Abstract

Reporter genes are useful scientific tools for analyzing promoter activity, transfection efficiency, and cell migration. The current study has validated the use of tyrosinase (involved in melanin production) as a dual reporter gene for magnetic resonance and photoacoustic imaging. MCF-7 cells expressing tyrosinase appear brown due to melanin. Magnetic resonance imaging of tyrosinase-expressing MCF-7 cells in 300 μL plastic tubes displayed a 34 to 40% reduction in T1 compared to normal MCF-7 cells when cells were incubated with 250 μM ferric citrate. Photoacoustic imaging of tyrosinase-expressing MCF-7 cells in 700 μm plastic tubes displayed a 20 to 57-fold increase in photoacoustic signal compared to normal MCF-7 cells. The photoacoustic signal from tyrosinase-expressing MCF-7 cells was significantly greater than blood at 650 nm, suggesting that tyrosinase-expressing cells can be differentiated from the vasculature with in vivo photoacoustic imaging. The imaging results suggest that tyrosinase is a useful reporter gene for both magnetic resonance and photoacoustic imaging.

© 2011 OSA

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    [CrossRef] [PubMed]
  3. W. S. Oetting, “The tyrosinase gene and oculocutaneous albinism type 1 (OCA1): A model for understanding the molecular biology of melanin formation,” Pigment Cell Res. 13(5), 320–325 (2000).
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  4. G. Zonios, A. Dimou, I. Bassukas, D. Galaris, A. Tsolakidis, and E. Kaxiras, “Melanin absorption spectroscopy: new method for noninvasive skin investigation and melanoma detection,” J. Biomed. Opt. 13(1), 014017 (2008).
    [CrossRef] [PubMed]
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    [CrossRef] [PubMed]
  17. T. Harrison, J. C. Ranasinghesagara, H. Lu, K. Mathewson, A. Walsh, and R. J. Zemp, “Combined photoacoustic and ultrasound biomicroscopy,” Opt. Express 17(24), 22041–22046 (2009).
    [CrossRef] [PubMed]
  18. J. C. Ranasinghesagara and R. J. Zemp, “Combined photoacoustic and oblique-incidence diffuse reflectance system for quantitative photoacoustic imaging in turbid media,” J. Biomed. Opt. 15(4), 046016 (2010).
    [CrossRef] [PubMed]

2010

J. C. Ranasinghesagara and R. J. Zemp, “Combined photoacoustic and oblique-incidence diffuse reflectance system for quantitative photoacoustic imaging in turbid media,” J. Biomed. Opt. 15(4), 046016 (2010).
[CrossRef] [PubMed]

2009

T. Harrison, J. C. Ranasinghesagara, H. Lu, K. Mathewson, A. Walsh, and R. J. Zemp, “Combined photoacoustic and ultrasound biomicroscopy,” Opt. Express 17(24), 22041–22046 (2009).
[CrossRef] [PubMed]

C. Li and L. V. Wang, “Photoacoustic tomography and sensing in biomedicine,” Phys. Med. Biol. 54(19), R59–R97 (2009).
[CrossRef] [PubMed]

E. I. Galanzha, E. V. Shashkov, P. M. Spring, J. Y. Suen, and V. P. Zharov, “In vivo, noninvasive, label-free detection and eradication of circulating metastatic melanoma cells using two-color photoacoustic flow cytometry with a diode laser,” Cancer Res. 69(20), 7926–7934 (2009).
[CrossRef] [PubMed]

2008

G. Zonios, A. Dimou, I. Bassukas, D. Galaris, A. Tsolakidis, and E. Kaxiras, “Melanin absorption spectroscopy: new method for noninvasive skin investigation and melanoma detection,” J. Biomed. Opt. 13(1), 014017 (2008).
[CrossRef] [PubMed]

L. Li, H. F. Zhang, R. J. Zemp, K. Maslov, and L. Wang, “Simultaneous imaging of a lacZ-marked tumor and microvasculature morphology in vivo by dual-wavelength photoacoustic microscopy,” J. Innov. Opt. Health Sci. 01(02), 207–215 (2008).
[CrossRef] [PubMed]

2007

L. Li, R. J. Zemp, G. Lungu, G. Stoica, and L. V. Wang, “Photoacoustic imaging of lacZ gene expression in vivo,” J. Biomed. Opt. 12(2), 020504 (2007).
[CrossRef] [PubMed]

A. M. Ponce, B. L. Viglianti, D. Yu, P. S. Yarmolenko, C. R. Michelich, J. Woo, M. B. Bally, and M. W. Dewhirst, “Magnetic resonance imaging of temperature-sensitive liposome release: drug dose painting and antitumor effects,” J. Natl. Cancer Inst. 99(1), 53–63 (2007).
[CrossRef] [PubMed]

2006

J. T. Oh, M. L. Li, H. F. Zhang, K. Maslov, G. Stoica, and L. V. Wang, “Three-dimensional imaging of skin melanoma in vivo by dual-wavelength photoacoustic microscopy,” J. Biomed. Opt. 11(3), 034032 (2006).
[CrossRef] [PubMed]

R. M. Weight, J. A. Viator, P. S. Dale, C. W. Caldwell, and A. E. Lisle, “Photoacoustic detection of metastatic melanoma cells in the human circulatory system,” Opt. Lett. 31(20), 2998–3000 (2006).
[CrossRef] [PubMed]

H. F. Zhang, K. Maslov, G. Stoica, and L. V. Wang, “Functional photoacoustic microscopy for high-resolution and noninvasive in vivo imaging,” Nat. Biotechnol. 24(7), 848–851 (2006).
[CrossRef] [PubMed]

2003

H. Alfke, H. Stöppler, F. Nocken, J. T. Heverhagen, B. Kleb, F. Czubayko, and K. J. Klose, “In vitro MR imaging of regulated gene expression,” Radiology 228(2), 488–492 (2003).
[CrossRef] [PubMed]

2002

L. F. Greer and A. A. Szalay, “Imaging of light emission from the expression of luciferases in living cells and organisms: a review,” Luminescence 17(1), 43–74 (2002).
[CrossRef] [PubMed]

2000

W. S. Oetting, “The tyrosinase gene and oculocutaneous albinism type 1 (OCA1): A model for understanding the molecular biology of melanin formation,” Pigment Cell Res. 13(5), 320–325 (2000).
[CrossRef] [PubMed]

1997

R. Weissleder, M. Simonova, A. Bogdanova, S. Bredow, W. S. Enochs, and A. Bogdanov., “MR imaging and scintigraphy of gene expression through melanin induction,” Radiology 204(2), 425–429 (1997).
[PubMed]

T. Misteli and D. L. Spector, “Applications of the green fluorescent protein in cell biology and biotechnology,” Nat. Biotechnol. 15(10), 961–964 (1997).
[CrossRef] [PubMed]

1993

E. K. Insko and L. Bolinger, “Mapping of the radiofrequency field,” J. Magn. Reson. A 103(1), 82–85 (1993).
[CrossRef]

Alfke, H.

H. Alfke, H. Stöppler, F. Nocken, J. T. Heverhagen, B. Kleb, F. Czubayko, and K. J. Klose, “In vitro MR imaging of regulated gene expression,” Radiology 228(2), 488–492 (2003).
[CrossRef] [PubMed]

Bally, M. B.

A. M. Ponce, B. L. Viglianti, D. Yu, P. S. Yarmolenko, C. R. Michelich, J. Woo, M. B. Bally, and M. W. Dewhirst, “Magnetic resonance imaging of temperature-sensitive liposome release: drug dose painting and antitumor effects,” J. Natl. Cancer Inst. 99(1), 53–63 (2007).
[CrossRef] [PubMed]

Bassukas, I.

G. Zonios, A. Dimou, I. Bassukas, D. Galaris, A. Tsolakidis, and E. Kaxiras, “Melanin absorption spectroscopy: new method for noninvasive skin investigation and melanoma detection,” J. Biomed. Opt. 13(1), 014017 (2008).
[CrossRef] [PubMed]

Bogdanov, A.

R. Weissleder, M. Simonova, A. Bogdanova, S. Bredow, W. S. Enochs, and A. Bogdanov., “MR imaging and scintigraphy of gene expression through melanin induction,” Radiology 204(2), 425–429 (1997).
[PubMed]

Bogdanova, A.

R. Weissleder, M. Simonova, A. Bogdanova, S. Bredow, W. S. Enochs, and A. Bogdanov., “MR imaging and scintigraphy of gene expression through melanin induction,” Radiology 204(2), 425–429 (1997).
[PubMed]

Bolinger, L.

E. K. Insko and L. Bolinger, “Mapping of the radiofrequency field,” J. Magn. Reson. A 103(1), 82–85 (1993).
[CrossRef]

Bredow, S.

R. Weissleder, M. Simonova, A. Bogdanova, S. Bredow, W. S. Enochs, and A. Bogdanov., “MR imaging and scintigraphy of gene expression through melanin induction,” Radiology 204(2), 425–429 (1997).
[PubMed]

Caldwell, C. W.

Czubayko, F.

H. Alfke, H. Stöppler, F. Nocken, J. T. Heverhagen, B. Kleb, F. Czubayko, and K. J. Klose, “In vitro MR imaging of regulated gene expression,” Radiology 228(2), 488–492 (2003).
[CrossRef] [PubMed]

Dale, P. S.

Dewhirst, M. W.

A. M. Ponce, B. L. Viglianti, D. Yu, P. S. Yarmolenko, C. R. Michelich, J. Woo, M. B. Bally, and M. W. Dewhirst, “Magnetic resonance imaging of temperature-sensitive liposome release: drug dose painting and antitumor effects,” J. Natl. Cancer Inst. 99(1), 53–63 (2007).
[CrossRef] [PubMed]

Dimou, A.

G. Zonios, A. Dimou, I. Bassukas, D. Galaris, A. Tsolakidis, and E. Kaxiras, “Melanin absorption spectroscopy: new method for noninvasive skin investigation and melanoma detection,” J. Biomed. Opt. 13(1), 014017 (2008).
[CrossRef] [PubMed]

Enochs, W. S.

R. Weissleder, M. Simonova, A. Bogdanova, S. Bredow, W. S. Enochs, and A. Bogdanov., “MR imaging and scintigraphy of gene expression through melanin induction,” Radiology 204(2), 425–429 (1997).
[PubMed]

Galanzha, E. I.

E. I. Galanzha, E. V. Shashkov, P. M. Spring, J. Y. Suen, and V. P. Zharov, “In vivo, noninvasive, label-free detection and eradication of circulating metastatic melanoma cells using two-color photoacoustic flow cytometry with a diode laser,” Cancer Res. 69(20), 7926–7934 (2009).
[CrossRef] [PubMed]

Galaris, D.

G. Zonios, A. Dimou, I. Bassukas, D. Galaris, A. Tsolakidis, and E. Kaxiras, “Melanin absorption spectroscopy: new method for noninvasive skin investigation and melanoma detection,” J. Biomed. Opt. 13(1), 014017 (2008).
[CrossRef] [PubMed]

Greer, L. F.

L. F. Greer and A. A. Szalay, “Imaging of light emission from the expression of luciferases in living cells and organisms: a review,” Luminescence 17(1), 43–74 (2002).
[CrossRef] [PubMed]

Harrison, T.

Heverhagen, J. T.

H. Alfke, H. Stöppler, F. Nocken, J. T. Heverhagen, B. Kleb, F. Czubayko, and K. J. Klose, “In vitro MR imaging of regulated gene expression,” Radiology 228(2), 488–492 (2003).
[CrossRef] [PubMed]

Insko, E. K.

E. K. Insko and L. Bolinger, “Mapping of the radiofrequency field,” J. Magn. Reson. A 103(1), 82–85 (1993).
[CrossRef]

Kaxiras, E.

G. Zonios, A. Dimou, I. Bassukas, D. Galaris, A. Tsolakidis, and E. Kaxiras, “Melanin absorption spectroscopy: new method for noninvasive skin investigation and melanoma detection,” J. Biomed. Opt. 13(1), 014017 (2008).
[CrossRef] [PubMed]

Kleb, B.

H. Alfke, H. Stöppler, F. Nocken, J. T. Heverhagen, B. Kleb, F. Czubayko, and K. J. Klose, “In vitro MR imaging of regulated gene expression,” Radiology 228(2), 488–492 (2003).
[CrossRef] [PubMed]

Klose, K. J.

H. Alfke, H. Stöppler, F. Nocken, J. T. Heverhagen, B. Kleb, F. Czubayko, and K. J. Klose, “In vitro MR imaging of regulated gene expression,” Radiology 228(2), 488–492 (2003).
[CrossRef] [PubMed]

Li, C.

C. Li and L. V. Wang, “Photoacoustic tomography and sensing in biomedicine,” Phys. Med. Biol. 54(19), R59–R97 (2009).
[CrossRef] [PubMed]

Li, L.

L. Li, H. F. Zhang, R. J. Zemp, K. Maslov, and L. Wang, “Simultaneous imaging of a lacZ-marked tumor and microvasculature morphology in vivo by dual-wavelength photoacoustic microscopy,” J. Innov. Opt. Health Sci. 01(02), 207–215 (2008).
[CrossRef] [PubMed]

L. Li, R. J. Zemp, G. Lungu, G. Stoica, and L. V. Wang, “Photoacoustic imaging of lacZ gene expression in vivo,” J. Biomed. Opt. 12(2), 020504 (2007).
[CrossRef] [PubMed]

Li, M. L.

J. T. Oh, M. L. Li, H. F. Zhang, K. Maslov, G. Stoica, and L. V. Wang, “Three-dimensional imaging of skin melanoma in vivo by dual-wavelength photoacoustic microscopy,” J. Biomed. Opt. 11(3), 034032 (2006).
[CrossRef] [PubMed]

Lisle, A. E.

Lu, H.

Lungu, G.

L. Li, R. J. Zemp, G. Lungu, G. Stoica, and L. V. Wang, “Photoacoustic imaging of lacZ gene expression in vivo,” J. Biomed. Opt. 12(2), 020504 (2007).
[CrossRef] [PubMed]

Maslov, K.

L. Li, H. F. Zhang, R. J. Zemp, K. Maslov, and L. Wang, “Simultaneous imaging of a lacZ-marked tumor and microvasculature morphology in vivo by dual-wavelength photoacoustic microscopy,” J. Innov. Opt. Health Sci. 01(02), 207–215 (2008).
[CrossRef] [PubMed]

H. F. Zhang, K. Maslov, G. Stoica, and L. V. Wang, “Functional photoacoustic microscopy for high-resolution and noninvasive in vivo imaging,” Nat. Biotechnol. 24(7), 848–851 (2006).
[CrossRef] [PubMed]

J. T. Oh, M. L. Li, H. F. Zhang, K. Maslov, G. Stoica, and L. V. Wang, “Three-dimensional imaging of skin melanoma in vivo by dual-wavelength photoacoustic microscopy,” J. Biomed. Opt. 11(3), 034032 (2006).
[CrossRef] [PubMed]

Mathewson, K.

Michelich, C. R.

A. M. Ponce, B. L. Viglianti, D. Yu, P. S. Yarmolenko, C. R. Michelich, J. Woo, M. B. Bally, and M. W. Dewhirst, “Magnetic resonance imaging of temperature-sensitive liposome release: drug dose painting and antitumor effects,” J. Natl. Cancer Inst. 99(1), 53–63 (2007).
[CrossRef] [PubMed]

Misteli, T.

T. Misteli and D. L. Spector, “Applications of the green fluorescent protein in cell biology and biotechnology,” Nat. Biotechnol. 15(10), 961–964 (1997).
[CrossRef] [PubMed]

Nocken, F.

H. Alfke, H. Stöppler, F. Nocken, J. T. Heverhagen, B. Kleb, F. Czubayko, and K. J. Klose, “In vitro MR imaging of regulated gene expression,” Radiology 228(2), 488–492 (2003).
[CrossRef] [PubMed]

Oetting, W. S.

W. S. Oetting, “The tyrosinase gene and oculocutaneous albinism type 1 (OCA1): A model for understanding the molecular biology of melanin formation,” Pigment Cell Res. 13(5), 320–325 (2000).
[CrossRef] [PubMed]

Oh, J. T.

J. T. Oh, M. L. Li, H. F. Zhang, K. Maslov, G. Stoica, and L. V. Wang, “Three-dimensional imaging of skin melanoma in vivo by dual-wavelength photoacoustic microscopy,” J. Biomed. Opt. 11(3), 034032 (2006).
[CrossRef] [PubMed]

Ponce, A. M.

A. M. Ponce, B. L. Viglianti, D. Yu, P. S. Yarmolenko, C. R. Michelich, J. Woo, M. B. Bally, and M. W. Dewhirst, “Magnetic resonance imaging of temperature-sensitive liposome release: drug dose painting and antitumor effects,” J. Natl. Cancer Inst. 99(1), 53–63 (2007).
[CrossRef] [PubMed]

Ranasinghesagara, J. C.

J. C. Ranasinghesagara and R. J. Zemp, “Combined photoacoustic and oblique-incidence diffuse reflectance system for quantitative photoacoustic imaging in turbid media,” J. Biomed. Opt. 15(4), 046016 (2010).
[CrossRef] [PubMed]

T. Harrison, J. C. Ranasinghesagara, H. Lu, K. Mathewson, A. Walsh, and R. J. Zemp, “Combined photoacoustic and ultrasound biomicroscopy,” Opt. Express 17(24), 22041–22046 (2009).
[CrossRef] [PubMed]

Shashkov, E. V.

E. I. Galanzha, E. V. Shashkov, P. M. Spring, J. Y. Suen, and V. P. Zharov, “In vivo, noninvasive, label-free detection and eradication of circulating metastatic melanoma cells using two-color photoacoustic flow cytometry with a diode laser,” Cancer Res. 69(20), 7926–7934 (2009).
[CrossRef] [PubMed]

Simonova, M.

R. Weissleder, M. Simonova, A. Bogdanova, S. Bredow, W. S. Enochs, and A. Bogdanov., “MR imaging and scintigraphy of gene expression through melanin induction,” Radiology 204(2), 425–429 (1997).
[PubMed]

Spector, D. L.

T. Misteli and D. L. Spector, “Applications of the green fluorescent protein in cell biology and biotechnology,” Nat. Biotechnol. 15(10), 961–964 (1997).
[CrossRef] [PubMed]

Spring, P. M.

E. I. Galanzha, E. V. Shashkov, P. M. Spring, J. Y. Suen, and V. P. Zharov, “In vivo, noninvasive, label-free detection and eradication of circulating metastatic melanoma cells using two-color photoacoustic flow cytometry with a diode laser,” Cancer Res. 69(20), 7926–7934 (2009).
[CrossRef] [PubMed]

Stoica, G.

L. Li, R. J. Zemp, G. Lungu, G. Stoica, and L. V. Wang, “Photoacoustic imaging of lacZ gene expression in vivo,” J. Biomed. Opt. 12(2), 020504 (2007).
[CrossRef] [PubMed]

H. F. Zhang, K. Maslov, G. Stoica, and L. V. Wang, “Functional photoacoustic microscopy for high-resolution and noninvasive in vivo imaging,” Nat. Biotechnol. 24(7), 848–851 (2006).
[CrossRef] [PubMed]

J. T. Oh, M. L. Li, H. F. Zhang, K. Maslov, G. Stoica, and L. V. Wang, “Three-dimensional imaging of skin melanoma in vivo by dual-wavelength photoacoustic microscopy,” J. Biomed. Opt. 11(3), 034032 (2006).
[CrossRef] [PubMed]

Stöppler, H.

H. Alfke, H. Stöppler, F. Nocken, J. T. Heverhagen, B. Kleb, F. Czubayko, and K. J. Klose, “In vitro MR imaging of regulated gene expression,” Radiology 228(2), 488–492 (2003).
[CrossRef] [PubMed]

Suen, J. Y.

E. I. Galanzha, E. V. Shashkov, P. M. Spring, J. Y. Suen, and V. P. Zharov, “In vivo, noninvasive, label-free detection and eradication of circulating metastatic melanoma cells using two-color photoacoustic flow cytometry with a diode laser,” Cancer Res. 69(20), 7926–7934 (2009).
[CrossRef] [PubMed]

Szalay, A. A.

L. F. Greer and A. A. Szalay, “Imaging of light emission from the expression of luciferases in living cells and organisms: a review,” Luminescence 17(1), 43–74 (2002).
[CrossRef] [PubMed]

Tsolakidis, A.

G. Zonios, A. Dimou, I. Bassukas, D. Galaris, A. Tsolakidis, and E. Kaxiras, “Melanin absorption spectroscopy: new method for noninvasive skin investigation and melanoma detection,” J. Biomed. Opt. 13(1), 014017 (2008).
[CrossRef] [PubMed]

Viator, J. A.

Viglianti, B. L.

A. M. Ponce, B. L. Viglianti, D. Yu, P. S. Yarmolenko, C. R. Michelich, J. Woo, M. B. Bally, and M. W. Dewhirst, “Magnetic resonance imaging of temperature-sensitive liposome release: drug dose painting and antitumor effects,” J. Natl. Cancer Inst. 99(1), 53–63 (2007).
[CrossRef] [PubMed]

Walsh, A.

Wang, L.

L. Li, H. F. Zhang, R. J. Zemp, K. Maslov, and L. Wang, “Simultaneous imaging of a lacZ-marked tumor and microvasculature morphology in vivo by dual-wavelength photoacoustic microscopy,” J. Innov. Opt. Health Sci. 01(02), 207–215 (2008).
[CrossRef] [PubMed]

Wang, L. V.

C. Li and L. V. Wang, “Photoacoustic tomography and sensing in biomedicine,” Phys. Med. Biol. 54(19), R59–R97 (2009).
[CrossRef] [PubMed]

L. Li, R. J. Zemp, G. Lungu, G. Stoica, and L. V. Wang, “Photoacoustic imaging of lacZ gene expression in vivo,” J. Biomed. Opt. 12(2), 020504 (2007).
[CrossRef] [PubMed]

H. F. Zhang, K. Maslov, G. Stoica, and L. V. Wang, “Functional photoacoustic microscopy for high-resolution and noninvasive in vivo imaging,” Nat. Biotechnol. 24(7), 848–851 (2006).
[CrossRef] [PubMed]

J. T. Oh, M. L. Li, H. F. Zhang, K. Maslov, G. Stoica, and L. V. Wang, “Three-dimensional imaging of skin melanoma in vivo by dual-wavelength photoacoustic microscopy,” J. Biomed. Opt. 11(3), 034032 (2006).
[CrossRef] [PubMed]

Weight, R. M.

Weissleder, R.

R. Weissleder, M. Simonova, A. Bogdanova, S. Bredow, W. S. Enochs, and A. Bogdanov., “MR imaging and scintigraphy of gene expression through melanin induction,” Radiology 204(2), 425–429 (1997).
[PubMed]

Woo, J.

A. M. Ponce, B. L. Viglianti, D. Yu, P. S. Yarmolenko, C. R. Michelich, J. Woo, M. B. Bally, and M. W. Dewhirst, “Magnetic resonance imaging of temperature-sensitive liposome release: drug dose painting and antitumor effects,” J. Natl. Cancer Inst. 99(1), 53–63 (2007).
[CrossRef] [PubMed]

Yarmolenko, P. S.

A. M. Ponce, B. L. Viglianti, D. Yu, P. S. Yarmolenko, C. R. Michelich, J. Woo, M. B. Bally, and M. W. Dewhirst, “Magnetic resonance imaging of temperature-sensitive liposome release: drug dose painting and antitumor effects,” J. Natl. Cancer Inst. 99(1), 53–63 (2007).
[CrossRef] [PubMed]

Yu, D.

A. M. Ponce, B. L. Viglianti, D. Yu, P. S. Yarmolenko, C. R. Michelich, J. Woo, M. B. Bally, and M. W. Dewhirst, “Magnetic resonance imaging of temperature-sensitive liposome release: drug dose painting and antitumor effects,” J. Natl. Cancer Inst. 99(1), 53–63 (2007).
[CrossRef] [PubMed]

Zemp, R. J.

J. C. Ranasinghesagara and R. J. Zemp, “Combined photoacoustic and oblique-incidence diffuse reflectance system for quantitative photoacoustic imaging in turbid media,” J. Biomed. Opt. 15(4), 046016 (2010).
[CrossRef] [PubMed]

T. Harrison, J. C. Ranasinghesagara, H. Lu, K. Mathewson, A. Walsh, and R. J. Zemp, “Combined photoacoustic and ultrasound biomicroscopy,” Opt. Express 17(24), 22041–22046 (2009).
[CrossRef] [PubMed]

L. Li, H. F. Zhang, R. J. Zemp, K. Maslov, and L. Wang, “Simultaneous imaging of a lacZ-marked tumor and microvasculature morphology in vivo by dual-wavelength photoacoustic microscopy,” J. Innov. Opt. Health Sci. 01(02), 207–215 (2008).
[CrossRef] [PubMed]

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Figures (5)

Fig. 1
Fig. 1

Tet-On® inducible system for TYR expression. The pTRE-Tight vector contains a promoter composed of the minimal cytomegalovirus (CMV) promoter as well as a modified tetracycline responsive element (TREMOD). The tetracycline-responsive transactivator (rTetR), containing three minimal transcription activation domains from the Herpes Simplex Virus VP16 protein, will only bind to the TREMOD sequence and induce expression of TYR in the presence of Doxycycline (Dox).

Fig. 5
Fig. 5

Combined ultrasound (grayscale) and photoacoustic (orange colormap) B-scans of tubes containing our test samples. White circles are manually drawn to further demarcate tube locations. From left to right the tubes are −/−, +/−, -/+, +/+, and blood (−/− = -Dox/MCF-7-TYR). Only the cells in the +/+ tube expressed melanin. (a) B-scan image at a wavelength of 576 nm. A threshold of 50% was used. Blood is seen best at this wavelength. (b) B-scan image at a wavelength of 650 nm in the same turbid medium as (a). A threshold of 50% maximum signal was used. Compared to the other samples, the melanin-expressing cells displayed the highest photoacoustic signal at 650 nm.

Fig. 2
Fig. 2

Microscopic analysis of TYR expression in MCF-7 cells. MCF-7-TYR (a + b) and MCF-7 + TYR cells (c + d) were incubated in growth medium with (b + d) or without (a + c) 1 μg/mL Dox. MCF-7 + TYR cells incubated with DOX appear dark brown due to melanin production. Scale bars represent 100 μm lengths.

Fig. 3
Fig. 3

(a) MR T1-map with intensity values given in milliseconds. Each of the four vials has a different combination of positive or negative TYR expression (MCF-7 ± TYR) and positive or negative Dox presence (+/−Dox). (b) T1-weighted image with a flip angle of 90 degrees and a TR of 250 ms.

Fig. 4
Fig. 4

Photoacoustic signal intensities of the five test tubes. The -\-, -\ + , and + \- test tubes have negligible signal compared to the + \ + and blood (−/− = -Dox/MCF-7-TYR).

Tables (1)

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Table 1 Number of Cells for unity SNR (V/V)

Equations (1)

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S = S 0 sin ( θ ) 1 exp ( T R T 1 ) 1 cos ( θ ) exp ( T R T 1 ) ,

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