Research Papers

Short-Pulse Laser-Based System for Detection of Tumors: Administration of Gold Nanoparticles Enhances Contrast

[+] Author and Article Information
K. Mitra

Department of Mechanical &
Aerospace Engineering,
Florida Institute of Technology,
Melbourne, FL 32901

M. S. Grace

Department of Biological Sciences,
Florida Institute of Technology,
Melbourne, FL 32901

Manuscript received January 26, 2012; final manuscript received July 12, 2012; published online September 24, 2012. Assoc. Editor: Henry Hess.

J. Nanotechnol. Eng. Med 3(2), 021002 (Sep 24, 2012) (6 pages) doi:10.1115/1.4007245 History: Received January 26, 2012; Revised July 12, 2012

The objective of this paper is to demonstrate the use of gold nanoparticles, which accumulate in tumors due to the leakiness of tumor vasculature, as contrast agents for enhanced imaging in a time-resolved optical tomography system using short-pulse lasers for skin cancer detection in mouse model. It is found that intravenously administrated spherical gold nanoparticles broadened the temporal profile of reflected optical signals and enhanced the contrast between surrounding normal tissue and tumors. These results show that gold nanoparticles tuned to the wavelength of the laser can enhance the resolution and precision of laser-based cancer detection system.

Copyright © 2012 by ASME
Your Session has timed out. Please sign back in to continue.


Hecht, B., Sick, B., Wild, U. P., Deckert, V., Zenobi, R., Martin, O. J. F., and Pohl, D. W., 2000, “Scanning Near-Field Optical Microscopy With Aperture Probes: Fundamentals and Applications,” J. Chem. Phys., 112(18), pp. 7761–7774. [CrossRef]
Schmitt, J. M., 1999, “Optical Coherence Tomography (OCT): A Review,” IEEE J. Sel. Topics Quantum Electron., 5(4), pp. 1205–1215. [CrossRef]
Boas, D. A., Brooks, D. H., Miller, E. L., DiMarzio, C. A., Kilmer, M., Gaudette, R. J., and Zhang, Q., 2001, “Imaging the Body With Diffuse Optical Tomography,” IEEE Signal Process. Mag., 18(6), pp. 57–75. [CrossRef]
Tadrous, P. J., 2000, “Methods for Imaging the Structure and Function of Living Tissues and Cells: 2. Fluorescence Lifetime Imaging,” J. Pathol., 191(3), pp. 229–234. [CrossRef] [PubMed]
Bkaily, G., Pothier, P., D'Orléans-Juste, P., Simaan, M., Jacques, D., Jaalouk, D., Belzile, F., Hassan, G., Boutin, C., Haddad, G., and Neugebauer, W., 1997, “The Use of Confocal Microscopy in the Investigation of Cell Structure and Function in the Heart, Vascular Endothelium and Smooth Muscle Cells,” Mol. Cell. Biochem., 172(1–2), pp. 171–194. [CrossRef] [PubMed]
Axelrod, D., 2001, “Total Internal Reflection Fluorescence Microscopy in Cell Biology,” Traffic, 2(11), pp. 764–774. [CrossRef] [PubMed]
Qian, J., Fu, T., Zhan, Q., and He, S., 2010, “Using Some Nanoparticles as Contrast Agents for Optical Bioimaging,” IEEE J. Sel. Topics Quantum Electron., 16(3), pp. 672–684. [CrossRef]
Chance, B., 1998, “Near-Infrared Images Using Continuous, Phase-Modulated, and Pulsed Light With Quantitation of Blood and Blood Oxygenation,” Ann. N.Y. Acad. Sci., 838, pp. 29–45. [CrossRef] [PubMed]
Chance, B., 1995, “Time-Resolved Spectroscopy and Imaging,” Optical Tomography, Photon Migration, and Spectroscopy of Tissue and Model Media: Theory, Human Studies, and Instrumentation, B.Chance and R. R.Alfano, eds., Proc. SPIE, 2389, pp. 122–139. [CrossRef]
Alfano, R. R., Demos, S. G., and Gayen, S. K., 1997, “Advances in Optical Imaging of Biomedical Media,” Ann. N.Y. Acad. Sci., 820, pp. 248–270. [CrossRef] [PubMed]
Arridge, S. R., and Hebden, J. C., 1997, “Optical Imaging in Medicine: II. Modelling and Reconstruction,” Phys. Med. Biol., 42, pp. 841–853. [CrossRef] [PubMed]
Hall, D. J., Hebden, J. C., and Delpy, D. T., 1997, “Imaging Very-Low Contrast Objects in Breastlike Scattering Media With a Time-Resolved Method,” Appl. Opt., 36, pp. 7270–7276. [CrossRef] [PubMed]
Proskurin, S., Yamada, Y., and Takahashi, Y., 1995, “Absorption Coefficient Measurements of Strongly Scattering Media Using Time-Resolved Transmittance of a Short Pulse in Near-Infrared (NIR) Wavelength Range,” Opt. Rev., 2, pp. 292–297. [CrossRef]
Minet, O., Muller, G., and Beuthan, J., 1998, “Selected Papers on Optical Tomography, Fundamentals and Applications,” SPIE Press, Bellingham, WA.
Gandjbakhche, A. H., Chernomordik, V., Hebden, J. C., and Nossal, R., 1998, “Time-Dependent Contrast Functions for Quantitative Imaging in Time-Resolved Transillumination Experiments,” Appl. Opt., 37, pp. 1973–1981. [CrossRef] [PubMed]
Schultz, D. A., 2003, “Plasmon Resonant Particles for Biological Detection,” Curr. Opin. Biotechnol., 14, pp. 13–22. [CrossRef] [PubMed]
Daniel, M. C., and Astruc, D., 2004, “Gold Nanoparticles: Assembly, Supramolecular Chemistry, Quantum-Size-Related Properties, and Applications Toward Biology, Catalysis, and Nanotechnology,” Chem. Rev., 104, pp. 293–346. [CrossRef] [PubMed]
Schmid, G., 2004, Clusters and Colloids: From Theory to Applications, VCH, New York.
Huang, X., El-Sayed, I. H., and El-Sayed, M. A., 2010, “Applications of Gold Nanorods for Cancer Imaging and Photothermal Therapy,” Methods Mol. Biol., 624, pp. 343–357. [CrossRef] [PubMed]
Jordan, A., Scholz, R., Wust, P., Fähling, H., and Felix, R., 1999, “Magnetic Fluid Hyperthermia (MFH): Cancer Treatment With AC Magnetic Field Induced Excitation of Biocompatible Superparamagnetic Nanoparticles,” J. Magn. Magn. Mater., 201(1–3), pp. 413–419. [CrossRef]
Gonzales, M., and Krishnan, K. M., 2005, “Synthesis of Magnetoliposomes With Monodisperse Iron Oxide Nanocrystal Cores for Hyperthermia,” J. Magn. Magn. Mater., 293, pp. 265–270. [CrossRef]
Rogers, W. J., Meyer, C. H., and Kramer, C. M., 2006, “Cardiovascular Medicine Technology Insight: In Vivo Cell Tracking by Use of MRI,” Nat. Clin. Pract. Cardiovasc. Med., 3, pp. 554–562. [CrossRef] [PubMed]
El-Sayed, I. H., Huang, X., and El-Sayed, M. A., 2005, “Surface Plasmon Resonance Scattering and Absorption of Anti-EGFR Antibody Conjugated Gold Nanoparticles in Cancer Diagnostics: Applications in Oral Cancer,” Nano Lett., 5, pp. 829–834. [CrossRef] [PubMed]
Lee, T. M., Oldenburg, A. L., and Sitafalwalla, S., 2003, “Engineered Microsphere Contrast Agents for Optical Coherence Tomography,” Opt. Lett., 28, pp. 1546–1548. [CrossRef] [PubMed]
Cang, H., Sun, T., and Li, Z. Y., 2005, “Gold Nanocages as Contrast Agents for Spectroscopic Optical Coherence Tomography,” Opt. Lett., 30, pp. 3048–3050. [CrossRef] [PubMed]
Lin, A. W., Lewinski, N. A., West, J. L., Halas, N. J., and Drezek, R. A., 2005, “Optically Tunable Nanoparticle Contrast Agents for Early Cancer Detection: Model-Based Analysis of Gold Nanoshells,” J. Biomed. Opt., 10, p. 064035. [CrossRef] [PubMed]
Agrawal, A., Huang, S., and Lin, A. W. H., 2006, “Quantitative Evaluation of Optical Coherence Tomography Signal Enhancement With Gold Nanoshells,” J. Biomed. Opt., 11, p. 041121. [CrossRef] [PubMed]
Elliott, A. M., Shetty, A. M., Wang, J., Hazle, J. D., and Stafford, R. J., 2010, “Use of Gold Nanoshells to Constrain and Enhance Laser Thermal Therapy of Metastatic Liver Tumours,” Int. J. Hyperthermia, 26(5), pp. 434–440. [CrossRef] [PubMed]
Khosroshahia, M. E., and Nourbakhsh, M. S., 2011, “Enhanced Laser Tissue Soldering Using Indocyanine Green Chromophore and Gold Nanoshells Combination,” J. Biomed. Opt., 16(8), p. 088002. [CrossRef] [PubMed]
Gupta, A. K., and Gupta, M., 2005, “Synthesis and Surface Engineering of Iron Oxide Nanoparticles for Biomedical Applications,” J. Biomater., 26, pp. 3995–4021. [CrossRef]
O'Neal, D. P., Hirsch, L. R., Halas, N. J., Payne, J. D., and West, J. L., 2004, “Photo-Thermal Tumor Ablation in Mice Using Near Infrared-Absorbing Nanoparticles,” Cancer Lett., 209, pp. 171–176. [CrossRef] [PubMed]
Jain, P. K., Lee, K. S., El-Sayed, I. H., and El-Sayed, M. A., 2006, “Calculated Absorption and Scattering Properties of Gold Nanoparticles of Different Size, Shape, and Composition: Applications in Biological Imaging and Biomedicine,” J. Phys. Chem. B, 110, pp. 7238–7248. [CrossRef] [PubMed]
Huang, X., El-Sayed, I. H., Qian, W., and El-Sayed, M. A., 2006, “Cancer Cell Imaging and Photothermal Therapy in the Near-Infrared Region by Using Gold Nanorods,” J. Am. Chem. Soc., 128, pp. 2115–2120. [CrossRef] [PubMed]
Shukla, R., Bansal, V., Chaudhary, M., Basu, A., Bhonde, R. R., and Sastry, M., 2005, “Biocompatibility of Gold Nanoparticles and Their Endocytotic Fate Inside the Cellular Compartment: A Microscopic Overview,” Langmuir, 21, pp. 10644–10654. [CrossRef] [PubMed]
Gobin, A. M., Lee, M. H., Halas, N. J., James, W. D., Drezek, R. A., and West, J. L., 2007, “Near-Infrared Resonant Nanoshells for Combined Optical Imaging and Photothermal Cancer Therapy,” Nano Lett., 7, pp. 1929–1934. [CrossRef] [PubMed]
Loo, C., Lowery, A., Halas, N., West, J., and Drezek, R., 2005, “Immunotargeted Nanoshells for Integrated Cancer Imaging and Therapy,” Nano Lett., 5, pp. 709–711. [CrossRef] [PubMed]
Troutman, T. S., Barton, J. K., and Romanowski, M., 2007, “Optical Coherence Tomography With Plasmon Resonant Nanorods of Gold,” Opt. Lett., 32, pp. 1438–1440. [CrossRef] [PubMed]
Day, E. S., Bickford, L. R., Slater, J. H., Riggall, N. S., Drezek, R. A., and West, J. L., 2010, “Antibody-Conjugated Gold-Gold Sulfide Nanoparticles as Multifunctional Agents for Imaging and Therapy of Breast Cancer,” Int. J. Nanomed., 5, pp. 445–454. [CrossRef]
Sajjadi, A. Y., Suratkar, A., Mitra, K., and Grace, M. S., 2011, “Short-Pulse Laser-Based System for Detection of Tumors: Administration of Gold Nanoparticles Enhances Contrast,” Proceeding of ASME International Mechanical Engineering Congress and Exposition, Denver, CO, Nov. 11–17, ASME Paper No. IMECE2011-64949. [CrossRef]
Pal, G., Basu, S., Mitra, K., and Vo-Dinh, T., 2006, “Time-Resolved Optical Tomography Using Short-Pulse Laser for Tumor Detection,” Appl. Opt., 45, pp. 6270–6282. [CrossRef] [PubMed]
Pal, G., Sajjadi, A., Mitra, K., and Grace, M. S., 2009, “Transient Radiation Modeling of Short-Pulse Laser Detection of Tumors in Animal Model,” Proceedings of the 43rd Asilomar Conference on Signals, Systems and Computers (Asilomar’09), M. B.Matthews, ed., Pacific Grove, CA, Nov. 1–4, IEEE Press, Piscataway, NJ, pp. 1609–1613. [CrossRef]
Sajjadi, A. Y., Mitra, K., and Grace, M., 2011, “Ablation of Subsurface Tumors Using an Ultra-Short Pulse Laser,” Opt. Lasers Eng., 49(3), pp. 451–456. [CrossRef]
Perrault, S. D., and Chan, W. C. W., 2010, “In Vivo Assembly of Nanoparticle Components to Improve Targeted Cancer Imaging,” Proc. Natl. Acad. Sci., 107(25), pp. 11194–11199. [CrossRef]


Grahic Jump Location
Fig. 3

Comparison of normalized contrast reflected intensity from live anesthetized mice with different injected mixtures of India ink or gold nanoparticles (7.2 × 1010 nanoparticles/ml in 50 μl PBS)

Grahic Jump Location
Fig. 2

Temporal broadening of the reflected signal in live anesthetized healthy mouse for different nanoparticle concentrations. Error bars represent total uncertainty (the product of precision index and standard deviation [42]).

Grahic Jump Location
Fig. 1

Schematic of the (a) experimental setup, (b) scanning technique, and (c) a cross section of the excitation-collector probe

Grahic Jump Location
Fig. 4

Temporal broadening of the reflected signals in live anesthetized tumor-mouse after intravenously injection with gold nanoparticles (1.6 × 1012 nanoparticles in 150 μl PBS)

Grahic Jump Location
Fig. 5

Comparison of (a) normalized temporal reflected intensity, and (b) contrast reflected signal intensity in live anesthetized tumorous-mice and anesthetized tumorous mouse injected intravenously with different concentrations of gold nanoparticles at 3 HPI

Grahic Jump Location
Fig. 6

Pixel representation of the reflected signals for (a) an anesthetized mouse with tumor, and (b) an anesthetized mouse with tumor injected intravenously with gold nanoparticles. 3D distribution of the reflected intensity for (c) an anesthetized mouse with tumor, and (d) an anesthetized mouse with tumor injected intravenously with gold nanoparticles.



Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging and repositioning the boxes below.

Related Journal Articles
Related eBook Content
Topic Collections

Sorry! You do not have access to this content. For assistance or to subscribe, please contact us:

  • TELEPHONE: 1-800-843-2763 (Toll-free in the USA)
  • EMAIL: asmedigitalcollection@asme.org
Sign In