Abstract

We demonstrate a highly sensitive THz molecular imaging (TMI) technique involving differential modulation of surface plasmons induced on nanoparticles and obtain target specific in vivo images of cancers. This technique can detect quantities of gold nanoparticles as small as 15 µM in vivo. A comparison of TMI images with near infrared absorption images shows the superior sensitivity of TMI. Furthermore, the quantification property of TMI is excellent, being linearly proportional to the concentration of nanoparticles. The target specificity issue is also addressed at the ex vivo and cell levels. The high thermal sensitivity of TMI can help extend photonic-based photothermal molecular imaging researches from the in vitro level to the in vivo level. The TMI technique can be used for monitoring drug delivery processes and for early cancer diagnosis.

© 2011 OSA

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  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]
  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. E. Pickwell and V. P. Wallace, “Biomedical applications of terahertz technology,” J. Phys. D Appl. Phys. 39(17), R301–R310 (2006).
    [CrossRef]
  4. J.-H. Son, “Terahertz electromagnetic interactions with biological matter and their applications,” J. Appl. Phys. 105(10), 102033 (2009).
    [CrossRef]
  5. B. Ferguson and X.-C. Zhang, “Materials for terahertz science and technology,” Nat. Mater. 1(1), 26–33 (2002).
    [CrossRef]
  6. K. Kawase, Y. Ogawa, Y. Watanabe, and H. Inoue, “Non-destructive terahertz imaging of illicit drugs using spectral fingerprints,” Opt. Express 11(20), 2549–2554 (2003).
    [CrossRef] [PubMed]
  7. S. J. Oh, J. Kang, I. Maeng, J.-S. Suh, Y.-M. Huh, S. Haam, and J.-H. Son, “Nanoparticle-enabled terahertz imaging for cancer diagnosis,” Opt. Express 17(5), 3469–3475 (2009).
    [CrossRef] [PubMed]
  8. J.-H. Lee, Y.-M. Huh, Y.-W. Jun, J.-W. Seo, J.-T. Jang, H.-T. Song, S. Kim, E.-J. Cho, H.-G. Yoon, J.-S. Suh, and J. Cheon, “Artificially engineered magnetic nanoparticles for ultra-sensitive molecular imaging,” Nat. Med. 13(1), 95–99 (2006).
    [CrossRef] [PubMed]
  9. R. Weissleder and V. Ntziachristos, “Shedding light onto live molecular targets,” Nat. Med. 9(1), 123–128 (2003).
    [CrossRef] [PubMed]
  10. J. Lee, J. Yang, H. Ko, S. J. Oh, J. Kang, J.-H. Son, K. Lee, S.-W. Lee, H.-G. Yoon, J.-S. Suh, Y.-M. Huh, and S. Haam, “Multifunctional magnetic gold nanocomposites: human epithelial cancer detection via magnetic resonance imaging and localized synchronous therapy,” Adv. Funct. Mater. 18(2), 258–264 (2008).
    [CrossRef]
  11. J. Yang, C.-H. Lee, H.-J. Ko, J.-S. Suh, H.-G. Yoon, K. Lee, Y.-M. Huh, and S. Haam, “Multifunctional magneto-polymeric nanohybrids for targeted detection and synergistic therapeutic effects on breast cancer,” Angew. Chem. Int. Ed. Engl. 46(46), 8836–8839 (2007).
    [CrossRef] [PubMed]
  12. J. R. McCarthy and R. Weissleder, “Multifunctional magnetic nanoparticles for targeted imaging and therapy,” Adv. Drug Deliv. Rev. 60(11), 1241–1251 (2008).
    [CrossRef] [PubMed]
  13. S. Santra, C. Kaittanis, J. Grimm, and J. M. Perez, “Drug/dye-loaded, multifunctional iron oxide nanoparticles for combined targeted cancer therapy and dual optical/magnetic resonance imaging,” small 5(16), 1862–1868 (2009).
    [CrossRef] [PubMed]
  14. L. Tong, Q. Wei, A. Wei, and J.-X. Cheng, “Gold nanorods as contrast agents for biological imaging: optical properties, surface conjugation and photothermal effects,” Photochem. Photobiol. 85(1), 21–32 (2009).
    [CrossRef] [PubMed]
  15. C. Ro̸nne, L. Thrane, P.-O. Åstrand, A. Wallqvist, K. V. Mikkelsen, and S. R. Keiding, “Investigation of the temperature dependence of dielectric relaxation in liquid water by THz reflection spectroscopy and molecular dynamics simulation,” J. Chem. Phys. 107(14), 5319–5331 (1997).
    [CrossRef]
  16. J. R. Collins, “Change in the infra-red absorption spectrum of water with temperature,” Phys. Rev. 26(6), 771–779 (1925).
    [CrossRef]
  17. R. Bardhan, W. Chen, M. Bartels, C. Perez-Torres, M. F. Botero, R. W. McAninch, A. Contreras, R. Schiff, R. G. Pautler, N. J. Halas, and A. Joshi, “Tracking of multimodal therapeutic nanocomplexes targeting breast cancer in vivo,” Nano Lett. 10(12), 4920–4928 (2010).
    [CrossRef]
  18. D. Boyer, P. Tamarat, A. Maali, B. Lounis, and M. Orrit, “Photothermal imaging of nanometer-sized metal particles among scatterers,” Science 297(5584), 1160–1163 (2002).
    [CrossRef] [PubMed]
  19. M. C. Skala, M. J. Crow, A. Wax, and J. A. Izatt, “Photothermal optical coherence tomography of epidermal growth factor receptor in live cells using immunotargeted gold nanospheres,” Nano Lett. 8(10), 3461–3467 (2008).
    [CrossRef] [PubMed]
  20. D. C. Adler, S.-W. Huang, R. Huber, and J. G. Fujimoto, “Photothermal detection of gold nanoparticles using phase-sensitive optical coherence tomography,” Opt. Express 16(7), 4376–4393 (2008).
    [CrossRef] [PubMed]

2010

R. Bardhan, W. Chen, M. Bartels, C. Perez-Torres, M. F. Botero, R. W. McAninch, A. Contreras, R. Schiff, R. G. Pautler, N. J. Halas, and A. Joshi, “Tracking of multimodal therapeutic nanocomplexes targeting breast cancer in vivo,” Nano Lett. 10(12), 4920–4928 (2010).
[CrossRef]

2009

J.-H. Son, “Terahertz electromagnetic interactions with biological matter and their applications,” J. Appl. Phys. 105(10), 102033 (2009).
[CrossRef]

S. Santra, C. Kaittanis, J. Grimm, and J. M. Perez, “Drug/dye-loaded, multifunctional iron oxide nanoparticles for combined targeted cancer therapy and dual optical/magnetic resonance imaging,” small 5(16), 1862–1868 (2009).
[CrossRef] [PubMed]

L. Tong, Q. Wei, A. Wei, and J.-X. Cheng, “Gold nanorods as contrast agents for biological imaging: optical properties, surface conjugation and photothermal effects,” Photochem. Photobiol. 85(1), 21–32 (2009).
[CrossRef] [PubMed]

S. J. Oh, J. Kang, I. Maeng, J.-S. Suh, Y.-M. Huh, S. Haam, and J.-H. Son, “Nanoparticle-enabled terahertz imaging for cancer diagnosis,” Opt. Express 17(5), 3469–3475 (2009).
[CrossRef] [PubMed]

2008

D. C. Adler, S.-W. Huang, R. Huber, and J. G. Fujimoto, “Photothermal detection of gold nanoparticles using phase-sensitive optical coherence tomography,” Opt. Express 16(7), 4376–4393 (2008).
[CrossRef] [PubMed]

J. Lee, J. Yang, H. Ko, S. J. Oh, J. Kang, J.-H. Son, K. Lee, S.-W. Lee, H.-G. Yoon, J.-S. Suh, Y.-M. Huh, and S. Haam, “Multifunctional magnetic gold nanocomposites: human epithelial cancer detection via magnetic resonance imaging and localized synchronous therapy,” Adv. Funct. Mater. 18(2), 258–264 (2008).
[CrossRef]

J. R. McCarthy and R. Weissleder, “Multifunctional magnetic nanoparticles for targeted imaging and therapy,” Adv. Drug Deliv. Rev. 60(11), 1241–1251 (2008).
[CrossRef] [PubMed]

M. C. Skala, M. J. Crow, A. Wax, and J. A. Izatt, “Photothermal optical coherence tomography of epidermal growth factor receptor in live cells using immunotargeted gold nanospheres,” Nano Lett. 8(10), 3461–3467 (2008).
[CrossRef] [PubMed]

2007

J. Yang, C.-H. Lee, H.-J. Ko, J.-S. Suh, H.-G. Yoon, K. Lee, Y.-M. Huh, and S. Haam, “Multifunctional magneto-polymeric nanohybrids for targeted detection and synergistic therapeutic effects on breast cancer,” Angew. Chem. Int. Ed. Engl. 46(46), 8836–8839 (2007).
[CrossRef] [PubMed]

2006

J.-H. Lee, Y.-M. Huh, Y.-W. Jun, J.-W. Seo, J.-T. Jang, H.-T. Song, S. Kim, E.-J. Cho, H.-G. Yoon, J.-S. Suh, and J. Cheon, “Artificially engineered magnetic nanoparticles for ultra-sensitive molecular imaging,” Nat. Med. 13(1), 95–99 (2006).
[CrossRef] [PubMed]

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]

E. Pickwell and V. P. Wallace, “Biomedical applications of terahertz technology,” J. Phys. D Appl. Phys. 39(17), R301–R310 (2006).
[CrossRef]

2003

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. Weissleder and V. Ntziachristos, “Shedding light onto live molecular targets,” Nat. Med. 9(1), 123–128 (2003).
[CrossRef] [PubMed]

K. Kawase, Y. Ogawa, Y. Watanabe, and H. Inoue, “Non-destructive terahertz imaging of illicit drugs using spectral fingerprints,” Opt. Express 11(20), 2549–2554 (2003).
[CrossRef] [PubMed]

2002

D. Boyer, P. Tamarat, A. Maali, B. Lounis, and M. Orrit, “Photothermal imaging of nanometer-sized metal particles among scatterers,” Science 297(5584), 1160–1163 (2002).
[CrossRef] [PubMed]

B. Ferguson and X.-C. Zhang, “Materials for terahertz science and technology,” Nat. Mater. 1(1), 26–33 (2002).
[CrossRef]

1997

C. Ro̸nne, L. Thrane, P.-O. Åstrand, A. Wallqvist, K. V. Mikkelsen, and S. R. Keiding, “Investigation of the temperature dependence of dielectric relaxation in liquid water by THz reflection spectroscopy and molecular dynamics simulation,” J. Chem. Phys. 107(14), 5319–5331 (1997).
[CrossRef]

1925

J. R. Collins, “Change in the infra-red absorption spectrum of water with temperature,” Phys. Rev. 26(6), 771–779 (1925).
[CrossRef]

Adler, D. C.

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]

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]

Åstrand, P.-O.

C. Ro̸nne, L. Thrane, P.-O. Åstrand, A. Wallqvist, K. V. Mikkelsen, and S. R. Keiding, “Investigation of the temperature dependence of dielectric relaxation in liquid water by THz reflection spectroscopy and molecular dynamics simulation,” J. Chem. Phys. 107(14), 5319–5331 (1997).
[CrossRef]

Bardhan, R.

R. Bardhan, W. Chen, M. Bartels, C. Perez-Torres, M. F. Botero, R. W. McAninch, A. Contreras, R. Schiff, R. G. Pautler, N. J. Halas, and A. Joshi, “Tracking of multimodal therapeutic nanocomplexes targeting breast cancer in vivo,” Nano Lett. 10(12), 4920–4928 (2010).
[CrossRef]

Bartels, M.

R. Bardhan, W. Chen, M. Bartels, C. Perez-Torres, M. F. Botero, R. W. McAninch, A. Contreras, R. Schiff, R. G. Pautler, N. J. Halas, and A. Joshi, “Tracking of multimodal therapeutic nanocomplexes targeting breast cancer in vivo,” Nano Lett. 10(12), 4920–4928 (2010).
[CrossRef]

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]

Botero, M. F.

R. Bardhan, W. Chen, M. Bartels, C. Perez-Torres, M. F. Botero, R. W. McAninch, A. Contreras, R. Schiff, R. G. Pautler, N. J. Halas, and A. Joshi, “Tracking of multimodal therapeutic nanocomplexes targeting breast cancer in vivo,” Nano Lett. 10(12), 4920–4928 (2010).
[CrossRef]

Boyer, D.

D. Boyer, P. Tamarat, A. Maali, B. Lounis, and M. Orrit, “Photothermal imaging of nanometer-sized metal particles among scatterers,” Science 297(5584), 1160–1163 (2002).
[CrossRef] [PubMed]

Chen, W.

R. Bardhan, W. Chen, M. Bartels, C. Perez-Torres, M. F. Botero, R. W. McAninch, A. Contreras, R. Schiff, R. G. Pautler, N. J. Halas, and A. Joshi, “Tracking of multimodal therapeutic nanocomplexes targeting breast cancer in vivo,” Nano Lett. 10(12), 4920–4928 (2010).
[CrossRef]

Cheng, J.-X.

L. Tong, Q. Wei, A. Wei, and J.-X. Cheng, “Gold nanorods as contrast agents for biological imaging: optical properties, surface conjugation and photothermal effects,” Photochem. Photobiol. 85(1), 21–32 (2009).
[CrossRef] [PubMed]

Cheon, J.

J.-H. Lee, Y.-M. Huh, Y.-W. Jun, J.-W. Seo, J.-T. Jang, H.-T. Song, S. Kim, E.-J. Cho, H.-G. Yoon, J.-S. Suh, and J. Cheon, “Artificially engineered magnetic nanoparticles for ultra-sensitive molecular imaging,” Nat. Med. 13(1), 95–99 (2006).
[CrossRef] [PubMed]

Cho, E.-J.

J.-H. Lee, Y.-M. Huh, Y.-W. Jun, J.-W. Seo, J.-T. Jang, H.-T. Song, S. Kim, E.-J. Cho, H.-G. Yoon, J.-S. Suh, and J. Cheon, “Artificially engineered magnetic nanoparticles for ultra-sensitive molecular imaging,” Nat. Med. 13(1), 95–99 (2006).
[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]

Collins, J. R.

J. R. Collins, “Change in the infra-red absorption spectrum of water with temperature,” Phys. Rev. 26(6), 771–779 (1925).
[CrossRef]

Contreras, A.

R. Bardhan, W. Chen, M. Bartels, C. Perez-Torres, M. F. Botero, R. W. McAninch, A. Contreras, R. Schiff, R. G. Pautler, N. J. Halas, and A. Joshi, “Tracking of multimodal therapeutic nanocomplexes targeting breast cancer in vivo,” Nano Lett. 10(12), 4920–4928 (2010).
[CrossRef]

Crow, M. J.

M. C. Skala, M. J. Crow, A. Wax, and J. A. Izatt, “Photothermal optical coherence tomography of epidermal growth factor receptor in live cells using immunotargeted gold nanospheres,” Nano Lett. 8(10), 3461–3467 (2008).
[CrossRef] [PubMed]

Ferguson, B.

B. Ferguson and X.-C. Zhang, “Materials for terahertz science and technology,” Nat. Mater. 1(1), 26–33 (2002).
[CrossRef]

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]

Fujimoto, J. G.

Grimm, J.

S. Santra, C. Kaittanis, J. Grimm, and J. M. Perez, “Drug/dye-loaded, multifunctional iron oxide nanoparticles for combined targeted cancer therapy and dual optical/magnetic resonance imaging,” small 5(16), 1862–1868 (2009).
[CrossRef] [PubMed]

Haam, S.

S. J. Oh, J. Kang, I. Maeng, J.-S. Suh, Y.-M. Huh, S. Haam, and J.-H. Son, “Nanoparticle-enabled terahertz imaging for cancer diagnosis,” Opt. Express 17(5), 3469–3475 (2009).
[CrossRef] [PubMed]

J. Lee, J. Yang, H. Ko, S. J. Oh, J. Kang, J.-H. Son, K. Lee, S.-W. Lee, H.-G. Yoon, J.-S. Suh, Y.-M. Huh, and S. Haam, “Multifunctional magnetic gold nanocomposites: human epithelial cancer detection via magnetic resonance imaging and localized synchronous therapy,” Adv. Funct. Mater. 18(2), 258–264 (2008).
[CrossRef]

J. Yang, C.-H. Lee, H.-J. Ko, J.-S. Suh, H.-G. Yoon, K. Lee, Y.-M. Huh, and S. Haam, “Multifunctional magneto-polymeric nanohybrids for targeted detection and synergistic therapeutic effects on breast cancer,” Angew. Chem. Int. Ed. Engl. 46(46), 8836–8839 (2007).
[CrossRef] [PubMed]

Halas, N. J.

R. Bardhan, W. Chen, M. Bartels, C. Perez-Torres, M. F. Botero, R. W. McAninch, A. Contreras, R. Schiff, R. G. Pautler, N. J. Halas, and A. Joshi, “Tracking of multimodal therapeutic nanocomplexes targeting breast cancer in vivo,” Nano Lett. 10(12), 4920–4928 (2010).
[CrossRef]

Huang, S.-W.

Huber, R.

Huh, Y.-M.

S. J. Oh, J. Kang, I. Maeng, J.-S. Suh, Y.-M. Huh, S. Haam, and J.-H. Son, “Nanoparticle-enabled terahertz imaging for cancer diagnosis,” Opt. Express 17(5), 3469–3475 (2009).
[CrossRef] [PubMed]

J. Lee, J. Yang, H. Ko, S. J. Oh, J. Kang, J.-H. Son, K. Lee, S.-W. Lee, H.-G. Yoon, J.-S. Suh, Y.-M. Huh, and S. Haam, “Multifunctional magnetic gold nanocomposites: human epithelial cancer detection via magnetic resonance imaging and localized synchronous therapy,” Adv. Funct. Mater. 18(2), 258–264 (2008).
[CrossRef]

J. Yang, C.-H. Lee, H.-J. Ko, J.-S. Suh, H.-G. Yoon, K. Lee, Y.-M. Huh, and S. Haam, “Multifunctional magneto-polymeric nanohybrids for targeted detection and synergistic therapeutic effects on breast cancer,” Angew. Chem. Int. Ed. Engl. 46(46), 8836–8839 (2007).
[CrossRef] [PubMed]

J.-H. Lee, Y.-M. Huh, Y.-W. Jun, J.-W. Seo, J.-T. Jang, H.-T. Song, S. Kim, E.-J. Cho, H.-G. Yoon, J.-S. Suh, and J. Cheon, “Artificially engineered magnetic nanoparticles for ultra-sensitive molecular imaging,” Nat. Med. 13(1), 95–99 (2006).
[CrossRef] [PubMed]

Inoue, H.

Izatt, J. A.

M. C. Skala, M. J. Crow, A. Wax, and J. A. Izatt, “Photothermal optical coherence tomography of epidermal growth factor receptor in live cells using immunotargeted gold nanospheres,” Nano Lett. 8(10), 3461–3467 (2008).
[CrossRef] [PubMed]

Jang, J.-T.

J.-H. Lee, Y.-M. Huh, Y.-W. Jun, J.-W. Seo, J.-T. Jang, H.-T. Song, S. Kim, E.-J. Cho, H.-G. Yoon, J.-S. Suh, and J. Cheon, “Artificially engineered magnetic nanoparticles for ultra-sensitive molecular imaging,” Nat. Med. 13(1), 95–99 (2006).
[CrossRef] [PubMed]

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]

Joshi, A.

R. Bardhan, W. Chen, M. Bartels, C. Perez-Torres, M. F. Botero, R. W. McAninch, A. Contreras, R. Schiff, R. G. Pautler, N. J. Halas, and A. Joshi, “Tracking of multimodal therapeutic nanocomplexes targeting breast cancer in vivo,” Nano Lett. 10(12), 4920–4928 (2010).
[CrossRef]

Jun, Y.-W.

J.-H. Lee, Y.-M. Huh, Y.-W. Jun, J.-W. Seo, J.-T. Jang, H.-T. Song, S. Kim, E.-J. Cho, H.-G. Yoon, J.-S. Suh, and J. Cheon, “Artificially engineered magnetic nanoparticles for ultra-sensitive molecular imaging,” Nat. Med. 13(1), 95–99 (2006).
[CrossRef] [PubMed]

Kaittanis, C.

S. Santra, C. Kaittanis, J. Grimm, and J. M. Perez, “Drug/dye-loaded, multifunctional iron oxide nanoparticles for combined targeted cancer therapy and dual optical/magnetic resonance imaging,” small 5(16), 1862–1868 (2009).
[CrossRef] [PubMed]

Kang, J.

S. J. Oh, J. Kang, I. Maeng, J.-S. Suh, Y.-M. Huh, S. Haam, and J.-H. Son, “Nanoparticle-enabled terahertz imaging for cancer diagnosis,” Opt. Express 17(5), 3469–3475 (2009).
[CrossRef] [PubMed]

J. Lee, J. Yang, H. Ko, S. J. Oh, J. Kang, J.-H. Son, K. Lee, S.-W. Lee, H.-G. Yoon, J.-S. Suh, Y.-M. Huh, and S. Haam, “Multifunctional magnetic gold nanocomposites: human epithelial cancer detection via magnetic resonance imaging and localized synchronous therapy,” Adv. Funct. Mater. 18(2), 258–264 (2008).
[CrossRef]

Kawase, K.

Keiding, S. R.

C. Ro̸nne, L. Thrane, P.-O. Åstrand, A. Wallqvist, K. V. Mikkelsen, and S. R. Keiding, “Investigation of the temperature dependence of dielectric relaxation in liquid water by THz reflection spectroscopy and molecular dynamics simulation,” J. Chem. Phys. 107(14), 5319–5331 (1997).
[CrossRef]

Kim, S.

J.-H. Lee, Y.-M. Huh, Y.-W. Jun, J.-W. Seo, J.-T. Jang, H.-T. Song, S. Kim, E.-J. Cho, H.-G. Yoon, J.-S. Suh, and J. Cheon, “Artificially engineered magnetic nanoparticles for ultra-sensitive molecular imaging,” Nat. Med. 13(1), 95–99 (2006).
[CrossRef] [PubMed]

Ko, H.

J. Lee, J. Yang, H. Ko, S. J. Oh, J. Kang, J.-H. Son, K. Lee, S.-W. Lee, H.-G. Yoon, J.-S. Suh, Y.-M. Huh, and S. Haam, “Multifunctional magnetic gold nanocomposites: human epithelial cancer detection via magnetic resonance imaging and localized synchronous therapy,” Adv. Funct. Mater. 18(2), 258–264 (2008).
[CrossRef]

Ko, H.-J.

J. Yang, C.-H. Lee, H.-J. Ko, J.-S. Suh, H.-G. Yoon, K. Lee, Y.-M. Huh, and S. Haam, “Multifunctional magneto-polymeric nanohybrids for targeted detection and synergistic therapeutic effects on breast cancer,” Angew. Chem. Int. Ed. Engl. 46(46), 8836–8839 (2007).
[CrossRef] [PubMed]

Lee, C.-H.

J. Yang, C.-H. Lee, H.-J. Ko, J.-S. Suh, H.-G. Yoon, K. Lee, Y.-M. Huh, and S. Haam, “Multifunctional magneto-polymeric nanohybrids for targeted detection and synergistic therapeutic effects on breast cancer,” Angew. Chem. Int. Ed. Engl. 46(46), 8836–8839 (2007).
[CrossRef] [PubMed]

Lee, J.

J. Lee, J. Yang, H. Ko, S. J. Oh, J. Kang, J.-H. Son, K. Lee, S.-W. Lee, H.-G. Yoon, J.-S. Suh, Y.-M. Huh, and S. Haam, “Multifunctional magnetic gold nanocomposites: human epithelial cancer detection via magnetic resonance imaging and localized synchronous therapy,” Adv. Funct. Mater. 18(2), 258–264 (2008).
[CrossRef]

Lee, J.-H.

J.-H. Lee, Y.-M. Huh, Y.-W. Jun, J.-W. Seo, J.-T. Jang, H.-T. Song, S. Kim, E.-J. Cho, H.-G. Yoon, J.-S. Suh, and J. Cheon, “Artificially engineered magnetic nanoparticles for ultra-sensitive molecular imaging,” Nat. Med. 13(1), 95–99 (2006).
[CrossRef] [PubMed]

Lee, K.

J. Lee, J. Yang, H. Ko, S. J. Oh, J. Kang, J.-H. Son, K. Lee, S.-W. Lee, H.-G. Yoon, J.-S. Suh, Y.-M. Huh, and S. Haam, “Multifunctional magnetic gold nanocomposites: human epithelial cancer detection via magnetic resonance imaging and localized synchronous therapy,” Adv. Funct. Mater. 18(2), 258–264 (2008).
[CrossRef]

J. Yang, C.-H. Lee, H.-J. Ko, J.-S. Suh, H.-G. Yoon, K. Lee, Y.-M. Huh, and S. Haam, “Multifunctional magneto-polymeric nanohybrids for targeted detection and synergistic therapeutic effects on breast cancer,” Angew. Chem. Int. Ed. Engl. 46(46), 8836–8839 (2007).
[CrossRef] [PubMed]

Lee, S.-W.

J. Lee, J. Yang, H. Ko, S. J. Oh, J. Kang, J.-H. Son, K. Lee, S.-W. Lee, H.-G. Yoon, J.-S. Suh, Y.-M. Huh, and S. Haam, “Multifunctional magnetic gold nanocomposites: human epithelial cancer detection via magnetic resonance imaging and localized synchronous therapy,” Adv. Funct. Mater. 18(2), 258–264 (2008).
[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]

Lounis, B.

D. Boyer, P. Tamarat, A. Maali, B. Lounis, and M. Orrit, “Photothermal imaging of nanometer-sized metal particles among scatterers,” Science 297(5584), 1160–1163 (2002).
[CrossRef] [PubMed]

Maali, A.

D. Boyer, P. Tamarat, A. Maali, B. Lounis, and M. Orrit, “Photothermal imaging of nanometer-sized metal particles among scatterers,” Science 297(5584), 1160–1163 (2002).
[CrossRef] [PubMed]

Maeng, I.

McAninch, R. W.

R. Bardhan, W. Chen, M. Bartels, C. Perez-Torres, M. F. Botero, R. W. McAninch, A. Contreras, R. Schiff, R. G. Pautler, N. J. Halas, and A. Joshi, “Tracking of multimodal therapeutic nanocomplexes targeting breast cancer in vivo,” Nano Lett. 10(12), 4920–4928 (2010).
[CrossRef]

McCarthy, J. R.

J. R. McCarthy and R. Weissleder, “Multifunctional magnetic nanoparticles for targeted imaging and therapy,” Adv. Drug Deliv. Rev. 60(11), 1241–1251 (2008).
[CrossRef] [PubMed]

Mikkelsen, K. V.

C. Ro̸nne, L. Thrane, P.-O. Åstrand, A. Wallqvist, K. V. Mikkelsen, and S. R. Keiding, “Investigation of the temperature dependence of dielectric relaxation in liquid water by THz reflection spectroscopy and molecular dynamics simulation,” J. Chem. Phys. 107(14), 5319–5331 (1997).
[CrossRef]

Ntziachristos, V.

R. Weissleder and V. Ntziachristos, “Shedding light onto live molecular targets,” Nat. Med. 9(1), 123–128 (2003).
[CrossRef] [PubMed]

Ogawa, Y.

Oh, S. J.

S. J. Oh, J. Kang, I. Maeng, J.-S. Suh, Y.-M. Huh, S. Haam, and J.-H. Son, “Nanoparticle-enabled terahertz imaging for cancer diagnosis,” Opt. Express 17(5), 3469–3475 (2009).
[CrossRef] [PubMed]

J. Lee, J. Yang, H. Ko, S. J. Oh, J. Kang, J.-H. Son, K. Lee, S.-W. Lee, H.-G. Yoon, J.-S. Suh, Y.-M. Huh, and S. Haam, “Multifunctional magnetic gold nanocomposites: human epithelial cancer detection via magnetic resonance imaging and localized synchronous therapy,” Adv. Funct. Mater. 18(2), 258–264 (2008).
[CrossRef]

Orrit, M.

D. Boyer, P. Tamarat, A. Maali, B. Lounis, and M. Orrit, “Photothermal imaging of nanometer-sized metal particles among scatterers,” Science 297(5584), 1160–1163 (2002).
[CrossRef] [PubMed]

Pautler, R. G.

R. Bardhan, W. Chen, M. Bartels, C. Perez-Torres, M. F. Botero, R. W. McAninch, A. Contreras, R. Schiff, R. G. Pautler, N. J. Halas, and A. Joshi, “Tracking of multimodal therapeutic nanocomplexes targeting breast cancer in vivo,” Nano Lett. 10(12), 4920–4928 (2010).
[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]

Perez, J. M.

S. Santra, C. Kaittanis, J. Grimm, and J. M. Perez, “Drug/dye-loaded, multifunctional iron oxide nanoparticles for combined targeted cancer therapy and dual optical/magnetic resonance imaging,” small 5(16), 1862–1868 (2009).
[CrossRef] [PubMed]

Perez-Torres, C.

R. Bardhan, W. Chen, M. Bartels, C. Perez-Torres, M. F. Botero, R. W. McAninch, A. Contreras, R. Schiff, R. G. Pautler, N. J. Halas, and A. Joshi, “Tracking of multimodal therapeutic nanocomplexes targeting breast cancer in vivo,” Nano Lett. 10(12), 4920–4928 (2010).
[CrossRef]

Pickwell, E.

E. Pickwell and V. P. Wallace, “Biomedical applications of terahertz technology,” J. Phys. D Appl. Phys. 39(17), R301–R310 (2006).
[CrossRef]

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. 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]

Ro?nne, C.

C. Ro̸nne, L. Thrane, P.-O. Åstrand, A. Wallqvist, K. V. Mikkelsen, and S. R. Keiding, “Investigation of the temperature dependence of dielectric relaxation in liquid water by THz reflection spectroscopy and molecular dynamics simulation,” J. Chem. Phys. 107(14), 5319–5331 (1997).
[CrossRef]

Santra, S.

S. Santra, C. Kaittanis, J. Grimm, and J. M. Perez, “Drug/dye-loaded, multifunctional iron oxide nanoparticles for combined targeted cancer therapy and dual optical/magnetic resonance imaging,” small 5(16), 1862–1868 (2009).
[CrossRef] [PubMed]

Schiff, R.

R. Bardhan, W. Chen, M. Bartels, C. Perez-Torres, M. F. Botero, R. W. McAninch, A. Contreras, R. Schiff, R. G. Pautler, N. J. Halas, and A. Joshi, “Tracking of multimodal therapeutic nanocomplexes targeting breast cancer in vivo,” Nano Lett. 10(12), 4920–4928 (2010).
[CrossRef]

Seo, J.-W.

J.-H. Lee, Y.-M. Huh, Y.-W. Jun, J.-W. Seo, J.-T. Jang, H.-T. Song, S. Kim, E.-J. Cho, H.-G. Yoon, J.-S. Suh, and J. Cheon, “Artificially engineered magnetic nanoparticles for ultra-sensitive molecular imaging,” Nat. Med. 13(1), 95–99 (2006).
[CrossRef] [PubMed]

Skala, M. C.

M. C. Skala, M. J. Crow, A. Wax, and J. A. Izatt, “Photothermal optical coherence tomography of epidermal growth factor receptor in live cells using immunotargeted gold nanospheres,” Nano Lett. 8(10), 3461–3467 (2008).
[CrossRef] [PubMed]

Son, J.-H.

J.-H. Son, “Terahertz electromagnetic interactions with biological matter and their applications,” J. Appl. Phys. 105(10), 102033 (2009).
[CrossRef]

S. J. Oh, J. Kang, I. Maeng, J.-S. Suh, Y.-M. Huh, S. Haam, and J.-H. Son, “Nanoparticle-enabled terahertz imaging for cancer diagnosis,” Opt. Express 17(5), 3469–3475 (2009).
[CrossRef] [PubMed]

J. Lee, J. Yang, H. Ko, S. J. Oh, J. Kang, J.-H. Son, K. Lee, S.-W. Lee, H.-G. Yoon, J.-S. Suh, Y.-M. Huh, and S. Haam, “Multifunctional magnetic gold nanocomposites: human epithelial cancer detection via magnetic resonance imaging and localized synchronous therapy,” Adv. Funct. Mater. 18(2), 258–264 (2008).
[CrossRef]

Song, H.-T.

J.-H. Lee, Y.-M. Huh, Y.-W. Jun, J.-W. Seo, J.-T. Jang, H.-T. Song, S. Kim, E.-J. Cho, H.-G. Yoon, J.-S. Suh, and J. Cheon, “Artificially engineered magnetic nanoparticles for ultra-sensitive molecular imaging,” Nat. Med. 13(1), 95–99 (2006).
[CrossRef] [PubMed]

Suh, J.-S.

S. J. Oh, J. Kang, I. Maeng, J.-S. Suh, Y.-M. Huh, S. Haam, and J.-H. Son, “Nanoparticle-enabled terahertz imaging for cancer diagnosis,” Opt. Express 17(5), 3469–3475 (2009).
[CrossRef] [PubMed]

J. Lee, J. Yang, H. Ko, S. J. Oh, J. Kang, J.-H. Son, K. Lee, S.-W. Lee, H.-G. Yoon, J.-S. Suh, Y.-M. Huh, and S. Haam, “Multifunctional magnetic gold nanocomposites: human epithelial cancer detection via magnetic resonance imaging and localized synchronous therapy,” Adv. Funct. Mater. 18(2), 258–264 (2008).
[CrossRef]

J. Yang, C.-H. Lee, H.-J. Ko, J.-S. Suh, H.-G. Yoon, K. Lee, Y.-M. Huh, and S. Haam, “Multifunctional magneto-polymeric nanohybrids for targeted detection and synergistic therapeutic effects on breast cancer,” Angew. Chem. Int. Ed. Engl. 46(46), 8836–8839 (2007).
[CrossRef] [PubMed]

J.-H. Lee, Y.-M. Huh, Y.-W. Jun, J.-W. Seo, J.-T. Jang, H.-T. Song, S. Kim, E.-J. Cho, H.-G. Yoon, J.-S. Suh, and J. Cheon, “Artificially engineered magnetic nanoparticles for ultra-sensitive molecular imaging,” Nat. Med. 13(1), 95–99 (2006).
[CrossRef] [PubMed]

Tamarat, P.

D. Boyer, P. Tamarat, A. Maali, B. Lounis, and M. Orrit, “Photothermal imaging of nanometer-sized metal particles among scatterers,” Science 297(5584), 1160–1163 (2002).
[CrossRef] [PubMed]

Thrane, L.

C. Ro̸nne, L. Thrane, P.-O. Åstrand, A. Wallqvist, K. V. Mikkelsen, and S. R. Keiding, “Investigation of the temperature dependence of dielectric relaxation in liquid water by THz reflection spectroscopy and molecular dynamics simulation,” J. Chem. Phys. 107(14), 5319–5331 (1997).
[CrossRef]

Tong, L.

L. Tong, Q. Wei, A. Wei, and J.-X. Cheng, “Gold nanorods as contrast agents for biological imaging: optical properties, surface conjugation and photothermal effects,” Photochem. Photobiol. 85(1), 21–32 (2009).
[CrossRef] [PubMed]

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]

E. Pickwell and V. P. Wallace, “Biomedical applications of terahertz technology,” J. Phys. D Appl. Phys. 39(17), R301–R310 (2006).
[CrossRef]

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]

Wallqvist, A.

C. Ro̸nne, L. Thrane, P.-O. Åstrand, A. Wallqvist, K. V. Mikkelsen, and S. R. Keiding, “Investigation of the temperature dependence of dielectric relaxation in liquid water by THz reflection spectroscopy and molecular dynamics simulation,” J. Chem. Phys. 107(14), 5319–5331 (1997).
[CrossRef]

Watanabe, Y.

Wax, A.

M. C. Skala, M. J. Crow, A. Wax, and J. A. Izatt, “Photothermal optical coherence tomography of epidermal growth factor receptor in live cells using immunotargeted gold nanospheres,” Nano Lett. 8(10), 3461–3467 (2008).
[CrossRef] [PubMed]

Wei, A.

L. Tong, Q. Wei, A. Wei, and J.-X. Cheng, “Gold nanorods as contrast agents for biological imaging: optical properties, surface conjugation and photothermal effects,” Photochem. Photobiol. 85(1), 21–32 (2009).
[CrossRef] [PubMed]

Wei, Q.

L. Tong, Q. Wei, A. Wei, and J.-X. Cheng, “Gold nanorods as contrast agents for biological imaging: optical properties, surface conjugation and photothermal effects,” Photochem. Photobiol. 85(1), 21–32 (2009).
[CrossRef] [PubMed]

Weissleder, R.

J. R. McCarthy and R. Weissleder, “Multifunctional magnetic nanoparticles for targeted imaging and therapy,” Adv. Drug Deliv. Rev. 60(11), 1241–1251 (2008).
[CrossRef] [PubMed]

R. Weissleder and V. Ntziachristos, “Shedding light onto live molecular targets,” Nat. Med. 9(1), 123–128 (2003).
[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]

Yang, J.

J. Lee, J. Yang, H. Ko, S. J. Oh, J. Kang, J.-H. Son, K. Lee, S.-W. Lee, H.-G. Yoon, J.-S. Suh, Y.-M. Huh, and S. Haam, “Multifunctional magnetic gold nanocomposites: human epithelial cancer detection via magnetic resonance imaging and localized synchronous therapy,” Adv. Funct. Mater. 18(2), 258–264 (2008).
[CrossRef]

J. Yang, C.-H. Lee, H.-J. Ko, J.-S. Suh, H.-G. Yoon, K. Lee, Y.-M. Huh, and S. Haam, “Multifunctional magneto-polymeric nanohybrids for targeted detection and synergistic therapeutic effects on breast cancer,” Angew. Chem. Int. Ed. Engl. 46(46), 8836–8839 (2007).
[CrossRef] [PubMed]

Yoon, H.-G.

J. Lee, J. Yang, H. Ko, S. J. Oh, J. Kang, J.-H. Son, K. Lee, S.-W. Lee, H.-G. Yoon, J.-S. Suh, Y.-M. Huh, and S. Haam, “Multifunctional magnetic gold nanocomposites: human epithelial cancer detection via magnetic resonance imaging and localized synchronous therapy,” Adv. Funct. Mater. 18(2), 258–264 (2008).
[CrossRef]

J. Yang, C.-H. Lee, H.-J. Ko, J.-S. Suh, H.-G. Yoon, K. Lee, Y.-M. Huh, and S. Haam, “Multifunctional magneto-polymeric nanohybrids for targeted detection and synergistic therapeutic effects on breast cancer,” Angew. Chem. Int. Ed. Engl. 46(46), 8836–8839 (2007).
[CrossRef] [PubMed]

J.-H. Lee, Y.-M. Huh, Y.-W. Jun, J.-W. Seo, J.-T. Jang, H.-T. Song, S. Kim, E.-J. Cho, H.-G. Yoon, J.-S. Suh, and J. Cheon, “Artificially engineered magnetic nanoparticles for ultra-sensitive molecular imaging,” Nat. Med. 13(1), 95–99 (2006).
[CrossRef] [PubMed]

Zhang, X.-C.

B. Ferguson and X.-C. Zhang, “Materials for terahertz science and technology,” Nat. Mater. 1(1), 26–33 (2002).
[CrossRef]

Adv. Drug Deliv. Rev.

J. R. McCarthy and R. Weissleder, “Multifunctional magnetic nanoparticles for targeted imaging and therapy,” Adv. Drug Deliv. Rev. 60(11), 1241–1251 (2008).
[CrossRef] [PubMed]

Adv. Funct. Mater.

J. Lee, J. Yang, H. Ko, S. J. Oh, J. Kang, J.-H. Son, K. Lee, S.-W. Lee, H.-G. Yoon, J.-S. Suh, Y.-M. Huh, and S. Haam, “Multifunctional magnetic gold nanocomposites: human epithelial cancer detection via magnetic resonance imaging and localized synchronous therapy,” Adv. Funct. Mater. 18(2), 258–264 (2008).
[CrossRef]

Angew. Chem. Int. Ed. Engl.

J. Yang, C.-H. Lee, H.-J. Ko, J.-S. Suh, H.-G. Yoon, K. Lee, Y.-M. Huh, and S. Haam, “Multifunctional magneto-polymeric nanohybrids for targeted detection and synergistic therapeutic effects on breast cancer,” Angew. Chem. Int. Ed. Engl. 46(46), 8836–8839 (2007).
[CrossRef] [PubMed]

J. Appl. Phys.

J.-H. Son, “Terahertz electromagnetic interactions with biological matter and their applications,” J. Appl. Phys. 105(10), 102033 (2009).
[CrossRef]

J. Chem. Phys.

C. Ro̸nne, L. Thrane, P.-O. Åstrand, A. Wallqvist, K. V. Mikkelsen, and S. R. Keiding, “Investigation of the temperature dependence of dielectric relaxation in liquid water by THz reflection spectroscopy and molecular dynamics simulation,” J. Chem. Phys. 107(14), 5319–5331 (1997).
[CrossRef]

J. Invest. Dermatol.

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]

J. Phys. D Appl. Phys.

E. Pickwell and V. P. Wallace, “Biomedical applications of terahertz technology,” J. Phys. D Appl. Phys. 39(17), R301–R310 (2006).
[CrossRef]

Nano Lett.

R. Bardhan, W. Chen, M. Bartels, C. Perez-Torres, M. F. Botero, R. W. McAninch, A. Contreras, R. Schiff, R. G. Pautler, N. J. Halas, and A. Joshi, “Tracking of multimodal therapeutic nanocomplexes targeting breast cancer in vivo,” Nano Lett. 10(12), 4920–4928 (2010).
[CrossRef]

M. C. Skala, M. J. Crow, A. Wax, and J. A. Izatt, “Photothermal optical coherence tomography of epidermal growth factor receptor in live cells using immunotargeted gold nanospheres,” Nano Lett. 8(10), 3461–3467 (2008).
[CrossRef] [PubMed]

Nat. Mater.

B. Ferguson and X.-C. Zhang, “Materials for terahertz science and technology,” Nat. Mater. 1(1), 26–33 (2002).
[CrossRef]

Nat. Med.

J.-H. Lee, Y.-M. Huh, Y.-W. Jun, J.-W. Seo, J.-T. Jang, H.-T. Song, S. Kim, E.-J. Cho, H.-G. Yoon, J.-S. Suh, and J. Cheon, “Artificially engineered magnetic nanoparticles for ultra-sensitive molecular imaging,” Nat. Med. 13(1), 95–99 (2006).
[CrossRef] [PubMed]

R. Weissleder and V. Ntziachristos, “Shedding light onto live molecular targets,” Nat. Med. 9(1), 123–128 (2003).
[CrossRef] [PubMed]

Opt. Express

Photochem. Photobiol.

L. Tong, Q. Wei, A. Wei, and J.-X. Cheng, “Gold nanorods as contrast agents for biological imaging: optical properties, surface conjugation and photothermal effects,” Photochem. Photobiol. 85(1), 21–32 (2009).
[CrossRef] [PubMed]

Phys. Rev.

J. R. Collins, “Change in the infra-red absorption spectrum of water with temperature,” Phys. Rev. 26(6), 771–779 (1925).
[CrossRef]

Radiology

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]

Science

D. Boyer, P. Tamarat, A. Maali, B. Lounis, and M. Orrit, “Photothermal imaging of nanometer-sized metal particles among scatterers,” Science 297(5584), 1160–1163 (2002).
[CrossRef] [PubMed]

small

S. Santra, C. Kaittanis, J. Grimm, and J. M. Perez, “Drug/dye-loaded, multifunctional iron oxide nanoparticles for combined targeted cancer therapy and dual optical/magnetic resonance imaging,” small 5(16), 1862–1868 (2009).
[CrossRef] [PubMed]

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Figures (8)

Fig. 1
Fig. 1

Schematic of the THz molecular imaging system.

Fig. 2
Fig. 2

THz response under NIR modulation. (a) shows the NIR signal modulated by a mechanical shutter (black line). (b) shows the THz responses of water using GNRs under NIR irradiation (red line), GNRs without NIR irradiation (green line), and without GNRs under NIR irradiation (blue line). The power of the NIR beam was 15 W/cm2 and the diameters of the THz and NIR beams were 0.8 mm. The GNR solution was 100 μM. The time dependent THz signals were acquired by an oscilloscope triggered by the modulation signal of the NIR beam.

Fig. 3
Fig. 3

In vivo and ex vivo THz molecular images of tumors. (a) and (b) show visible images of the mouse with an A431 tumor (size = 2.1 cm3). (c) shows the THz molecular image of (b). (d) shows the visible images of the tumor, liver, spleen, kidney, and brain. (e) shows the THz molecular image of (d). The power of the NIR beam was 80 W/cm2 and the diameters of the THz and NIR beams were 0.8 mm. The image was taken with a scan step of 250 μm and a time delay of 3 s per pixel, 24 h after the injection of 100 μL of CET-PGNRs at a concentration of 1 mM.

Fig. 4
Fig. 4

In vivo and ex vivo NIR absorption images. (a) and (b) show the NIR absorption images of the mouse shown in Fig. 2 before the injection of nanoprobes and 24 h after the injection. (c) and (d) show the NIR absorption images of the tumor, spleen, kidney, liver, and brain before and after the injection of nanoprobes.

Fig. 5
Fig. 5

Quantification of THz molecular imaging in solution. (a) shows the THz molecular images of the solutions with various concentrations of CET-PGNRs from 332 μM to 10 μM (n/2 for each concentration). (b) shows the THz reflectivity of the solutions with various concentrations of CET-PGNRs from 3.3 mM to 10 μM (n/2 for each concentration) (solid circles). The experimental data were fitted by a linear line (red line).

Fig. 6
Fig. 6

Quantification of THz molecular imaging in vivo. (a) shows the in vivo THz molecular images of artificial tumors with various concentrations of CET-PGNRs. (b) shows the peak values from the images of (a) (solid circles). The experimental data is fitted with a linear line (red line).

Fig. 7
Fig. 7

In vivo quantification of detection sensitivity by the NIR absorption imaging technique. Shown is the top view of in vivo NIR absorption images of artificial tumors with various concentrations of CET-PGNRs. The artificial tumors on the left leg are without nanoprobes and the artificial tumors on the right leg are with nanoprobes.

Fig. 8
Fig. 8

In vitro target specificity and sensitivity of THz molecular imaging. The grey bar is the THz response from the A431 cells without nanoprobes serving as a control. The red bars represent the A431 cells targeted with nanoprobes. The blue bars represent the MCF7 cells targeted with nanoprobes. The bars and the error bars are the mean values and standard deviations, respectively, at four random positions of each cell.

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