Abstract

We present the real-time single snapshot multiple frequency demodulation - spatial frequency domain imaging (SSMD-SFDI) platform implemented with a visible digital mirror device that is capable of imaging and monitoring dynamic turbid medium and processes over a large field of view. One challenge in quantitative imaging of biological tissue such as the skin is the complex structure rendering techniques based on homogeneous medium models to fail. To address this difficulty we have also developed a novel method that maps the layered structure to a homogeneous medium for spatial frequency domain imaging. The varying penetration depth of spatially modulated light on its wavelength and modulation frequency is used to resolve the layered structure. The efficacy of the real-time SSMD-SFDI platform and this two-layer model is demonstrated by imaging forearms of 6 healthy subjects under the reactive hyperemia protocol. The results show that our approach not only successfully decouples light absorption by melanin from that by hemoglobin and yields accurate determination of cutaneous hemoglobin concentration and oxygen saturation, but also provides reliable estimation of the scattering properties, the melanin content and the epidermal thickness in real time. Potential applications of our system in imaging skin physiological and functional states, cancer screening, and microcirculation monitoring are discussed at the end.

© 2017 Optical Society of America

Full Article  |  PDF Article
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References

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2017 (3)

A. Yafi, F. K. Muakkassa, T. Pasupneti, J. Fulton, D. J. Cuccia, A. Mazhar, K. N. Blasiole, and E. N. Mostow, “Quantitative skin assessment using spatial frequency domain imaging (SFDI) in patients with or at high risk for pressure ulcers,” Lasers Surg. Med. 49(9), 827–834 (2017).
[PubMed]

M. Xu, “Plum pudding random medium model of biological tissue toward remote microscopy from spectroscopic light scattering,” Biomed. Opt. Express 8(6), 2879–2895 (2017).
[PubMed]

J. B. Travers, C. Poon, D. J. Rohrbach, N. M. Weir, E. Cates, F. Hager, and U. Sunar, “Noninvasive mesoscopic imaging of actinic skin damage using spatial frequency domain imaging,” Biomed. Opt. Express 8(6), 3045–3052 (2017).
[PubMed]

2016 (8)

M. Ghijsen, B. Choi, A. J. Durkin, S. Gioux, and B. J. Tromberg, “Real-time simultaneous single snapshot of optical properties and blood flow using coherent spatial frequency domain imaging (cSFDI),” Biomed. Opt. Express 7(3), 870–882 (2016).
[PubMed]

B. Yang, “Color structured light imaging of skin,” J. Biomed. Opt.  5(10), 050503 (2016).

C. Fink and H. A. Haenssle, “Non-invasive tools for the diagnosis of cutaneous melanoma,” J. Ski. Res. Technol. 5, 1–11 (2016).

N. Mackinnon, “Separating melanin from hemodynamics in nevi using multimode hyperspectral dermoscopy and spatial frequency domain spectroscopy,” J. Biomed. Opt. 21(11), 114001 (2016).

M. Xu, Z. Cao, W. Lin, X. Chen, L. Zheng, and B. Zeng, “Single snapshot multiple frequency modulated imaging of subsurface optical properties of turbid media with structured light,” AIP Adv. 6(12), 125208 (2016).

M. Xu, “Diagnosis of the phase function of random media from light reflectance,” Sci. Rep. 6, 22535 (2016).

P. O’Herron, P. Y. Chhatbar, M. Levy, Z. Shen, A. E. Schramm, Z. Lu, and P. Kara, “Neural correlates of single-vessel haemodynamic responses in vivo,” Nature 534(7607), 378–382 (2016).
[PubMed]

A. Sitek, I. Rosset, E. Żądzińska, A. Kasielska-Trojan, A. Neskoromna-Jędrzejczak, and B. Antoszewski, “Skin color parameters and Fitzpatrick phototypes in estimating the risk of skin cancer: a case-control study in the Polish population,” J. Am. Acad. Dermatol. 74(4), 716–723 (2016).
[PubMed]

2015 (4)

M. Reilly and M. Xu, “Analytical model for sub-diffusive light reflection and the application to spatial frequency-domain imaging,” Proc. SPIE 9319, 93191A (2015).

R. B. Saager, A. J. Durkin, K. M. Kelly, and B. J. Tromberg, “In vivo measurements of cutaneous melanin across spatial scales: using multiphoton microscopy and spatial frequency domain spectroscopy,” J. Biomed. Opt. 20, 066005 (2015).

J. M. Kainerstorfer, A. Sassaroli, K. T. Tgavalekos, and S. Fantini, “Cerebral autoregulation in the microvasculature measured with near-infrared spectroscopy,” J. Cereb. Blood Flow Metab. 35(6), 959–966 (2015).
[PubMed]

D. J. Rohrbach, N. C. Zeitouni, D. Muffoletto, R. Saager, B. J. Tromberg, and U. Sunar, “Characterization of nonmelanoma skin cancer for light therapy using spatial frequency domain imaging,” Biomed. Opt. Express 6(5), 1761–1766 (2015).
[PubMed]

2014 (2)

D. J. Rohrbach, D. Muffoletto, J. Huihui, R. Saager, K. Keymel, A. Paquette, J. Morgan, N. Zeitouni, and U. Sunar, “Preoperative mapping of nonmelanoma skin cancer using spatial frequency domain and ultrasound imaging,” Acad. Radiol. 21(2), 263–270 (2014).
[PubMed]

M. Mackiewicz-Wysocka, A. Araszkiewicz, J. Schlaffke, S. Kuczynski, I. Micek, and D. Zozulinska-Ziolkiewicz, “Lower melanin content in the skin of type 1 diabetic patients and the risk of microangiopathy,” Exp. Clin. Endocrinol. Diabetes 122(4), 231–235 (2014).
[PubMed]

2012 (2)

T. W. L. Scheeren, P. Schober, and L. A. Schwarte, “Monitoring tissue oxygenation by near infrared spectroscopy (NIRS): Background and current applications,” J. Clin. Monit. Comput. 26(4), 279–287 (2012).
[PubMed]

D. Yudovsky, J. Q. M. Nguyen, and A. J. Durkin, “In vivo spatial frequency domain spectroscopy of two layer media,” J. Biomed. Opt. 17(10), 107006 (2012).
[PubMed]

2011 (4)

R. B. Saager, A. Truong, D. J. Cuccia, and A. J. Durkin, “Method for depth-resolved quantitation of optical properties in layered media using spatially modulated quantitative spectroscopy,” J. Biomed. Opt. 16(7), 077002 (2011).
[PubMed]

I. Tachtsidis, M. M. Tisdall, C. Pritchard, T. S. Leung, C. E. Elwell, and M. Smith, “Hemoglobin and myoglobin contributions to skeletal muscle oxygenation in response to exercise,” J. Adv. Exp. Med Biol. 701(2), 347–352 (2011).

A. N. Bashkatov, E. A. Genina, and V. V. Tuchin, “Optical properties of skin, subcutaneous, and muscle tissues: a review,” J. Innov. Opt. Health Sci. 4(1), 9–38 (2011).

T.-Y. Tseng, C.-Y. Chen, Y.-S. Li, and K.-B. Sung, “Quantification of the optical properties of two-layered turbid media by simultaneously analyzing the spectral and spatial information of steady-state diffuse reflectance spectroscopy,” Biomed. Opt. Express 2(4), 901–914 (2011).
[PubMed]

2009 (7)

F. R. Ayers, D. J. Cuccia, K. M. Kelly, and A. J. Durkin, “Wide-field spatial mapping of in vivo tattoo skin optical properties using modulated imaging,” Lasers Surg. Med. 41(6), 442–453 (2009).
[PubMed]

M. R. Pharaon, “Early detection of complete venous occlusion in a rodent and swine pedicle flap model using modulated imaging, a new novel multispectral imaging technique,” J. Am. Coll. Surg. 209(3), S77–S78 (2009).

J. R. Weber, D. J. Cuccia, A. J. Durkin, and B. J. Tromberg, “Noncontact imaging of absorption and scattering in layered tissue using spatially modulated structured light,” J. Appl. Phys. 105(10), 1–9 (2009).

M. Mogensen, L. Thrane, T. M. Jørgensen, P. E. Andersen, and G. B. E. Jemec, “OCT imaging of skin cancer and other dermatological diseases,” J. Biophotonics 2(6-7), 442–451 (2009).
[PubMed]

S. G. Sagraves, “Tissue oxygenation monitoring in the field: a new EMS vital sign,” J. Trauma 67(3), 441–4442009.

S. B. Chakravarti, A. J. C. Mittnacht, J. C. Katz, K. Nguyen, U. Joashi, and S. Srivastava, “Multisite near-infrared spectroscopy predicts elevated blood lactate level in children after cardiac surgery,” J. Cardiothorac. Vasc. Anesth. 23(5), 663–667 (2009).
[PubMed]

D. J. Cuccia, F. Bevilacqua, A. J. Durkin, F. R. Ayers, and B. J. Tromberg, “Quantitation and mapping of tissue optical properties using modulated imaging,” J. Biomed. Opt. 14(2), 024012 (2009).
[PubMed]

2008 (2)

M. Xu, “Low-coherence enhanced backscattering beyond diffusion,” Opt. Lett. 33(11), 1246–1248 (2008).
[PubMed]

M. Xu, T. T. Wu, and J. Y. Qu, “Unified Mie and fractal scattering by cells and experimental study on application in optical characterization of cellular and subcellular structures,” J. Biomed. Opt. 13(2), 024015 (2008).
[PubMed]

2007 (2)

C. B. Wolff, “Normal cardiac output, oxygen delivery and oxygen extraction,” Adv. Exp. Med. Biol. 599, 169–182 (2007).
[PubMed]

T. T. Wu, J. Y. Qu, and M. Xu, “Unified Mie and fractal scattering by biological cells and subcellular structures,” Opt. Lett. 32(16), 2324–2326 (2007).
[PubMed]

2005 (3)

2004 (1)

2002 (1)

S. Alaluf, D. Atkins, K. Barrett, M. Blount, N. Carter, and A. Heath, “Ethnic variation in melanin content and composition in photoexposed and photoprotected human skin,” Pigment Cell Res. 15(2), 112–118 (2002).
[PubMed]

1986 (2)

K. Wasserman, “The anaerobic threshold: definition, physiological significance and identification,” Adv. Cardiol. 35(1), 1–23 (1986).
[PubMed]

A. A. Nurmatov, A. V. Samoĭlenko, and B. I. Tkachenko, “Systemic hemodynamic shifts in the arterial and venous portions of the vascular bed in hypoxia,” Fiziologicheski Zhurnal SSSR Imeni I.m.sechenova 72(11), 1515 (1986).

Alaluf, S.

S. Alaluf, D. Atkins, K. Barrett, M. Blount, N. Carter, and A. Heath, “Ethnic variation in melanin content and composition in photoexposed and photoprotected human skin,” Pigment Cell Res. 15(2), 112–118 (2002).
[PubMed]

Alfano, R. R.

Andersen, P. E.

M. Mogensen, L. Thrane, T. M. Jørgensen, P. E. Andersen, and G. B. E. Jemec, “OCT imaging of skin cancer and other dermatological diseases,” J. Biophotonics 2(6-7), 442–451 (2009).
[PubMed]

Antoszewski, B.

A. Sitek, I. Rosset, E. Żądzińska, A. Kasielska-Trojan, A. Neskoromna-Jędrzejczak, and B. Antoszewski, “Skin color parameters and Fitzpatrick phototypes in estimating the risk of skin cancer: a case-control study in the Polish population,” J. Am. Acad. Dermatol. 74(4), 716–723 (2016).
[PubMed]

Araszkiewicz, A.

M. Mackiewicz-Wysocka, A. Araszkiewicz, J. Schlaffke, S. Kuczynski, I. Micek, and D. Zozulinska-Ziolkiewicz, “Lower melanin content in the skin of type 1 diabetic patients and the risk of microangiopathy,” Exp. Clin. Endocrinol. Diabetes 122(4), 231–235 (2014).
[PubMed]

Atkins, D.

S. Alaluf, D. Atkins, K. Barrett, M. Blount, N. Carter, and A. Heath, “Ethnic variation in melanin content and composition in photoexposed and photoprotected human skin,” Pigment Cell Res. 15(2), 112–118 (2002).
[PubMed]

Ayers, F. R.

D. J. Cuccia, F. Bevilacqua, A. J. Durkin, F. R. Ayers, and B. J. Tromberg, “Quantitation and mapping of tissue optical properties using modulated imaging,” J. Biomed. Opt. 14(2), 024012 (2009).
[PubMed]

F. R. Ayers, D. J. Cuccia, K. M. Kelly, and A. J. Durkin, “Wide-field spatial mapping of in vivo tattoo skin optical properties using modulated imaging,” Lasers Surg. Med. 41(6), 442–453 (2009).
[PubMed]

Barrett, K.

S. Alaluf, D. Atkins, K. Barrett, M. Blount, N. Carter, and A. Heath, “Ethnic variation in melanin content and composition in photoexposed and photoprotected human skin,” Pigment Cell Res. 15(2), 112–118 (2002).
[PubMed]

Bashkatov, A. N.

A. N. Bashkatov, E. A. Genina, and V. V. Tuchin, “Optical properties of skin, subcutaneous, and muscle tissues: a review,” J. Innov. Opt. Health Sci. 4(1), 9–38 (2011).

Bevilacqua, F.

D. J. Cuccia, F. Bevilacqua, A. J. Durkin, F. R. Ayers, and B. J. Tromberg, “Quantitation and mapping of tissue optical properties using modulated imaging,” J. Biomed. Opt. 14(2), 024012 (2009).
[PubMed]

D. J. Cuccia, F. Bevilacqua, A. J. Durkin, and B. J. Tromberg, “Modulated imaging: quantitative analysis and tomography of turbid media in the spatial-frequency domain,” Opt. Lett. 30(11), 1354–1356 (2005).
[PubMed]

Blasiole, K. N.

A. Yafi, F. K. Muakkassa, T. Pasupneti, J. Fulton, D. J. Cuccia, A. Mazhar, K. N. Blasiole, and E. N. Mostow, “Quantitative skin assessment using spatial frequency domain imaging (SFDI) in patients with or at high risk for pressure ulcers,” Lasers Surg. Med. 49(9), 827–834 (2017).
[PubMed]

Blount, M.

S. Alaluf, D. Atkins, K. Barrett, M. Blount, N. Carter, and A. Heath, “Ethnic variation in melanin content and composition in photoexposed and photoprotected human skin,” Pigment Cell Res. 15(2), 112–118 (2002).
[PubMed]

Cao, Z.

M. Xu, Z. Cao, W. Lin, X. Chen, L. Zheng, and B. Zeng, “Single snapshot multiple frequency modulated imaging of subsurface optical properties of turbid media with structured light,” AIP Adv. 6(12), 125208 (2016).

Carter, N.

S. Alaluf, D. Atkins, K. Barrett, M. Blount, N. Carter, and A. Heath, “Ethnic variation in melanin content and composition in photoexposed and photoprotected human skin,” Pigment Cell Res. 15(2), 112–118 (2002).
[PubMed]

Cates, E.

Chakravarti, S. B.

S. B. Chakravarti, A. J. C. Mittnacht, J. C. Katz, K. Nguyen, U. Joashi, and S. Srivastava, “Multisite near-infrared spectroscopy predicts elevated blood lactate level in children after cardiac surgery,” J. Cardiothorac. Vasc. Anesth. 23(5), 663–667 (2009).
[PubMed]

Chen, C.-Y.

Chen, X.

M. Xu, Z. Cao, W. Lin, X. Chen, L. Zheng, and B. Zeng, “Single snapshot multiple frequency modulated imaging of subsurface optical properties of turbid media with structured light,” AIP Adv. 6(12), 125208 (2016).

Chhatbar, P. Y.

P. O’Herron, P. Y. Chhatbar, M. Levy, Z. Shen, A. E. Schramm, Z. Lu, and P. Kara, “Neural correlates of single-vessel haemodynamic responses in vivo,” Nature 534(7607), 378–382 (2016).
[PubMed]

Choi, B.

Cuccia, D. J.

A. Yafi, F. K. Muakkassa, T. Pasupneti, J. Fulton, D. J. Cuccia, A. Mazhar, K. N. Blasiole, and E. N. Mostow, “Quantitative skin assessment using spatial frequency domain imaging (SFDI) in patients with or at high risk for pressure ulcers,” Lasers Surg. Med. 49(9), 827–834 (2017).
[PubMed]

R. B. Saager, A. Truong, D. J. Cuccia, and A. J. Durkin, “Method for depth-resolved quantitation of optical properties in layered media using spatially modulated quantitative spectroscopy,” J. Biomed. Opt. 16(7), 077002 (2011).
[PubMed]

D. J. Cuccia, F. Bevilacqua, A. J. Durkin, F. R. Ayers, and B. J. Tromberg, “Quantitation and mapping of tissue optical properties using modulated imaging,” J. Biomed. Opt. 14(2), 024012 (2009).
[PubMed]

F. R. Ayers, D. J. Cuccia, K. M. Kelly, and A. J. Durkin, “Wide-field spatial mapping of in vivo tattoo skin optical properties using modulated imaging,” Lasers Surg. Med. 41(6), 442–453 (2009).
[PubMed]

J. R. Weber, D. J. Cuccia, A. J. Durkin, and B. J. Tromberg, “Noncontact imaging of absorption and scattering in layered tissue using spatially modulated structured light,” J. Appl. Phys. 105(10), 1–9 (2009).

D. J. Cuccia, F. Bevilacqua, A. J. Durkin, and B. J. Tromberg, “Modulated imaging: quantitative analysis and tomography of turbid media in the spatial-frequency domain,” Opt. Lett. 30(11), 1354–1356 (2005).
[PubMed]

Diffey, B.

A. Hennessy, C. Oh, B. Diffey, K. Wakamatsu, S. Ito, and J. Rees, “Eumelanin and pheomelanin concentrations in human epidermis before and after UVB irradiation,” Pigment Cell Res. 18(3), 220–223 (2005).
[PubMed]

Durkin, A. J.

M. Ghijsen, B. Choi, A. J. Durkin, S. Gioux, and B. J. Tromberg, “Real-time simultaneous single snapshot of optical properties and blood flow using coherent spatial frequency domain imaging (cSFDI),” Biomed. Opt. Express 7(3), 870–882 (2016).
[PubMed]

R. B. Saager, A. J. Durkin, K. M. Kelly, and B. J. Tromberg, “In vivo measurements of cutaneous melanin across spatial scales: using multiphoton microscopy and spatial frequency domain spectroscopy,” J. Biomed. Opt. 20, 066005 (2015).

D. Yudovsky, J. Q. M. Nguyen, and A. J. Durkin, “In vivo spatial frequency domain spectroscopy of two layer media,” J. Biomed. Opt. 17(10), 107006 (2012).
[PubMed]

R. B. Saager, A. Truong, D. J. Cuccia, and A. J. Durkin, “Method for depth-resolved quantitation of optical properties in layered media using spatially modulated quantitative spectroscopy,” J. Biomed. Opt. 16(7), 077002 (2011).
[PubMed]

D. J. Cuccia, F. Bevilacqua, A. J. Durkin, F. R. Ayers, and B. J. Tromberg, “Quantitation and mapping of tissue optical properties using modulated imaging,” J. Biomed. Opt. 14(2), 024012 (2009).
[PubMed]

F. R. Ayers, D. J. Cuccia, K. M. Kelly, and A. J. Durkin, “Wide-field spatial mapping of in vivo tattoo skin optical properties using modulated imaging,” Lasers Surg. Med. 41(6), 442–453 (2009).
[PubMed]

J. R. Weber, D. J. Cuccia, A. J. Durkin, and B. J. Tromberg, “Noncontact imaging of absorption and scattering in layered tissue using spatially modulated structured light,” J. Appl. Phys. 105(10), 1–9 (2009).

D. J. Cuccia, F. Bevilacqua, A. J. Durkin, and B. J. Tromberg, “Modulated imaging: quantitative analysis and tomography of turbid media in the spatial-frequency domain,” Opt. Lett. 30(11), 1354–1356 (2005).
[PubMed]

Elwell, C. E.

I. Tachtsidis, M. M. Tisdall, C. Pritchard, T. S. Leung, C. E. Elwell, and M. Smith, “Hemoglobin and myoglobin contributions to skeletal muscle oxygenation in response to exercise,” J. Adv. Exp. Med Biol. 701(2), 347–352 (2011).

Fantini, S.

J. M. Kainerstorfer, A. Sassaroli, K. T. Tgavalekos, and S. Fantini, “Cerebral autoregulation in the microvasculature measured with near-infrared spectroscopy,” J. Cereb. Blood Flow Metab. 35(6), 959–966 (2015).
[PubMed]

Fink, C.

C. Fink and H. A. Haenssle, “Non-invasive tools for the diagnosis of cutaneous melanoma,” J. Ski. Res. Technol. 5, 1–11 (2016).

Fulton, J.

A. Yafi, F. K. Muakkassa, T. Pasupneti, J. Fulton, D. J. Cuccia, A. Mazhar, K. N. Blasiole, and E. N. Mostow, “Quantitative skin assessment using spatial frequency domain imaging (SFDI) in patients with or at high risk for pressure ulcers,” Lasers Surg. Med. 49(9), 827–834 (2017).
[PubMed]

Genina, E. A.

A. N. Bashkatov, E. A. Genina, and V. V. Tuchin, “Optical properties of skin, subcutaneous, and muscle tissues: a review,” J. Innov. Opt. Health Sci. 4(1), 9–38 (2011).

Ghijsen, M.

Gioux, S.

Haenssle, H. A.

C. Fink and H. A. Haenssle, “Non-invasive tools for the diagnosis of cutaneous melanoma,” J. Ski. Res. Technol. 5, 1–11 (2016).

Hager, F.

Heath, A.

S. Alaluf, D. Atkins, K. Barrett, M. Blount, N. Carter, and A. Heath, “Ethnic variation in melanin content and composition in photoexposed and photoprotected human skin,” Pigment Cell Res. 15(2), 112–118 (2002).
[PubMed]

Hennessy, A.

A. Hennessy, C. Oh, B. Diffey, K. Wakamatsu, S. Ito, and J. Rees, “Eumelanin and pheomelanin concentrations in human epidermis before and after UVB irradiation,” Pigment Cell Res. 18(3), 220–223 (2005).
[PubMed]

Huihui, J.

D. J. Rohrbach, D. Muffoletto, J. Huihui, R. Saager, K. Keymel, A. Paquette, J. Morgan, N. Zeitouni, and U. Sunar, “Preoperative mapping of nonmelanoma skin cancer using spatial frequency domain and ultrasound imaging,” Acad. Radiol. 21(2), 263–270 (2014).
[PubMed]

Ito, S.

A. Hennessy, C. Oh, B. Diffey, K. Wakamatsu, S. Ito, and J. Rees, “Eumelanin and pheomelanin concentrations in human epidermis before and after UVB irradiation,” Pigment Cell Res. 18(3), 220–223 (2005).
[PubMed]

Jemec, G. B. E.

M. Mogensen, L. Thrane, T. M. Jørgensen, P. E. Andersen, and G. B. E. Jemec, “OCT imaging of skin cancer and other dermatological diseases,” J. Biophotonics 2(6-7), 442–451 (2009).
[PubMed]

Joashi, U.

S. B. Chakravarti, A. J. C. Mittnacht, J. C. Katz, K. Nguyen, U. Joashi, and S. Srivastava, “Multisite near-infrared spectroscopy predicts elevated blood lactate level in children after cardiac surgery,” J. Cardiothorac. Vasc. Anesth. 23(5), 663–667 (2009).
[PubMed]

Jørgensen, T. M.

M. Mogensen, L. Thrane, T. M. Jørgensen, P. E. Andersen, and G. B. E. Jemec, “OCT imaging of skin cancer and other dermatological diseases,” J. Biophotonics 2(6-7), 442–451 (2009).
[PubMed]

Kainerstorfer, J. M.

J. M. Kainerstorfer, A. Sassaroli, K. T. Tgavalekos, and S. Fantini, “Cerebral autoregulation in the microvasculature measured with near-infrared spectroscopy,” J. Cereb. Blood Flow Metab. 35(6), 959–966 (2015).
[PubMed]

Kara, P.

P. O’Herron, P. Y. Chhatbar, M. Levy, Z. Shen, A. E. Schramm, Z. Lu, and P. Kara, “Neural correlates of single-vessel haemodynamic responses in vivo,” Nature 534(7607), 378–382 (2016).
[PubMed]

Kasielska-Trojan, A.

A. Sitek, I. Rosset, E. Żądzińska, A. Kasielska-Trojan, A. Neskoromna-Jędrzejczak, and B. Antoszewski, “Skin color parameters and Fitzpatrick phototypes in estimating the risk of skin cancer: a case-control study in the Polish population,” J. Am. Acad. Dermatol. 74(4), 716–723 (2016).
[PubMed]

Katz, J. C.

S. B. Chakravarti, A. J. C. Mittnacht, J. C. Katz, K. Nguyen, U. Joashi, and S. Srivastava, “Multisite near-infrared spectroscopy predicts elevated blood lactate level in children after cardiac surgery,” J. Cardiothorac. Vasc. Anesth. 23(5), 663–667 (2009).
[PubMed]

Kelly, K. M.

R. B. Saager, A. J. Durkin, K. M. Kelly, and B. J. Tromberg, “In vivo measurements of cutaneous melanin across spatial scales: using multiphoton microscopy and spatial frequency domain spectroscopy,” J. Biomed. Opt. 20, 066005 (2015).

F. R. Ayers, D. J. Cuccia, K. M. Kelly, and A. J. Durkin, “Wide-field spatial mapping of in vivo tattoo skin optical properties using modulated imaging,” Lasers Surg. Med. 41(6), 442–453 (2009).
[PubMed]

Keymel, K.

D. J. Rohrbach, D. Muffoletto, J. Huihui, R. Saager, K. Keymel, A. Paquette, J. Morgan, N. Zeitouni, and U. Sunar, “Preoperative mapping of nonmelanoma skin cancer using spatial frequency domain and ultrasound imaging,” Acad. Radiol. 21(2), 263–270 (2014).
[PubMed]

Kuczynski, S.

M. Mackiewicz-Wysocka, A. Araszkiewicz, J. Schlaffke, S. Kuczynski, I. Micek, and D. Zozulinska-Ziolkiewicz, “Lower melanin content in the skin of type 1 diabetic patients and the risk of microangiopathy,” Exp. Clin. Endocrinol. Diabetes 122(4), 231–235 (2014).
[PubMed]

Leung, T. S.

I. Tachtsidis, M. M. Tisdall, C. Pritchard, T. S. Leung, C. E. Elwell, and M. Smith, “Hemoglobin and myoglobin contributions to skeletal muscle oxygenation in response to exercise,” J. Adv. Exp. Med Biol. 701(2), 347–352 (2011).

Levy, M.

P. O’Herron, P. Y. Chhatbar, M. Levy, Z. Shen, A. E. Schramm, Z. Lu, and P. Kara, “Neural correlates of single-vessel haemodynamic responses in vivo,” Nature 534(7607), 378–382 (2016).
[PubMed]

Li, Y.-S.

Lin, W.

M. Xu, Z. Cao, W. Lin, X. Chen, L. Zheng, and B. Zeng, “Single snapshot multiple frequency modulated imaging of subsurface optical properties of turbid media with structured light,” AIP Adv. 6(12), 125208 (2016).

Lu, Z.

P. O’Herron, P. Y. Chhatbar, M. Levy, Z. Shen, A. E. Schramm, Z. Lu, and P. Kara, “Neural correlates of single-vessel haemodynamic responses in vivo,” Nature 534(7607), 378–382 (2016).
[PubMed]

Mackiewicz-Wysocka, M.

M. Mackiewicz-Wysocka, A. Araszkiewicz, J. Schlaffke, S. Kuczynski, I. Micek, and D. Zozulinska-Ziolkiewicz, “Lower melanin content in the skin of type 1 diabetic patients and the risk of microangiopathy,” Exp. Clin. Endocrinol. Diabetes 122(4), 231–235 (2014).
[PubMed]

Mackinnon, N.

N. Mackinnon, “Separating melanin from hemodynamics in nevi using multimode hyperspectral dermoscopy and spatial frequency domain spectroscopy,” J. Biomed. Opt. 21(11), 114001 (2016).

Mazhar, A.

A. Yafi, F. K. Muakkassa, T. Pasupneti, J. Fulton, D. J. Cuccia, A. Mazhar, K. N. Blasiole, and E. N. Mostow, “Quantitative skin assessment using spatial frequency domain imaging (SFDI) in patients with or at high risk for pressure ulcers,” Lasers Surg. Med. 49(9), 827–834 (2017).
[PubMed]

Micek, I.

M. Mackiewicz-Wysocka, A. Araszkiewicz, J. Schlaffke, S. Kuczynski, I. Micek, and D. Zozulinska-Ziolkiewicz, “Lower melanin content in the skin of type 1 diabetic patients and the risk of microangiopathy,” Exp. Clin. Endocrinol. Diabetes 122(4), 231–235 (2014).
[PubMed]

Mittnacht, A. J. C.

S. B. Chakravarti, A. J. C. Mittnacht, J. C. Katz, K. Nguyen, U. Joashi, and S. Srivastava, “Multisite near-infrared spectroscopy predicts elevated blood lactate level in children after cardiac surgery,” J. Cardiothorac. Vasc. Anesth. 23(5), 663–667 (2009).
[PubMed]

Mogensen, M.

M. Mogensen, L. Thrane, T. M. Jørgensen, P. E. Andersen, and G. B. E. Jemec, “OCT imaging of skin cancer and other dermatological diseases,” J. Biophotonics 2(6-7), 442–451 (2009).
[PubMed]

Morgan, J.

D. J. Rohrbach, D. Muffoletto, J. Huihui, R. Saager, K. Keymel, A. Paquette, J. Morgan, N. Zeitouni, and U. Sunar, “Preoperative mapping of nonmelanoma skin cancer using spatial frequency domain and ultrasound imaging,” Acad. Radiol. 21(2), 263–270 (2014).
[PubMed]

Mostow, E. N.

A. Yafi, F. K. Muakkassa, T. Pasupneti, J. Fulton, D. J. Cuccia, A. Mazhar, K. N. Blasiole, and E. N. Mostow, “Quantitative skin assessment using spatial frequency domain imaging (SFDI) in patients with or at high risk for pressure ulcers,” Lasers Surg. Med. 49(9), 827–834 (2017).
[PubMed]

Muakkassa, F. K.

A. Yafi, F. K. Muakkassa, T. Pasupneti, J. Fulton, D. J. Cuccia, A. Mazhar, K. N. Blasiole, and E. N. Mostow, “Quantitative skin assessment using spatial frequency domain imaging (SFDI) in patients with or at high risk for pressure ulcers,” Lasers Surg. Med. 49(9), 827–834 (2017).
[PubMed]

Muffoletto, D.

D. J. Rohrbach, N. C. Zeitouni, D. Muffoletto, R. Saager, B. J. Tromberg, and U. Sunar, “Characterization of nonmelanoma skin cancer for light therapy using spatial frequency domain imaging,” Biomed. Opt. Express 6(5), 1761–1766 (2015).
[PubMed]

D. J. Rohrbach, D. Muffoletto, J. Huihui, R. Saager, K. Keymel, A. Paquette, J. Morgan, N. Zeitouni, and U. Sunar, “Preoperative mapping of nonmelanoma skin cancer using spatial frequency domain and ultrasound imaging,” Acad. Radiol. 21(2), 263–270 (2014).
[PubMed]

Neskoromna-Jedrzejczak, A.

A. Sitek, I. Rosset, E. Żądzińska, A. Kasielska-Trojan, A. Neskoromna-Jędrzejczak, and B. Antoszewski, “Skin color parameters and Fitzpatrick phototypes in estimating the risk of skin cancer: a case-control study in the Polish population,” J. Am. Acad. Dermatol. 74(4), 716–723 (2016).
[PubMed]

Nguyen, J. Q. M.

D. Yudovsky, J. Q. M. Nguyen, and A. J. Durkin, “In vivo spatial frequency domain spectroscopy of two layer media,” J. Biomed. Opt. 17(10), 107006 (2012).
[PubMed]

Nguyen, K.

S. B. Chakravarti, A. J. C. Mittnacht, J. C. Katz, K. Nguyen, U. Joashi, and S. Srivastava, “Multisite near-infrared spectroscopy predicts elevated blood lactate level in children after cardiac surgery,” J. Cardiothorac. Vasc. Anesth. 23(5), 663–667 (2009).
[PubMed]

Nurmatov, A. A.

A. A. Nurmatov, A. V. Samoĭlenko, and B. I. Tkachenko, “Systemic hemodynamic shifts in the arterial and venous portions of the vascular bed in hypoxia,” Fiziologicheski Zhurnal SSSR Imeni I.m.sechenova 72(11), 1515 (1986).

O’Herron, P.

P. O’Herron, P. Y. Chhatbar, M. Levy, Z. Shen, A. E. Schramm, Z. Lu, and P. Kara, “Neural correlates of single-vessel haemodynamic responses in vivo,” Nature 534(7607), 378–382 (2016).
[PubMed]

Oh, C.

A. Hennessy, C. Oh, B. Diffey, K. Wakamatsu, S. Ito, and J. Rees, “Eumelanin and pheomelanin concentrations in human epidermis before and after UVB irradiation,” Pigment Cell Res. 18(3), 220–223 (2005).
[PubMed]

Paquette, A.

D. J. Rohrbach, D. Muffoletto, J. Huihui, R. Saager, K. Keymel, A. Paquette, J. Morgan, N. Zeitouni, and U. Sunar, “Preoperative mapping of nonmelanoma skin cancer using spatial frequency domain and ultrasound imaging,” Acad. Radiol. 21(2), 263–270 (2014).
[PubMed]

Pasupneti, T.

A. Yafi, F. K. Muakkassa, T. Pasupneti, J. Fulton, D. J. Cuccia, A. Mazhar, K. N. Blasiole, and E. N. Mostow, “Quantitative skin assessment using spatial frequency domain imaging (SFDI) in patients with or at high risk for pressure ulcers,” Lasers Surg. Med. 49(9), 827–834 (2017).
[PubMed]

Pharaon, M. R.

M. R. Pharaon, “Early detection of complete venous occlusion in a rodent and swine pedicle flap model using modulated imaging, a new novel multispectral imaging technique,” J. Am. Coll. Surg. 209(3), S77–S78 (2009).

Poon, C.

Pritchard, C.

I. Tachtsidis, M. M. Tisdall, C. Pritchard, T. S. Leung, C. E. Elwell, and M. Smith, “Hemoglobin and myoglobin contributions to skeletal muscle oxygenation in response to exercise,” J. Adv. Exp. Med Biol. 701(2), 347–352 (2011).

Qu, J. Y.

M. Xu, T. T. Wu, and J. Y. Qu, “Unified Mie and fractal scattering by cells and experimental study on application in optical characterization of cellular and subcellular structures,” J. Biomed. Opt. 13(2), 024015 (2008).
[PubMed]

T. T. Wu, J. Y. Qu, and M. Xu, “Unified Mie and fractal scattering by biological cells and subcellular structures,” Opt. Lett. 32(16), 2324–2326 (2007).
[PubMed]

Rees, J.

A. Hennessy, C. Oh, B. Diffey, K. Wakamatsu, S. Ito, and J. Rees, “Eumelanin and pheomelanin concentrations in human epidermis before and after UVB irradiation,” Pigment Cell Res. 18(3), 220–223 (2005).
[PubMed]

Reilly, M.

M. Reilly and M. Xu, “Analytical model for sub-diffusive light reflection and the application to spatial frequency-domain imaging,” Proc. SPIE 9319, 93191A (2015).

Rohrbach, D. J.

Rosset, I.

A. Sitek, I. Rosset, E. Żądzińska, A. Kasielska-Trojan, A. Neskoromna-Jędrzejczak, and B. Antoszewski, “Skin color parameters and Fitzpatrick phototypes in estimating the risk of skin cancer: a case-control study in the Polish population,” J. Am. Acad. Dermatol. 74(4), 716–723 (2016).
[PubMed]

Saager, R.

D. J. Rohrbach, N. C. Zeitouni, D. Muffoletto, R. Saager, B. J. Tromberg, and U. Sunar, “Characterization of nonmelanoma skin cancer for light therapy using spatial frequency domain imaging,” Biomed. Opt. Express 6(5), 1761–1766 (2015).
[PubMed]

D. J. Rohrbach, D. Muffoletto, J. Huihui, R. Saager, K. Keymel, A. Paquette, J. Morgan, N. Zeitouni, and U. Sunar, “Preoperative mapping of nonmelanoma skin cancer using spatial frequency domain and ultrasound imaging,” Acad. Radiol. 21(2), 263–270 (2014).
[PubMed]

Saager, R. B.

R. B. Saager, A. J. Durkin, K. M. Kelly, and B. J. Tromberg, “In vivo measurements of cutaneous melanin across spatial scales: using multiphoton microscopy and spatial frequency domain spectroscopy,” J. Biomed. Opt. 20, 066005 (2015).

R. B. Saager, A. Truong, D. J. Cuccia, and A. J. Durkin, “Method for depth-resolved quantitation of optical properties in layered media using spatially modulated quantitative spectroscopy,” J. Biomed. Opt. 16(7), 077002 (2011).
[PubMed]

Sagraves, S. G.

S. G. Sagraves, “Tissue oxygenation monitoring in the field: a new EMS vital sign,” J. Trauma 67(3), 441–4442009.

Samoilenko, A. V.

A. A. Nurmatov, A. V. Samoĭlenko, and B. I. Tkachenko, “Systemic hemodynamic shifts in the arterial and venous portions of the vascular bed in hypoxia,” Fiziologicheski Zhurnal SSSR Imeni I.m.sechenova 72(11), 1515 (1986).

Sassaroli, A.

J. M. Kainerstorfer, A. Sassaroli, K. T. Tgavalekos, and S. Fantini, “Cerebral autoregulation in the microvasculature measured with near-infrared spectroscopy,” J. Cereb. Blood Flow Metab. 35(6), 959–966 (2015).
[PubMed]

Scheeren, T. W. L.

T. W. L. Scheeren, P. Schober, and L. A. Schwarte, “Monitoring tissue oxygenation by near infrared spectroscopy (NIRS): Background and current applications,” J. Clin. Monit. Comput. 26(4), 279–287 (2012).
[PubMed]

Schlaffke, J.

M. Mackiewicz-Wysocka, A. Araszkiewicz, J. Schlaffke, S. Kuczynski, I. Micek, and D. Zozulinska-Ziolkiewicz, “Lower melanin content in the skin of type 1 diabetic patients and the risk of microangiopathy,” Exp. Clin. Endocrinol. Diabetes 122(4), 231–235 (2014).
[PubMed]

Schober, P.

T. W. L. Scheeren, P. Schober, and L. A. Schwarte, “Monitoring tissue oxygenation by near infrared spectroscopy (NIRS): Background and current applications,” J. Clin. Monit. Comput. 26(4), 279–287 (2012).
[PubMed]

Schramm, A. E.

P. O’Herron, P. Y. Chhatbar, M. Levy, Z. Shen, A. E. Schramm, Z. Lu, and P. Kara, “Neural correlates of single-vessel haemodynamic responses in vivo,” Nature 534(7607), 378–382 (2016).
[PubMed]

Schwarte, L. A.

T. W. L. Scheeren, P. Schober, and L. A. Schwarte, “Monitoring tissue oxygenation by near infrared spectroscopy (NIRS): Background and current applications,” J. Clin. Monit. Comput. 26(4), 279–287 (2012).
[PubMed]

Shen, Z.

P. O’Herron, P. Y. Chhatbar, M. Levy, Z. Shen, A. E. Schramm, Z. Lu, and P. Kara, “Neural correlates of single-vessel haemodynamic responses in vivo,” Nature 534(7607), 378–382 (2016).
[PubMed]

Sitek, A.

A. Sitek, I. Rosset, E. Żądzińska, A. Kasielska-Trojan, A. Neskoromna-Jędrzejczak, and B. Antoszewski, “Skin color parameters and Fitzpatrick phototypes in estimating the risk of skin cancer: a case-control study in the Polish population,” J. Am. Acad. Dermatol. 74(4), 716–723 (2016).
[PubMed]

Smith, M.

I. Tachtsidis, M. M. Tisdall, C. Pritchard, T. S. Leung, C. E. Elwell, and M. Smith, “Hemoglobin and myoglobin contributions to skeletal muscle oxygenation in response to exercise,” J. Adv. Exp. Med Biol. 701(2), 347–352 (2011).

Srivastava, S.

S. B. Chakravarti, A. J. C. Mittnacht, J. C. Katz, K. Nguyen, U. Joashi, and S. Srivastava, “Multisite near-infrared spectroscopy predicts elevated blood lactate level in children after cardiac surgery,” J. Cardiothorac. Vasc. Anesth. 23(5), 663–667 (2009).
[PubMed]

Sunar, U.

Sung, K.-B.

Tachtsidis, I.

I. Tachtsidis, M. M. Tisdall, C. Pritchard, T. S. Leung, C. E. Elwell, and M. Smith, “Hemoglobin and myoglobin contributions to skeletal muscle oxygenation in response to exercise,” J. Adv. Exp. Med Biol. 701(2), 347–352 (2011).

Tgavalekos, K. T.

J. M. Kainerstorfer, A. Sassaroli, K. T. Tgavalekos, and S. Fantini, “Cerebral autoregulation in the microvasculature measured with near-infrared spectroscopy,” J. Cereb. Blood Flow Metab. 35(6), 959–966 (2015).
[PubMed]

Thrane, L.

M. Mogensen, L. Thrane, T. M. Jørgensen, P. E. Andersen, and G. B. E. Jemec, “OCT imaging of skin cancer and other dermatological diseases,” J. Biophotonics 2(6-7), 442–451 (2009).
[PubMed]

Tisdall, M. M.

I. Tachtsidis, M. M. Tisdall, C. Pritchard, T. S. Leung, C. E. Elwell, and M. Smith, “Hemoglobin and myoglobin contributions to skeletal muscle oxygenation in response to exercise,” J. Adv. Exp. Med Biol. 701(2), 347–352 (2011).

Tkachenko, B. I.

A. A. Nurmatov, A. V. Samoĭlenko, and B. I. Tkachenko, “Systemic hemodynamic shifts in the arterial and venous portions of the vascular bed in hypoxia,” Fiziologicheski Zhurnal SSSR Imeni I.m.sechenova 72(11), 1515 (1986).

Travers, J. B.

Tromberg, B. J.

M. Ghijsen, B. Choi, A. J. Durkin, S. Gioux, and B. J. Tromberg, “Real-time simultaneous single snapshot of optical properties and blood flow using coherent spatial frequency domain imaging (cSFDI),” Biomed. Opt. Express 7(3), 870–882 (2016).
[PubMed]

R. B. Saager, A. J. Durkin, K. M. Kelly, and B. J. Tromberg, “In vivo measurements of cutaneous melanin across spatial scales: using multiphoton microscopy and spatial frequency domain spectroscopy,” J. Biomed. Opt. 20, 066005 (2015).

D. J. Rohrbach, N. C. Zeitouni, D. Muffoletto, R. Saager, B. J. Tromberg, and U. Sunar, “Characterization of nonmelanoma skin cancer for light therapy using spatial frequency domain imaging,” Biomed. Opt. Express 6(5), 1761–1766 (2015).
[PubMed]

D. J. Cuccia, F. Bevilacqua, A. J. Durkin, F. R. Ayers, and B. J. Tromberg, “Quantitation and mapping of tissue optical properties using modulated imaging,” J. Biomed. Opt. 14(2), 024012 (2009).
[PubMed]

J. R. Weber, D. J. Cuccia, A. J. Durkin, and B. J. Tromberg, “Noncontact imaging of absorption and scattering in layered tissue using spatially modulated structured light,” J. Appl. Phys. 105(10), 1–9 (2009).

D. J. Cuccia, F. Bevilacqua, A. J. Durkin, and B. J. Tromberg, “Modulated imaging: quantitative analysis and tomography of turbid media in the spatial-frequency domain,” Opt. Lett. 30(11), 1354–1356 (2005).
[PubMed]

Truong, A.

R. B. Saager, A. Truong, D. J. Cuccia, and A. J. Durkin, “Method for depth-resolved quantitation of optical properties in layered media using spatially modulated quantitative spectroscopy,” J. Biomed. Opt. 16(7), 077002 (2011).
[PubMed]

Tseng, T.-Y.

Tuchin, V. V.

A. N. Bashkatov, E. A. Genina, and V. V. Tuchin, “Optical properties of skin, subcutaneous, and muscle tissues: a review,” J. Innov. Opt. Health Sci. 4(1), 9–38 (2011).

Wakamatsu, K.

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Figures (8)

Fig. 1
Fig. 1

Comparison of SSMD and the three-phase demodulation methods. See text.

Fig. 2
Fig. 2

Schematic diagram of the SSMD-SFDI imaging system.

Fig. 3
Fig. 3

(a) Oxygenated hemoglobin concentration, (b) deoxygenated hemoglobin concentration, (c) total hemoglobin concentration, and (d) blood oxygen saturation for a typical subject under the forearm reactive hyperemia protocol.

Fig. 4
Fig. 4

The recovered melanin concentration and the epidermal thickness under the forearm reactive hyperemia protocol.

Fig. 5
Fig. 5

The absorption coefficient of epidermis (a-c) and dermis (d-f), the scattering coefficient at 540 nm (g), and the scattering power (h) for the same subject under the forearm reactive hyperemia protocol.

Fig. 6
Fig. 6

The average oxy- and deoxy-hemoglobin concentration, melanin content, epidermal thickness, the scattering coefficient (540 nm) and the scattering power for six volunteers (2 males and 4 females) during baseline, occlusion, and release states. The values for each individual are computed by averaging over one minute immediately before cuff for the baseline, the last minute during cuff for the occlusion state, and the first minute immediately after cuff release for the release state.

Fig. 7
Fig. 7

(a) The reflectance simulated with the two-layer structure and the equivalent homogeneous medium. The error bars show the standard deviation from five repeated simulations. (b) Mean maximum penetration of the spatially modulated light at wavelengths of 460 nm, 540 nm, 623 nm and 800 nm.

Fig. 8
Fig. 8

(a) The hemoglobin concentration, (b) the partial pressure of oxygen, (c) the scattering coefficient at 540 nm, and (d) the scattering power for the same subject under the forearm reactive hyperemia protocol.

Tables (3)

Tables Icon

Table 1 The molar extinction coefficients of oxygenated hemoglobin, deoxygenated hemoglobin and melanin at the three wavelengths (623 nm, 540 nm and 460 nm).

Tables Icon

Table 2 Color correction under white light illumination.

Tables Icon

Table 3 The p-values from t-tests on the average oxy-, deoxy-, and total hemoglobin concentrations, melanin content, epidermal thickness, the scattering coefficient (540 nm) and the scattering power during baseline, occlusion, and release states.

Equations (14)

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I AC = 2 3 ( I 0 I 120 ) 2 + ( I 120 I 240 ) 2 + ( I 240 I 0 ) 2 .
I AC,i = [ σ I(x,y)cos(2π f x,i x+2π f y,i y)dxdy ] 2 + [ σ I(x,y)sin(2π f x,i x+2π f y,i y)dxdy ] 2 σ cos 2 (2π f x,i x+2π f y,i y)dxdy .
μ a,epidermis ( λ )= ε melanin ( λ ) c melanin ,
μ a,dermis ( λ )= ε Hb ( λ ) c Hb + ε Hb O 2 ( λ ) c HbO ,
μ a L= μ a,epidermis ( λ )h+ μ a,dermis ( λ )(Lh),
I( q,z )= 1 4π μ s ' 2 0 + d z ' 0 + d z '' exp[ μ t ' ( z'+z'' ) ] g( q,z,z' )g( q,z,z'' )
g( q,z,z' )= 1 2Q D 0 e Q| ZZ' | 1 2Q D 0 1Ql 1+Ql e Q( z+z' ) ,
L( q,λ )= zI( q,z )dz I( q,z )dz = ( 1+Ql ) 2 ( 2 μ t ' ) 2 + ( 1+ μ t ' l ) 2 ( 2Q ) 2 2( 1+Ql )( 1+ μ t ' l ) ( Q+ μ t ' ) 2 ( 1+Ql ) 2 ( 2 μ t ' ) 1 + ( 1+ μ t ' l ) 2 ( 2Q ) 1 2( 1+Ql )( 1+ μ t ' l ) ( Q+ μ t ' ) 1 .
μ a = μ a,dermis +( μ a,epidermis μ a,dermis ) h L .
μ s '( λ )= μ s '( 540 nm ) ( λ 540 nm ) b .
P= [ r 1 r 2 r 3 g 1 g 2 g 3 b 1 b 2 b 3 ] .
P[ R raw G raw B raw ]=[ R mix G mix B mix ].
[ R raw G raw B raw ]= P 1 [ R mix G mix B mix ].
error= i=1 3 [ ( MT F AC ( λ i )mt f AC ( λ i ) ) 2 + ( MT F DC ( λ i )mt f DC ( λ i ) ) 2 ]