Abstract

We present terahertz images of 10 μm thick histopathologic sections obtained in reflection geometry with a time-domain spectrometer, and demonstrate improved contrast for sections measured in paraffin with water. Automated segmentation is applied to the complex refractive index data to generate clustered terahertz images distinguishing cancer from healthy tissues. The degree of classification of pixels is then evaluated using registered visible microscope images. Principal component analysis and propagation simulations are employed to investigate the origin and the gain of image contrast.

©2010 Optical Society of America

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References

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  1. R. M. Woodward, B. E. Cole, V. P. Wallace, R. J. Pye, D. D. Arnone, E. H. Linfield, and M. Pepper, “Terahertz pulse imaging in reflection geometry of human skin cancer and skin tissue,” Phys. Med. Biol. 47(21), 3853–3863 (2002).
    [Crossref] [PubMed]
  2. R. M. Woodward, V. P. Wallace, R. J. Pye, B. E. Cole, D. D. Arnone, E. H. Linfield, and M. Pepper, “Terahertz pulse imaging of ex vivo basal cell carcinoma,” J. Invest. Dermatol. 120(1), 72–78 (2003).
    [Crossref] [PubMed]
  3. V. P. Wallace, A. J. Fitzgerald, S. Shankar, N. Flanagan, R. Pye, J. Cluff, and D. D. Arnone, “Terahertz pulsed imaging of basal cell carcinoma ex vivo and in vivo,” Br. J. Dermatol. 151(2), 424–432 (2004).
    [Crossref] [PubMed]
  4. A. J. Fitzgerald, V. P. Wallace, M. Jimenez-Linan, L. Bobrow, R. J. Pye, A. D. Purushotham, and D. D. Arnone, “Terahertz pulsed imaging of human breast tumors,” Radiology 239(2), 533–540 (2006).
    [Crossref] [PubMed]
  5. T. Löffler, T. Bauer, K. J. Siebert, H. G. Roskos, A. Fitzgerald, and S. Czasch, “Terahertz dark-field imaging of biomedical tissue,” Opt. Express 9(12), 616–621 (2001).
    [Crossref] [PubMed]
  6. P. Knobloch, C. Schildknecht, T. Kleine-Ostmann, M. Koch, S. Hoffmann, M. Hofmann, E. Rehberg, M. Sperling, K. Donhuijsen, G. Hein, and K. Pierz, “Medical THz imaging: an investigation of histo-pathological samples,” Phys. Med. Biol. 47(21), 3875–3884 (2002).
    [Crossref] [PubMed]
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    [Crossref]
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    [Crossref] [PubMed]
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    [Crossref]
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    [Crossref]
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    [Crossref] [PubMed]
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    [Crossref]
  14. M.-A. Brun, F. Formanek, A. Yasuda, M. Sekine, N. Ando, and Y. Eishii, “Terahertz imaging applied to cancer diagnosis,” Phys. Med. Biol. 55(16), 4615–4623 (2010).
    [Crossref] [PubMed]
  15. P. U. Jepsen, U. Møller, and H. Merbold, “Investigation of aqueous alcohol and sugar solutions with reflection terahertz time-domain spectroscopy,” Opt. Express 15(22), 14717–14737 (2007).
    [Crossref] [PubMed]
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  18. J. R. Fletcher, G. P. Swift, D. C. Dai, J. M. Chamberlain, and P. C. Upadhya, “Pulsed terahertz signal reconstruction,” J. Appl. Phys. 102(11), 113105 (2007).
    [Crossref]

2010 (1)

M.-A. Brun, F. Formanek, A. Yasuda, M. Sekine, N. Ando, and Y. Eishii, “Terahertz imaging applied to cancer diagnosis,” Phys. Med. Biol. 55(16), 4615–4623 (2010).
[Crossref] [PubMed]

2009 (1)

H. Hoshina, A. Hayashi, N. Miyoshi, F. Miyamaru, and C. Otani, “Terahertz pulsed imaging of frozen biological tissues,” Appl. Phys. Lett. 94(12), 123901 (2009).
[Crossref]

2008 (1)

G. M. Png, J. W. Choi, B. W.-H. Ng, S. P. Mickan, D. Abbott, and X.-C. Zhang, “The impact of hydration changes in fresh bio-tissue on THz spectroscopic measurements,” Phys. Med. Biol. 53(13), 3501–3517 (2008).
[Crossref] [PubMed]

2007 (3)

S. Nakajima, H. Hoshina, M. Yamashita, C. Otani, and N. Miyoshi, “Terahertz imaging diagnostics of cancer tissues with a chemometrics technique,” Appl. Phys. Lett. 90(4), 041102 (2007).
[Crossref]

J. R. Fletcher, G. P. Swift, D. C. Dai, J. M. Chamberlain, and P. C. Upadhya, “Pulsed terahertz signal reconstruction,” J. Appl. Phys. 102(11), 113105 (2007).
[Crossref]

P. U. Jepsen, U. Møller, and H. Merbold, “Investigation of aqueous alcohol and sugar solutions with reflection terahertz time-domain spectroscopy,” Opt. Express 15(22), 14717–14737 (2007).
[Crossref] [PubMed]

2006 (2)

A. J. Fitzgerald, V. P. Wallace, M. Jimenez-Linan, L. Bobrow, R. J. Pye, A. D. Purushotham, and D. D. Arnone, “Terahertz pulsed imaging of human breast tumors,” Radiology 239(2), 533–540 (2006).
[Crossref] [PubMed]

S. M. Kim, F. Hatami, J. S. Harris, A. W. Kurian, J. Ford, D. King, G. Scalari, M. Giovannini, N. Hoyler, J. Faist, and G. Harris, “Biomedical terahertz imaging with a quantum cascade laser,” Appl. Phys. Lett. 88(15), 153903 (2006).
[Crossref]

2005 (1)

J. Nishizawa, T. Sasaki, T. Ken Suto, T. Yamada, T. Tanabe, T. Tanno, T. Sawai, and Y. Miura, “THz imaging of nucleobases and cancerous tissue using a GaP THz-wave generator,” Opt. Commun. 244(1-6), 469–474 (2005).
[Crossref]

2004 (2)

E. Berry, J. W. Handley, A. J. Fitzgerald, W. J. Merchant, R. D. Boyle, N. N. Zinov’ev, R. E. Miles, J. M. Chamberlain, and M. A. Smith, “Multispectral classification techniques for terahertz pulsed imaging: an example in histopathology,” Med. Eng. Phys. 26(5), 423–430 (2004).
[Crossref] [PubMed]

V. P. Wallace, A. J. Fitzgerald, S. Shankar, N. Flanagan, R. Pye, J. Cluff, and D. D. Arnone, “Terahertz pulsed imaging of basal cell carcinoma ex vivo and in vivo,” Br. J. Dermatol. 151(2), 424–432 (2004).
[Crossref] [PubMed]

2003 (1)

R. M. Woodward, V. P. Wallace, R. J. Pye, B. E. Cole, D. D. Arnone, E. H. Linfield, and M. Pepper, “Terahertz pulse imaging of ex vivo basal cell carcinoma,” J. Invest. Dermatol. 120(1), 72–78 (2003).
[Crossref] [PubMed]

2002 (3)

T. Löffler, K. Siebert, S. Czasch, T. Bauer, and H. G. Roskos, “Visualization and classification in biomedical terahertz pulsed imaging,” Phys. Med. Biol. 47(21), 3847–3852 (2002).
[Crossref] [PubMed]

P. Knobloch, C. Schildknecht, T. Kleine-Ostmann, M. Koch, S. Hoffmann, M. Hofmann, E. Rehberg, M. Sperling, K. Donhuijsen, G. Hein, and K. Pierz, “Medical THz imaging: an investigation of histo-pathological samples,” Phys. Med. Biol. 47(21), 3875–3884 (2002).
[Crossref] [PubMed]

R. M. Woodward, B. E. Cole, V. P. Wallace, R. J. Pye, D. D. Arnone, E. H. Linfield, and M. Pepper, “Terahertz pulse imaging in reflection geometry of human skin cancer and skin tissue,” Phys. Med. Biol. 47(21), 3853–3863 (2002).
[Crossref] [PubMed]

2001 (1)

Abbott, D.

G. M. Png, J. W. Choi, B. W.-H. Ng, S. P. Mickan, D. Abbott, and X.-C. Zhang, “The impact of hydration changes in fresh bio-tissue on THz spectroscopic measurements,” Phys. Med. Biol. 53(13), 3501–3517 (2008).
[Crossref] [PubMed]

Ando, N.

M.-A. Brun, F. Formanek, A. Yasuda, M. Sekine, N. Ando, and Y. Eishii, “Terahertz imaging applied to cancer diagnosis,” Phys. Med. Biol. 55(16), 4615–4623 (2010).
[Crossref] [PubMed]

Arnone, D. D.

A. J. Fitzgerald, V. P. Wallace, M. Jimenez-Linan, L. Bobrow, R. J. Pye, A. D. Purushotham, and D. D. Arnone, “Terahertz pulsed imaging of human breast tumors,” Radiology 239(2), 533–540 (2006).
[Crossref] [PubMed]

V. P. Wallace, A. J. Fitzgerald, S. Shankar, N. Flanagan, R. Pye, J. Cluff, and D. D. Arnone, “Terahertz pulsed imaging of basal cell carcinoma ex vivo and in vivo,” Br. J. Dermatol. 151(2), 424–432 (2004).
[Crossref] [PubMed]

R. M. Woodward, V. P. Wallace, R. J. Pye, B. E. Cole, D. D. Arnone, E. H. Linfield, and M. Pepper, “Terahertz pulse imaging of ex vivo basal cell carcinoma,” J. Invest. Dermatol. 120(1), 72–78 (2003).
[Crossref] [PubMed]

R. M. Woodward, B. E. Cole, V. P. Wallace, R. J. Pye, D. D. Arnone, E. H. Linfield, and M. Pepper, “Terahertz pulse imaging in reflection geometry of human skin cancer and skin tissue,” Phys. Med. Biol. 47(21), 3853–3863 (2002).
[Crossref] [PubMed]

Bauer, T.

T. Löffler, K. Siebert, S. Czasch, T. Bauer, and H. G. Roskos, “Visualization and classification in biomedical terahertz pulsed imaging,” Phys. Med. Biol. 47(21), 3847–3852 (2002).
[Crossref] [PubMed]

T. Löffler, T. Bauer, K. J. Siebert, H. G. Roskos, A. Fitzgerald, and S. Czasch, “Terahertz dark-field imaging of biomedical tissue,” Opt. Express 9(12), 616–621 (2001).
[Crossref] [PubMed]

Berry, E.

E. Berry, J. W. Handley, A. J. Fitzgerald, W. J. Merchant, R. D. Boyle, N. N. Zinov’ev, R. E. Miles, J. M. Chamberlain, and M. A. Smith, “Multispectral classification techniques for terahertz pulsed imaging: an example in histopathology,” Med. Eng. Phys. 26(5), 423–430 (2004).
[Crossref] [PubMed]

Bobrow, L.

A. J. Fitzgerald, V. P. Wallace, M. Jimenez-Linan, L. Bobrow, R. J. Pye, A. D. Purushotham, and D. D. Arnone, “Terahertz pulsed imaging of human breast tumors,” Radiology 239(2), 533–540 (2006).
[Crossref] [PubMed]

Boyle, R. D.

E. Berry, J. W. Handley, A. J. Fitzgerald, W. J. Merchant, R. D. Boyle, N. N. Zinov’ev, R. E. Miles, J. M. Chamberlain, and M. A. Smith, “Multispectral classification techniques for terahertz pulsed imaging: an example in histopathology,” Med. Eng. Phys. 26(5), 423–430 (2004).
[Crossref] [PubMed]

Brun, M.-A.

M.-A. Brun, F. Formanek, A. Yasuda, M. Sekine, N. Ando, and Y. Eishii, “Terahertz imaging applied to cancer diagnosis,” Phys. Med. Biol. 55(16), 4615–4623 (2010).
[Crossref] [PubMed]

Chamberlain, J. M.

J. R. Fletcher, G. P. Swift, D. C. Dai, J. M. Chamberlain, and P. C. Upadhya, “Pulsed terahertz signal reconstruction,” J. Appl. Phys. 102(11), 113105 (2007).
[Crossref]

E. Berry, J. W. Handley, A. J. Fitzgerald, W. J. Merchant, R. D. Boyle, N. N. Zinov’ev, R. E. Miles, J. M. Chamberlain, and M. A. Smith, “Multispectral classification techniques for terahertz pulsed imaging: an example in histopathology,” Med. Eng. Phys. 26(5), 423–430 (2004).
[Crossref] [PubMed]

Choi, J. W.

G. M. Png, J. W. Choi, B. W.-H. Ng, S. P. Mickan, D. Abbott, and X.-C. Zhang, “The impact of hydration changes in fresh bio-tissue on THz spectroscopic measurements,” Phys. Med. Biol. 53(13), 3501–3517 (2008).
[Crossref] [PubMed]

Cluff, J.

V. P. Wallace, A. J. Fitzgerald, S. Shankar, N. Flanagan, R. Pye, J. Cluff, and D. D. Arnone, “Terahertz pulsed imaging of basal cell carcinoma ex vivo and in vivo,” Br. J. Dermatol. 151(2), 424–432 (2004).
[Crossref] [PubMed]

Cole, B. E.

R. M. Woodward, V. P. Wallace, R. J. Pye, B. E. Cole, D. D. Arnone, E. H. Linfield, and M. Pepper, “Terahertz pulse imaging of ex vivo basal cell carcinoma,” J. Invest. Dermatol. 120(1), 72–78 (2003).
[Crossref] [PubMed]

R. M. Woodward, B. E. Cole, V. P. Wallace, R. J. Pye, D. D. Arnone, E. H. Linfield, and M. Pepper, “Terahertz pulse imaging in reflection geometry of human skin cancer and skin tissue,” Phys. Med. Biol. 47(21), 3853–3863 (2002).
[Crossref] [PubMed]

Czasch, S.

T. Löffler, K. Siebert, S. Czasch, T. Bauer, and H. G. Roskos, “Visualization and classification in biomedical terahertz pulsed imaging,” Phys. Med. Biol. 47(21), 3847–3852 (2002).
[Crossref] [PubMed]

T. Löffler, T. Bauer, K. J. Siebert, H. G. Roskos, A. Fitzgerald, and S. Czasch, “Terahertz dark-field imaging of biomedical tissue,” Opt. Express 9(12), 616–621 (2001).
[Crossref] [PubMed]

Dai, D. C.

J. R. Fletcher, G. P. Swift, D. C. Dai, J. M. Chamberlain, and P. C. Upadhya, “Pulsed terahertz signal reconstruction,” J. Appl. Phys. 102(11), 113105 (2007).
[Crossref]

Donhuijsen, K.

P. Knobloch, C. Schildknecht, T. Kleine-Ostmann, M. Koch, S. Hoffmann, M. Hofmann, E. Rehberg, M. Sperling, K. Donhuijsen, G. Hein, and K. Pierz, “Medical THz imaging: an investigation of histo-pathological samples,” Phys. Med. Biol. 47(21), 3875–3884 (2002).
[Crossref] [PubMed]

Eishii, Y.

M.-A. Brun, F. Formanek, A. Yasuda, M. Sekine, N. Ando, and Y. Eishii, “Terahertz imaging applied to cancer diagnosis,” Phys. Med. Biol. 55(16), 4615–4623 (2010).
[Crossref] [PubMed]

Faist, J.

S. M. Kim, F. Hatami, J. S. Harris, A. W. Kurian, J. Ford, D. King, G. Scalari, M. Giovannini, N. Hoyler, J. Faist, and G. Harris, “Biomedical terahertz imaging with a quantum cascade laser,” Appl. Phys. Lett. 88(15), 153903 (2006).
[Crossref]

Fitzgerald, A.

Fitzgerald, A. J.

A. J. Fitzgerald, V. P. Wallace, M. Jimenez-Linan, L. Bobrow, R. J. Pye, A. D. Purushotham, and D. D. Arnone, “Terahertz pulsed imaging of human breast tumors,” Radiology 239(2), 533–540 (2006).
[Crossref] [PubMed]

V. P. Wallace, A. J. Fitzgerald, S. Shankar, N. Flanagan, R. Pye, J. Cluff, and D. D. Arnone, “Terahertz pulsed imaging of basal cell carcinoma ex vivo and in vivo,” Br. J. Dermatol. 151(2), 424–432 (2004).
[Crossref] [PubMed]

E. Berry, J. W. Handley, A. J. Fitzgerald, W. J. Merchant, R. D. Boyle, N. N. Zinov’ev, R. E. Miles, J. M. Chamberlain, and M. A. Smith, “Multispectral classification techniques for terahertz pulsed imaging: an example in histopathology,” Med. Eng. Phys. 26(5), 423–430 (2004).
[Crossref] [PubMed]

Flanagan, N.

V. P. Wallace, A. J. Fitzgerald, S. Shankar, N. Flanagan, R. Pye, J. Cluff, and D. D. Arnone, “Terahertz pulsed imaging of basal cell carcinoma ex vivo and in vivo,” Br. J. Dermatol. 151(2), 424–432 (2004).
[Crossref] [PubMed]

Fletcher, J. R.

J. R. Fletcher, G. P. Swift, D. C. Dai, J. M. Chamberlain, and P. C. Upadhya, “Pulsed terahertz signal reconstruction,” J. Appl. Phys. 102(11), 113105 (2007).
[Crossref]

Ford, J.

S. M. Kim, F. Hatami, J. S. Harris, A. W. Kurian, J. Ford, D. King, G. Scalari, M. Giovannini, N. Hoyler, J. Faist, and G. Harris, “Biomedical terahertz imaging with a quantum cascade laser,” Appl. Phys. Lett. 88(15), 153903 (2006).
[Crossref]

Formanek, F.

M.-A. Brun, F. Formanek, A. Yasuda, M. Sekine, N. Ando, and Y. Eishii, “Terahertz imaging applied to cancer diagnosis,” Phys. Med. Biol. 55(16), 4615–4623 (2010).
[Crossref] [PubMed]

Giovannini, M.

S. M. Kim, F. Hatami, J. S. Harris, A. W. Kurian, J. Ford, D. King, G. Scalari, M. Giovannini, N. Hoyler, J. Faist, and G. Harris, “Biomedical terahertz imaging with a quantum cascade laser,” Appl. Phys. Lett. 88(15), 153903 (2006).
[Crossref]

Handley, J. W.

E. Berry, J. W. Handley, A. J. Fitzgerald, W. J. Merchant, R. D. Boyle, N. N. Zinov’ev, R. E. Miles, J. M. Chamberlain, and M. A. Smith, “Multispectral classification techniques for terahertz pulsed imaging: an example in histopathology,” Med. Eng. Phys. 26(5), 423–430 (2004).
[Crossref] [PubMed]

Harris, G.

S. M. Kim, F. Hatami, J. S. Harris, A. W. Kurian, J. Ford, D. King, G. Scalari, M. Giovannini, N. Hoyler, J. Faist, and G. Harris, “Biomedical terahertz imaging with a quantum cascade laser,” Appl. Phys. Lett. 88(15), 153903 (2006).
[Crossref]

Harris, J. S.

S. M. Kim, F. Hatami, J. S. Harris, A. W. Kurian, J. Ford, D. King, G. Scalari, M. Giovannini, N. Hoyler, J. Faist, and G. Harris, “Biomedical terahertz imaging with a quantum cascade laser,” Appl. Phys. Lett. 88(15), 153903 (2006).
[Crossref]

Hatami, F.

S. M. Kim, F. Hatami, J. S. Harris, A. W. Kurian, J. Ford, D. King, G. Scalari, M. Giovannini, N. Hoyler, J. Faist, and G. Harris, “Biomedical terahertz imaging with a quantum cascade laser,” Appl. Phys. Lett. 88(15), 153903 (2006).
[Crossref]

Hayashi, A.

H. Hoshina, A. Hayashi, N. Miyoshi, F. Miyamaru, and C. Otani, “Terahertz pulsed imaging of frozen biological tissues,” Appl. Phys. Lett. 94(12), 123901 (2009).
[Crossref]

Hein, G.

P. Knobloch, C. Schildknecht, T. Kleine-Ostmann, M. Koch, S. Hoffmann, M. Hofmann, E. Rehberg, M. Sperling, K. Donhuijsen, G. Hein, and K. Pierz, “Medical THz imaging: an investigation of histo-pathological samples,” Phys. Med. Biol. 47(21), 3875–3884 (2002).
[Crossref] [PubMed]

Hoffmann, S.

P. Knobloch, C. Schildknecht, T. Kleine-Ostmann, M. Koch, S. Hoffmann, M. Hofmann, E. Rehberg, M. Sperling, K. Donhuijsen, G. Hein, and K. Pierz, “Medical THz imaging: an investigation of histo-pathological samples,” Phys. Med. Biol. 47(21), 3875–3884 (2002).
[Crossref] [PubMed]

Hofmann, M.

P. Knobloch, C. Schildknecht, T. Kleine-Ostmann, M. Koch, S. Hoffmann, M. Hofmann, E. Rehberg, M. Sperling, K. Donhuijsen, G. Hein, and K. Pierz, “Medical THz imaging: an investigation of histo-pathological samples,” Phys. Med. Biol. 47(21), 3875–3884 (2002).
[Crossref] [PubMed]

Hoshina, H.

H. Hoshina, A. Hayashi, N. Miyoshi, F. Miyamaru, and C. Otani, “Terahertz pulsed imaging of frozen biological tissues,” Appl. Phys. Lett. 94(12), 123901 (2009).
[Crossref]

S. Nakajima, H. Hoshina, M. Yamashita, C. Otani, and N. Miyoshi, “Terahertz imaging diagnostics of cancer tissues with a chemometrics technique,” Appl. Phys. Lett. 90(4), 041102 (2007).
[Crossref]

Hoyler, N.

S. M. Kim, F. Hatami, J. S. Harris, A. W. Kurian, J. Ford, D. King, G. Scalari, M. Giovannini, N. Hoyler, J. Faist, and G. Harris, “Biomedical terahertz imaging with a quantum cascade laser,” Appl. Phys. Lett. 88(15), 153903 (2006).
[Crossref]

Jepsen, P. U.

Jimenez-Linan, M.

A. J. Fitzgerald, V. P. Wallace, M. Jimenez-Linan, L. Bobrow, R. J. Pye, A. D. Purushotham, and D. D. Arnone, “Terahertz pulsed imaging of human breast tumors,” Radiology 239(2), 533–540 (2006).
[Crossref] [PubMed]

Ken Suto, T.

J. Nishizawa, T. Sasaki, T. Ken Suto, T. Yamada, T. Tanabe, T. Tanno, T. Sawai, and Y. Miura, “THz imaging of nucleobases and cancerous tissue using a GaP THz-wave generator,” Opt. Commun. 244(1-6), 469–474 (2005).
[Crossref]

Kim, S. M.

S. M. Kim, F. Hatami, J. S. Harris, A. W. Kurian, J. Ford, D. King, G. Scalari, M. Giovannini, N. Hoyler, J. Faist, and G. Harris, “Biomedical terahertz imaging with a quantum cascade laser,” Appl. Phys. Lett. 88(15), 153903 (2006).
[Crossref]

King, D.

S. M. Kim, F. Hatami, J. S. Harris, A. W. Kurian, J. Ford, D. King, G. Scalari, M. Giovannini, N. Hoyler, J. Faist, and G. Harris, “Biomedical terahertz imaging with a quantum cascade laser,” Appl. Phys. Lett. 88(15), 153903 (2006).
[Crossref]

Kleine-Ostmann, T.

P. Knobloch, C. Schildknecht, T. Kleine-Ostmann, M. Koch, S. Hoffmann, M. Hofmann, E. Rehberg, M. Sperling, K. Donhuijsen, G. Hein, and K. Pierz, “Medical THz imaging: an investigation of histo-pathological samples,” Phys. Med. Biol. 47(21), 3875–3884 (2002).
[Crossref] [PubMed]

Knobloch, P.

P. Knobloch, C. Schildknecht, T. Kleine-Ostmann, M. Koch, S. Hoffmann, M. Hofmann, E. Rehberg, M. Sperling, K. Donhuijsen, G. Hein, and K. Pierz, “Medical THz imaging: an investigation of histo-pathological samples,” Phys. Med. Biol. 47(21), 3875–3884 (2002).
[Crossref] [PubMed]

Koch, M.

P. Knobloch, C. Schildknecht, T. Kleine-Ostmann, M. Koch, S. Hoffmann, M. Hofmann, E. Rehberg, M. Sperling, K. Donhuijsen, G. Hein, and K. Pierz, “Medical THz imaging: an investigation of histo-pathological samples,” Phys. Med. Biol. 47(21), 3875–3884 (2002).
[Crossref] [PubMed]

Kurian, A. W.

S. M. Kim, F. Hatami, J. S. Harris, A. W. Kurian, J. Ford, D. King, G. Scalari, M. Giovannini, N. Hoyler, J. Faist, and G. Harris, “Biomedical terahertz imaging with a quantum cascade laser,” Appl. Phys. Lett. 88(15), 153903 (2006).
[Crossref]

Linfield, E. H.

R. M. Woodward, V. P. Wallace, R. J. Pye, B. E. Cole, D. D. Arnone, E. H. Linfield, and M. Pepper, “Terahertz pulse imaging of ex vivo basal cell carcinoma,” J. Invest. Dermatol. 120(1), 72–78 (2003).
[Crossref] [PubMed]

R. M. Woodward, B. E. Cole, V. P. Wallace, R. J. Pye, D. D. Arnone, E. H. Linfield, and M. Pepper, “Terahertz pulse imaging in reflection geometry of human skin cancer and skin tissue,” Phys. Med. Biol. 47(21), 3853–3863 (2002).
[Crossref] [PubMed]

Löffler, T.

T. Löffler, K. Siebert, S. Czasch, T. Bauer, and H. G. Roskos, “Visualization and classification in biomedical terahertz pulsed imaging,” Phys. Med. Biol. 47(21), 3847–3852 (2002).
[Crossref] [PubMed]

T. Löffler, T. Bauer, K. J. Siebert, H. G. Roskos, A. Fitzgerald, and S. Czasch, “Terahertz dark-field imaging of biomedical tissue,” Opt. Express 9(12), 616–621 (2001).
[Crossref] [PubMed]

Merbold, H.

Merchant, W. J.

E. Berry, J. W. Handley, A. J. Fitzgerald, W. J. Merchant, R. D. Boyle, N. N. Zinov’ev, R. E. Miles, J. M. Chamberlain, and M. A. Smith, “Multispectral classification techniques for terahertz pulsed imaging: an example in histopathology,” Med. Eng. Phys. 26(5), 423–430 (2004).
[Crossref] [PubMed]

Mickan, S. P.

G. M. Png, J. W. Choi, B. W.-H. Ng, S. P. Mickan, D. Abbott, and X.-C. Zhang, “The impact of hydration changes in fresh bio-tissue on THz spectroscopic measurements,” Phys. Med. Biol. 53(13), 3501–3517 (2008).
[Crossref] [PubMed]

Miles, R. E.

E. Berry, J. W. Handley, A. J. Fitzgerald, W. J. Merchant, R. D. Boyle, N. N. Zinov’ev, R. E. Miles, J. M. Chamberlain, and M. A. Smith, “Multispectral classification techniques for terahertz pulsed imaging: an example in histopathology,” Med. Eng. Phys. 26(5), 423–430 (2004).
[Crossref] [PubMed]

Miura, Y.

J. Nishizawa, T. Sasaki, T. Ken Suto, T. Yamada, T. Tanabe, T. Tanno, T. Sawai, and Y. Miura, “THz imaging of nucleobases and cancerous tissue using a GaP THz-wave generator,” Opt. Commun. 244(1-6), 469–474 (2005).
[Crossref]

Miyamaru, F.

H. Hoshina, A. Hayashi, N. Miyoshi, F. Miyamaru, and C. Otani, “Terahertz pulsed imaging of frozen biological tissues,” Appl. Phys. Lett. 94(12), 123901 (2009).
[Crossref]

Miyoshi, N.

H. Hoshina, A. Hayashi, N. Miyoshi, F. Miyamaru, and C. Otani, “Terahertz pulsed imaging of frozen biological tissues,” Appl. Phys. Lett. 94(12), 123901 (2009).
[Crossref]

S. Nakajima, H. Hoshina, M. Yamashita, C. Otani, and N. Miyoshi, “Terahertz imaging diagnostics of cancer tissues with a chemometrics technique,” Appl. Phys. Lett. 90(4), 041102 (2007).
[Crossref]

Møller, U.

Nakajima, S.

S. Nakajima, H. Hoshina, M. Yamashita, C. Otani, and N. Miyoshi, “Terahertz imaging diagnostics of cancer tissues with a chemometrics technique,” Appl. Phys. Lett. 90(4), 041102 (2007).
[Crossref]

Ng, B. W.-H.

G. M. Png, J. W. Choi, B. W.-H. Ng, S. P. Mickan, D. Abbott, and X.-C. Zhang, “The impact of hydration changes in fresh bio-tissue on THz spectroscopic measurements,” Phys. Med. Biol. 53(13), 3501–3517 (2008).
[Crossref] [PubMed]

Nishizawa, J.

J. Nishizawa, T. Sasaki, T. Ken Suto, T. Yamada, T. Tanabe, T. Tanno, T. Sawai, and Y. Miura, “THz imaging of nucleobases and cancerous tissue using a GaP THz-wave generator,” Opt. Commun. 244(1-6), 469–474 (2005).
[Crossref]

Otani, C.

H. Hoshina, A. Hayashi, N. Miyoshi, F. Miyamaru, and C. Otani, “Terahertz pulsed imaging of frozen biological tissues,” Appl. Phys. Lett. 94(12), 123901 (2009).
[Crossref]

S. Nakajima, H. Hoshina, M. Yamashita, C. Otani, and N. Miyoshi, “Terahertz imaging diagnostics of cancer tissues with a chemometrics technique,” Appl. Phys. Lett. 90(4), 041102 (2007).
[Crossref]

Pepper, M.

R. M. Woodward, V. P. Wallace, R. J. Pye, B. E. Cole, D. D. Arnone, E. H. Linfield, and M. Pepper, “Terahertz pulse imaging of ex vivo basal cell carcinoma,” J. Invest. Dermatol. 120(1), 72–78 (2003).
[Crossref] [PubMed]

R. M. Woodward, B. E. Cole, V. P. Wallace, R. J. Pye, D. D. Arnone, E. H. Linfield, and M. Pepper, “Terahertz pulse imaging in reflection geometry of human skin cancer and skin tissue,” Phys. Med. Biol. 47(21), 3853–3863 (2002).
[Crossref] [PubMed]

Pierz, K.

P. Knobloch, C. Schildknecht, T. Kleine-Ostmann, M. Koch, S. Hoffmann, M. Hofmann, E. Rehberg, M. Sperling, K. Donhuijsen, G. Hein, and K. Pierz, “Medical THz imaging: an investigation of histo-pathological samples,” Phys. Med. Biol. 47(21), 3875–3884 (2002).
[Crossref] [PubMed]

Png, G. M.

G. M. Png, J. W. Choi, B. W.-H. Ng, S. P. Mickan, D. Abbott, and X.-C. Zhang, “The impact of hydration changes in fresh bio-tissue on THz spectroscopic measurements,” Phys. Med. Biol. 53(13), 3501–3517 (2008).
[Crossref] [PubMed]

Purushotham, A. D.

A. J. Fitzgerald, V. P. Wallace, M. Jimenez-Linan, L. Bobrow, R. J. Pye, A. D. Purushotham, and D. D. Arnone, “Terahertz pulsed imaging of human breast tumors,” Radiology 239(2), 533–540 (2006).
[Crossref] [PubMed]

Pye, R.

V. P. Wallace, A. J. Fitzgerald, S. Shankar, N. Flanagan, R. Pye, J. Cluff, and D. D. Arnone, “Terahertz pulsed imaging of basal cell carcinoma ex vivo and in vivo,” Br. J. Dermatol. 151(2), 424–432 (2004).
[Crossref] [PubMed]

Pye, R. J.

A. J. Fitzgerald, V. P. Wallace, M. Jimenez-Linan, L. Bobrow, R. J. Pye, A. D. Purushotham, and D. D. Arnone, “Terahertz pulsed imaging of human breast tumors,” Radiology 239(2), 533–540 (2006).
[Crossref] [PubMed]

R. M. Woodward, V. P. Wallace, R. J. Pye, B. E. Cole, D. D. Arnone, E. H. Linfield, and M. Pepper, “Terahertz pulse imaging of ex vivo basal cell carcinoma,” J. Invest. Dermatol. 120(1), 72–78 (2003).
[Crossref] [PubMed]

R. M. Woodward, B. E. Cole, V. P. Wallace, R. J. Pye, D. D. Arnone, E. H. Linfield, and M. Pepper, “Terahertz pulse imaging in reflection geometry of human skin cancer and skin tissue,” Phys. Med. Biol. 47(21), 3853–3863 (2002).
[Crossref] [PubMed]

Rehberg, E.

P. Knobloch, C. Schildknecht, T. Kleine-Ostmann, M. Koch, S. Hoffmann, M. Hofmann, E. Rehberg, M. Sperling, K. Donhuijsen, G. Hein, and K. Pierz, “Medical THz imaging: an investigation of histo-pathological samples,” Phys. Med. Biol. 47(21), 3875–3884 (2002).
[Crossref] [PubMed]

Roskos, H. G.

T. Löffler, K. Siebert, S. Czasch, T. Bauer, and H. G. Roskos, “Visualization and classification in biomedical terahertz pulsed imaging,” Phys. Med. Biol. 47(21), 3847–3852 (2002).
[Crossref] [PubMed]

T. Löffler, T. Bauer, K. J. Siebert, H. G. Roskos, A. Fitzgerald, and S. Czasch, “Terahertz dark-field imaging of biomedical tissue,” Opt. Express 9(12), 616–621 (2001).
[Crossref] [PubMed]

Sasaki, T.

J. Nishizawa, T. Sasaki, T. Ken Suto, T. Yamada, T. Tanabe, T. Tanno, T. Sawai, and Y. Miura, “THz imaging of nucleobases and cancerous tissue using a GaP THz-wave generator,” Opt. Commun. 244(1-6), 469–474 (2005).
[Crossref]

Sawai, T.

J. Nishizawa, T. Sasaki, T. Ken Suto, T. Yamada, T. Tanabe, T. Tanno, T. Sawai, and Y. Miura, “THz imaging of nucleobases and cancerous tissue using a GaP THz-wave generator,” Opt. Commun. 244(1-6), 469–474 (2005).
[Crossref]

Scalari, G.

S. M. Kim, F. Hatami, J. S. Harris, A. W. Kurian, J. Ford, D. King, G. Scalari, M. Giovannini, N. Hoyler, J. Faist, and G. Harris, “Biomedical terahertz imaging with a quantum cascade laser,” Appl. Phys. Lett. 88(15), 153903 (2006).
[Crossref]

Schildknecht, C.

P. Knobloch, C. Schildknecht, T. Kleine-Ostmann, M. Koch, S. Hoffmann, M. Hofmann, E. Rehberg, M. Sperling, K. Donhuijsen, G. Hein, and K. Pierz, “Medical THz imaging: an investigation of histo-pathological samples,” Phys. Med. Biol. 47(21), 3875–3884 (2002).
[Crossref] [PubMed]

Sekine, M.

M.-A. Brun, F. Formanek, A. Yasuda, M. Sekine, N. Ando, and Y. Eishii, “Terahertz imaging applied to cancer diagnosis,” Phys. Med. Biol. 55(16), 4615–4623 (2010).
[Crossref] [PubMed]

Shankar, S.

V. P. Wallace, A. J. Fitzgerald, S. Shankar, N. Flanagan, R. Pye, J. Cluff, and D. D. Arnone, “Terahertz pulsed imaging of basal cell carcinoma ex vivo and in vivo,” Br. J. Dermatol. 151(2), 424–432 (2004).
[Crossref] [PubMed]

Siebert, K.

T. Löffler, K. Siebert, S. Czasch, T. Bauer, and H. G. Roskos, “Visualization and classification in biomedical terahertz pulsed imaging,” Phys. Med. Biol. 47(21), 3847–3852 (2002).
[Crossref] [PubMed]

Siebert, K. J.

Smith, M. A.

E. Berry, J. W. Handley, A. J. Fitzgerald, W. J. Merchant, R. D. Boyle, N. N. Zinov’ev, R. E. Miles, J. M. Chamberlain, and M. A. Smith, “Multispectral classification techniques for terahertz pulsed imaging: an example in histopathology,” Med. Eng. Phys. 26(5), 423–430 (2004).
[Crossref] [PubMed]

Sperling, M.

P. Knobloch, C. Schildknecht, T. Kleine-Ostmann, M. Koch, S. Hoffmann, M. Hofmann, E. Rehberg, M. Sperling, K. Donhuijsen, G. Hein, and K. Pierz, “Medical THz imaging: an investigation of histo-pathological samples,” Phys. Med. Biol. 47(21), 3875–3884 (2002).
[Crossref] [PubMed]

Swift, G. P.

J. R. Fletcher, G. P. Swift, D. C. Dai, J. M. Chamberlain, and P. C. Upadhya, “Pulsed terahertz signal reconstruction,” J. Appl. Phys. 102(11), 113105 (2007).
[Crossref]

Tanabe, T.

J. Nishizawa, T. Sasaki, T. Ken Suto, T. Yamada, T. Tanabe, T. Tanno, T. Sawai, and Y. Miura, “THz imaging of nucleobases and cancerous tissue using a GaP THz-wave generator,” Opt. Commun. 244(1-6), 469–474 (2005).
[Crossref]

Tanno, T.

J. Nishizawa, T. Sasaki, T. Ken Suto, T. Yamada, T. Tanabe, T. Tanno, T. Sawai, and Y. Miura, “THz imaging of nucleobases and cancerous tissue using a GaP THz-wave generator,” Opt. Commun. 244(1-6), 469–474 (2005).
[Crossref]

Upadhya, P. C.

J. R. Fletcher, G. P. Swift, D. C. Dai, J. M. Chamberlain, and P. C. Upadhya, “Pulsed terahertz signal reconstruction,” J. Appl. Phys. 102(11), 113105 (2007).
[Crossref]

Wallace, V. P.

A. J. Fitzgerald, V. P. Wallace, M. Jimenez-Linan, L. Bobrow, R. J. Pye, A. D. Purushotham, and D. D. Arnone, “Terahertz pulsed imaging of human breast tumors,” Radiology 239(2), 533–540 (2006).
[Crossref] [PubMed]

V. P. Wallace, A. J. Fitzgerald, S. Shankar, N. Flanagan, R. Pye, J. Cluff, and D. D. Arnone, “Terahertz pulsed imaging of basal cell carcinoma ex vivo and in vivo,” Br. J. Dermatol. 151(2), 424–432 (2004).
[Crossref] [PubMed]

R. M. Woodward, V. P. Wallace, R. J. Pye, B. E. Cole, D. D. Arnone, E. H. Linfield, and M. Pepper, “Terahertz pulse imaging of ex vivo basal cell carcinoma,” J. Invest. Dermatol. 120(1), 72–78 (2003).
[Crossref] [PubMed]

R. M. Woodward, B. E. Cole, V. P. Wallace, R. J. Pye, D. D. Arnone, E. H. Linfield, and M. Pepper, “Terahertz pulse imaging in reflection geometry of human skin cancer and skin tissue,” Phys. Med. Biol. 47(21), 3853–3863 (2002).
[Crossref] [PubMed]

Woodward, R. M.

R. M. Woodward, V. P. Wallace, R. J. Pye, B. E. Cole, D. D. Arnone, E. H. Linfield, and M. Pepper, “Terahertz pulse imaging of ex vivo basal cell carcinoma,” J. Invest. Dermatol. 120(1), 72–78 (2003).
[Crossref] [PubMed]

R. M. Woodward, B. E. Cole, V. P. Wallace, R. J. Pye, D. D. Arnone, E. H. Linfield, and M. Pepper, “Terahertz pulse imaging in reflection geometry of human skin cancer and skin tissue,” Phys. Med. Biol. 47(21), 3853–3863 (2002).
[Crossref] [PubMed]

Yamada, T.

J. Nishizawa, T. Sasaki, T. Ken Suto, T. Yamada, T. Tanabe, T. Tanno, T. Sawai, and Y. Miura, “THz imaging of nucleobases and cancerous tissue using a GaP THz-wave generator,” Opt. Commun. 244(1-6), 469–474 (2005).
[Crossref]

Yamashita, M.

S. Nakajima, H. Hoshina, M. Yamashita, C. Otani, and N. Miyoshi, “Terahertz imaging diagnostics of cancer tissues with a chemometrics technique,” Appl. Phys. Lett. 90(4), 041102 (2007).
[Crossref]

Yasuda, A.

M.-A. Brun, F. Formanek, A. Yasuda, M. Sekine, N. Ando, and Y. Eishii, “Terahertz imaging applied to cancer diagnosis,” Phys. Med. Biol. 55(16), 4615–4623 (2010).
[Crossref] [PubMed]

Zhang, X.-C.

G. M. Png, J. W. Choi, B. W.-H. Ng, S. P. Mickan, D. Abbott, and X.-C. Zhang, “The impact of hydration changes in fresh bio-tissue on THz spectroscopic measurements,” Phys. Med. Biol. 53(13), 3501–3517 (2008).
[Crossref] [PubMed]

Zinov’ev, N. N.

E. Berry, J. W. Handley, A. J. Fitzgerald, W. J. Merchant, R. D. Boyle, N. N. Zinov’ev, R. E. Miles, J. M. Chamberlain, and M. A. Smith, “Multispectral classification techniques for terahertz pulsed imaging: an example in histopathology,” Med. Eng. Phys. 26(5), 423–430 (2004).
[Crossref] [PubMed]

Appl. Phys. Lett. (3)

S. Nakajima, H. Hoshina, M. Yamashita, C. Otani, and N. Miyoshi, “Terahertz imaging diagnostics of cancer tissues with a chemometrics technique,” Appl. Phys. Lett. 90(4), 041102 (2007).
[Crossref]

S. M. Kim, F. Hatami, J. S. Harris, A. W. Kurian, J. Ford, D. King, G. Scalari, M. Giovannini, N. Hoyler, J. Faist, and G. Harris, “Biomedical terahertz imaging with a quantum cascade laser,” Appl. Phys. Lett. 88(15), 153903 (2006).
[Crossref]

H. Hoshina, A. Hayashi, N. Miyoshi, F. Miyamaru, and C. Otani, “Terahertz pulsed imaging of frozen biological tissues,” Appl. Phys. Lett. 94(12), 123901 (2009).
[Crossref]

Br. J. Dermatol. (1)

V. P. Wallace, A. J. Fitzgerald, S. Shankar, N. Flanagan, R. Pye, J. Cluff, and D. D. Arnone, “Terahertz pulsed imaging of basal cell carcinoma ex vivo and in vivo,” Br. J. Dermatol. 151(2), 424–432 (2004).
[Crossref] [PubMed]

J. Appl. Phys. (1)

J. R. Fletcher, G. P. Swift, D. C. Dai, J. M. Chamberlain, and P. C. Upadhya, “Pulsed terahertz signal reconstruction,” J. Appl. Phys. 102(11), 113105 (2007).
[Crossref]

J. Invest. Dermatol. (1)

R. M. Woodward, V. P. Wallace, R. J. Pye, B. E. Cole, D. D. Arnone, E. H. Linfield, and M. Pepper, “Terahertz pulse imaging of ex vivo basal cell carcinoma,” J. Invest. Dermatol. 120(1), 72–78 (2003).
[Crossref] [PubMed]

Med. Eng. Phys. (1)

E. Berry, J. W. Handley, A. J. Fitzgerald, W. J. Merchant, R. D. Boyle, N. N. Zinov’ev, R. E. Miles, J. M. Chamberlain, and M. A. Smith, “Multispectral classification techniques for terahertz pulsed imaging: an example in histopathology,” Med. Eng. Phys. 26(5), 423–430 (2004).
[Crossref] [PubMed]

Opt. Commun. (1)

J. Nishizawa, T. Sasaki, T. Ken Suto, T. Yamada, T. Tanabe, T. Tanno, T. Sawai, and Y. Miura, “THz imaging of nucleobases and cancerous tissue using a GaP THz-wave generator,” Opt. Commun. 244(1-6), 469–474 (2005).
[Crossref]

Opt. Express (2)

Phys. Med. Biol. (5)

P. Knobloch, C. Schildknecht, T. Kleine-Ostmann, M. Koch, S. Hoffmann, M. Hofmann, E. Rehberg, M. Sperling, K. Donhuijsen, G. Hein, and K. Pierz, “Medical THz imaging: an investigation of histo-pathological samples,” Phys. Med. Biol. 47(21), 3875–3884 (2002).
[Crossref] [PubMed]

T. Löffler, K. Siebert, S. Czasch, T. Bauer, and H. G. Roskos, “Visualization and classification in biomedical terahertz pulsed imaging,” Phys. Med. Biol. 47(21), 3847–3852 (2002).
[Crossref] [PubMed]

R. M. Woodward, B. E. Cole, V. P. Wallace, R. J. Pye, D. D. Arnone, E. H. Linfield, and M. Pepper, “Terahertz pulse imaging in reflection geometry of human skin cancer and skin tissue,” Phys. Med. Biol. 47(21), 3853–3863 (2002).
[Crossref] [PubMed]

M.-A. Brun, F. Formanek, A. Yasuda, M. Sekine, N. Ando, and Y. Eishii, “Terahertz imaging applied to cancer diagnosis,” Phys. Med. Biol. 55(16), 4615–4623 (2010).
[Crossref] [PubMed]

G. M. Png, J. W. Choi, B. W.-H. Ng, S. P. Mickan, D. Abbott, and X.-C. Zhang, “The impact of hydration changes in fresh bio-tissue on THz spectroscopic measurements,” Phys. Med. Biol. 53(13), 3501–3517 (2008).
[Crossref] [PubMed]

Radiology (1)

A. J. Fitzgerald, V. P. Wallace, M. Jimenez-Linan, L. Bobrow, R. J. Pye, A. D. Purushotham, and D. D. Arnone, “Terahertz pulsed imaging of human breast tumors,” Radiology 239(2), 533–540 (2006).
[Crossref] [PubMed]

Other (2)

S. W. Smith, “Linear image processing,” in Digital Signal Processing: a Practical Guide for Engineers and Scientists, (Newnes, 2003), pp. 397–422.

B. Balasko, J. Abonyi, and B. Feil, Fuzzy clustering and data analysis toolbox (2005). http://www.fmt.vein.hu/softcomp/fclusttoolbox/

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Figures (7)

Fig. 1
Fig. 1 Schematic diagram of the three measurement geometries.
Fig. 2
Fig. 2 Graph showing the refractive index (solid lines) and the extinction coefficient (dashed lines) of the healthy tissues calculated from the measurements performed on sample 1 in the three different geometries (water, paraffin + water, paraffin).
Fig. 3
Fig. 3 (a), (b) Registered visible microphotographs of the histopathologic sections stained with hematoxylin and eosin (H&E). (c)-(h) Segmented THz images obtained in the different measurement geometries. Images are 21 x 17 mm2 (288 x 232 pixels) and 17.4 x 19 mm2 (228 x 248 pixels) for sample 1 (top row) and sample 2, respectively.
Fig. 4
Fig. 4 (a), (b) Images segmented according to the stained sections visible in Fig. 3 (c) and used for comparison with the THz images. Percentage of pixels per THz image correctly assigned to each clusters depending on the measurement geometry.
Fig. 5
Fig. 5 Score plot of the first principal values versus the second principal values, obtained from the clusters of Fig. 3(g). The crosses indicate the median point within each cluster.
Fig. 6
Fig. 6 (a), (b) Initial incident pulse used in the simulation and corresponding frequency-domain spectrum defined to reproduce the experimental usable bandwidth. (c)-(e) Calculated reflected pulses for the different geometries, with the initial time-delay values reset to zero. The insets show 250% magnification close-ups of the pulses' peak.
Fig. 7
Fig. 7 Calculated spectra of the difference in amplitude between pulses reflected over healthy and cancer tissues, considering different numbers of reflections within a 10 µm thick section.

Equations (5)

Equations on this page are rendered with MathJax. Learn more.

F ~ ( ω ) = e i ω t 0 [ cos ( ω 4 f c ) ] p [ i sin ( ω 2 f c ) ] q | ω | 2 π f c ,
F ~ ( ω ) = 0 | ω | > 2 π f c ;
n c a n c e r p a r a f f i n = 1.545 , n h e a l t h y p a r a f f i n = 1.455 ,
n c a n c e r p a r a f f i n + w a t e r = 1.8025 - 0.1802i,  n h e a l t h y p a r a f f i n + w a t e r = 1.6975 - 0.1697i,
n c a n c e r w a t e r = n w a t e r * 0.824 , n h e a l t h y w a t e r = n w a t e r * 0.7760.

Metrics