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Biomedical Optics Express

Biomedical Optics Express

  • Editor: Joseph A. Izatt
  • Vol. 3, Iss. 1 — Jan. 1, 2012
  • pp: 178–191

Fluorescence-guided optical coherence tomography imaging for colon cancer screening: a preliminary mouse study

Nicusor Iftimia, Arun K. Iyer, Daniel X. Hammer, Niyom Lue, Mircea Mujat, Martha Pitman, R. Daniel Ferguson, and Mansoor Amiji  »View Author Affiliations

Biomedical Optics Express, Vol. 3, Issue 1, pp. 178-191 (2012)

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A new concept for cancer screening has been preliminarily investigated. A cancer targeting agent loaded with a near-infrared (NIR) dye was topically applied on the tissue to highlight cancer-suspect locations and guide optical coherence tomography (OCT) imaging, which was used to further investigate tissue morphology at the micron scale. A pilot study on ApcMin mice has been performed to preliminarily test this new cancer screening approach. As a cancer-targeting agent, poly(epsilon-caprolactone) microparticles (PCLMPs), labeled with a NIR dye and functionalized with an RGD (argenine-glycine-aspartic acid) peptide, were used. This agent recognizes the ανβ3 integrin receptor (ABIR), which is over-expressed by epithelial cancer cells. The contrast agent was administered topically in vivo in mouse colon. After incubation, the animals were sacrificed and fluorescence-guided high resolution optical coherence tomography (OCT) imaging was used to visualize colon morphology. The preliminary results show preferential staining of the abnormal tissue, as indicated by both microscopy and laser-induced fluorescence imaging, and OCT’s capability to differentiate between normal mucosal areas, early dysplasia, and adenocarcinoma. Although very preliminary, the results of this study suggest that fluorescence-guided OCT imaging might be a suitable approach for cancer screening. If successful, this approach could be used by clinicians to more reliably diagnose early stage cancers in vivo.

© 2011 OSA

OCIS Codes
(170.0170) Medical optics and biotechnology : Medical optics and biotechnology
(170.4500) Medical optics and biotechnology : Optical coherence tomography
(170.4580) Medical optics and biotechnology : Optical diagnostics for medicine
(170.6935) Medical optics and biotechnology : Tissue characterization

ToC Category:
Optical Coherence Tomography

Original Manuscript: November 7, 2011
Revised Manuscript: December 7, 2011
Manuscript Accepted: December 18, 2011
Published: December 19, 2011

Nicusor Iftimia, Arun K. Iyer, Daniel X. Hammer, Niyom Lue, Mircea Mujat, Martha Pitman, R. Daniel Ferguson, and Mansoor Amiji, "Fluorescence-guided optical coherence tomography imaging for colon cancer screening: a preliminary mouse study," Biomed. Opt. Express 3, 178-191 (2012)

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  1. H. Tajiri, A. Ohtsu, N. Boku, M. Muto, K. Chin, S. Matsumoto, and S. Yoshida, “Routine endoscopy using electronic endoscopes for gastric cancer diagnosis: retrospective study of inconsistencies between endoscopic and biopsy diagnoses,” Cancer Detect. Prev.25(2), 166–173 (2001). [PubMed]
  2. G. Jeffery, B. Hickey, and P. N. Hilder, “Follow up strategies for patients treated for non-metastatic colorectal cancer (Review),” Cochrane Database Syst. Rev.1, 1–27 (2008), http://generalsurgery.utoronto.ca/Assets/GenSurgery+Digital+Assets/Hospitals/cochranereview.pdf .
  3. O. Hosokawa, K. Watanabe, M. Hatorri, K. Douden, H. Hayashi, and Y. Kaizaki, “Detection of gastric cancer by repeat endoscopy within a short time after negative examination,” Endoscopy33(4), 301–305 (2001). [CrossRef] [PubMed]
  4. R. Lambert and J. F. Rey, “Endoscopy and early neoplasia: better but not the best,” Endoscopy33(4), 348–352 (2001). [CrossRef] [PubMed]
  5. J. J. Ott, A. Ullrich, and A. B. Miller, “The importance of early symptom recognition in the context of early detection and cancer survival,” Eur. J. Cancer45(16), 2743–2748 (2009). [CrossRef] [PubMed]
  6. E. D. A. Westcott and A. C. J. Windsor, “Can we improve the outcome of colorectal cancer by early diagnosis?” Postgrad. Med. J.78(919), 255–256 (2002). [CrossRef] [PubMed]
  7. W. A. Weber, J. Czernin, M. E. Phelps, and H. R. Herschman, “Technology Insight: novel imaging of molecular targets is an emerging area crucial to the development of targeted drugs,” Nat. Clin. Pract. Oncol.5(1), 44–54 (2008). [CrossRef] [PubMed]
  8. T. F. Massoud and S. S. Gambhir, “Integrating noninvasive molecular imaging into molecular medicine: an evolving paradigm,” Trends Mol. Med.13(5), 183–191 (2007). [CrossRef] [PubMed]
  9. N. K. Tafreshi, V. Kumar, D. L. Morse, and R. A. Gatenby, “Molecular and functional imaging of breast cancer,” Cancer Contr.17(3), 143–155 (2010). [PubMed]
  10. K. Brindle, “New approaches for imaging tumour responses to treatment,” Nat. Rev. Cancer8(2), 94–107 (2008). [CrossRef] [PubMed]
  11. M. A. Rosen and M. D. Schnall, “Dynamic contrast-enhanced magnetic resonance imaging for assessing tumor vascularity and vascular effects of targeted therapies in renal cell carcinoma,” Clin. Cancer Res.13(2), 770s–776s (2007). [CrossRef] [PubMed]
  12. M. C. Pierce, D. J. Javier, and R. Richards-Kortum, “Optical contrast agents and imaging systems for detection and diagnosis of cancer,” Int. J. Cancer123(9), 1979–1990 (2008). [CrossRef] [PubMed]
  13. M. V. Sivak, K. Kobayashi, J. A. Izatt, A. M. Rollins, R. Ung-Runyawee, A. Chak, R. C. Wong, G. A. Isenberg, and J. Willis, “High-resolution endoscopic imaging of the GI tract using optical coherence tomography,” Gastrointest. Endosc.51(4), 474–479 (2000). [CrossRef] [PubMed]
  14. R. A. Drezek, T. Collier, C. K. Brookner, A. Malpica, R. Lotan, R. R. Richards-Kortum, and M. Follen, “Laser scanning confocal microscopy of cervical tissue before and after application of acetic acid,” Am. J. Obstet. Gynecol.182(5), 1135–1139 (2000). [CrossRef] [PubMed]
  15. L. P. Hariri, G. T. Bonnema, K. Schmidt, A. M. Winkler, V. Korde, K. D. Hatch, J. R. Davis, M. A. Brewer, and J. K. Barton, “Laparoscopic optical coherence tomography imaging of human ovarian cancer,” Gynecol. Oncol.114(2), 188–194 (2009). [CrossRef] [PubMed]
  16. M. Kraft, H. Glanz, S. von Gerlach, H. Wisweh, H. Lubatschowski, and C. Arens, “Clinical value of optical coherence tomography in laryngology,” Head Neck30(12), 1628–1635 (2008). [CrossRef] [PubMed]
  17. J. A. Evans, B. E. Bouma, J. Bressner, M. Shishkov, G. Y. Lauwers, M. Mino-Kenudson, N. S. Nishioka, and G. J. Tearney, “Identifying intestinal metaplasia at the squamocolumnar junction by using optical coherence tomography,” Gastrointest. Endosc.65(1), 50–56 (2007). [CrossRef] [PubMed]
  18. B. E. Bouma, G. J. Tearney, C. C. Compton, and N. S. Nishioka, “High-resolution imaging of the human esophagus and stomach in vivo using optical coherence tomography,” Gastrointest. Endosc.51(4), 467–474 (2000). [CrossRef] [PubMed]
  19. P. A. Testoni, A. Mariani, B. Mangiavillano, P. G. Arcidiacono, S. Di Pietro, and E. Masci, “Intraductal optical coherence tomography for investigating main pancreatic duct strictures,” Am. J. Gastroenterol.102(2), 269–274 (2007). [CrossRef] [PubMed]
  20. N. Iftimia, S. Cizginer, V. Deshpande, M. Pitman, S. Tatli, N. A. Iftimia, D. X. Hammer, M. Mujat, T. Ustun, R. D. Ferguson, and W. R. Brugge, “Differentiation of pancreatic cysts with optical coherence tomography (OCT) imaging: an ex vivo pilot study,” Biomed. Opt. Express2(8), 2372–2382 (2011). [CrossRef] [PubMed]
  21. J. Ai, E. Biazar, M. Jafarpour, M. Montazeri, A. Majdi, S. Aminifard, M. Zafari, H. R. Akbari, and H. G. Rad, “Nanotoxicology and nanoparticle safety in biomedical designs,” Int. J. Nanomedicine6, 1117–1127 (2011). [PubMed]
  22. N. Lue, S. Ganta, D. X. Hammer, M. Mujat, A. E. Stevens, L. Harrison, R. D. Ferguson, D. Rosen, M. Amiji, and N. Iftimia, “Preliminary evaluation of a nanotechnology-based approach for the more effective diagnosis of colon cancers,” Nanomedicine (Lond.)5(9), 1467–1479 (2010). [CrossRef] [PubMed]
  23. G.-Y. Yang, K.-S. Xu, Z.-Q. Pan, Z.-Y. Zhang, Y.-T. Mi, J.-S. Wang, R. Chen, and J. Niu, “Integrin alphavbeta6 mediates the potential for colon cancer cells to colonize in and metastasize to the liver,” Cancer Sci.99(5), 879–887 (2008). [CrossRef]
  24. R. Del Buono, M. Pignatelli, W. F. Bodmer, and N. A. Wright, “The role of the arginine-glycine-aspartic acid-directed cellular binding to type I collagen and rat mesenchymal cells in colorectal tumour differentiation,” Differentiation46(2), 97–103 (1991). [CrossRef] [PubMed]
  25. D. Meyer, G. Nickols, J. Pegg, and W. Westlin, “An oral alpha-v-beta-3 antagonist, S-247, induces tumor regression and inhibits hypercalcemia of malignancy in a syngeneic mouse colon model,” Proc. Am. Assoc. Cancer Res.42, 825 (2001).
  26. D. Griggs, K. Shannon, S. Settle, T. Duffin, M. Nickols, S. Schroeter, N. Gickols, and W. Westlin, “Anti-metastatic efficacy mediated by peptidomimetic alpha-v-beta-3 integrin antagonists in orthotopic and experimental models,” Proc. Am. Assoc. Cancer Res.42, 263 (2001).
  27. T. E. Ustun, N. V. Iftimia, R. D. Ferguson, and D. X. Hammer, “Real-time processing for Fourier domain optical coherence tomography using a field programmable gate array,” Rev. Sci. Instrum.79(11), 114301 (2008). [CrossRef] [PubMed]
  28. H. L. Kettunen, A. S. L. Kettunen, and N. E. Rautonen, “Intestinal immune responses in wild-type and Apcmin/+ mouse, a model for colon cancer,” Cancer Res.63(16), 5136–5142 (2003). [PubMed]
  29. N. Howlader, A. M. Noone, M. Krapcho, N. Neyman, R. Aminou, W. Waldron, S. F. Altekruse, C. L. Kosary, J. Ruhl, Z. Tatalovich, H. Cho, A. Mariotto, M. P. Eisner, D. R. Lewis, H. S. Chen, E. J. Feuer, K. A. Cronin, and B. K. Edwards, eds., Surveillance Epidemiology and End Results, Cancer Statistics Review, 1975–2008, National Cancer Institute, Bethesda MD, http://seer.cancer.gov/csr/1975-2008 .
  30. M. S. Cappell, “Pathophysiology, clinical presentation, and management of colon cancer,” Gastroenterol. Clin. North Am.37(1), 1–24, v (2008). [CrossRef] [PubMed]
  31. C. E. Desch, A. B. Benson, M. R. Somerfield, P. J. Flynn, C. Krause, C. L. Loprinzi, B. D. Minsky, D. G. Pfister, K. S. Virgo, N. J. Petrelli, and American Society of Clinical Oncology, “Colorectal cancer surveillance: 2005 update of an American Society of Clinical Oncology practice guideline,” J. Clin. Oncol.23(33), 8512–8519 (2005). [CrossRef] [PubMed]
  32. P. R. Pfau, M. V. Sivak, A. Chak, M. Kinnard, R. C. Wong, G. A. Isenberg, J. A. Izatt, A. Rollins, and V. Westphal, “Criteria for the diagnosis of dysplasia by endoscopic optical coherence tomography,” Gastrointest. Endosc.58(2), 196–202 (2003). [CrossRef] [PubMed]
  33. A. R. Tumlinson, L. P. Hariri, U. Utzinger, and J. K. Barton, “Miniature endoscope for simultaneous optical coherence tomography and laser-induced fluorescence measurement,” Appl. Opt.43(1), 113–121 (2004). [CrossRef] [PubMed]
  34. S. Y. Ryu, H. Y. Choi, J. Na, E. S. Choi, and B. H. Lee, “Combined system of optical coherence tomography and fluorescence spectroscopy based on double-cladding fiber,” Opt. Lett.33(20), 2347–2349 (2008). [CrossRef] [PubMed]
  35. J. Park, J. A. Jo, S. Shrestha, P. Pande, Q. Wan, and B. E. Applegate, “A dual-modality optical coherence tomography and fluorescence lifetime imaging microscopy system for simultaneous morphological and biochemical tissue characterization,” Biomed. Opt. Express1(1), 186–200 (2010). [CrossRef] [PubMed]
  36. S. Yuan, C. A. Roney, J. Wierwille, C. W. Chen, B. Xu, G. Griffiths, J. Jiang, H. Ma, A. Cable, R. M. Summers, and Y. Chen, “Co-registered optical coherence tomography and fluorescence molecular imaging for simultaneous morphological and molecular imaging,” Phys. Med. Biol.55(1), 191–206 (2010). [CrossRef] [PubMed]
  37. C. A. Roney, B. Xu, J. Xie, S. Yuan, J. Wierwille, C. W. Chen, Y. Chen, G. L. Griffiths, and R. M. Summers, “Rh-I-UEA-1 polymerized liposomes target and image adenomatous polyps in the APC(Min/+) mouse using optical colonography,” Mol. Imaging10(4), 305–316 (2011). [PubMed]

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