M. Freundlich, G. Zilleruelo, and C. L. Abitbol, “Capillary rarefaction : an early marker of microvascular disease in young hemodialysis patients,” Clin. Kidney J.569–574 (2014).
[Crossref]

Agostini, D.

B. I. Levy, E. L. Schiffrin, J. Mourad, D. Agostini, E. Vicaut, M. E. Safar, and H. A. J. Struijker-boudier, “Impaired Tissue Perfusion A Pathology Common to Hypertension, Obesity, and Diabetes Mellitus,” Circulation 118(9), 968–976 (2008).

Ameer, G. A.

R. Liu, J. A. Winkelmann, G. Spicer, Y. Zhu, A. Eid, G. A. Ameer, V. Backman, and J. Yi, “Single capillary oximetry and tissue ultrastructural sensing by dual-band dual-scan inverse spectroscopic optical coherence tomography,” Light Sci. Appl. 7(1), 57 (2018).
[Crossref]

Backman, V.

R. Liu, J. A. Winkelmann, G. Spicer, Y. Zhu, A. Eid, G. A. Ameer, V. Backman, and J. Yi, “Single capillary oximetry and tissue ultrastructural sensing by dual-band dual-scan inverse spectroscopic optical coherence tomography,” Light Sci. Appl. 7(1), 57 (2018).
[Crossref]

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, S. Chen, V. Backman, and H. F. Zhang, “In vivo functional microangiography by visible-light optical coherence tomography,” Biomed. Opt. Express 5(10), 3603–3612 (2014).
[Crossref] [PubMed]

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. Quantum Electron. 20(2), 7000514 (2013).
[PubMed]

J. Yi, A. J. Radosevich, J. D. Rogers, S. C. P. Norris, İ. R. Çapoğlu, A. Taflove, and V. Backman, “Can OCT be sensitive to nanoscale structural alterations in biological tissue?” Opt. Express 21(7), 9043–9059 (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]

Balderas-Mata, S.

Beckmann, L.

X. Shu, L. Beckmann, and H. Zhang, “Visible-light optical coherence tomography: a review,” J. Biomed. Opt. 22(12), 1–14 (2017).
[Crossref] [PubMed]

Burns, S. A.

Bykowski, J.

G. Zonios, J. Bykowski, and N. Kollias, “Skin melanin, hemoglobin, and light scattering properties can be quantitatively assessed in vivo using diffuse reflectance spectroscopy,” J. Invest. Dermatol. 117(6), 1452–1457 (2001).
[Crossref] [PubMed]

Çapoglu, I. R.

Carroll, J.

Chen, S.

Chong, S. P.

Chowdhury, S.

Chui, T. Y.

Chui, T. Y. P.

Defreitas, M.

A. Edwards-richards, M. Defreitas, C. P. Katsou, W. Seeherunvong, N. Sasaki, M. Freundlich, G. Zilleruelo, and C. L. Abitbol, “Capillary rarefaction : an early marker of microvascular disease in young hemodialysis patients,” Clin. Kidney J.569–574 (2014).
[Crossref]

Deng, C.

Desai, M.

Dubow, M.

Dubra, A.

Edwards-richards, A.

A. Edwards-richards, M. Defreitas, C. P. Katsou, W. Seeherunvong, N. Sasaki, M. Freundlich, G. Zilleruelo, and C. L. Abitbol, “Capillary rarefaction : an early marker of microvascular disease in young hemodialysis patients,” Clin. Kidney J.569–574 (2014).
[Crossref]

Eid, A.

R. Liu, J. A. Winkelmann, G. Spicer, Y. Zhu, A. Eid, G. A. Ameer, V. Backman, and J. Yi, “Single capillary oximetry and tissue ultrastructural sensing by dual-band dual-scan inverse spectroscopic optical coherence tomography,” Light Sci. Appl. 7(1), 57 (2018).
[Crossref]

Faber, D. J.

Ferguson, R. D.

Freundlich, M.

A. Edwards-richards, M. Defreitas, C. P. Katsou, W. Seeherunvong, N. Sasaki, M. Freundlich, G. Zilleruelo, and C. L. Abitbol, “Capillary rarefaction : an early marker of microvascular disease in young hemodialysis patients,” Clin. Kidney J.569–574 (2014).
[Crossref]

Fujimoto, J. G.

Y. Jia, O. Tan, J. Tokayer, B. Potsaid, Y. Wang, J. Jonathan, M. F. Kraus, H. Subhash, J. G. Fujimoto, J. Hornegger, and D. Huang, “Split-spectrum amplitude-decorrelation angiography with optical coherence tomography,” Opt. Express 20(4), 3116–3121 (2012).
[Crossref]

L. Kagemann, G. Wollstein, M. Wojtkowski, H. Ishikawa, K. A. Townsend, M. L. Gabriele, V. J. Srinivasan, J. G. Fujimoto, and J. S. Schuman, “Spectral oximetry assessed with high-speed ultra-high-resolution optical coherence tomography,” J. Biomed. Opt. 12(4), 041212 (2007).
[Crossref] [PubMed]

Gabriele, M. L.

L. Kagemann, G. Wollstein, M. Wojtkowski, H. Ishikawa, K. A. Townsend, M. L. Gabriele, V. J. Srinivasan, J. G. Fujimoto, and J. S. Schuman, “Spectral oximetry assessed with high-speed ultra-high-resolution optical coherence tomography,” J. Biomed. Opt. 12(4), 041212 (2007).
[Crossref] [PubMed]

Grant, G.

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]

Hammer, D. X.

Hornegger, J.

Y. Jia, O. Tan, J. Tokayer, B. Potsaid, Y. Wang, J. Jonathan, M. F. Kraus, H. Subhash, J. G. Fujimoto, J. Hornegger, and D. Huang, “Split-spectrum amplitude-decorrelation angiography with optical coherence tomography,” Opt. Express 20(4), 3116–3121 (2012).
[Crossref]

Huang, D.

Y. Jia, O. Tan, J. Tokayer, B. Potsaid, Y. Wang, J. Jonathan, M. F. Kraus, H. Subhash, J. G. Fujimoto, J. Hornegger, and D. Huang, “Split-spectrum amplitude-decorrelation angiography with optical coherence tomography,” Opt. Express 20(4), 3116–3121 (2012).
[Crossref]

Ishikawa, H.

L. Kagemann, G. Wollstein, M. Wojtkowski, H. Ishikawa, K. A. Townsend, M. L. Gabriele, V. J. Srinivasan, J. G. Fujimoto, and J. S. Schuman, “Spectral oximetry assessed with high-speed ultra-high-resolution optical coherence tomography,” J. Biomed. Opt. 12(4), 041212 (2007).
[Crossref] [PubMed]

Jacques, S. L.

L. Scolaro, R. A. Mclaughlin, B. R. Klyen, B. A. Wood, P. D. Robbins, C. M. Saunders, S. L. Jacques, and D. D. Sampson, “Parametric imaging of the local attenuation coefficient in human axillary lymph nodes assessed using optical coherence tomography,” Biomed. Opt. Express 3 (2), 1122–1128 (2012).
[Crossref]

Ji, Y.

Jia, Y.

Y. Jia, O. Tan, J. Tokayer, B. Potsaid, Y. Wang, J. Jonathan, M. F. Kraus, H. Subhash, J. G. Fujimoto, J. Hornegger, and D. Huang, “Split-spectrum amplitude-decorrelation angiography with optical coherence tomography,” Opt. Express 20(4), 3116–3121 (2012).
[Crossref]

Jonathan, J.

Y. Jia, O. Tan, J. Tokayer, B. Potsaid, Y. Wang, J. Jonathan, M. F. Kraus, H. Subhash, J. G. Fujimoto, J. Hornegger, and D. Huang, “Split-spectrum amplitude-decorrelation angiography with optical coherence tomography,” Opt. Express 20(4), 3116–3121 (2012).
[Crossref]

Jones, S. M.

Kagemann, L.

L. Kagemann, G. Wollstein, M. Wojtkowski, H. Ishikawa, K. A. Townsend, M. L. Gabriele, V. J. Srinivasan, J. G. Fujimoto, and J. S. Schuman, “Spectral oximetry assessed with high-speed ultra-high-resolution optical coherence tomography,” J. Biomed. Opt. 12(4), 041212 (2007).
[Crossref] [PubMed]

Kalaria, R. N.

R. N. Kalaria, “Neurodegenerative disease: Diabetes, microvascular pathology and Alzheimer disease,” Nat. Rev. Neurol. 5(6), 305–306 (2009).
[Crossref] [PubMed]

Katsou, C. P.

A. Edwards-richards, M. Defreitas, C. P. Katsou, W. Seeherunvong, N. Sasaki, M. Freundlich, G. Zilleruelo, and C. L. Abitbol, “Capillary rarefaction : an early marker of microvascular disease in young hemodialysis patients,” Clin. Kidney J.569–574 (2014).
[Crossref]

Kim, D. Y.

Klyen, B. R.

L. Scolaro, R. A. Mclaughlin, B. R. Klyen, B. A. Wood, P. D. Robbins, C. M. Saunders, S. L. Jacques, and D. D. Sampson, “Parametric imaging of the local attenuation coefficient in human axillary lymph nodes assessed using optical coherence tomography,” Biomed. Opt. Express 3 (2), 1122–1128 (2012).
[Crossref]

Kollias, N.

G. Zonios, J. Bykowski, and N. Kollias, “Skin melanin, hemoglobin, and light scattering properties can be quantitatively assessed in vivo using diffuse reflectance spectroscopy,” J. Invest. Dermatol. 117(6), 1452–1457 (2001).
[Crossref] [PubMed]

Kraus, M. F.

Y. Jia, O. Tan, J. Tokayer, B. Potsaid, Y. Wang, J. Jonathan, M. F. Kraus, H. Subhash, J. G. Fujimoto, J. Hornegger, and D. Huang, “Split-spectrum amplitude-decorrelation angiography with optical coherence tomography,” Opt. Express 20(4), 3116–3121 (2012).
[Crossref]

Leahy, C.

Levy, B. I.

B. I. Levy, E. L. Schiffrin, J. Mourad, D. Agostini, E. Vicaut, M. E. Safar, and H. A. J. Struijker-boudier, “Impaired Tissue Perfusion A Pathology Common to Hypertension, Obesity, and Diabetes Mellitus,” Circulation 118(9), 968–976 (2008).

Lihong V., W.

Y. Wang, H. Song, K. Maslov, Z. Yu, X. Younan, and W. Lihong V., “In vivo integrated photoacoustic and confocal microscopy of hemoglobin oxygen saturation and oxygen partial pressure,” Opt. Lett. 141(4), 520–529 (2008).

Liu, R.

R. Liu, J. A. Winkelmann, G. Spicer, Y. Zhu, A. Eid, G. A. Ameer, V. Backman, and J. Yi, “Single capillary oximetry and tissue ultrastructural sensing by dual-band dual-scan inverse spectroscopic optical coherence tomography,” Light Sci. Appl. 7(1), 57 (2018).
[Crossref]

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.

Manishi, D.

Maslov, K.

Y. Wang, H. Song, K. Maslov, Z. Yu, X. Younan, and W. Lihong V., “In vivo integrated photoacoustic and confocal microscopy of hemoglobin oxygen saturation and oxygen partial pressure,” Opt. Lett. 141(4), 520–529 (2008).

Mclaughlin, R. A.

L. Scolaro, R. A. Mclaughlin, B. R. Klyen, B. A. Wood, P. D. Robbins, C. M. Saunders, S. L. Jacques, and D. D. Sampson, “Parametric imaging of the local attenuation coefficient in human axillary lymph nodes assessed using optical coherence tomography,” Biomed. Opt. Express 3 (2), 1122–1128 (2012).
[Crossref]

Menger, M. D.

P. Vajkoczy, A. Ullrich, and M. D. Menger, “Intravital Fluorescence Videomicroscopy to Study Tumor Angiogenesis and Microcirculation,” Neoplasia 2(1-2), 53–61 (2000).
[Crossref] [PubMed]

Merkle, C. W.

Mik, E. G.

Miyaki, K.

M. Unekawa, M. Tomita, Y. Tomita, H. Toriumi, K. Miyaki, and N. Suzuki, “RBC velocities in single capillaries of mouse and rat brains are the same, despite 10-fold difference in body size,” Brain Res. 1320, 69–73 (2010).
[Crossref] [PubMed]

Mourad, J.

B. I. Levy, E. L. Schiffrin, J. Mourad, D. Agostini, E. Vicaut, M. E. Safar, and H. A. J. Struijker-boudier, “Impaired Tissue Perfusion A Pathology Common to Hypertension, Obesity, and Diabetes Mellitus,” Circulation 118(9), 968–976 (2008).

Mujat, M.

Ness, S.

Norris, S. C. P.

Olivier, S. S.

Patel, A. H.

Pilli, S.

Pinhas, A.

Potsaid, B.

Y. Jia, O. Tan, J. Tokayer, B. Potsaid, Y. Wang, J. Jonathan, M. F. Kraus, H. Subhash, J. G. Fujimoto, J. Hornegger, and D. Huang, “Split-spectrum amplitude-decorrelation angiography with optical coherence tomography,” Opt. Express 20(4), 3116–3121 (2012).
[Crossref]

Radhakrishnan, H.

Radosevich, A. 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. Quantum Electron. 20(2), 7000514 (2013).
[PubMed]

J. Yi, A. J. Radosevich, J. D. Rogers, S. C. P. Norris, İ. R. Çapoğlu, A. Taflove, and V. Backman, “Can OCT be sensitive to nanoscale structural alterations in biological tissue?” Opt. Express 21(7), 9043–9059 (2013).
[Crossref] [PubMed]

Robbins, P. D.

L. Scolaro, R. A. Mclaughlin, B. R. Klyen, B. A. Wood, P. D. Robbins, C. M. Saunders, S. L. Jacques, and D. D. Sampson, “Parametric imaging of the local attenuation coefficient in human axillary lymph nodes assessed using optical coherence tomography,” Biomed. Opt. Express 3 (2), 1122–1128 (2012).
[Crossref]

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]

F. E. Robles, S. Chowdhury, and A. Wax, “Assessing hemoglobin concentration using spectroscopic optical coherence tomography for feasibility of tissue diagnostics,” Biomed. Opt. Express 1(1), 310–317 (2010).
[Crossref] [PubMed]

Rogers, J. D.

J. Yi, A. J. Radosevich, J. D. Rogers, S. C. P. Norris, İ. R. Çapoğlu, A. Taflove, and V. Backman, “Can OCT be sensitive to nanoscale structural alterations in biological tissue?” Opt. Express 21(7), 9043–9059 (2013).
[Crossref] [PubMed]

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. Quantum Electron. 20(2), 7000514 (2013).
[PubMed]

Rosen, R. B.

Roy, S.

Safar, M. E.

B. I. Levy, E. L. Schiffrin, J. Mourad, D. Agostini, E. Vicaut, M. E. Safar, and H. A. J. Struijker-boudier, “Impaired Tissue Perfusion A Pathology Common to Hypertension, Obesity, and Diabetes Mellitus,” Circulation 118(9), 968–976 (2008).

Sampson, D. D.

L. Scolaro, R. A. Mclaughlin, B. R. Klyen, B. A. Wood, P. D. Robbins, C. M. Saunders, S. L. Jacques, and D. D. Sampson, “Parametric imaging of the local attenuation coefficient in human axillary lymph nodes assessed using optical coherence tomography,” Biomed. Opt. Express 3 (2), 1122–1128 (2012).
[Crossref]

Sasaki, N.

A. Edwards-richards, M. Defreitas, C. P. Katsou, W. Seeherunvong, N. Sasaki, M. Freundlich, G. Zilleruelo, and C. L. Abitbol, “Capillary rarefaction : an early marker of microvascular disease in young hemodialysis patients,” Clin. Kidney J.569–574 (2014).
[Crossref]

Saunders, C. M.

L. Scolaro, R. A. Mclaughlin, B. R. Klyen, B. A. Wood, P. D. Robbins, C. M. Saunders, S. L. Jacques, and D. D. Sampson, “Parametric imaging of the local attenuation coefficient in human axillary lymph nodes assessed using optical coherence tomography,” Biomed. Opt. Express 3 (2), 1122–1128 (2012).
[Crossref]

Schiffrin, E. L.

B. I. Levy, E. L. Schiffrin, J. Mourad, D. Agostini, E. Vicaut, M. E. Safar, and H. A. J. Struijker-boudier, “Impaired Tissue Perfusion A Pathology Common to Hypertension, Obesity, and Diabetes Mellitus,” Circulation 118(9), 968–976 (2008).

Schuman, J. S.

L. Kagemann, G. Wollstein, M. Wojtkowski, H. Ishikawa, K. A. Townsend, M. L. Gabriele, V. J. Srinivasan, J. G. Fujimoto, and J. S. Schuman, “Spectral oximetry assessed with high-speed ultra-high-resolution optical coherence tomography,” J. Biomed. Opt. 12(4), 041212 (2007).
[Crossref] [PubMed]

Scolaro, L.

L. Scolaro, R. A. Mclaughlin, B. R. Klyen, B. A. Wood, P. D. Robbins, C. M. Saunders, S. L. Jacques, and D. D. Sampson, “Parametric imaging of the local attenuation coefficient in human axillary lymph nodes assessed using optical coherence tomography,” Biomed. Opt. Express 3 (2), 1122–1128 (2012).
[Crossref]

Scoles, D.

Seeherunvong, W.

A. Edwards-richards, M. Defreitas, C. P. Katsou, W. Seeherunvong, N. Sasaki, M. Freundlich, G. Zilleruelo, and C. L. Abitbol, “Capillary rarefaction : an early marker of microvascular disease in young hemodialysis patients,” Clin. Kidney J.569–574 (2014).
[Crossref]

Shah, N.

Shao, D.

Shu, X.

X. Shu, L. Beckmann, and H. Zhang, “Visible-light optical coherence tomography: a review,” J. Biomed. Opt. 22(12), 1–14 (2017).
[Crossref] [PubMed]

Song, H.

Y. Wang, H. Song, K. Maslov, Z. Yu, X. Younan, and W. Lihong V., “In vivo integrated photoacoustic and confocal microscopy of hemoglobin oxygen saturation and oxygen partial pressure,” Opt. Lett. 141(4), 520–529 (2008).

Song, W.

Spicer, G.

R. Liu, J. A. Winkelmann, G. Spicer, Y. Zhu, A. Eid, G. A. Ameer, V. Backman, and J. Yi, “Single capillary oximetry and tissue ultrastructural sensing by dual-band dual-scan inverse spectroscopic optical coherence tomography,” Light Sci. Appl. 7(1), 57 (2018).
[Crossref]

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]

Srinivasan, V. J.

S. P. Chong, C. W. Merkle, C. Leahy, H. Radhakrishnan, and V. J. Srinivasan, “Quantitative microvascular hemoglobin mapping using visible light spectroscopic Optical Coherence Tomography,” Biomed. Opt. Express 6(4), 1429–1450 (2015).
[Crossref] [PubMed]

L. Kagemann, G. Wollstein, M. Wojtkowski, H. Ishikawa, K. A. Townsend, M. L. Gabriele, V. J. Srinivasan, J. G. Fujimoto, and J. S. Schuman, “Spectral oximetry assessed with high-speed ultra-high-resolution optical coherence tomography,” J. Biomed. Opt. 12(4), 041212 (2007).
[Crossref] [PubMed]

Stefansson, E.

E. Stefansson, “Ocular Oxygenation and the Treatment of Diabetic Retinopathy,” Surv. Ophyhalmology 51(4), 364–380 (2006).

Struijker-boudier, H. A. J.

B. I. Levy, E. L. Schiffrin, J. Mourad, D. Agostini, E. Vicaut, M. E. Safar, and H. A. J. Struijker-boudier, “Impaired Tissue Perfusion A Pathology Common to Hypertension, Obesity, and Diabetes Mellitus,” Circulation 118(9), 968–976 (2008).

Subhash, H.

Y. Jia, O. Tan, J. Tokayer, B. Potsaid, Y. Wang, J. Jonathan, M. F. Kraus, H. Subhash, J. G. Fujimoto, J. Hornegger, and D. Huang, “Split-spectrum amplitude-decorrelation angiography with optical coherence tomography,” Opt. Express 20(4), 3116–3121 (2012).
[Crossref]

Sulai, Y. N.

Suzuki, N.

M. Unekawa, M. Tomita, Y. Tomita, H. Toriumi, K. Miyaki, and N. Suzuki, “RBC velocities in single capillaries of mouse and rat brains are the same, despite 10-fold difference in body size,” Brain Res. 1320, 69–73 (2010).
[Crossref] [PubMed]

Taflove, A.

Tan, O.

Y. Jia, O. Tan, J. Tokayer, B. Potsaid, Y. Wang, J. Jonathan, M. F. Kraus, H. Subhash, J. G. Fujimoto, J. Hornegger, and D. Huang, “Split-spectrum amplitude-decorrelation angiography with optical coherence tomography,” Opt. Express 20(4), 3116–3121 (2012).
[Crossref]

Tokayer, J.

Y. Jia, O. Tan, J. Tokayer, B. Potsaid, Y. Wang, J. Jonathan, M. F. Kraus, H. Subhash, J. G. Fujimoto, J. Hornegger, and D. Huang, “Split-spectrum amplitude-decorrelation angiography with optical coherence tomography,” Opt. Express 20(4), 3116–3121 (2012).
[Crossref]

Tomita, M.

M. Unekawa, M. Tomita, Y. Tomita, H. Toriumi, K. Miyaki, and N. Suzuki, “RBC velocities in single capillaries of mouse and rat brains are the same, despite 10-fold difference in body size,” Brain Res. 1320, 69–73 (2010).
[Crossref] [PubMed]

Tomita, Y.

M. Unekawa, M. Tomita, Y. Tomita, H. Toriumi, K. Miyaki, and N. Suzuki, “RBC velocities in single capillaries of mouse and rat brains are the same, despite 10-fold difference in body size,” Brain Res. 1320, 69–73 (2010).
[Crossref] [PubMed]

Toriumi, H.

M. Unekawa, M. Tomita, Y. Tomita, H. Toriumi, K. Miyaki, and N. Suzuki, “RBC velocities in single capillaries of mouse and rat brains are the same, despite 10-fold difference in body size,” Brain Res. 1320, 69–73 (2010).
[Crossref] [PubMed]

Townsend, K. A.

L. Kagemann, G. Wollstein, M. Wojtkowski, H. Ishikawa, K. A. Townsend, M. L. Gabriele, V. J. Srinivasan, J. G. Fujimoto, and J. S. Schuman, “Spectral oximetry assessed with high-speed ultra-high-resolution optical coherence tomography,” J. Biomed. Opt. 12(4), 041212 (2007).
[Crossref] [PubMed]

Ullrich, A.

P. Vajkoczy, A. Ullrich, and M. D. Menger, “Intravital Fluorescence Videomicroscopy to Study Tumor Angiogenesis and Microcirculation,” Neoplasia 2(1-2), 53–61 (2000).
[Crossref] [PubMed]

Unekawa, M.

M. Unekawa, M. Tomita, Y. Tomita, H. Toriumi, K. Miyaki, and N. Suzuki, “RBC velocities in single capillaries of mouse and rat brains are the same, despite 10-fold difference in body size,” Brain Res. 1320, 69–73 (2010).
[Crossref] [PubMed]

Vajkoczy, P.

P. Vajkoczy, A. Ullrich, and M. D. Menger, “Intravital Fluorescence Videomicroscopy to Study Tumor Angiogenesis and Microcirculation,” Neoplasia 2(1-2), 53–61 (2000).
[Crossref] [PubMed]

van Leeuwen, T. G.

Vannasdale, D. A.

Vicaut, E.

B. I. Levy, E. L. Schiffrin, J. Mourad, D. Agostini, E. Vicaut, M. E. Safar, and H. A. J. Struijker-boudier, “Impaired Tissue Perfusion A Pathology Common to Hypertension, Obesity, and Diabetes Mellitus,” Circulation 118(9), 968–976 (2008).

Walsh, J. B.

Wang, Y.

Y. Jia, O. Tan, J. Tokayer, B. Potsaid, Y. Wang, J. Jonathan, M. F. Kraus, H. Subhash, J. G. Fujimoto, J. Hornegger, and D. Huang, “Split-spectrum amplitude-decorrelation angiography with optical coherence tomography,” Opt. Express 20(4), 3116–3121 (2012).
[Crossref]

Y. Wang, H. Song, K. Maslov, Z. Yu, X. Younan, and W. Lihong V., “In vivo integrated photoacoustic and confocal microscopy of hemoglobin oxygen saturation and oxygen partial pressure,” Opt. Lett. 141(4), 520–529 (2008).

Wax, A.

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]

F. E. Robles, S. Chowdhury, and A. Wax, “Assessing hemoglobin concentration using spectroscopic optical coherence tomography for feasibility of tissue diagnostics,” Biomed. Opt. Express 1(1), 310–317 (2010).
[Crossref] [PubMed]

Wei, Q.

Weitz, R.

Werner, J. S.

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]

Winkelmann, J. A.

R. Liu, J. A. Winkelmann, G. Spicer, Y. Zhu, A. Eid, G. A. Ameer, V. Backman, and J. Yi, “Single capillary oximetry and tissue ultrastructural sensing by dual-band dual-scan inverse spectroscopic optical coherence tomography,” Light Sci. Appl. 7(1), 57 (2018).
[Crossref]

Wojtkowski, M.

L. Kagemann, G. Wollstein, M. Wojtkowski, H. Ishikawa, K. A. Townsend, M. L. Gabriele, V. J. Srinivasan, J. G. Fujimoto, and J. S. Schuman, “Spectral oximetry assessed with high-speed ultra-high-resolution optical coherence tomography,” J. Biomed. Opt. 12(4), 041212 (2007).
[Crossref] [PubMed]

Wollstein, G.

L. Kagemann, G. Wollstein, M. Wojtkowski, H. Ishikawa, K. A. Townsend, M. L. Gabriele, V. J. Srinivasan, J. G. Fujimoto, and J. S. Schuman, “Spectral oximetry assessed with high-speed ultra-high-resolution optical coherence tomography,” J. Biomed. Opt. 12(4), 041212 (2007).
[Crossref] [PubMed]

Wood, B. A.

L. Scolaro, R. A. Mclaughlin, B. R. Klyen, B. A. Wood, P. D. Robbins, C. M. Saunders, S. L. Jacques, and D. D. Sampson, “Parametric imaging of the local attenuation coefficient in human axillary lymph nodes assessed using optical coherence tomography,” Biomed. Opt. Express 3 (2), 1122–1128 (2012).
[Crossref]

Yi, J.

R. Liu, J. A. Winkelmann, G. Spicer, Y. Zhu, A. Eid, G. A. Ameer, V. Backman, and J. Yi, “Single capillary oximetry and tissue ultrastructural sensing by dual-band dual-scan inverse spectroscopic optical coherence tomography,” Light Sci. Appl. 7(1), 57 (2018).
[Crossref]

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]

L. Zhang, W. Song, D. Shao, S. Zhang, M. Desai, S. Ness, S. Roy, and J. Yi, “Volumetric fluorescence retinal imaging in vivo over a 30-degree field of view by oblique scanning laser ophthalmoscopy (oSLO),” Biomed. Opt. Express 9(1), 25–40 (2017).
[Crossref] [PubMed]

S. Chen, J. Yi, and H. F. Zhang, “Measuring oxygen saturation in retinal and choroidal circulations in rats using visible light optical coherence tomography angiography,” Biomed. Opt. Express 6(8), 2840–2853 (2015).
[Crossref] [PubMed]

J. Yi, S. Chen, V. Backman, and H. F. Zhang, “In vivo functional microangiography by visible-light optical coherence tomography,” Biomed. Opt. Express 5(10), 3603–3612 (2014).
[Crossref] [PubMed]

J. Yi, A. J. Radosevich, J. D. Rogers, S. C. P. Norris, İ. R. Çapoğlu, A. Taflove, and V. Backman, “Can OCT be sensitive to nanoscale structural alterations in biological tissue?” Opt. Express 21(7), 9043–9059 (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]

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. Quantum Electron. 20(2), 7000514 (2013).
[PubMed]

Younan, X.

Y. Wang, H. Song, K. Maslov, Z. Yu, X. Younan, and W. Lihong V., “In vivo integrated photoacoustic and confocal microscopy of hemoglobin oxygen saturation and oxygen partial pressure,” Opt. Lett. 141(4), 520–529 (2008).

Yu, Z.

Y. Wang, H. Song, K. Maslov, Z. Yu, X. Younan, and W. Lihong V., “In vivo integrated photoacoustic and confocal microscopy of hemoglobin oxygen saturation and oxygen partial pressure,” Opt. Lett. 141(4), 520–529 (2008).

Zawadzki, R. J.

Zhang, H.

X. Shu, L. Beckmann, and H. Zhang, “Visible-light optical coherence tomography: a review,” J. Biomed. Opt. 22(12), 1–14 (2017).
[Crossref] [PubMed]

Zhang, H. F.

Zhang, L.

Zhang, S.

Zhong, Z.

Zhou, L.

Zhu, Y.

R. Liu, J. A. Winkelmann, G. Spicer, Y. Zhu, A. Eid, G. A. Ameer, V. Backman, and J. Yi, “Single capillary oximetry and tissue ultrastructural sensing by dual-band dual-scan inverse spectroscopic optical coherence tomography,” Light Sci. Appl. 7(1), 57 (2018).
[Crossref]

Zilleruelo, G.

A. Edwards-richards, M. Defreitas, C. P. Katsou, W. Seeherunvong, N. Sasaki, M. Freundlich, G. Zilleruelo, and C. L. Abitbol, “Capillary rarefaction : an early marker of microvascular disease in young hemodialysis patients,” Clin. Kidney J.569–574 (2014).
[Crossref]

Zonios, G.

G. Zonios, J. Bykowski, and N. Kollias, “Skin melanin, hemoglobin, and light scattering properties can be quantitatively assessed in vivo using diffuse reflectance spectroscopy,” J. Invest. Dermatol. 117(6), 1452–1457 (2001).
[Crossref] [PubMed]

Zou, W.

Biomed. Opt. Express (10)

J. Yi, S. Chen, V. Backman, and H. F. Zhang, “In vivo functional microangiography by visible-light optical coherence tomography,” Biomed. Opt. Express 5(10), 3603–3612 (2014).
[Crossref] [PubMed]

S. Chen, J. Yi, and H. F. Zhang, “Measuring oxygen saturation in retinal and choroidal circulations in rats using visible light optical coherence tomography angiography,” Biomed. Opt. Express 6(8), 2840–2853 (2015).
[Crossref] [PubMed]

S. P. Chong, C. W. Merkle, C. Leahy, H. Radhakrishnan, and V. J. Srinivasan, “Quantitative microvascular hemoglobin mapping using visible light spectroscopic Optical Coherence Tomography,” Biomed. Opt. Express 6(4), 1429–1450 (2015).
[Crossref] [PubMed]

A. Pinhas, M. Dubow, N. Shah, T. Y. Chui, D. Scoles, Y. N. Sulai, R. Weitz, J. B. Walsh, J. Carroll, A. Dubra, and R. B. Rosen, “In vivo imaging of human retinal microvasculature using adaptive optics scanning light ophthalmoscope fluorescein angiography,” Biomed. Opt. Express 4(8), 1305–1317 (2013).
[Crossref] [PubMed]

R. J. Zawadzki, S. M. Jones, S. Pilli, S. Balderas-Mata, D. Y. Kim, S. S. Olivier, and J. S. Werner, “Integrated adaptive optics optical coherence tomography and adaptive optics scanning laser ophthalmoscope system for simultaneous cellular resolution in vivo retinal imaging,” Biomed. Opt. Express 2(6), 1674–1686 (2011).
[Crossref] [PubMed]

T. Y. P. Chui, D. A. Vannasdale, and S. A. Burns, “The use of forward scatter to improve retinal vascular imaging with an adaptive optics scanning laser ophthalmoscope,” Biomed. Opt. Express 3(10), 2537–2549 (2012).
[Crossref] [PubMed]

W. Song, L. Zhou, S. Zhang, S. Ness, D. Manishi, and Y. Ji, “Fiber-based visible and near infrared optical coherence tomography (vnOCT) enables quantitative elastic light scattering spectroscopy in human retina,” Biomed. Opt. Express 9(7), 3464–3480 (2018).
[Crossref]

L. Scolaro, R. A. Mclaughlin, B. R. Klyen, B. A. Wood, P. D. Robbins, C. M. Saunders, S. L. Jacques, and D. D. Sampson, “Parametric imaging of the local attenuation coefficient in human axillary lymph nodes assessed using optical coherence tomography,” Biomed. Opt. Express 3 (2), 1122–1128 (2012).
[Crossref]

L. Zhang, W. Song, D. Shao, S. Zhang, M. Desai, S. Ness, S. Roy, and J. Yi, “Volumetric fluorescence retinal imaging in vivo over a 30-degree field of view by oblique scanning laser ophthalmoscopy (oSLO),” Biomed. Opt. Express 9(1), 25–40 (2017).
[Crossref] [PubMed]

F. E. Robles, S. Chowdhury, and A. Wax, “Assessing hemoglobin concentration using spectroscopic optical coherence tomography for feasibility of tissue diagnostics,” Biomed. Opt. Express 1(1), 310–317 (2010).
[Crossref] [PubMed]

Brain Res. (1)

M. Unekawa, M. Tomita, Y. Tomita, H. Toriumi, K. Miyaki, and N. Suzuki, “RBC velocities in single capillaries of mouse and rat brains are the same, despite 10-fold difference in body size,” Brain Res. 1320, 69–73 (2010).
[Crossref] [PubMed]

Circulation (1)

B. I. Levy, E. L. Schiffrin, J. Mourad, D. Agostini, E. Vicaut, M. E. Safar, and H. A. J. Struijker-boudier, “Impaired Tissue Perfusion A Pathology Common to Hypertension, Obesity, and Diabetes Mellitus,” Circulation 118(9), 968–976 (2008).

IEEE J. Sel. Top. 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. Quantum Electron. 20(2), 7000514 (2013).
[PubMed]

J. Biomed. Opt. (3)

L. Kagemann, G. Wollstein, M. Wojtkowski, H. Ishikawa, K. A. Townsend, M. L. Gabriele, V. J. Srinivasan, J. G. Fujimoto, and J. S. Schuman, “Spectral oximetry assessed with high-speed ultra-high-resolution optical coherence tomography,” J. Biomed. Opt. 12(4), 041212 (2007).
[Crossref] [PubMed]

X. Shu, L. Beckmann, and H. Zhang, “Visible-light optical coherence tomography: a review,” J. Biomed. Opt. 22(12), 1–14 (2017).
[Crossref] [PubMed]

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. Invest. Dermatol. (1)

G. Zonios, J. Bykowski, and N. Kollias, “Skin melanin, hemoglobin, and light scattering properties can be quantitatively assessed in vivo using diffuse reflectance spectroscopy,” J. Invest. Dermatol. 117(6), 1452–1457 (2001).
[Crossref] [PubMed]

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

Light Sci. Appl. (1)

R. Liu, J. A. Winkelmann, G. Spicer, Y. Zhu, A. Eid, G. A. Ameer, V. Backman, and J. Yi, “Single capillary oximetry and tissue ultrastructural sensing by dual-band dual-scan inverse spectroscopic optical coherence tomography,” Light Sci. Appl. 7(1), 57 (2018).
[Crossref]

Nat. Photonics (1)

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]

Nat. Rev. Neurol. (1)

R. N. Kalaria, “Neurodegenerative disease: Diabetes, microvascular pathology and Alzheimer disease,” Nat. Rev. Neurol. 5(6), 305–306 (2009).
[Crossref] [PubMed]

Neoplasia (1)

P. Vajkoczy, A. Ullrich, and M. D. Menger, “Intravital Fluorescence Videomicroscopy to Study Tumor Angiogenesis and Microcirculation,” Neoplasia 2(1-2), 53–61 (2000).
[Crossref] [PubMed]

Opt. Express (2)

J. Yi, A. J. Radosevich, J. D. Rogers, S. C. P. Norris, İ. R. Çapoğlu, A. Taflove, and V. Backman, “Can OCT be sensitive to nanoscale structural alterations in biological tissue?” Opt. Express 21(7), 9043–9059 (2013).
[Crossref] [PubMed]

Y. Jia, O. Tan, J. Tokayer, B. Potsaid, Y. Wang, J. Jonathan, M. F. Kraus, H. Subhash, J. G. Fujimoto, J. Hornegger, and D. Huang, “Split-spectrum amplitude-decorrelation angiography with optical coherence tomography,” Opt. Express 20(4), 3116–3121 (2012).
[Crossref]

Opt. Lett. (3)

Surv. Ophyhalmology (1)

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A. Edwards-richards, M. Defreitas, C. P. Katsou, W. Seeherunvong, N. Sasaki, M. Freundlich, G. Zilleruelo, and C. L. Abitbol, “Capillary rarefaction : an early marker of microvascular disease in young hemodialysis patients,” Clin. Kidney J.569–574 (2014).
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J. Yi, W. Liu, S. Chen, V. Backman, N. Sheibani, C. M. Sorenson, A. A. Fawzi, R. A. Linsenmeier, and H. F. Zhang, “Visible light optical coherence tomography measures retinal oxygen metabolic response to systemic oxygenation,” Light Sci. Appl. 3, 1–10 (2015).
[Crossref]

W. Song, L. Zhou, K. L. Kot, H. Fan, J. Han, and J. Yi, “Measurement of flow-mediated dilation of mouse femoral artery in vivo by optical coherence tomography,” J. Biophotonics 5, 1–9 (2018).
[Crossref]

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Figures (13)

Fig. 1
Fig. 1 Schematic and scanning protocols of the visible light spectroscopic optical coherence tomography (vis-OCT) imaging system. (a) Illustration of a blood vessel embedded in tissue. (b) Optical setup of vis-OCT. SL: supercontinuum source; DM: dichroic mirror; PBS: polarization beam splitter; DSM: D-shaped mirror; P: prism; B: block; M: mirror; BT: beam trap; L: lens (f = 10 mm); SPEC: spectrometer; OFC: wide band optical fiber coupler; PC: polarization controller; VNDF: variable neutral density filter; DC: dispersion control; GV: galvanometer mirror; OL: objective lens (Effective working length: 39 mm). (c) Illustration of scanning protocol 1. (d) Illustration of scanning protocol 2.
Fig. 2
Fig. 2 Flow chart of the three-step statistical data-cleaning process of vis-OCT raw spectra. SNR: signal to noise ratio; x i : the i th spectrum of all repetitive spectra of a blood vessel;μ: the mean spectra of all repetitive B-scans of a blood vessel; d( x i ,μ): the Mahalanobis distance (MD) between x i andμ;θ: the intersection angle between simulated and vis-OCT measured spectra of a blood vessel; sO2: oxygen saturation.
Fig. 3
Fig. 3 Data quality control of vis-OCT spectra from six different sized blood vessels. (a) The en face angiography of wild-type C57BL/6J mouse lower extremity microvasculature acquired by scanning protocol 1. The red vertical line marks the location of a B-scan to be repetitively scanned. (b) The en face angiography of the marked B-scan in (a) acquired by scanning protocol 2. The color bar encodes depth locations of vessel central axis within 100 μm from sample top surface. Scale bar: 100 μm. Correspondence to the same blood vessels shown in (a) and (b) is indicated by red arrows in between. Blood vessels are numbered as Vessel 1, Vessel 2, Vessel 3, Vessel 4, Vessel 5, and Vessel 6, respectively. (c) The CV of L( μ n ), the mean MD between the validation samples and randomly selected training samples, for six vessels, respectively. V1 - V6: Vessel 1 to Vessel 6. The red dashed line indicates CV = 5%. The black box zooms in on the region where CVs are around 5%. (d) – (i) The vis-OCT measured spectra processed by the data-cleaning and their corresponding simulated oxygenated, deoxygenated, and sO2 fitted spectra for V1 to V6, respectively. Simulated spectra are normalized by the maximum of oxygenated spectra within 555 – 572 nm, indicated by black vertical dashed lines; vis-OCT measured spectra are scaled to have the same mean as sO2 fitted spectra. Sim. O/D: simulated oxygenated/deoxygenated spectra; Exp.: Experimental measurements; sO2 fit: sO2 fitted spectra; Org./Cld CV: the coefficients of variation (CV) of the averaging OCT spectra before (original) and after (cleaned) the data-cleaning process. CV = S.D./Mean.
Fig. 4
Fig. 4 Validation of the data quality-control protocol for in vivo vis-OCT Oximetry by supplying normal air and 100% oxygen to a wild-type C57BL/6J mouse. (a) The en face angiography of the mouse lower extremity microvasculature at normal air condition. (b) The en face angiography of the same imaging site in (a) ventilated by 100% pure oxygen. In (a) and (b), A: arteriole; V: venule; 3-9: vessel 3 to vessel 9. The color bar encodes depth of vessel central axis within 100 μm from sample top surface. Scale bar: 100 μm. (c) The sizes of blood vessels in (a) and (b) at normal and 100% oxygen conditions in descending order. (d) The quantified sO2 of blood vessels in (a) and (b) at normal and 100% oxygen conditions, respectively. In (c) and (d), A: arteriole; V: venule; V3 – V9: vessel 3 to vessel 9.
Fig. 5
Fig. 5 The en face sO2 map of C57BL/6J mouse ear microvasculature. The blue arrows indicate locations of the arteriole and the venule. A: arteriole; V: venule. Scale bar: 100 μm.
Fig. 6
Fig. 6 Simulation results of OCT spectra in log scale for oxygenated and deoxygenated blood vessels with diameters of 10 μm, 30 μm, 70 μm, and 150 μm, respectively. O: oxygenated state; D: deoxygenated state.
Fig. 7
Fig. 7 Scatter plots of Vessel 1 in Fig. 3 at iterations 1, 4, 7, and 11 during the anomaly detection and outlier removal process. Red lines indicate the thresholds for the Mahalanobis distance (MD) between each repetitive spectrum of the blood vessel ( x i ) and their mean (μ), represented by d ^ =μ+1.645σ, whereσ is variance. The values of d ^ at iterations 1, 4, 7, and 11 are 4.9483, 4.4383, 4.3801, and 4.3672, respectively. Blue dots above the red lines at each iteration were discarded as outliers. The number of data points with MD lower than the thresholds at iterations 1, 4, 7, and 11 are 463, 373, 340, and 332, respectively.
Fig. 8
Fig. 8 The number of repetitive B-scans detected as normal at each iteration of the anomaly detection and outlier removal process for (a): Vessel 1, (b): Vessel 2, (c): Vessel 3, (d): Vessel 4, (e): Vessel 5, and (f): Vessel 6 shown in Fig. 3. The total iteration numbers of vessel 1 to vessel 6 are 12, 15, 19, 9, 28, and 35, respectively.
Fig. 9
Fig. 9 The sO2 histograms of blood vessels in Figs. 4(a) and (b) without and with the data-quality process at normal (a) and 100% oxygen (b) conditions.
Fig. 10
Fig. 10 The en face sO2 map of C57BL/6J mouse ear microvasculature without data quality control process. Scale bar: 100 μm.
Fig. 11
Fig. 11 The spectroscopic angiography image SNR of the six vessels marked in Figs. 3(a) and 3(b). V1-V6: Vessel 1 to Vessel 6.
Fig. 12
Fig. 12 The intersection angles between simulated OCT spectra with and without different zero-mean Gaussian white noise for three different spectral bands. The standard deviations ( σ G ) of the Gaussian white noise were approximately 10%, 5%, and 2%, respectively, of the mean of the simulated spectrum (μ) with sO2 asα. The oxygen saturations of the simulated OCT spectra are (a): 60%, (b): 70%, (c): 80% and (d): 90%. The three spectral bands are 546 nm - 584 nm, 549 nm - 578 nm, and 552 nm - 572 nm, indicated by red, green, and blue, respectively. All curves are the mean of 100 iterations of the simulations.
Fig. 13
Fig. 13 The intersection angles between simulated spectra of blood vessels with sO2 as α and α±5% added by a zero-mean Gaussian white noise. The standard deviations ( σ G ) of the Gaussian white noise were approximately 10%, 5%, and 2% of the mean of the simulated spectrum (μ) with sO2 asα. (a): α = 60%, (b): α = 75%, and (c): α = 90%. All curves are the mean of 100 iterations of the simulations.

Tables (1)

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Table 1 Parameters of blood vessels and their sO2

Equations (7)

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I(λ, z 0 +z)= I 0 (λ) I t (λ, z 0 ) μ b (λ) e 2 μ t (λ)z
μ t (λ)=a(g(λ)) μ s (λ)+ μ a (λ)
I vessel (λ, z l )= 0 z l I(λ, z 0 +z) I 0 (λ) I t (λ, z 0 ) dz= 0 z l μ b (λ) e 2 μ t (λ)z dz= μ b (λ) 2 μ t (λ) [1 e 2 μ t (λ) z l ]
d( s i , μ n )= ( s i μ n ) T S 1 ( s i μ n )
L( μ n )= 1 N val i=1 N val d( s i , μ n )
I fit =s O 2 × I vessel O (λ, z l )+(1s O 2 )× I vessel D (λ, z l )
θ= cos 1 | I fit ·μ | I fit |·| μ | |

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