Abstract

Pulse oximetry is a ubiquitous optical technology, widely used for diagnosis and treatment guidance. Current pulse oximeters provide indications of arterial oxygen saturation. We present here a new quantitative methodology that extends the capability of pulse oximetry and provides real-time molar concentrations of oxy- and deoxy-hemoglobin at rates of up to 27 Hz by using advanced digital hardware, real-time firmware processing, and ultra-fast optical property calculations with a deep neural network (DNN). The technique utilizes a high-speed frequency domain spectroscopy system with five frequency-multiplexed wavelengths. High-speed demultiplexing and data reduction were performed in firmware. The DNN inversion algorithm was benchmarked as five orders of magnitude faster than conventional iterative methods for optical property extractions. The DNN provided unbiased optical property extractions, with an average error of 0 ± 5.6% in absorption and 0 ± 1.4% in reduced scattering. Together, these improvements enabled the measurement, calculation, and real-time continuous display of hemoglobin concentrations. A proof-of-concept cuff occlusion measurement was performed to demonstrate the ability of the device to track oxy- and deoxy-hemoglobin, and measure quantitative photoplethysmographic changes during the cardiac cycle. This technique substantially extends the capability of pulse oximetry and provides unprecedented real-time non-invasive functional information with broad applicability for cardiopulmonary applications.

© 2018 Optical Society of America under the terms of the OSA Open Access Publishing Agreement

Full Article  |  PDF Article
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References

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    [Crossref] [PubMed]
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    [Crossref] [PubMed]
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    [Crossref] [PubMed]
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    [Crossref] [PubMed]
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    [Crossref] [PubMed]
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    [Crossref] [PubMed]

2018 (1)

2017 (1)

A. Torjesen, R. Istfan, and D. Roblyer, “Ultrafast wavelength multiplexed broad bandwidth digital diffuse optical spectroscopy for in vivo extraction of tissue optical properties,” J. Biomed. Opt. 22(3), 036009 (2017).
[Crossref] [PubMed]

2016 (2)

B. J. Tromberg, Z. Zhang, A. Leproux, T. D. O’Sullivan, A. E. Cerussi, P. M. Carpenter, R. S. Mehta, D. Roblyer, W. Yang, K. D. Paulsen, B. W. Pogue, S. Jiang, P. A. Kaufman, A. G. Yodh, S. H. Chung, M. Schnall, B. S. Snyder, N. Hylton, D. A. Boas, S. A. Carp, S. J. Isakoff, and D. Mankoff, “Predicting Responses to Neoadjuvant Chemotherapy in Breast Cancer: ACRIN 6691 Trial of Diffuse Optical Spectroscopic Imaging,” Cancer Res. 76(20), 5933–5944 (2016).
[Crossref] [PubMed]

B. B. Zimmermann, Q. Fang, D. A. Boas, and S. A. Carp, “Frequency domain near-infrared multiwavelength imager design using high-speed, direct analog-to-digital conversion,” J. Biomed. Opt. 21(1), 016010 (2016).
[Crossref] [PubMed]

2014 (1)

A. Shander, M. Javidroozi, S. Naqvi, O. Aregbeyen, M. Çaylan, S. Demir, and A. Juhl, “An update on mortality and morbidity in patients with very low postoperative hemoglobin levels who decline blood transfusion (CME),” Transfusion 54(10), 2688–2695 (2014).
[Crossref] [PubMed]

2013 (2)

P. Farzam, P. Zirak, T. Binzoni, and T. Durduran, “Pulsatile and steady-state hemodynamics of the human patella bone by diffuse optical spectroscopy,” Physiol. Meas. 34(8), 839–857 (2013).
[Crossref] [PubMed]

S. H. Geyer, M. M. Nöhammer, I. E. Tinhofer, and W. J. Weninger, “The dermal arteries of the human thumb pad,” J. Anat. 223(6), 603–609 (2013).
[Crossref] [PubMed]

2011 (1)

D. Roblyer, S. Ueda, A. Cerussi, W. Tanamai, A. Durkin, R. Mehta, D. Hsiang, J. A. Butler, C. McLaren, W. P. Chen, and B. Tromberg, “Optical imaging of breast cancer oxyhemoglobin flare correlates with neoadjuvant chemotherapy response one day after starting treatment,” Proc. Natl. Acad. Sci. U.S.A. 108(35), 14626–14631 (2011).
[Crossref] [PubMed]

2010 (1)

S. Schreml, R. M. Szeimies, L. Prantl, S. Karrer, M. Landthaler, and P. Babilas, “Oxygen in acute and chronic wound healing,” Br. J. Dermatol. 163(2), 257–268 (2010).
[Crossref] [PubMed]

2008 (1)

K.-S. No, R. Kwong, P. H. Chou, and A. Cerussi, “Design and testing of a miniature broadband frequency domain photon migration instrument,” J. Biomed. Opt. 13(5), 050509 (2008).
[Crossref] [PubMed]

2007 (2)

K. H. Shelley, “Photoplethysmography: beyond the calculation of arterial oxygen saturation and heart rate,” Anesth. Analg. 105(6Suppl), S31–S36 (2007).
[Crossref] [PubMed]

M. Calderon-Arnulphi, A. Alaraj, S. Amin-Hanjani, W. W. Mantulin, C. M. Polzonetti, E. Gratton, and F. T. Charbel, “Detection of cerebral ischemia in neurovascular surgery using quantitative frequency-domain near-infrared spectroscopy,” J. Neurosurg. 106(2), 283–290 (2007).
[Crossref] [PubMed]

2006 (1)

J. Lee, D. J. Saltzman, A. E. Cerussi, D. V. Gelfand, J. Milliken, T. Waddington, B. J. Tromberg, and M. Brenner, “Broadband diffuse optical spectroscopy measurement of hemoglobin concentration during hypovolemia in rabbits,” Physiol. Meas. 27(8), 757–767 (2006).
[Crossref] [PubMed]

2005 (1)

P. Thavendiranathan, A. Bagai, A. Ebidia, A. S. Detsky, and N. K. Choudhry, “Do blood tests cause anemia in hospitalized patients? The effect of diagnostic phlebotomy on hemoglobin and hematocrit levels,” J. Gen. Intern. Med. 20(6), 520–524 (2005).
[Crossref] [PubMed]

2003 (1)

G. Strangman, M. A. Franceschini, and D. A. Boas, “Factors affecting the accuracy of near-infrared spectroscopy concentration calculations for focal changes in oxygenation parameters,” Neuroimage 18(4), 865–879 (2003).
[Crossref] [PubMed]

2002 (1)

M. A. Franceschini, D. A. Boas, A. Zourabian, S. G. Diamond, S. Nadgir, D. W. Lin, J. B. Moore, and S. Fantini, “Near-infrared spiroximetry: noninvasive measurements of venous saturation in piglets and human subjects,” J. Appl. Physiol. 92(1), 372–384 (2002).
[Crossref] [PubMed]

2001 (1)

R. Beck, A. G. Dempster, and I. Kale, “Finite-precision goertzel filters used for signal tone detection,” IEEE Trans. Circuits Syst. II Analog Digit. Signal Process. 48(7), 691–700 (2001).
[Crossref]

2000 (2)

F. Bevilacqua, A. J. Berger, A. E. Cerussi, D. Jakubowski, and B. J. Tromberg, “Broadband absorption spectroscopy in turbid media by combined frequency-domain and steady-state methods,” Appl. Opt. 39(34), 6498–6507 (2000).
[Crossref] [PubMed]

T. H. Pham, O. Coquoz, J. B. Fishkin, E. Anderson, and B. J. Tromberg, “Broad bandwidth frequency domain instrument for quantitative tissue optical spectroscopy,” Rev. Sci. Instrum. 71(6), 2500–2513 (2000).
[Crossref]

1999 (3)

J. E. Sinex, “Pulse oximetry: Principles and limitations,” Am. J. Emerg. Med. 17(1), 59–66 (1999).
[Crossref] [PubMed]

D. Solé, M. K. Komatsu, K. V. T. Carvalho, and C. K. Naspitz, “Pulse oximetry in the evaluation of the severity of acute asthma and/or wheezing in children,” J. Asthma 36(4), 327–333 (1999).
[Crossref] [PubMed]

M. A. Franceschini, E. Gratton, and S. Fantini, “Noninvasive optical method of measuring tissue and arterial saturation: an application to absolute pulse oximetry of the brain,” Opt. Lett. 24(12), 829–831 (1999).
[Crossref] [PubMed]

1998 (2)

W. R. Mower, G. Myers, E. L. Nicklin, K. T. Kearin, L. J. Baraff, and C. Sachs, “Pulse oximetry as a fifth vital sign in emergency geriatric assessment,” Acad. Emerg. Med. 5(9), 858–865 (1998).
[Crossref] [PubMed]

R. L. Summers, R. M. Anders, L. H. Woodward, A. K. Jenkins, and R. L. Galli, “Effect of routine pulse oximetry measurements on ED triage classification,” Am. J. Emerg. Med. 16(1), 5–7 (1998).
[Crossref] [PubMed]

1997 (2)

W. R. Mower, C. Sachs, E. L. Nicklin, and L. J. Baraff, “Pulse oximetry as a fifth pediatric vital sign,” Pediatrics 99(5), 681–686 (1997).
[Crossref] [PubMed]

D. T. Delpy and M. Cope, “Quantification in tissue near-infrared spectroscopy,” Philos. Trans. R. Soc. Lond. B Biol. Sci. 352, 11–20 (1997).

1994 (2)

B. W. Poguet and M. S. Pattersonil, “Frequency-domain optical absorption spectroscopy of finite tissue volumes using diffusion theory Frequency-domain optical absorption spectroscopy of finite tissue volumes using diffusion theory,” Phys. Med. Biol. 39, 1157 (1994).

P. Sliwiński, M. Lagosz, D. Górecka, and J. Zieliński, “The adequacy of oxygenation in COPD patients undergoing long-term oxygen therapy assessed by pulse oximetry at home,” Eur. Respir. J. 7(2), 274–278 (1994).
[Crossref] [PubMed]

1993 (1)

1992 (3)

Y. Mendelson, “Pulse Oximetry: Theory and Applications for Noninvasive Monitoring,” Clin. Chem. 38(9), 1601–1607 (1992).
[PubMed]

J. T. Moller, P. F. Jensen, N. W. Johannessen, and K. Espersen, “Hypoxaemia is Reduced by Pulse Oximetry Monitoring in the Operating Theatre and in the Recovery Room,” Br. J. Anaesth. 68(2), 146–150 (1992).
[Crossref] [PubMed]

M. I. Bierman, K. L. Stein, and J. V. Snyder, “Pulse oximetry in the postoperative care of cardiac surgical patients. A randomized controlled trail,” Chest 102(5), 1367–1370 (1992).
[Crossref] [PubMed]

1991 (1)

W. Zijlstra, A. Buursma, and W. Meeuwsen-van der Roest, “Absorption Spectra of Human Fetal and Adult Oxyhemoglobin, De-Oxyhemoglobin, and Methemoglobin,” Clin. Chem. 37(9), 1633–1638 (1991).
[PubMed]

1948 (1)

I. Lindgren, “Continuous Measurement of Arterial Oxygen Saturation in Man; Clinical Oximetry with a Swedish Oximeter According to Millikan,” Cardiologia 13(4), 226–240 (1948).
[Crossref] [PubMed]

Alaraj, A.

M. Calderon-Arnulphi, A. Alaraj, S. Amin-Hanjani, W. W. Mantulin, C. M. Polzonetti, E. Gratton, and F. T. Charbel, “Detection of cerebral ischemia in neurovascular surgery using quantitative frequency-domain near-infrared spectroscopy,” J. Neurosurg. 106(2), 283–290 (2007).
[Crossref] [PubMed]

Amin-Hanjani, S.

M. Calderon-Arnulphi, A. Alaraj, S. Amin-Hanjani, W. W. Mantulin, C. M. Polzonetti, E. Gratton, and F. T. Charbel, “Detection of cerebral ischemia in neurovascular surgery using quantitative frequency-domain near-infrared spectroscopy,” J. Neurosurg. 106(2), 283–290 (2007).
[Crossref] [PubMed]

Anders, R. M.

R. L. Summers, R. M. Anders, L. H. Woodward, A. K. Jenkins, and R. L. Galli, “Effect of routine pulse oximetry measurements on ED triage classification,” Am. J. Emerg. Med. 16(1), 5–7 (1998).
[Crossref] [PubMed]

Anderson, E.

T. H. Pham, O. Coquoz, J. B. Fishkin, E. Anderson, and B. J. Tromberg, “Broad bandwidth frequency domain instrument for quantitative tissue optical spectroscopy,” Rev. Sci. Instrum. 71(6), 2500–2513 (2000).
[Crossref]

Aregbeyen, O.

A. Shander, M. Javidroozi, S. Naqvi, O. Aregbeyen, M. Çaylan, S. Demir, and A. Juhl, “An update on mortality and morbidity in patients with very low postoperative hemoglobin levels who decline blood transfusion (CME),” Transfusion 54(10), 2688–2695 (2014).
[Crossref] [PubMed]

Ba, J.

D. P. Kingma and J. Ba, “Adam: A Method for Stochastic Optimization,” arXiv Prepr. 1–15 (2014).

Babilas, P.

S. Schreml, R. M. Szeimies, L. Prantl, S. Karrer, M. Landthaler, and P. Babilas, “Oxygen in acute and chronic wound healing,” Br. J. Dermatol. 163(2), 257–268 (2010).
[Crossref] [PubMed]

Bagai, A.

P. Thavendiranathan, A. Bagai, A. Ebidia, A. S. Detsky, and N. K. Choudhry, “Do blood tests cause anemia in hospitalized patients? The effect of diagnostic phlebotomy on hemoglobin and hematocrit levels,” J. Gen. Intern. Med. 20(6), 520–524 (2005).
[Crossref] [PubMed]

Baraff, L. J.

W. R. Mower, G. Myers, E. L. Nicklin, K. T. Kearin, L. J. Baraff, and C. Sachs, “Pulse oximetry as a fifth vital sign in emergency geriatric assessment,” Acad. Emerg. Med. 5(9), 858–865 (1998).
[Crossref] [PubMed]

W. R. Mower, C. Sachs, E. L. Nicklin, and L. J. Baraff, “Pulse oximetry as a fifth pediatric vital sign,” Pediatrics 99(5), 681–686 (1997).
[Crossref] [PubMed]

Beck, R.

R. Beck, A. G. Dempster, and I. Kale, “Finite-precision goertzel filters used for signal tone detection,” IEEE Trans. Circuits Syst. II Analog Digit. Signal Process. 48(7), 691–700 (2001).
[Crossref]

Berger, A. J.

Bevilacqua, F.

Bierman, M. I.

M. I. Bierman, K. L. Stein, and J. V. Snyder, “Pulse oximetry in the postoperative care of cardiac surgical patients. A randomized controlled trail,” Chest 102(5), 1367–1370 (1992).
[Crossref] [PubMed]

Binzoni, T.

P. Farzam, P. Zirak, T. Binzoni, and T. Durduran, “Pulsatile and steady-state hemodynamics of the human patella bone by diffuse optical spectroscopy,” Physiol. Meas. 34(8), 839–857 (2013).
[Crossref] [PubMed]

Boas, D. A.

B. B. Zimmermann, Q. Fang, D. A. Boas, and S. A. Carp, “Frequency domain near-infrared multiwavelength imager design using high-speed, direct analog-to-digital conversion,” J. Biomed. Opt. 21(1), 016010 (2016).
[Crossref] [PubMed]

B. J. Tromberg, Z. Zhang, A. Leproux, T. D. O’Sullivan, A. E. Cerussi, P. M. Carpenter, R. S. Mehta, D. Roblyer, W. Yang, K. D. Paulsen, B. W. Pogue, S. Jiang, P. A. Kaufman, A. G. Yodh, S. H. Chung, M. Schnall, B. S. Snyder, N. Hylton, D. A. Boas, S. A. Carp, S. J. Isakoff, and D. Mankoff, “Predicting Responses to Neoadjuvant Chemotherapy in Breast Cancer: ACRIN 6691 Trial of Diffuse Optical Spectroscopic Imaging,” Cancer Res. 76(20), 5933–5944 (2016).
[Crossref] [PubMed]

G. Strangman, M. A. Franceschini, and D. A. Boas, “Factors affecting the accuracy of near-infrared spectroscopy concentration calculations for focal changes in oxygenation parameters,” Neuroimage 18(4), 865–879 (2003).
[Crossref] [PubMed]

M. A. Franceschini, D. A. Boas, A. Zourabian, S. G. Diamond, S. Nadgir, D. W. Lin, J. B. Moore, and S. Fantini, “Near-infrared spiroximetry: noninvasive measurements of venous saturation in piglets and human subjects,” J. Appl. Physiol. 92(1), 372–384 (2002).
[Crossref] [PubMed]

Brenner, M.

J. Lee, D. J. Saltzman, A. E. Cerussi, D. V. Gelfand, J. Milliken, T. Waddington, B. J. Tromberg, and M. Brenner, “Broadband diffuse optical spectroscopy measurement of hemoglobin concentration during hypovolemia in rabbits,” Physiol. Meas. 27(8), 757–767 (2006).
[Crossref] [PubMed]

Butler, J. A.

D. Roblyer, S. Ueda, A. Cerussi, W. Tanamai, A. Durkin, R. Mehta, D. Hsiang, J. A. Butler, C. McLaren, W. P. Chen, and B. Tromberg, “Optical imaging of breast cancer oxyhemoglobin flare correlates with neoadjuvant chemotherapy response one day after starting treatment,” Proc. Natl. Acad. Sci. U.S.A. 108(35), 14626–14631 (2011).
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W. Zijlstra, A. Buursma, and W. Meeuwsen-van der Roest, “Absorption Spectra of Human Fetal and Adult Oxyhemoglobin, De-Oxyhemoglobin, and Methemoglobin,” Clin. Chem. 37(9), 1633–1638 (1991).
[PubMed]

Calderon-Arnulphi, M.

M. Calderon-Arnulphi, A. Alaraj, S. Amin-Hanjani, W. W. Mantulin, C. M. Polzonetti, E. Gratton, and F. T. Charbel, “Detection of cerebral ischemia in neurovascular surgery using quantitative frequency-domain near-infrared spectroscopy,” J. Neurosurg. 106(2), 283–290 (2007).
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Carp, S. A.

B. B. Zimmermann, Q. Fang, D. A. Boas, and S. A. Carp, “Frequency domain near-infrared multiwavelength imager design using high-speed, direct analog-to-digital conversion,” J. Biomed. Opt. 21(1), 016010 (2016).
[Crossref] [PubMed]

B. J. Tromberg, Z. Zhang, A. Leproux, T. D. O’Sullivan, A. E. Cerussi, P. M. Carpenter, R. S. Mehta, D. Roblyer, W. Yang, K. D. Paulsen, B. W. Pogue, S. Jiang, P. A. Kaufman, A. G. Yodh, S. H. Chung, M. Schnall, B. S. Snyder, N. Hylton, D. A. Boas, S. A. Carp, S. J. Isakoff, and D. Mankoff, “Predicting Responses to Neoadjuvant Chemotherapy in Breast Cancer: ACRIN 6691 Trial of Diffuse Optical Spectroscopic Imaging,” Cancer Res. 76(20), 5933–5944 (2016).
[Crossref] [PubMed]

Carpenter, P. M.

B. J. Tromberg, Z. Zhang, A. Leproux, T. D. O’Sullivan, A. E. Cerussi, P. M. Carpenter, R. S. Mehta, D. Roblyer, W. Yang, K. D. Paulsen, B. W. Pogue, S. Jiang, P. A. Kaufman, A. G. Yodh, S. H. Chung, M. Schnall, B. S. Snyder, N. Hylton, D. A. Boas, S. A. Carp, S. J. Isakoff, and D. Mankoff, “Predicting Responses to Neoadjuvant Chemotherapy in Breast Cancer: ACRIN 6691 Trial of Diffuse Optical Spectroscopic Imaging,” Cancer Res. 76(20), 5933–5944 (2016).
[Crossref] [PubMed]

Carvalho, K. V. T.

D. Solé, M. K. Komatsu, K. V. T. Carvalho, and C. K. Naspitz, “Pulse oximetry in the evaluation of the severity of acute asthma and/or wheezing in children,” J. Asthma 36(4), 327–333 (1999).
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Çaylan, M.

A. Shander, M. Javidroozi, S. Naqvi, O. Aregbeyen, M. Çaylan, S. Demir, and A. Juhl, “An update on mortality and morbidity in patients with very low postoperative hemoglobin levels who decline blood transfusion (CME),” Transfusion 54(10), 2688–2695 (2014).
[Crossref] [PubMed]

Cerussi, A.

D. Roblyer, S. Ueda, A. Cerussi, W. Tanamai, A. Durkin, R. Mehta, D. Hsiang, J. A. Butler, C. McLaren, W. P. Chen, and B. Tromberg, “Optical imaging of breast cancer oxyhemoglobin flare correlates with neoadjuvant chemotherapy response one day after starting treatment,” Proc. Natl. Acad. Sci. U.S.A. 108(35), 14626–14631 (2011).
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K.-S. No, R. Kwong, P. H. Chou, and A. Cerussi, “Design and testing of a miniature broadband frequency domain photon migration instrument,” J. Biomed. Opt. 13(5), 050509 (2008).
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Cerussi, A. E.

B. J. Tromberg, Z. Zhang, A. Leproux, T. D. O’Sullivan, A. E. Cerussi, P. M. Carpenter, R. S. Mehta, D. Roblyer, W. Yang, K. D. Paulsen, B. W. Pogue, S. Jiang, P. A. Kaufman, A. G. Yodh, S. H. Chung, M. Schnall, B. S. Snyder, N. Hylton, D. A. Boas, S. A. Carp, S. J. Isakoff, and D. Mankoff, “Predicting Responses to Neoadjuvant Chemotherapy in Breast Cancer: ACRIN 6691 Trial of Diffuse Optical Spectroscopic Imaging,” Cancer Res. 76(20), 5933–5944 (2016).
[Crossref] [PubMed]

J. Lee, D. J. Saltzman, A. E. Cerussi, D. V. Gelfand, J. Milliken, T. Waddington, B. J. Tromberg, and M. Brenner, “Broadband diffuse optical spectroscopy measurement of hemoglobin concentration during hypovolemia in rabbits,” Physiol. Meas. 27(8), 757–767 (2006).
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F. Bevilacqua, A. J. Berger, A. E. Cerussi, D. Jakubowski, and B. J. Tromberg, “Broadband absorption spectroscopy in turbid media by combined frequency-domain and steady-state methods,” Appl. Opt. 39(34), 6498–6507 (2000).
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Charbel, F. T.

M. Calderon-Arnulphi, A. Alaraj, S. Amin-Hanjani, W. W. Mantulin, C. M. Polzonetti, E. Gratton, and F. T. Charbel, “Detection of cerebral ischemia in neurovascular surgery using quantitative frequency-domain near-infrared spectroscopy,” J. Neurosurg. 106(2), 283–290 (2007).
[Crossref] [PubMed]

Chen, W. P.

D. Roblyer, S. Ueda, A. Cerussi, W. Tanamai, A. Durkin, R. Mehta, D. Hsiang, J. A. Butler, C. McLaren, W. P. Chen, and B. Tromberg, “Optical imaging of breast cancer oxyhemoglobin flare correlates with neoadjuvant chemotherapy response one day after starting treatment,” Proc. Natl. Acad. Sci. U.S.A. 108(35), 14626–14631 (2011).
[Crossref] [PubMed]

Chou, P. H.

K.-S. No, R. Kwong, P. H. Chou, and A. Cerussi, “Design and testing of a miniature broadband frequency domain photon migration instrument,” J. Biomed. Opt. 13(5), 050509 (2008).
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P. Thavendiranathan, A. Bagai, A. Ebidia, A. S. Detsky, and N. K. Choudhry, “Do blood tests cause anemia in hospitalized patients? The effect of diagnostic phlebotomy on hemoglobin and hematocrit levels,” J. Gen. Intern. Med. 20(6), 520–524 (2005).
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B. J. Tromberg, Z. Zhang, A. Leproux, T. D. O’Sullivan, A. E. Cerussi, P. M. Carpenter, R. S. Mehta, D. Roblyer, W. Yang, K. D. Paulsen, B. W. Pogue, S. Jiang, P. A. Kaufman, A. G. Yodh, S. H. Chung, M. Schnall, B. S. Snyder, N. Hylton, D. A. Boas, S. A. Carp, S. J. Isakoff, and D. Mankoff, “Predicting Responses to Neoadjuvant Chemotherapy in Breast Cancer: ACRIN 6691 Trial of Diffuse Optical Spectroscopic Imaging,” Cancer Res. 76(20), 5933–5944 (2016).
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T. H. Pham, O. Coquoz, J. B. Fishkin, E. Anderson, and B. J. Tromberg, “Broad bandwidth frequency domain instrument for quantitative tissue optical spectroscopy,” Rev. Sci. Instrum. 71(6), 2500–2513 (2000).
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D. T. Delpy and M. Cope, “Quantification in tissue near-infrared spectroscopy,” Philos. Trans. R. Soc. Lond. B Biol. Sci. 352, 11–20 (1997).

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A. Shander, M. Javidroozi, S. Naqvi, O. Aregbeyen, M. Çaylan, S. Demir, and A. Juhl, “An update on mortality and morbidity in patients with very low postoperative hemoglobin levels who decline blood transfusion (CME),” Transfusion 54(10), 2688–2695 (2014).
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Dempster, A. G.

R. Beck, A. G. Dempster, and I. Kale, “Finite-precision goertzel filters used for signal tone detection,” IEEE Trans. Circuits Syst. II Analog Digit. Signal Process. 48(7), 691–700 (2001).
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P. Thavendiranathan, A. Bagai, A. Ebidia, A. S. Detsky, and N. K. Choudhry, “Do blood tests cause anemia in hospitalized patients? The effect of diagnostic phlebotomy on hemoglobin and hematocrit levels,” J. Gen. Intern. Med. 20(6), 520–524 (2005).
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M. A. Franceschini, D. A. Boas, A. Zourabian, S. G. Diamond, S. Nadgir, D. W. Lin, J. B. Moore, and S. Fantini, “Near-infrared spiroximetry: noninvasive measurements of venous saturation in piglets and human subjects,” J. Appl. Physiol. 92(1), 372–384 (2002).
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P. Farzam, P. Zirak, T. Binzoni, and T. Durduran, “Pulsatile and steady-state hemodynamics of the human patella bone by diffuse optical spectroscopy,” Physiol. Meas. 34(8), 839–857 (2013).
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Durkin, A.

D. Roblyer, S. Ueda, A. Cerussi, W. Tanamai, A. Durkin, R. Mehta, D. Hsiang, J. A. Butler, C. McLaren, W. P. Chen, and B. Tromberg, “Optical imaging of breast cancer oxyhemoglobin flare correlates with neoadjuvant chemotherapy response one day after starting treatment,” Proc. Natl. Acad. Sci. U.S.A. 108(35), 14626–14631 (2011).
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P. Thavendiranathan, A. Bagai, A. Ebidia, A. S. Detsky, and N. K. Choudhry, “Do blood tests cause anemia in hospitalized patients? The effect of diagnostic phlebotomy on hemoglobin and hematocrit levels,” J. Gen. Intern. Med. 20(6), 520–524 (2005).
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J. T. Moller, P. F. Jensen, N. W. Johannessen, and K. Espersen, “Hypoxaemia is Reduced by Pulse Oximetry Monitoring in the Operating Theatre and in the Recovery Room,” Br. J. Anaesth. 68(2), 146–150 (1992).
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B. B. Zimmermann, Q. Fang, D. A. Boas, and S. A. Carp, “Frequency domain near-infrared multiwavelength imager design using high-speed, direct analog-to-digital conversion,” J. Biomed. Opt. 21(1), 016010 (2016).
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M. A. Franceschini, D. A. Boas, A. Zourabian, S. G. Diamond, S. Nadgir, D. W. Lin, J. B. Moore, and S. Fantini, “Near-infrared spiroximetry: noninvasive measurements of venous saturation in piglets and human subjects,” J. Appl. Physiol. 92(1), 372–384 (2002).
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M. A. Franceschini, E. Gratton, and S. Fantini, “Noninvasive optical method of measuring tissue and arterial saturation: an application to absolute pulse oximetry of the brain,” Opt. Lett. 24(12), 829–831 (1999).
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P. Farzam, P. Zirak, T. Binzoni, and T. Durduran, “Pulsatile and steady-state hemodynamics of the human patella bone by diffuse optical spectroscopy,” Physiol. Meas. 34(8), 839–857 (2013).
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T. H. Pham, O. Coquoz, J. B. Fishkin, E. Anderson, and B. J. Tromberg, “Broad bandwidth frequency domain instrument for quantitative tissue optical spectroscopy,” Rev. Sci. Instrum. 71(6), 2500–2513 (2000).
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G. Strangman, M. A. Franceschini, and D. A. Boas, “Factors affecting the accuracy of near-infrared spectroscopy concentration calculations for focal changes in oxygenation parameters,” Neuroimage 18(4), 865–879 (2003).
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M. A. Franceschini, D. A. Boas, A. Zourabian, S. G. Diamond, S. Nadgir, D. W. Lin, J. B. Moore, and S. Fantini, “Near-infrared spiroximetry: noninvasive measurements of venous saturation in piglets and human subjects,” J. Appl. Physiol. 92(1), 372–384 (2002).
[Crossref] [PubMed]

M. A. Franceschini, E. Gratton, and S. Fantini, “Noninvasive optical method of measuring tissue and arterial saturation: an application to absolute pulse oximetry of the brain,” Opt. Lett. 24(12), 829–831 (1999).
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R. L. Summers, R. M. Anders, L. H. Woodward, A. K. Jenkins, and R. L. Galli, “Effect of routine pulse oximetry measurements on ED triage classification,” Am. J. Emerg. Med. 16(1), 5–7 (1998).
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J. Lee, D. J. Saltzman, A. E. Cerussi, D. V. Gelfand, J. Milliken, T. Waddington, B. J. Tromberg, and M. Brenner, “Broadband diffuse optical spectroscopy measurement of hemoglobin concentration during hypovolemia in rabbits,” Physiol. Meas. 27(8), 757–767 (2006).
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S. H. Geyer, M. M. Nöhammer, I. E. Tinhofer, and W. J. Weninger, “The dermal arteries of the human thumb pad,” J. Anat. 223(6), 603–609 (2013).
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P. Sliwiński, M. Lagosz, D. Górecka, and J. Zieliński, “The adequacy of oxygenation in COPD patients undergoing long-term oxygen therapy assessed by pulse oximetry at home,” Eur. Respir. J. 7(2), 274–278 (1994).
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Gratton, E.

M. Calderon-Arnulphi, A. Alaraj, S. Amin-Hanjani, W. W. Mantulin, C. M. Polzonetti, E. Gratton, and F. T. Charbel, “Detection of cerebral ischemia in neurovascular surgery using quantitative frequency-domain near-infrared spectroscopy,” J. Neurosurg. 106(2), 283–290 (2007).
[Crossref] [PubMed]

M. A. Franceschini, E. Gratton, and S. Fantini, “Noninvasive optical method of measuring tissue and arterial saturation: an application to absolute pulse oximetry of the brain,” Opt. Lett. 24(12), 829–831 (1999).
[Crossref] [PubMed]

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Hsiang, D.

D. Roblyer, S. Ueda, A. Cerussi, W. Tanamai, A. Durkin, R. Mehta, D. Hsiang, J. A. Butler, C. McLaren, W. P. Chen, and B. Tromberg, “Optical imaging of breast cancer oxyhemoglobin flare correlates with neoadjuvant chemotherapy response one day after starting treatment,” Proc. Natl. Acad. Sci. U.S.A. 108(35), 14626–14631 (2011).
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B. J. Tromberg, Z. Zhang, A. Leproux, T. D. O’Sullivan, A. E. Cerussi, P. M. Carpenter, R. S. Mehta, D. Roblyer, W. Yang, K. D. Paulsen, B. W. Pogue, S. Jiang, P. A. Kaufman, A. G. Yodh, S. H. Chung, M. Schnall, B. S. Snyder, N. Hylton, D. A. Boas, S. A. Carp, S. J. Isakoff, and D. Mankoff, “Predicting Responses to Neoadjuvant Chemotherapy in Breast Cancer: ACRIN 6691 Trial of Diffuse Optical Spectroscopic Imaging,” Cancer Res. 76(20), 5933–5944 (2016).
[Crossref] [PubMed]

Isakoff, S. J.

B. J. Tromberg, Z. Zhang, A. Leproux, T. D. O’Sullivan, A. E. Cerussi, P. M. Carpenter, R. S. Mehta, D. Roblyer, W. Yang, K. D. Paulsen, B. W. Pogue, S. Jiang, P. A. Kaufman, A. G. Yodh, S. H. Chung, M. Schnall, B. S. Snyder, N. Hylton, D. A. Boas, S. A. Carp, S. J. Isakoff, and D. Mankoff, “Predicting Responses to Neoadjuvant Chemotherapy in Breast Cancer: ACRIN 6691 Trial of Diffuse Optical Spectroscopic Imaging,” Cancer Res. 76(20), 5933–5944 (2016).
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A. Torjesen, R. Istfan, and D. Roblyer, “Ultrafast wavelength multiplexed broad bandwidth digital diffuse optical spectroscopy for in vivo extraction of tissue optical properties,” J. Biomed. Opt. 22(3), 036009 (2017).
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Javidroozi, M.

A. Shander, M. Javidroozi, S. Naqvi, O. Aregbeyen, M. Çaylan, S. Demir, and A. Juhl, “An update on mortality and morbidity in patients with very low postoperative hemoglobin levels who decline blood transfusion (CME),” Transfusion 54(10), 2688–2695 (2014).
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Jenkins, A. K.

R. L. Summers, R. M. Anders, L. H. Woodward, A. K. Jenkins, and R. L. Galli, “Effect of routine pulse oximetry measurements on ED triage classification,” Am. J. Emerg. Med. 16(1), 5–7 (1998).
[Crossref] [PubMed]

Jensen, P. F.

J. T. Moller, P. F. Jensen, N. W. Johannessen, and K. Espersen, “Hypoxaemia is Reduced by Pulse Oximetry Monitoring in the Operating Theatre and in the Recovery Room,” Br. J. Anaesth. 68(2), 146–150 (1992).
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B. J. Tromberg, Z. Zhang, A. Leproux, T. D. O’Sullivan, A. E. Cerussi, P. M. Carpenter, R. S. Mehta, D. Roblyer, W. Yang, K. D. Paulsen, B. W. Pogue, S. Jiang, P. A. Kaufman, A. G. Yodh, S. H. Chung, M. Schnall, B. S. Snyder, N. Hylton, D. A. Boas, S. A. Carp, S. J. Isakoff, and D. Mankoff, “Predicting Responses to Neoadjuvant Chemotherapy in Breast Cancer: ACRIN 6691 Trial of Diffuse Optical Spectroscopic Imaging,” Cancer Res. 76(20), 5933–5944 (2016).
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J. T. Moller, P. F. Jensen, N. W. Johannessen, and K. Espersen, “Hypoxaemia is Reduced by Pulse Oximetry Monitoring in the Operating Theatre and in the Recovery Room,” Br. J. Anaesth. 68(2), 146–150 (1992).
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A. Shander, M. Javidroozi, S. Naqvi, O. Aregbeyen, M. Çaylan, S. Demir, and A. Juhl, “An update on mortality and morbidity in patients with very low postoperative hemoglobin levels who decline blood transfusion (CME),” Transfusion 54(10), 2688–2695 (2014).
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R. Beck, A. G. Dempster, and I. Kale, “Finite-precision goertzel filters used for signal tone detection,” IEEE Trans. Circuits Syst. II Analog Digit. Signal Process. 48(7), 691–700 (2001).
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Kaufman, P. A.

B. J. Tromberg, Z. Zhang, A. Leproux, T. D. O’Sullivan, A. E. Cerussi, P. M. Carpenter, R. S. Mehta, D. Roblyer, W. Yang, K. D. Paulsen, B. W. Pogue, S. Jiang, P. A. Kaufman, A. G. Yodh, S. H. Chung, M. Schnall, B. S. Snyder, N. Hylton, D. A. Boas, S. A. Carp, S. J. Isakoff, and D. Mankoff, “Predicting Responses to Neoadjuvant Chemotherapy in Breast Cancer: ACRIN 6691 Trial of Diffuse Optical Spectroscopic Imaging,” Cancer Res. 76(20), 5933–5944 (2016).
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D. Solé, M. K. Komatsu, K. V. T. Carvalho, and C. K. Naspitz, “Pulse oximetry in the evaluation of the severity of acute asthma and/or wheezing in children,” J. Asthma 36(4), 327–333 (1999).
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K.-S. No, R. Kwong, P. H. Chou, and A. Cerussi, “Design and testing of a miniature broadband frequency domain photon migration instrument,” J. Biomed. Opt. 13(5), 050509 (2008).
[Crossref] [PubMed]

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P. Sliwiński, M. Lagosz, D. Górecka, and J. Zieliński, “The adequacy of oxygenation in COPD patients undergoing long-term oxygen therapy assessed by pulse oximetry at home,” Eur. Respir. J. 7(2), 274–278 (1994).
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S. Schreml, R. M. Szeimies, L. Prantl, S. Karrer, M. Landthaler, and P. Babilas, “Oxygen in acute and chronic wound healing,” Br. J. Dermatol. 163(2), 257–268 (2010).
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J. Lee, D. J. Saltzman, A. E. Cerussi, D. V. Gelfand, J. Milliken, T. Waddington, B. J. Tromberg, and M. Brenner, “Broadband diffuse optical spectroscopy measurement of hemoglobin concentration during hypovolemia in rabbits,” Physiol. Meas. 27(8), 757–767 (2006).
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Leproux, A.

B. J. Tromberg, Z. Zhang, A. Leproux, T. D. O’Sullivan, A. E. Cerussi, P. M. Carpenter, R. S. Mehta, D. Roblyer, W. Yang, K. D. Paulsen, B. W. Pogue, S. Jiang, P. A. Kaufman, A. G. Yodh, S. H. Chung, M. Schnall, B. S. Snyder, N. Hylton, D. A. Boas, S. A. Carp, S. J. Isakoff, and D. Mankoff, “Predicting Responses to Neoadjuvant Chemotherapy in Breast Cancer: ACRIN 6691 Trial of Diffuse Optical Spectroscopic Imaging,” Cancer Res. 76(20), 5933–5944 (2016).
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M. A. Franceschini, D. A. Boas, A. Zourabian, S. G. Diamond, S. Nadgir, D. W. Lin, J. B. Moore, and S. Fantini, “Near-infrared spiroximetry: noninvasive measurements of venous saturation in piglets and human subjects,” J. Appl. Physiol. 92(1), 372–384 (2002).
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M. Calderon-Arnulphi, A. Alaraj, S. Amin-Hanjani, W. W. Mantulin, C. M. Polzonetti, E. Gratton, and F. T. Charbel, “Detection of cerebral ischemia in neurovascular surgery using quantitative frequency-domain near-infrared spectroscopy,” J. Neurosurg. 106(2), 283–290 (2007).
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McLaren, C.

D. Roblyer, S. Ueda, A. Cerussi, W. Tanamai, A. Durkin, R. Mehta, D. Hsiang, J. A. Butler, C. McLaren, W. P. Chen, and B. Tromberg, “Optical imaging of breast cancer oxyhemoglobin flare correlates with neoadjuvant chemotherapy response one day after starting treatment,” Proc. Natl. Acad. Sci. U.S.A. 108(35), 14626–14631 (2011).
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W. Zijlstra, A. Buursma, and W. Meeuwsen-van der Roest, “Absorption Spectra of Human Fetal and Adult Oxyhemoglobin, De-Oxyhemoglobin, and Methemoglobin,” Clin. Chem. 37(9), 1633–1638 (1991).
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D. Roblyer, S. Ueda, A. Cerussi, W. Tanamai, A. Durkin, R. Mehta, D. Hsiang, J. A. Butler, C. McLaren, W. P. Chen, and B. Tromberg, “Optical imaging of breast cancer oxyhemoglobin flare correlates with neoadjuvant chemotherapy response one day after starting treatment,” Proc. Natl. Acad. Sci. U.S.A. 108(35), 14626–14631 (2011).
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B. J. Tromberg, Z. Zhang, A. Leproux, T. D. O’Sullivan, A. E. Cerussi, P. M. Carpenter, R. S. Mehta, D. Roblyer, W. Yang, K. D. Paulsen, B. W. Pogue, S. Jiang, P. A. Kaufman, A. G. Yodh, S. H. Chung, M. Schnall, B. S. Snyder, N. Hylton, D. A. Boas, S. A. Carp, S. J. Isakoff, and D. Mankoff, “Predicting Responses to Neoadjuvant Chemotherapy in Breast Cancer: ACRIN 6691 Trial of Diffuse Optical Spectroscopic Imaging,” Cancer Res. 76(20), 5933–5944 (2016).
[Crossref] [PubMed]

Mendelson, Y.

Y. Mendelson, “Pulse Oximetry: Theory and Applications for Noninvasive Monitoring,” Clin. Chem. 38(9), 1601–1607 (1992).
[PubMed]

Milliken, J.

J. Lee, D. J. Saltzman, A. E. Cerussi, D. V. Gelfand, J. Milliken, T. Waddington, B. J. Tromberg, and M. Brenner, “Broadband diffuse optical spectroscopy measurement of hemoglobin concentration during hypovolemia in rabbits,” Physiol. Meas. 27(8), 757–767 (2006).
[Crossref] [PubMed]

Moller, J. T.

J. T. Moller, P. F. Jensen, N. W. Johannessen, and K. Espersen, “Hypoxaemia is Reduced by Pulse Oximetry Monitoring in the Operating Theatre and in the Recovery Room,” Br. J. Anaesth. 68(2), 146–150 (1992).
[Crossref] [PubMed]

Moore, J. B.

M. A. Franceschini, D. A. Boas, A. Zourabian, S. G. Diamond, S. Nadgir, D. W. Lin, J. B. Moore, and S. Fantini, “Near-infrared spiroximetry: noninvasive measurements of venous saturation in piglets and human subjects,” J. Appl. Physiol. 92(1), 372–384 (2002).
[Crossref] [PubMed]

Mower, W. R.

W. R. Mower, G. Myers, E. L. Nicklin, K. T. Kearin, L. J. Baraff, and C. Sachs, “Pulse oximetry as a fifth vital sign in emergency geriatric assessment,” Acad. Emerg. Med. 5(9), 858–865 (1998).
[Crossref] [PubMed]

W. R. Mower, C. Sachs, E. L. Nicklin, and L. J. Baraff, “Pulse oximetry as a fifth pediatric vital sign,” Pediatrics 99(5), 681–686 (1997).
[Crossref] [PubMed]

Myers, G.

W. R. Mower, G. Myers, E. L. Nicklin, K. T. Kearin, L. J. Baraff, and C. Sachs, “Pulse oximetry as a fifth vital sign in emergency geriatric assessment,” Acad. Emerg. Med. 5(9), 858–865 (1998).
[Crossref] [PubMed]

Nadgir, S.

M. A. Franceschini, D. A. Boas, A. Zourabian, S. G. Diamond, S. Nadgir, D. W. Lin, J. B. Moore, and S. Fantini, “Near-infrared spiroximetry: noninvasive measurements of venous saturation in piglets and human subjects,” J. Appl. Physiol. 92(1), 372–384 (2002).
[Crossref] [PubMed]

Naqvi, S.

A. Shander, M. Javidroozi, S. Naqvi, O. Aregbeyen, M. Çaylan, S. Demir, and A. Juhl, “An update on mortality and morbidity in patients with very low postoperative hemoglobin levels who decline blood transfusion (CME),” Transfusion 54(10), 2688–2695 (2014).
[Crossref] [PubMed]

Naspitz, C. K.

D. Solé, M. K. Komatsu, K. V. T. Carvalho, and C. K. Naspitz, “Pulse oximetry in the evaluation of the severity of acute asthma and/or wheezing in children,” J. Asthma 36(4), 327–333 (1999).
[Crossref] [PubMed]

Nicklin, E. L.

W. R. Mower, G. Myers, E. L. Nicklin, K. T. Kearin, L. J. Baraff, and C. Sachs, “Pulse oximetry as a fifth vital sign in emergency geriatric assessment,” Acad. Emerg. Med. 5(9), 858–865 (1998).
[Crossref] [PubMed]

W. R. Mower, C. Sachs, E. L. Nicklin, and L. J. Baraff, “Pulse oximetry as a fifth pediatric vital sign,” Pediatrics 99(5), 681–686 (1997).
[Crossref] [PubMed]

No, K.-S.

K.-S. No, R. Kwong, P. H. Chou, and A. Cerussi, “Design and testing of a miniature broadband frequency domain photon migration instrument,” J. Biomed. Opt. 13(5), 050509 (2008).
[Crossref] [PubMed]

Nöhammer, M. M.

S. H. Geyer, M. M. Nöhammer, I. E. Tinhofer, and W. J. Weninger, “The dermal arteries of the human thumb pad,” J. Anat. 223(6), 603–609 (2013).
[Crossref] [PubMed]

O’Sullivan, T. D.

B. J. Tromberg, Z. Zhang, A. Leproux, T. D. O’Sullivan, A. E. Cerussi, P. M. Carpenter, R. S. Mehta, D. Roblyer, W. Yang, K. D. Paulsen, B. W. Pogue, S. Jiang, P. A. Kaufman, A. G. Yodh, S. H. Chung, M. Schnall, B. S. Snyder, N. Hylton, D. A. Boas, S. A. Carp, S. J. Isakoff, and D. Mankoff, “Predicting Responses to Neoadjuvant Chemotherapy in Breast Cancer: ACRIN 6691 Trial of Diffuse Optical Spectroscopic Imaging,” Cancer Res. 76(20), 5933–5944 (2016).
[Crossref] [PubMed]

Pattersonil, M. S.

B. W. Poguet and M. S. Pattersonil, “Frequency-domain optical absorption spectroscopy of finite tissue volumes using diffusion theory Frequency-domain optical absorption spectroscopy of finite tissue volumes using diffusion theory,” Phys. Med. Biol. 39, 1157 (1994).

Paulsen, K. D.

B. J. Tromberg, Z. Zhang, A. Leproux, T. D. O’Sullivan, A. E. Cerussi, P. M. Carpenter, R. S. Mehta, D. Roblyer, W. Yang, K. D. Paulsen, B. W. Pogue, S. Jiang, P. A. Kaufman, A. G. Yodh, S. H. Chung, M. Schnall, B. S. Snyder, N. Hylton, D. A. Boas, S. A. Carp, S. J. Isakoff, and D. Mankoff, “Predicting Responses to Neoadjuvant Chemotherapy in Breast Cancer: ACRIN 6691 Trial of Diffuse Optical Spectroscopic Imaging,” Cancer Res. 76(20), 5933–5944 (2016).
[Crossref] [PubMed]

Pera, V.

Pham, T. H.

T. H. Pham, O. Coquoz, J. B. Fishkin, E. Anderson, and B. J. Tromberg, “Broad bandwidth frequency domain instrument for quantitative tissue optical spectroscopy,” Rev. Sci. Instrum. 71(6), 2500–2513 (2000).
[Crossref]

Pogue, B. W.

B. J. Tromberg, Z. Zhang, A. Leproux, T. D. O’Sullivan, A. E. Cerussi, P. M. Carpenter, R. S. Mehta, D. Roblyer, W. Yang, K. D. Paulsen, B. W. Pogue, S. Jiang, P. A. Kaufman, A. G. Yodh, S. H. Chung, M. Schnall, B. S. Snyder, N. Hylton, D. A. Boas, S. A. Carp, S. J. Isakoff, and D. Mankoff, “Predicting Responses to Neoadjuvant Chemotherapy in Breast Cancer: ACRIN 6691 Trial of Diffuse Optical Spectroscopic Imaging,” Cancer Res. 76(20), 5933–5944 (2016).
[Crossref] [PubMed]

Poguet, B. W.

B. W. Poguet and M. S. Pattersonil, “Frequency-domain optical absorption spectroscopy of finite tissue volumes using diffusion theory Frequency-domain optical absorption spectroscopy of finite tissue volumes using diffusion theory,” Phys. Med. Biol. 39, 1157 (1994).

Polzonetti, C. M.

M. Calderon-Arnulphi, A. Alaraj, S. Amin-Hanjani, W. W. Mantulin, C. M. Polzonetti, E. Gratton, and F. T. Charbel, “Detection of cerebral ischemia in neurovascular surgery using quantitative frequency-domain near-infrared spectroscopy,” J. Neurosurg. 106(2), 283–290 (2007).
[Crossref] [PubMed]

Prantl, L.

S. Schreml, R. M. Szeimies, L. Prantl, S. Karrer, M. Landthaler, and P. Babilas, “Oxygen in acute and chronic wound healing,” Br. J. Dermatol. 163(2), 257–268 (2010).
[Crossref] [PubMed]

Roblyer, D.

V. Pera, K. Karrobi, S. Tabassum, F. Teng, and D. Roblyer, “Optical property uncertainty estimates for spatial frequency domain imaging,” Biomed. Opt. Express 9(2), 661–678 (2018).
[Crossref] [PubMed]

A. Torjesen, R. Istfan, and D. Roblyer, “Ultrafast wavelength multiplexed broad bandwidth digital diffuse optical spectroscopy for in vivo extraction of tissue optical properties,” J. Biomed. Opt. 22(3), 036009 (2017).
[Crossref] [PubMed]

B. J. Tromberg, Z. Zhang, A. Leproux, T. D. O’Sullivan, A. E. Cerussi, P. M. Carpenter, R. S. Mehta, D. Roblyer, W. Yang, K. D. Paulsen, B. W. Pogue, S. Jiang, P. A. Kaufman, A. G. Yodh, S. H. Chung, M. Schnall, B. S. Snyder, N. Hylton, D. A. Boas, S. A. Carp, S. J. Isakoff, and D. Mankoff, “Predicting Responses to Neoadjuvant Chemotherapy in Breast Cancer: ACRIN 6691 Trial of Diffuse Optical Spectroscopic Imaging,” Cancer Res. 76(20), 5933–5944 (2016).
[Crossref] [PubMed]

D. Roblyer, S. Ueda, A. Cerussi, W. Tanamai, A. Durkin, R. Mehta, D. Hsiang, J. A. Butler, C. McLaren, W. P. Chen, and B. Tromberg, “Optical imaging of breast cancer oxyhemoglobin flare correlates with neoadjuvant chemotherapy response one day after starting treatment,” Proc. Natl. Acad. Sci. U.S.A. 108(35), 14626–14631 (2011).
[Crossref] [PubMed]

Sachs, C.

W. R. Mower, G. Myers, E. L. Nicklin, K. T. Kearin, L. J. Baraff, and C. Sachs, “Pulse oximetry as a fifth vital sign in emergency geriatric assessment,” Acad. Emerg. Med. 5(9), 858–865 (1998).
[Crossref] [PubMed]

W. R. Mower, C. Sachs, E. L. Nicklin, and L. J. Baraff, “Pulse oximetry as a fifth pediatric vital sign,” Pediatrics 99(5), 681–686 (1997).
[Crossref] [PubMed]

Saltzman, D. J.

J. Lee, D. J. Saltzman, A. E. Cerussi, D. V. Gelfand, J. Milliken, T. Waddington, B. J. Tromberg, and M. Brenner, “Broadband diffuse optical spectroscopy measurement of hemoglobin concentration during hypovolemia in rabbits,” Physiol. Meas. 27(8), 757–767 (2006).
[Crossref] [PubMed]

Schnall, M.

B. J. Tromberg, Z. Zhang, A. Leproux, T. D. O’Sullivan, A. E. Cerussi, P. M. Carpenter, R. S. Mehta, D. Roblyer, W. Yang, K. D. Paulsen, B. W. Pogue, S. Jiang, P. A. Kaufman, A. G. Yodh, S. H. Chung, M. Schnall, B. S. Snyder, N. Hylton, D. A. Boas, S. A. Carp, S. J. Isakoff, and D. Mankoff, “Predicting Responses to Neoadjuvant Chemotherapy in Breast Cancer: ACRIN 6691 Trial of Diffuse Optical Spectroscopic Imaging,” Cancer Res. 76(20), 5933–5944 (2016).
[Crossref] [PubMed]

Schotland, J. C.

Schreml, S.

S. Schreml, R. M. Szeimies, L. Prantl, S. Karrer, M. Landthaler, and P. Babilas, “Oxygen in acute and chronic wound healing,” Br. J. Dermatol. 163(2), 257–268 (2010).
[Crossref] [PubMed]

Shander, A.

A. Shander, M. Javidroozi, S. Naqvi, O. Aregbeyen, M. Çaylan, S. Demir, and A. Juhl, “An update on mortality and morbidity in patients with very low postoperative hemoglobin levels who decline blood transfusion (CME),” Transfusion 54(10), 2688–2695 (2014).
[Crossref] [PubMed]

Shelley, K. H.

K. H. Shelley, “Photoplethysmography: beyond the calculation of arterial oxygen saturation and heart rate,” Anesth. Analg. 105(6Suppl), S31–S36 (2007).
[Crossref] [PubMed]

Sinex, J. E.

J. E. Sinex, “Pulse oximetry: Principles and limitations,” Am. J. Emerg. Med. 17(1), 59–66 (1999).
[Crossref] [PubMed]

Sliwinski, P.

P. Sliwiński, M. Lagosz, D. Górecka, and J. Zieliński, “The adequacy of oxygenation in COPD patients undergoing long-term oxygen therapy assessed by pulse oximetry at home,” Eur. Respir. J. 7(2), 274–278 (1994).
[Crossref] [PubMed]

Snyder, B. S.

B. J. Tromberg, Z. Zhang, A. Leproux, T. D. O’Sullivan, A. E. Cerussi, P. M. Carpenter, R. S. Mehta, D. Roblyer, W. Yang, K. D. Paulsen, B. W. Pogue, S. Jiang, P. A. Kaufman, A. G. Yodh, S. H. Chung, M. Schnall, B. S. Snyder, N. Hylton, D. A. Boas, S. A. Carp, S. J. Isakoff, and D. Mankoff, “Predicting Responses to Neoadjuvant Chemotherapy in Breast Cancer: ACRIN 6691 Trial of Diffuse Optical Spectroscopic Imaging,” Cancer Res. 76(20), 5933–5944 (2016).
[Crossref] [PubMed]

Snyder, J. V.

M. I. Bierman, K. L. Stein, and J. V. Snyder, “Pulse oximetry in the postoperative care of cardiac surgical patients. A randomized controlled trail,” Chest 102(5), 1367–1370 (1992).
[Crossref] [PubMed]

Solé, D.

D. Solé, M. K. Komatsu, K. V. T. Carvalho, and C. K. Naspitz, “Pulse oximetry in the evaluation of the severity of acute asthma and/or wheezing in children,” J. Asthma 36(4), 327–333 (1999).
[Crossref] [PubMed]

Stein, K. L.

M. I. Bierman, K. L. Stein, and J. V. Snyder, “Pulse oximetry in the postoperative care of cardiac surgical patients. A randomized controlled trail,” Chest 102(5), 1367–1370 (1992).
[Crossref] [PubMed]

Strangman, G.

G. Strangman, M. A. Franceschini, and D. A. Boas, “Factors affecting the accuracy of near-infrared spectroscopy concentration calculations for focal changes in oxygenation parameters,” Neuroimage 18(4), 865–879 (2003).
[Crossref] [PubMed]

Summers, R. L.

R. L. Summers, R. M. Anders, L. H. Woodward, A. K. Jenkins, and R. L. Galli, “Effect of routine pulse oximetry measurements on ED triage classification,” Am. J. Emerg. Med. 16(1), 5–7 (1998).
[Crossref] [PubMed]

Szeimies, R. M.

S. Schreml, R. M. Szeimies, L. Prantl, S. Karrer, M. Landthaler, and P. Babilas, “Oxygen in acute and chronic wound healing,” Br. J. Dermatol. 163(2), 257–268 (2010).
[Crossref] [PubMed]

Tabassum, S.

Tanamai, W.

D. Roblyer, S. Ueda, A. Cerussi, W. Tanamai, A. Durkin, R. Mehta, D. Hsiang, J. A. Butler, C. McLaren, W. P. Chen, and B. Tromberg, “Optical imaging of breast cancer oxyhemoglobin flare correlates with neoadjuvant chemotherapy response one day after starting treatment,” Proc. Natl. Acad. Sci. U.S.A. 108(35), 14626–14631 (2011).
[Crossref] [PubMed]

Teng, F.

Thavendiranathan, P.

P. Thavendiranathan, A. Bagai, A. Ebidia, A. S. Detsky, and N. K. Choudhry, “Do blood tests cause anemia in hospitalized patients? The effect of diagnostic phlebotomy on hemoglobin and hematocrit levels,” J. Gen. Intern. Med. 20(6), 520–524 (2005).
[Crossref] [PubMed]

Tinhofer, I. E.

S. H. Geyer, M. M. Nöhammer, I. E. Tinhofer, and W. J. Weninger, “The dermal arteries of the human thumb pad,” J. Anat. 223(6), 603–609 (2013).
[Crossref] [PubMed]

Torjesen, A.

A. Torjesen, R. Istfan, and D. Roblyer, “Ultrafast wavelength multiplexed broad bandwidth digital diffuse optical spectroscopy for in vivo extraction of tissue optical properties,” J. Biomed. Opt. 22(3), 036009 (2017).
[Crossref] [PubMed]

Tromberg, B.

D. Roblyer, S. Ueda, A. Cerussi, W. Tanamai, A. Durkin, R. Mehta, D. Hsiang, J. A. Butler, C. McLaren, W. P. Chen, and B. Tromberg, “Optical imaging of breast cancer oxyhemoglobin flare correlates with neoadjuvant chemotherapy response one day after starting treatment,” Proc. Natl. Acad. Sci. U.S.A. 108(35), 14626–14631 (2011).
[Crossref] [PubMed]

Tromberg, B. J.

B. J. Tromberg, Z. Zhang, A. Leproux, T. D. O’Sullivan, A. E. Cerussi, P. M. Carpenter, R. S. Mehta, D. Roblyer, W. Yang, K. D. Paulsen, B. W. Pogue, S. Jiang, P. A. Kaufman, A. G. Yodh, S. H. Chung, M. Schnall, B. S. Snyder, N. Hylton, D. A. Boas, S. A. Carp, S. J. Isakoff, and D. Mankoff, “Predicting Responses to Neoadjuvant Chemotherapy in Breast Cancer: ACRIN 6691 Trial of Diffuse Optical Spectroscopic Imaging,” Cancer Res. 76(20), 5933–5944 (2016).
[Crossref] [PubMed]

J. Lee, D. J. Saltzman, A. E. Cerussi, D. V. Gelfand, J. Milliken, T. Waddington, B. J. Tromberg, and M. Brenner, “Broadband diffuse optical spectroscopy measurement of hemoglobin concentration during hypovolemia in rabbits,” Physiol. Meas. 27(8), 757–767 (2006).
[Crossref] [PubMed]

T. H. Pham, O. Coquoz, J. B. Fishkin, E. Anderson, and B. J. Tromberg, “Broad bandwidth frequency domain instrument for quantitative tissue optical spectroscopy,” Rev. Sci. Instrum. 71(6), 2500–2513 (2000).
[Crossref]

F. Bevilacqua, A. J. Berger, A. E. Cerussi, D. Jakubowski, and B. J. Tromberg, “Broadband absorption spectroscopy in turbid media by combined frequency-domain and steady-state methods,” Appl. Opt. 39(34), 6498–6507 (2000).
[Crossref] [PubMed]

Ueda, S.

D. Roblyer, S. Ueda, A. Cerussi, W. Tanamai, A. Durkin, R. Mehta, D. Hsiang, J. A. Butler, C. McLaren, W. P. Chen, and B. Tromberg, “Optical imaging of breast cancer oxyhemoglobin flare correlates with neoadjuvant chemotherapy response one day after starting treatment,” Proc. Natl. Acad. Sci. U.S.A. 108(35), 14626–14631 (2011).
[Crossref] [PubMed]

Waddington, T.

J. Lee, D. J. Saltzman, A. E. Cerussi, D. V. Gelfand, J. Milliken, T. Waddington, B. J. Tromberg, and M. Brenner, “Broadband diffuse optical spectroscopy measurement of hemoglobin concentration during hypovolemia in rabbits,” Physiol. Meas. 27(8), 757–767 (2006).
[Crossref] [PubMed]

Weninger, W. J.

S. H. Geyer, M. M. Nöhammer, I. E. Tinhofer, and W. J. Weninger, “The dermal arteries of the human thumb pad,” J. Anat. 223(6), 603–609 (2013).
[Crossref] [PubMed]

Woodward, L. H.

R. L. Summers, R. M. Anders, L. H. Woodward, A. K. Jenkins, and R. L. Galli, “Effect of routine pulse oximetry measurements on ED triage classification,” Am. J. Emerg. Med. 16(1), 5–7 (1998).
[Crossref] [PubMed]

Yang, W.

B. J. Tromberg, Z. Zhang, A. Leproux, T. D. O’Sullivan, A. E. Cerussi, P. M. Carpenter, R. S. Mehta, D. Roblyer, W. Yang, K. D. Paulsen, B. W. Pogue, S. Jiang, P. A. Kaufman, A. G. Yodh, S. H. Chung, M. Schnall, B. S. Snyder, N. Hylton, D. A. Boas, S. A. Carp, S. J. Isakoff, and D. Mankoff, “Predicting Responses to Neoadjuvant Chemotherapy in Breast Cancer: ACRIN 6691 Trial of Diffuse Optical Spectroscopic Imaging,” Cancer Res. 76(20), 5933–5944 (2016).
[Crossref] [PubMed]

Yodh, A. G.

B. J. Tromberg, Z. Zhang, A. Leproux, T. D. O’Sullivan, A. E. Cerussi, P. M. Carpenter, R. S. Mehta, D. Roblyer, W. Yang, K. D. Paulsen, B. W. Pogue, S. Jiang, P. A. Kaufman, A. G. Yodh, S. H. Chung, M. Schnall, B. S. Snyder, N. Hylton, D. A. Boas, S. A. Carp, S. J. Isakoff, and D. Mankoff, “Predicting Responses to Neoadjuvant Chemotherapy in Breast Cancer: ACRIN 6691 Trial of Diffuse Optical Spectroscopic Imaging,” Cancer Res. 76(20), 5933–5944 (2016).
[Crossref] [PubMed]

Zhang, Z.

B. J. Tromberg, Z. Zhang, A. Leproux, T. D. O’Sullivan, A. E. Cerussi, P. M. Carpenter, R. S. Mehta, D. Roblyer, W. Yang, K. D. Paulsen, B. W. Pogue, S. Jiang, P. A. Kaufman, A. G. Yodh, S. H. Chung, M. Schnall, B. S. Snyder, N. Hylton, D. A. Boas, S. A. Carp, S. J. Isakoff, and D. Mankoff, “Predicting Responses to Neoadjuvant Chemotherapy in Breast Cancer: ACRIN 6691 Trial of Diffuse Optical Spectroscopic Imaging,” Cancer Res. 76(20), 5933–5944 (2016).
[Crossref] [PubMed]

Zielinski, J.

P. Sliwiński, M. Lagosz, D. Górecka, and J. Zieliński, “The adequacy of oxygenation in COPD patients undergoing long-term oxygen therapy assessed by pulse oximetry at home,” Eur. Respir. J. 7(2), 274–278 (1994).
[Crossref] [PubMed]

Zijlstra, W.

W. Zijlstra, A. Buursma, and W. Meeuwsen-van der Roest, “Absorption Spectra of Human Fetal and Adult Oxyhemoglobin, De-Oxyhemoglobin, and Methemoglobin,” Clin. Chem. 37(9), 1633–1638 (1991).
[PubMed]

Zimmermann, B. B.

B. B. Zimmermann, Q. Fang, D. A. Boas, and S. A. Carp, “Frequency domain near-infrared multiwavelength imager design using high-speed, direct analog-to-digital conversion,” J. Biomed. Opt. 21(1), 016010 (2016).
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Zirak, P.

P. Farzam, P. Zirak, T. Binzoni, and T. Durduran, “Pulsatile and steady-state hemodynamics of the human patella bone by diffuse optical spectroscopy,” Physiol. Meas. 34(8), 839–857 (2013).
[Crossref] [PubMed]

Zourabian, A.

M. A. Franceschini, D. A. Boas, A. Zourabian, S. G. Diamond, S. Nadgir, D. W. Lin, J. B. Moore, and S. Fantini, “Near-infrared spiroximetry: noninvasive measurements of venous saturation in piglets and human subjects,” J. Appl. Physiol. 92(1), 372–384 (2002).
[Crossref] [PubMed]

Acad. Emerg. Med. (1)

W. R. Mower, G. Myers, E. L. Nicklin, K. T. Kearin, L. J. Baraff, and C. Sachs, “Pulse oximetry as a fifth vital sign in emergency geriatric assessment,” Acad. Emerg. Med. 5(9), 858–865 (1998).
[Crossref] [PubMed]

Am. J. Emerg. Med. (2)

R. L. Summers, R. M. Anders, L. H. Woodward, A. K. Jenkins, and R. L. Galli, “Effect of routine pulse oximetry measurements on ED triage classification,” Am. J. Emerg. Med. 16(1), 5–7 (1998).
[Crossref] [PubMed]

J. E. Sinex, “Pulse oximetry: Principles and limitations,” Am. J. Emerg. Med. 17(1), 59–66 (1999).
[Crossref] [PubMed]

Anesth. Analg. (1)

K. H. Shelley, “Photoplethysmography: beyond the calculation of arterial oxygen saturation and heart rate,” Anesth. Analg. 105(6Suppl), S31–S36 (2007).
[Crossref] [PubMed]

Appl. Opt. (2)

Biomed. Opt. Express (1)

Br. J. Anaesth. (1)

J. T. Moller, P. F. Jensen, N. W. Johannessen, and K. Espersen, “Hypoxaemia is Reduced by Pulse Oximetry Monitoring in the Operating Theatre and in the Recovery Room,” Br. J. Anaesth. 68(2), 146–150 (1992).
[Crossref] [PubMed]

Br. J. Dermatol. (1)

S. Schreml, R. M. Szeimies, L. Prantl, S. Karrer, M. Landthaler, and P. Babilas, “Oxygen in acute and chronic wound healing,” Br. J. Dermatol. 163(2), 257–268 (2010).
[Crossref] [PubMed]

Cancer Res. (1)

B. J. Tromberg, Z. Zhang, A. Leproux, T. D. O’Sullivan, A. E. Cerussi, P. M. Carpenter, R. S. Mehta, D. Roblyer, W. Yang, K. D. Paulsen, B. W. Pogue, S. Jiang, P. A. Kaufman, A. G. Yodh, S. H. Chung, M. Schnall, B. S. Snyder, N. Hylton, D. A. Boas, S. A. Carp, S. J. Isakoff, and D. Mankoff, “Predicting Responses to Neoadjuvant Chemotherapy in Breast Cancer: ACRIN 6691 Trial of Diffuse Optical Spectroscopic Imaging,” Cancer Res. 76(20), 5933–5944 (2016).
[Crossref] [PubMed]

Cardiologia (1)

I. Lindgren, “Continuous Measurement of Arterial Oxygen Saturation in Man; Clinical Oximetry with a Swedish Oximeter According to Millikan,” Cardiologia 13(4), 226–240 (1948).
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Chest (1)

M. I. Bierman, K. L. Stein, and J. V. Snyder, “Pulse oximetry in the postoperative care of cardiac surgical patients. A randomized controlled trail,” Chest 102(5), 1367–1370 (1992).
[Crossref] [PubMed]

Clin. Chem. (2)

Y. Mendelson, “Pulse Oximetry: Theory and Applications for Noninvasive Monitoring,” Clin. Chem. 38(9), 1601–1607 (1992).
[PubMed]

W. Zijlstra, A. Buursma, and W. Meeuwsen-van der Roest, “Absorption Spectra of Human Fetal and Adult Oxyhemoglobin, De-Oxyhemoglobin, and Methemoglobin,” Clin. Chem. 37(9), 1633–1638 (1991).
[PubMed]

Eur. Respir. J. (1)

P. Sliwiński, M. Lagosz, D. Górecka, and J. Zieliński, “The adequacy of oxygenation in COPD patients undergoing long-term oxygen therapy assessed by pulse oximetry at home,” Eur. Respir. J. 7(2), 274–278 (1994).
[Crossref] [PubMed]

IEEE Trans. Circuits Syst. II Analog Digit. Signal Process. (1)

R. Beck, A. G. Dempster, and I. Kale, “Finite-precision goertzel filters used for signal tone detection,” IEEE Trans. Circuits Syst. II Analog Digit. Signal Process. 48(7), 691–700 (2001).
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Supplementary Material (1)

NameDescription
» Visualization 1       A video showing real-time measurement and chromophore extraction at the speed of 27 Hz.

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Figures (5)

Fig. 1
Fig. 1 (a) Schematic diagram of the system. A system on a chip (SOC) drives 5 direct digital synthesis boards (DDS) to modulate 5 lasers which were combined and passed through a sample. An optical fiber collected the multiply scattered light, which was detected by an avalanche photo diode (APD). The APD signal was digitized by one channel of an analog to digital converter (ADC). The second channel of the ADC digitized a reference signal from the DDS boards. Each time the system was restarted, a measurement was taken on a calibration phantom (not shown) to calculate the instrument response. (b) Schematic diagram of the signal processing pathway. Items inside the blue box (solid line) were performed on the SOC. Items in the red box (dashed line) were performed on the host computer.
Fig. 2
Fig. 2 Diagram of the structure of the deep neural network used to estimate absorption and scattering from calibrated amplitude and phase. Input nodes are shown in yellow, open circles indicate neurons, solid lines represent connections between layers, and the output layer is shown in green. Asterisks denote scaling of the input amplitude at the beginning and descaling at the end. The structure was chosen to have relatively few free parameters to decrease training time and reduce the likelihood of overfitting.
Fig. 3
Fig. 3 A still image from Visualization 1 depicting the instrument front-end showing real-time traces of oxy- and deoxy-hemoglobin during the measurement procedure. Inset: synchronized video of the subject’s hand during acquisition. Light from the source-fiber (right silver ferrule) passes through the thumb and is collected by the detector fiber (left silver ferrule).
Fig. 4
Fig. 4 (a) Comparison of optical property values between the iterative and DNN methods using simulated data without adding noise. The root mean squared difference between the two methods is noted in each plot along with the black dashed identity line. (b) The same comparison using experimental data from a human subject. The gap in scattering values from ~0.8 to ~0.9 mm−1 is due to the wavelength dependent nature of scattering. Scattering coefficients clustered around 1 mm−1 are from 690 nm photons which experience significantly more scattering than the longer wavelengths used.
Fig. 5
Fig. 5 (a) Tissue oxyhemoglobin (top) and deoxyhemoglobin (bottom) traces from the thumb of a human subject. Dotted lines indicate the start and end of an arterial occlusion on the upper arm. Gray boxes indicate the regions that are zoomed in in panels (b)-(d). Note the disappearance of the pulsatile signal during the occlusion in panel (c). Inset: Oxyhemoglobin changes over a single pulse. Data points are indicated with circles and the line is a 7-point loess fit to those points. Features of the pulse such as the systolic peak (SP), dicrotic notch (DN), and diastolic peak (DP) are readily appreciated.

Tables (2)

Tables Icon

Table 1 Average ± standard deviation percent error in optical property extraction based on 10,000 randomly generated optical property pairs for the iterative and deep neural network (DNN) methods. Gaussian noise with the noted standard deviation was added to both amplitude and phase.

Tables Icon

Table 2 Average ± standard deviation of execution times for the indicated number of optical property extractions. Measurement was repeated 10 times. 2% and 8% Gaussian noise was added to amplitude and phase respectively to simulate an experimental measurement.