A Raman-based endoscopic strategy for multiplexed molecular imaging
Open accessAbstract
Endoscopic imaging is an invaluable diagnostic tool allowing minimally invasive access to tissues deep within the body. It has played a key role in screening colon cancer and is credited with preventing deaths through the detection and removal of precancerous polyps. However, conventional white-light endoscopy offers physicians structural information without the biochemical information that would be advantageous for early detection and is essential for molecular typing. To address this unmet need, we have developed a unique accessory, noncontact, fiber optic-based Raman spectroscopy device that has the potential to provide real-time, multiplexed functional information during routine endoscopy. This device is ideally suited for detection of functionalized surface-enhanced Raman scattering (SERS) nanoparticles as molecular imaging contrast agents. This device was designed for insertion through a clinical endoscope and has the potential to detect and quantify the presence of a multiplexed panel of tumor-targeting SERS nanoparticles. Characterization of the Raman instrument was performed with SERS particles on excised human tissue samples, and it has shown unsurpassed sensitivity and multiplexing capabilities, detecting 326-fM concentrations of SERS nanoparticles and unmixing 10 variations of colocalized SERS nanoparticles. Another unique feature of our noncontact Raman endoscope is that it has been designed for efficient use over a wide range of working distances from 1 to 10 mm. This is necessary to accommodate for imperfect centering during endoscopy and the nonuniform surface topology of human tissue. Using this endoscope as a key part of a multiplexed detection approach could allow endoscopists to distinguish between normal and precancerous tissues rapidly and to identify flat lesions that are otherwise missed.
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Cites
Raman spectra of pyridine adsorbed at a silver electrode
Fleischmann, M., Hendra, P. J., & McQuillan, A. J. (1974) · Chemical Physics Letters · doi:10.1016/0009-2614(74)85388-1 · Cited by 7,172 · see citing works
Levin, B., Lieberman, D. A., McFarland, B. G., Andrews, K. S., Brooks, D. D., Bond, J. H., Dash, C., Giardiello, F. M., Glick, S. N., Johnson, D., et al. (2008) · Gastroenterology · doi:10.1053/j.gastro.2008.02.002 · Cited by 2,987 · see citing works
In vivo tumor targeting and spectroscopic detection with surface-enhanced Raman nanoparticle tags
Qian, X., Peng, X.-H., Ansari, D. O., Yin-Goen, Q., Chen, G. Z., Shin, D. M., Yang, L., Young, A. N., Wang, M. D., & Nie, S. (2008) · Nature Biotechnology · doi:10.1038/nbt1377 · Cited by 2,201 · see citing works
Immunological properties of engineered nanomaterials
Dobrovolskaia, M. A., & McNeil, S. E. (2007) · Nature Nanotechnology · doi:10.1038/nnano.2007.223 · Cited by 1,823 · see citing works
Kircher, M. F., de la Zerda, A., Jokerst, J. V., Zavaleta, C. L., Kempen, P. J., Mittra, E., Pitter, K. L., Huang, R., Campos, C., Habte, F. G., et al. (2012) · Nature Medicine · doi:10.1038/nm.2721 · Cited by 1,066 · see citing works
Self-citationAMIDE: A Free Software Tool for Multimodality Medical Image Analysis
Loening, A. M., & Gambhir, S. S. (2003) · Molecular Imaging · doi:10.1162/153535003322556877 · Cited by 967 · see citing works
Self-citationA pilot toxicology study of single-walled carbon nanotubes in a small sample of mice
Schipper, M. L., Nakayama-Ratchford, N., Davis, C. R., Kam, N. W. S., Chu, P., Liu, Z., Sun, X., Dai, H., & Gambhir, S. S. (2008) · Nature Nanotechnology · doi:10.1038/nnano.2008.68 · Cited by 744 · see citing works
Self-citationZavaleta, C. L., Smith, B. R., Walton, I., Doering, W., Davis, G., Shojaei, B., Natan, M. J., & Gambhir, S. S. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0813327106 · Cited by 714 · see citing works
Self-citationMicro-Raman Spectroscopy Detects Individual Neoplastic and Normal Hematopoietic Cells
Chan, J. W., Taylor, D. S., Zwerdling, T., Lane, S. M., Ihara, K., & Huser, T. R. (2005) · Biophysical Journal · doi:10.1529/biophysj.105.066761 · Cited by 679 · see citing works
Soetikno, R. M. (2008) · JAMA · doi:10.1001/jama.299.9.1027 · Cited by 618 · see citing works
Noninvasive molecular imaging of small living subjects using Raman spectroscopy
Keren, S., Zavaleta, C. L., Cheng, Z., de la Zerda, A., Gheysens, O. S., & Gambhir, S. S. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0710575105 · Cited by 604 · see citing works
Self-citationNanotechnology Safety Concerns Revisited
Stern, S. T., & McNeil, S. E. (2008) · Toxicological Sciences · doi:10.1093/toxsci/kfm169 · Cited by 560 · see citing works
Balasubramanian, S. K., Jittiwat, J., Manikandan, J., Ong, C. N., Yu, L. E., & Ong, W. (2009) · Biomaterials · doi:10.1016/j.biomaterials.2009.11.079 · Cited by 523 · see citing works
Detection of colonic dysplasia in vivo using a targeted heptapeptide and confocal microendoscopy
Hsiung, P.-L., Hardy, J., Friedland, S., Soetikno, R., Du, C. B., Wu, A. P., Sahbaie, P., Crawford, J., Lowe, A. W., Contag, C. H., et al. (2008) · Nature Medicine · doi:10.1038/nm1692 · Cited by 489 · see citing works
Self-citationvon Maltzahn, G., Centrone, A., Park, J., Ramanathan, R., Sailor, M. J., Hatton, T. A., & Bhatia, S. N. (2009) · Advanced Materials · doi:10.1002/adma.200803464 · Cited by 457 · see citing works
SERS as a Foundation for Nanoscale, Optically Detected Biological Labels
Doering, W. E., Piotti, M. E., Natan, M. J., & Freeman, R. G. (2007) · Advanced Materials · doi:10.1002/adma.200701984 · Cited by 362 · see citing works
Sha, M. Y., Xu, H., Natan, M. J., & Cromer, R. (2008) · Journal of the American Chemical Society · doi:10.1021/ja804494m · Cited by 320 · see citing works
Vibrational spectroscopy: a clinical tool for cancer diagnostics
Kendall, C. A., Isabelle, M., Bazant-Hegemark, F., Hutchings, J. C., Orr, L. E., Babrah, J., Baker, R. N., & Stone, N. (2009) · The Analyst · doi:10.1039/b822130h · Cited by 290 · see citing works
Biodistribution and toxicity of intravenously administered silica nanoparticles in mice
Xie, G., Sun, J., Zhong, G., Shi, L., & Zhang, D. (2009) · Archives of Toxicology · doi:10.1007/s00204-009-0488-x · Cited by 280 · see citing works
Molckovsky, A., Song, L. W. K., Shim, M. G., et al. (2003) · Gastrointestinal Endoscopy · doi:10.1067/mge.2003.105 · Cited by 265 · see citing works
Zavaleta, C. L., de la Zerda, A., Liu, Z., Keren, S., Cheng, Z., Schipper, M. L., Chen, X. S., Dai, H., & Gambhir, S. S. (2008) · Nano Letters · doi:10.1021/nl801362a · Cited by 263 · see citing works
Self-citationNanomaterial standards for efficacy and toxicity assessment
Adiseshaiah, P. P., Hall, J. B., & McNeil, S. E. (2009) · Wiley Interdisciplinary Reviews Nanomedicine and Nanobiotechnology · doi:10.1002/wnan.66 · Cited by 238 · see citing works
Raman, C. V. (1953) · Proceedings of the Indian Academy of Sciences - Section A · doi:10.1007/bf03052651 · Cited by 236 · see citing works
Nanoparticle therapeutics: a personal perspective
McNeil, S. E. (2009) · Wiley Interdisciplinary Reviews Nanomedicine and Nanobiotechnology · doi:10.1002/wnan.6 · Cited by 231 · see citing works
Computational and Ultrastructural Toxicology of a Nanoparticle, Quantum Dot 705, in Mice
Lin, P., Chen, J.-W., Chang, L. W., Wu, J.-P., Redding, L. E., Chang, H., Yeh, T., Yang, C. S., Tsai, M., Wang, H., et al. (2008) · Environmental Science & Technology · doi:10.1021/es800254a · Cited by 214 · see citing works
Mohs, A. M., Mancini, M. C., Singhal, S. K., Provenzale, J. M., Leyland-Jones, B. R., Wang, M. D., & Nie, S. (2010) · Analytical Chemistry · doi:10.1021/ac102058k · Cited by 210 · see citing works
Crow, P., Molckovsky, A., Stone, N., Uff, J., Wilson, B. C., & Wongkeesong, L. (2005) · Urology · doi:10.1016/j.urology.2004.12.058 · Cited by 208 · see citing works
Biodistribution of TNF-α-Coated Gold Nanoparticles in An In Vivo Model System
Goel, R., Shah, N. B., Visaria, R. K., Paciotti, G. F., & Bischof, J. C. (2009) · Nanomedicine · doi:10.2217/nnm.09.21 · Cited by 188 · see citing works
Uddin, M. J., Crews, B. C., Blobaum, A. L., Kingsley, P. J., Gorden, D. L., McIntyre, J. O., Matrisian, L. M., Subbaramaiah, K., Dannenberg, A. J., Piston, D. W., et al. (2010) · Cancer Research · doi:10.1158/0008-5472.can-09-2664 · Cited by 173 · see citing works
The Fate and Toxicity of Raman-Active Silica-Gold Nanoparticles in Mice
Thakor, A. S., Luong, R., Paulmurugan, R., Lin, F. I., Kempen, P., Zavaleta, C., Chu, P., Massoud, T. F., Sinclair, R., & Gambhir, S. S. (2011) · Science Translational Medicine · doi:10.1126/scitranslmed.3001963 · Cited by 159 · see citing works
Self-citationNew optical technologies for earlier endoscopic diagnosis of premalignant gastrointestinal lesions
DaCosta, R. S., Wilson, B. C., & Marcon, N. E. (2002) · Journal of Gastroenterology and Hepatology · doi:10.1046/j.1440-1746.17.s1.8.x · Cited by 155 · see citing works
Raman spectroscopic imaging for in vivo detection of cerebral brain metastases
Kirsch, M., Schackert, G., Salzer, R., et al. (2010) · Analytical and Bioanalytical Chemistry · doi:10.1007/s00216-010-4116-7 · Cited by 154 · see citing works
Qian, J., Jiang, L., Cai, F., Wang, D., & He, S. (2010) · Biomaterials · doi:10.1016/j.biomaterials.2010.10.058 · Cited by 149 · see citing works
Jokerst, J. V., Miao, Z., Zavaleta, C. L., Cheng, Z., & Gambhir, S. S. (2011) · Small · doi:10.1002/smll.201002291 · Cited by 144 · see citing works
Self-citationYong, K., Roy, I., Ding, H. Y., et al. (2009) · Small · doi:10.1002/smll.200900547 · Cited by 140 · see citing works
Spectral Analysis of Multiplex Raman Probe Signatures
Lutz, B. R., Dentinger, C. E., Nguyen, L. N., Sun, L., Zhang, J., Allen, A. N., Chan, S., & Knudsen, B. S. (2008) · ACS Nano · doi:10.1021/nn800243g · Cited by 135 · see citing works
Noninvasive MRI-SERS Imaging in Living Mice Using an Innately Bimodal Nanomaterial
Yigit, M. V., Zhu, L., Ifediba, M. A., Zhang, Y., Carr, K., Moore, A. V., & Medarova, Z. O. (2010) · ACS Nano · doi:10.1021/nn102587h · Cited by 111 · see citing works
Optical Techniques for the Endoscopic Detection of Early Dysplastic Colonic Lesions
DaCosta, R. S., Wilson, B. C., & Marcon, N. E. (2003) · Wiley eBooks · doi:10.1002/9780470986943.ch44 · Cited by 109 · see citing works
Zavaleta, C. L., Hartman, K. B., Miao, Z., James, M. L., Kempen, P. J., Thakor, A. S., Nielsen, C. H., Sinclair, R., Cheng, Z., & Gambhir, S. S. (2011) · Small · doi:10.1002/smll.201002317 · Cited by 89 · see citing works
Self-citationOxidative Stress Mediates the Effects of Raman‐Active Gold Nanoparticles in Human Cells
Thakor, A. S., Paulmurugan, R., Kempen, P. J., Zavaleta, C. L., Sinclair, R., Massoud, T. F., & Gambhir, S. S. (2010) · Small · doi:10.1002/smll.201001466 · Cited by 89 · see citing works
Self-citationApplication of Raman spectroscopy for cervical dysplasia diagnosis
Kanter, E. M., Vargis, E., Majumder, S. K., et al. (2009) · Journal of Biophotonics · doi:10.1002/jbio.200910001 · Cited by 87 · see citing works
de Wit, M., Jiménez, C. R., Carvalho, B. G., Beliën, J. A. M., Diemen, P. M. D., Mongera, S., Piersma, S. R., Maindad, V. C., Navani, S., Pontén, F., et al. (2011) · Gut · doi:10.1136/gutjnl-2011-300511 · Cited by 77 · see citing works
Ex vivo optical properties of human colon tissue
Marchesini, R., Pignoli, E., Tomatis, S., Fumagalli, S., Sichirollo, A. E., Palma, S. D., Fante, M. D., Spinelli, P., Croce, A. C., & Bottiroli, G. F. (1994) · Lasers in Surgery and Medicine · doi:10.1002/lsm.1900150404 · Cited by 75 · see citing works
Imaging methods for elemental, chemical, molecular, and morphological analyses of single cells
Petibois, C. (2010) · Analytical and Bioanalytical Chemistry · doi:10.1007/s00216-010-3618-7 · Cited by 63 · see citing works
Vibrational spectroscopy differentiates between multipotent and pluripotent stem cells
Pijanka, J. K., Kumar, D., Dale, T. P., et al. (2010) · The Analyst · doi:10.1039/c0an00525h · Cited by 62 · see citing works
Smith, B. R., Cheng, Z., De, A., Rosenberg, J., & Gambhir, S. S. (2010) · Small · doi:10.1002/smll.201001022 · Cited by 53 · see citing works
Self-citationGinty, F., Adak, S., Can, A., et al. (2008) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-08-0180 · Cited by 47 · see citing works
Funovics, M. A., Alencar, H., Montet, X., Weissleder, R., & Mahmood, U. (2006) · Gastrointestinal Endoscopy · doi:10.1016/j.gie.2006.02.048 · Cited by 44 · see citing works
Mallia, R. J., Veilleux, I., Wilson, B. C., & McVeigh, P. Z. (2012) · Journal of Biomedical Optics · doi:10.1117/1.jbo.17.7.076017 · Cited by 25 · see citing works
An unmet medical need: Advances in endoscopic imaging of colorectal neoplasia
Stallmach, A., Schmidt, C., Watson, A. J. M., et al. (2011) · Journal of Biophotonics · doi:10.1002/jbio.201100027 · Cited by 21 · see citing works
Development of a widefield SERS imaging endoscope
McVeigh, P. Z., Mallia, R. J., Veilleux, I., et al. (2012) · Proceedings of SPIE, the International Society for Optical Engineering/Proceedings of SPIE · doi:10.1117/12.907304 · Cited by 9 · see citing works
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Self-citation
- Authors
- Zavaleta, C. L., Garai, E., Liu, J. T. C., Sensarn, S., Mandella, M. J., Van de Sompel, D., Friedland, S., Van Dam, J., Contag, C. H., & Gambhir, S. S.
- Affiliations
- Stanford Medicine (US)
- Stony Brook University (US)
- Department of Radiology, Stanford University, Stanford, CA 94305;
- Division of Gastroenterology and Hepatology, University of Southern California, Los Angeles, CA 90089;
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2013-05-23
- Volume
- 110
- Issue
- 25
- Pages
- E2288-97
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3690865
- OpenAlex
- W2122296714
- Cited by
- 238
- References
- 51
- Citations by year
- 2026: 6 · 2025: 14 · 2024: 14 · 2023: 13 · 2022: 13 · 2021: 17 · 2020: 15 · 2019: 15 · 2018: 20 · 2017: 37 · 2016: 19 · 2015: 26 · 2014: 24 · 2013: 5
- FWCI
- 14.95
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Public Health Service (5-R01-EBB000312)
- National Cancer Institute (U54CA119367, P50CA114747, U54CA136465, T32CA009695)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Spectroscopy Techniques in Biomedical and Chemical Research
- Physical Sciences › Materials Science › Electronic, Optical and Magnetic Materials › Gold and Silver Nanoparticles Synthesis and Applications
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Optical Imaging and Spectroscopy Techniques
- Keywords
- Raman spectroscopy, endoscopic imaging, colon cancer detection, precancerous polyps, early cancer detection, working distance
- MeSH terms
- Colon, Colonic Neoplasms, Colonoscopy, Equipment Design, Humans, Male, Pilot Projects, Precancerous Conditions, Quartz, Scattering, Radiation, Sensitivity and Specificity, Spectrum Analysis, Raman, Models, Statistical, Adenomatous Polyps, Endoscopes, Nanoparticles, Optical Fibers
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