Abstract

Ultrasound optical tomography (UOT) is an imaging technique based on the acousto-optic effect that can perform optical imaging with ultrasound resolution inside turbid media, and is thus interesting for biomedical applications, e.g. for assessing tissue blood oxygenation. In this paper, we present near background free measurements of UOT signal strengths using slow light filter signal detection. We carefully analyze each part of our experimental setup and match measured signal strengths with calculations based on diffusion theory. This agreement between experiment and theory allows us to assert the deep tissue imaging potential of $\sim 5$ cm for UOT of real human tissues predicted by previous theoretical studies [Biomed. Opt. Express 8, 4523 (2017)] with greater confidence, and indicate that future theoretical analysis of optimized UOT systems can be expected to be reliable.

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

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2018 (4)

C. Venet, M. Bocoum, J.-B. Laudereau, T. Chaneliere, F. Ramaz, and A. Louchet-Chauvet, “Ultrasound-modulated optical tomography in scattering media: flux filtering based on persistent spectral hole burning in the optical diagnosis window,” Opt. Lett. 43(16), 3993–3996 (2018).
[Crossref]

J. E. Gunther, A. Walther, L. Rippe, S. Kröll, and S. Andersson-Engels, “Deep tissue imaging with acousto-optical tomography and spectral hole burning with slow light effect: a theoretical study,” J. Biomed. Opt. 23(07), 1–8 (2018).
[Crossref]

J. M. Kindem, J. G. Bartholomew, P. J. T. Woodburn, T. Zhong, I. Craiciu, R. L. Cone, C. W. Thiel, and A. Faraon, “Characterization of $^{171}\textrm {Yb}^{3+}:{\textrm {YVO}}_{4}$171Yb3+:YVO4 for photonic quantum technologies,” Phys. Rev. B 98(2), 024404 (2018).
[Crossref]

R. Oswald, M. G. Hansen, E. Wiens, A. Y. Nevsky, and S. Schiller, “Characteristics of long-lived persistent spectral holes in ${\mathrm {Eu}}^{3+}$Eu3+:${\mathrm {Y}}_{2}{\mathrm {SiO}}_{5}$Y2SiO5 at 1.2 K,” Phys. Rev. A 98(6), 062516 (2018).
[Crossref]

2017 (2)

2016 (3)

A. Kinos, Q. Li, L. Rippe, and S. Kröll, “Development and characterization of high suppression and high étendue narrowband spectral filters,” Appl. Opt. 55(36), 10442–10448 (2016).
[Crossref]

Y. Liu, Y. Shen, C. Ma, J. Shi, and L. V. Wang, “Lock-in camera based heterodyne holography for ultrasound-modulated optical tomography inside dynamic scattering media,” Appl. Phys. Lett. 108(23), 231106 (2016).
[Crossref]

M. Sabooni, A. N. Nilsson, G. Kristensson, and L. Rippe, “Wave propagation in birefringent materials with off-axis absorption or gain,” Phys. Rev. A 93(1), 013842 (2016).
[Crossref]

2015 (1)

P. Taroni, G. Quarto, A. Pifferi, F. Abbate, N. Balestreri, S. Menna, E. Cassano, and R. Cubeddu, “Breast tissue composition and its dependence on demographic risk factors for breast cancer: Non-invasive assessment by time domain diffuse optical spectroscopy,” PLoS One 10(6), e0128941 (2015).
[Crossref]

2014 (1)

2013 (2)

2012 (1)

H. Zhang, M. Sabooni, L. Rippe, C. Kim, S. Kröll, L. V. Wang, and P. R. Hemmer, “Slow light for deep tissue imaging with ultrasound modulation,” Appl. Phys. Lett. 100(13), 131102 (2012).
[Crossref]

2011 (3)

D. S. Elson, R. Li, C. Dunsby, R. Eckersley, and M.-X. Tang, “Ultrasound-mediated optical tomography: a review of current methods,” Interface Focus 1(4), 632–648 (2011).
[Crossref]

M. Tian, T. Chang, K. D. Merkel, and W. Randall, “Reconfiguration of spectral absorption features using a frequency-chirped laser pulse,” Appl. Opt. 50(36), 6548–6554 (2011).
[Crossref]

G. ter Haar, “Ultrasonic imaging: safety considerations,” Interface Focus 1(4), 686–697 (2011).
[Crossref]

2010 (1)

X. Xu, S.-R. Kothapalli, H. Liu, and L. V. Wang, “Spectral hole burning for ultrasound-modulated optical tomography of thick tissue,” J. Biomed. Opt. 15(6), 066018 (2010).
[Crossref]

2009 (1)

T. Böttger, C. W. Thiel, R. L. Cone, and Y. Sun, “Effects of magnetic field orientation on optical decoherence in ${\textrm {Er}}^{3+}:{\textrm {Y}}_{2}{\textrm {SiO}}_{5}$Er3+:Y2SiO5,” Phys. Rev. B 79(11), 115104 (2009).
[Crossref]

2008 (4)

Y. Li, H. Zhang, C. Kim, K. H. Wagner, P. Hemmer, and L. V. Wang, “Pulsed ultrasound-modulated optical tomography using spectral-hole burning as a narrowband spectral filter,” Appl. Phys. Lett. 93(1), 011111 (2008).
[Crossref]

Y. Li, P. Hemmer, C. Kim, H. Zhang, and L. V. Wang, “Detection of ultrasound-modulated diffuse photons using spectral-hole burning,” Opt. Express 16(19), 14862–14874 (2008).
[Crossref]

E. Alerstam, S. Andersson-Engels, and T. Svensson, “White Monte Carlo for time-resolved photon migration,” J. Biomed. Opt. 13(4), 041304 (2008).
[Crossref]

R. Michels, F. Foschum, and A. Kienle, “Optical properties of fat emulsions,” Opt. Express 16(8), 5907–5925 (2008).
[Crossref]

2007 (1)

A. Rebane, R. Shakhmuratov, P. Megret, and J. Odeurs, “Slow light with persistent spectral hole burning in waveguides,” J. Lumin. 127(1), 22–27 (2007).
[Crossref]

2004 (3)

2003 (3)

F. Könz, Y. Sun, C. W. Thiel, R. L. Cone, R. W. Equall, R. L. Hutcheson, and R. M. Macfarlane, “Temperature and concentration dependence of optical dephasing, spectral-hole lifetime, and anisotropic absorption in ${\mathrm {Eu}}^{3+}{:\mathrm {Y}}_{2}{\mathrm {SiO}}_{5}$Eu3+:Y2SiO5,” Phys. Rev. B 68(8), 085109 (2003).
[Crossref]

N. Ohlsson, M. Nilsson, and S. Kröll, “Experimental investigation of delayed self-interference for single photons,” Phys. Rev. A 68(6), 063812 (2003).
[Crossref]

P. R. Bargo, S. A. Prahl, and S. L. Jacques, “Collection efficiency of a single optical fiber in turbid media,” Appl. Opt. 42(16), 3187–3197 (2003).
[Crossref]

2002 (1)

1998 (1)

1997 (1)

R. Cubeddu, A. Pifferi, P. Taroni, A. Torricelli, and G. Valentini, “A solid tissue phantom for photon migration studies,” Phys. Med. Biol. 42(10), 1971–1979 (1997).
[Crossref]

1995 (1)

R. W. Equall, R. L. Cone, and R. M. Macfarlane, “Homogeneous broadening and hyperfine structure of optical transitions in Pr$^{3+}$3+:Y$_2$2SiO$_5$5,” Phys. Rev. B 52(6), 3963–3969 (1995).
[Crossref]

1988 (1)

1970 (1)

M. D. Crisp, “Propagation of small-area pulses of coherent light through a resonant medium,” Phys. Rev. A 1(6), 1604–1611 (1970).
[Crossref]

Abbate, F.

P. Taroni, G. Quarto, A. Pifferi, F. Abbate, N. Balestreri, S. Menna, E. Cassano, and R. Cubeddu, “Breast tissue composition and its dependence on demographic risk factors for breast cancer: Non-invasive assessment by time domain diffuse optical spectroscopy,” PLoS One 10(6), e0128941 (2015).
[Crossref]

Alerstam, E.

E. Alerstam, S. Andersson-Engels, and T. Svensson, “White Monte Carlo for time-resolved photon migration,” J. Biomed. Opt. 13(4), 041304 (2008).
[Crossref]

Andersson-Engels, S.

J. E. Gunther, A. Walther, L. Rippe, S. Kröll, and S. Andersson-Engels, “Deep tissue imaging with acousto-optical tomography and spectral hole burning with slow light effect: a theoretical study,” J. Biomed. Opt. 23(07), 1–8 (2018).
[Crossref]

J. Gunther and S. Andersson-Engels, “Review of current methods of acousto-optical tomography for biomedical applications,” Front. Optoelectron. 10(3), 211–238 (2017).
[Crossref]

A. Walther, L. Rippe, L. V. Wang, S. Andersson-Engels, and S. Kröll, “Analysis of the potential for non-invasive imaging of oxygenation at heart depth, using ultrasound optical tomography (UOT) or photo-acoustic tomography (PAT),” Biomed. Opt. Express 8(10), 4523–4536 (2017).
[Crossref]

L. Spinelli, M. Botwicz, N. Zolek, M. Kacprzak, D. Milej, P. Sawosz, A. Liebert, U. Weigel, T. Durduran, F. Foschum, A. Kienle, F. Baribeau, S. Leclair, J.-P. Bouchard, I. Noiseux, P. Gallant, O. Mermut, A. Farina, A. Pifferi, A. Torricelli, R. Cubeddu, H.-C. Ho, M. Mazurenka, H. Wabnitz, K. Klauenberg, O. Bodnar, C. Elster, M. Bénazech-Lavoué, Y. Bérubé-Lauzière, F. Lesage, D. Khoptyar, A. A. Subash, S. Andersson-Engels, P. D. Ninni, F. Martelli, and G. Zaccanti, “Determination of reference values for optical properties of liquid phantoms based on intralipid and india ink,” Biomed. Opt. Express 5(7), 2037–2053 (2014).
[Crossref]

D. Khoptyar, A. A. Subash, S. Johansson, M. Saleem, A. Sparén, J. Johansson, and S. Andersson-Engels, “Broadband photon time-of-flight spectroscopy of pharmaceuticals and highly scattering plastics in the vis and close nir spectral ranges,” Opt. Express 21(18), 20941–20953 (2013).
[Crossref]

E. Alerstam, S. Andersson-Engels, and T. Svensson, “White Monte Carlo for time-resolved photon migration,” J. Biomed. Opt. 13(4), 041304 (2008).
[Crossref]

Atlan, M.

Balestreri, N.

P. Taroni, G. Quarto, A. Pifferi, F. Abbate, N. Balestreri, S. Menna, E. Cassano, and R. Cubeddu, “Breast tissue composition and its dependence on demographic risk factors for breast cancer: Non-invasive assessment by time domain diffuse optical spectroscopy,” PLoS One 10(6), e0128941 (2015).
[Crossref]

Bargo, P. R.

Baribeau, F.

Bartholomew, J. G.

J. M. Kindem, J. G. Bartholomew, P. J. T. Woodburn, T. Zhong, I. Craiciu, R. L. Cone, C. W. Thiel, and A. Faraon, “Characterization of $^{171}\textrm {Yb}^{3+}:{\textrm {YVO}}_{4}$171Yb3+:YVO4 for photonic quantum technologies,” Phys. Rev. B 98(2), 024404 (2018).
[Crossref]

Bénazech-Lavoué, M.

Bérubé-Lauzière, Y.

Blonigen, F.

Boccara, A. C.

Bocoum, M.

Bodnar, O.

Böttger, T.

T. Böttger, C. W. Thiel, R. L. Cone, and Y. Sun, “Effects of magnetic field orientation on optical decoherence in ${\textrm {Er}}^{3+}:{\textrm {Y}}_{2}{\textrm {SiO}}_{5}$Er3+:Y2SiO5,” Phys. Rev. B 79(11), 115104 (2009).
[Crossref]

Botwicz, M.

Bouchard, J.-P.

Cassano, E.

P. Taroni, G. Quarto, A. Pifferi, F. Abbate, N. Balestreri, S. Menna, E. Cassano, and R. Cubeddu, “Breast tissue composition and its dependence on demographic risk factors for breast cancer: Non-invasive assessment by time domain diffuse optical spectroscopy,” PLoS One 10(6), e0128941 (2015).
[Crossref]

Chaneliere, T.

Chang, T.

Cone, R. L.

J. M. Kindem, J. G. Bartholomew, P. J. T. Woodburn, T. Zhong, I. Craiciu, R. L. Cone, C. W. Thiel, and A. Faraon, “Characterization of $^{171}\textrm {Yb}^{3+}:{\textrm {YVO}}_{4}$171Yb3+:YVO4 for photonic quantum technologies,” Phys. Rev. B 98(2), 024404 (2018).
[Crossref]

T. Böttger, C. W. Thiel, R. L. Cone, and Y. Sun, “Effects of magnetic field orientation on optical decoherence in ${\textrm {Er}}^{3+}:{\textrm {Y}}_{2}{\textrm {SiO}}_{5}$Er3+:Y2SiO5,” Phys. Rev. B 79(11), 115104 (2009).
[Crossref]

F. Könz, Y. Sun, C. W. Thiel, R. L. Cone, R. W. Equall, R. L. Hutcheson, and R. M. Macfarlane, “Temperature and concentration dependence of optical dephasing, spectral-hole lifetime, and anisotropic absorption in ${\mathrm {Eu}}^{3+}{:\mathrm {Y}}_{2}{\mathrm {SiO}}_{5}$Eu3+:Y2SiO5,” Phys. Rev. B 68(8), 085109 (2003).
[Crossref]

R. W. Equall, R. L. Cone, and R. M. Macfarlane, “Homogeneous broadening and hyperfine structure of optical transitions in Pr$^{3+}$3+:Y$_2$2SiO$_5$5,” Phys. Rev. B 52(6), 3963–3969 (1995).
[Crossref]

Craiciu, I.

J. M. Kindem, J. G. Bartholomew, P. J. T. Woodburn, T. Zhong, I. Craiciu, R. L. Cone, C. W. Thiel, and A. Faraon, “Characterization of $^{171}\textrm {Yb}^{3+}:{\textrm {YVO}}_{4}$171Yb3+:YVO4 for photonic quantum technologies,” Phys. Rev. B 98(2), 024404 (2018).
[Crossref]

Crisp, M. D.

M. D. Crisp, “Propagation of small-area pulses of coherent light through a resonant medium,” Phys. Rev. A 1(6), 1604–1611 (1970).
[Crossref]

Cubeddu, R.

P. Taroni, G. Quarto, A. Pifferi, F. Abbate, N. Balestreri, S. Menna, E. Cassano, and R. Cubeddu, “Breast tissue composition and its dependence on demographic risk factors for breast cancer: Non-invasive assessment by time domain diffuse optical spectroscopy,” PLoS One 10(6), e0128941 (2015).
[Crossref]

L. Spinelli, M. Botwicz, N. Zolek, M. Kacprzak, D. Milej, P. Sawosz, A. Liebert, U. Weigel, T. Durduran, F. Foschum, A. Kienle, F. Baribeau, S. Leclair, J.-P. Bouchard, I. Noiseux, P. Gallant, O. Mermut, A. Farina, A. Pifferi, A. Torricelli, R. Cubeddu, H.-C. Ho, M. Mazurenka, H. Wabnitz, K. Klauenberg, O. Bodnar, C. Elster, M. Bénazech-Lavoué, Y. Bérubé-Lauzière, F. Lesage, D. Khoptyar, A. A. Subash, S. Andersson-Engels, P. D. Ninni, F. Martelli, and G. Zaccanti, “Determination of reference values for optical properties of liquid phantoms based on intralipid and india ink,” Biomed. Opt. Express 5(7), 2037–2053 (2014).
[Crossref]

R. Cubeddu, A. Pifferi, P. Taroni, A. Torricelli, and G. Valentini, “A solid tissue phantom for photon migration studies,” Phys. Med. Biol. 42(10), 1971–1979 (1997).
[Crossref]

Delaye, P.

DiMarzio, C. A.

Dunsby, C.

D. S. Elson, R. Li, C. Dunsby, R. Eckersley, and M.-X. Tang, “Ultrasound-mediated optical tomography: a review of current methods,” Interface Focus 1(4), 632–648 (2011).
[Crossref]

Durduran, T.

Eckersley, R.

D. S. Elson, R. Li, C. Dunsby, R. Eckersley, and M.-X. Tang, “Ultrasound-mediated optical tomography: a review of current methods,” Interface Focus 1(4), 632–648 (2011).
[Crossref]

Elson, D. S.

D. S. Elson, R. Li, C. Dunsby, R. Eckersley, and M.-X. Tang, “Ultrasound-mediated optical tomography: a review of current methods,” Interface Focus 1(4), 632–648 (2011).
[Crossref]

Elster, C.

Equall, R. W.

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Appl. Opt. (5)

Appl. Phys. Lett. (3)

Y. Li, H. Zhang, C. Kim, K. H. Wagner, P. Hemmer, and L. V. Wang, “Pulsed ultrasound-modulated optical tomography using spectral-hole burning as a narrowband spectral filter,” Appl. Phys. Lett. 93(1), 011111 (2008).
[Crossref]

H. Zhang, M. Sabooni, L. Rippe, C. Kim, S. Kröll, L. V. Wang, and P. R. Hemmer, “Slow light for deep tissue imaging with ultrasound modulation,” Appl. Phys. Lett. 100(13), 131102 (2012).
[Crossref]

Y. Liu, Y. Shen, C. Ma, J. Shi, and L. V. Wang, “Lock-in camera based heterodyne holography for ultrasound-modulated optical tomography inside dynamic scattering media,” Appl. Phys. Lett. 108(23), 231106 (2016).
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Figures (9)

Fig. 1.
Fig. 1. The working principle of UOT using slow light filter (SLF) signal detection. $\textbf {(a)}$ Optical pumping techniques are used to create a transmission window in the absorption of a rare-earth-ion-doped material. Inside the transmission window the refractive index changes rapidly with frequency, which reduces the speed of light. Here, $n_0$ denotes the refractive index of the host material. $\textbf {(b)}$ A short ultrasound (US) pulse with frequency $f_{\textrm {US}}$ delivered by an ultrasound transducer (UST) tags diffuse light traversing it. Light is collected by a light guide (LG) and filtered through the SLF, which blocks the laser carrier at frequency $f_{\textrm {c}}$, while transmitting the tagged photons at frequency $f_{\textrm {s}}$, allowing for optical measurements with ultrasound spatial resolution. $\textbf {(c)}$ i) The light intensity in the frequency domain at the tissue output is characterized by a strong laser carrier and weak ultrasound generated sidebands. ii) The sideband and carrier overlap in time at the tissue output. $\textbf {(d)}$ The SLF, greatly suppresses the carrier light due to absorption by the dopant ions. Additionally, the carrier light arrives at the detector at time $t_c$ while the tagged photons arrive at a later time $t_s$ due to the slow light effect. This allows for further suppression of the laser carrier using time gating.
Fig. 2.
Fig. 2. Experimental setup. A beamsplitter picks off a small fraction of the light to a reference detector. A flip mirror is used to switch between burning the filter and probing the phantom. A half-wave ($\lambda$/2) plate and a polarizer are used to align the polarization of the burn beam parallel to the $D_2$ axis of the crystal. The ultrasound (US) transducer is mounted at a fixed position above the phantom. A liquid light guide collects diffuse light emerging from the phantom. Lenses are used to pass the light through the crystal, and a polarizer transmits the polarization along the $D_2$ axis. A photomultiplier tube (PMT) detects the signal. A mechanical shutter protects the PMT from overexposure during the burning. The ultrasound pulse is focused and timed to be at the center of the phantom when the light pulse is inside the phantom for all measurements.
Fig. 3.
Fig. 3. Optical power incident on the detector with and without ultrasound modulation for a $\textbf {(a)}$ 3.5 cm thick phantom and $\textbf {(b)}$ 6.8 cm thick phantom. The phantoms have $\mu _s' = 6.1$ cm $^{-1}$ and $\mu _a = 0.008$ cm $^{-1}$. All traces are obtained by averaging 1000 probe pulse. The shaded areas represent 2 standard errors. Note the different scales on the vertical axes for the two sub figures.
Fig. 4.
Fig. 4. Comparison between measured and simulated carrier and +1st order tagged photon numbers. Carrier measurement corresponds to photons recorded with the slow light filter at the carrier frequency and no ultrasound modulation, while tagged measurement corresponds to photons recorded with the slow light filter at the +1st order sideband frequency with ultrasound modulation. The phantoms have $\mu _s' = 6.1$ cm$^{-1}$ and $\mu _a = 0.008$ cm$^{-1}$. All values are obtained by averaging 1000 probe pulse. The vertical and horizontal error bars represent 2 standard errors and our estimated phantom thickness accuracy, respectively. Note, the data presented is photons incident on the detector. By multiplying with our measured degraded quantum efficiency, the number of detected photons, i.e., photons generating a photoelectron is obtained.
Fig. 5.
Fig. 5. Simulated number of tagged photons incident on the detector per probe pulse for an optimized UOT transmission mode setup. The ultrasound depth from which tagged photons are generated is set to half the tissue thickness.
Fig. 6.
Fig. 6. Validation of the PTOF spectrometer at 606 nm. (a) Measured values of $\mu _{\textrm {a}}$ using PTOF vs collimated transmission spectroscopy (CTS). (b) Measured values of $\mu _{\textrm {s}}'$ using PTOF vs reference values based on [36].
Fig. 7.
Fig. 7. Normalized output power of the two-fiber setup when (a) incrementally increasing $\mu _{\textrm {a}}$ following our calibration curves obtained from collimated transmission spectroscopy, and (b) when incrementally increasing $\mu _{\textrm {s}}'$ based on Ref. [36]. The black dots corresponds to measurements with errorbars representing 1 standard error and red lines are Monte Carlo simulations. An anisotropy factor $g=0.7$ was used in the simulations.
Fig. 8.
Fig. 8. $\textbf {(a)}$ Transverse max pressure cross section of the ultrasound pulse focused at a distance of 3.5 cm from the transducer. (b) & (c) Cross section of pulse along two orthogonal transverse translations ($x$ & $y$) and its longitudinal pressure projection, $v =$ 1.48 mm/µs. (d) Pressure color map for $\textbf {(a)} - \textbf {(c)}$. $\textbf {(e)}$ Normalized FFT of ultrasound pulse center line, center frequency is 1.6 MHz.
Fig. 9.
Fig. 9. Depiction of experiment with corresponding diffusion model where a phantom is illuminated with carrier light (illustrated by green filled lines) and ultrasound tagged light (illustrated by blue hollow lines). Both light fields are collected in a light guide for transport to the slow light filter and detection. The carrier sources are depicted with filled green plus signs and its drains with filled green minus signs. Similarly, the tagged sources are illustrated with blue hollow plus and minus signs.

Tables (1)

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Table 1. Parameters for the setup used in the experiments and for an improved setup.

Equations (8)

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v g = c n + f n f ,
v g π 2 Γ α ,
η tot = QE det T s e t u p T f i l t e r η L G ,
Φ ( r , t ) = i = 1 N Φ i ( r , r i , t )     ,         Φ i ( r , r i , t ) = σ i P ( t ) 4 π D | r r i | e x p ( μ eff | r r i | )   .
P s ( t ) = K Φ c ( r US , t ) ,
J ( r , t ) = D Φ ( r , t )   .
J o u t ( t ) = J ( r , t ) n ^   .
P d e t ( t ) = N side η L G A L G T s e t u p T f i l t e r J o u t ( t ) = N side A L G η t o t Q E d e t J o u t ( t )