Breast Cancer Research and Treatment

, Volume 84, Issue 2, pp 85–97 | Cite as

Optical Coherence Tomography: Feasibility for Basic Research and Image-guided Surgery of Breast Cancer

  • Stephen A. Boppart
  • Wei Luo
  • Daniel L. Marks
  • Keith W. Singletary


Diagnostic trends in medicine are being directed toward cellular and molecular processes, where treatment regimens are more amenable for cure. Optical imaging is capable of performing cellular and molecular imaging using the short wavelengths and spectroscopic properties of light. Diffuse optical tomography is an optical imaging technique that has been pursued as an alternative to X-ray mammography. While this technique permits non-invasive optical imaging of the whole breast, to date it is incapable of resolving features at the cellular level. Optical coherence tomography (OCT) is an emerging high-resolution biomedical imaging technology that for larger and undifferentiated cells can perform cellular-level imaging at the expense of imaging depth. OCT performs optical ranging in tissue and is analogous to ultrasound except reflections of near-infrared light are detected rather than sound. In this paper, an overview of the OCT technology is provided, followed by images demonstrating the feasibility of using OCT to image cellular features indicative of breast cancer. OCT images of a well-established carcinogen-induced rat mammary tumor model were acquired. Images from this common experimental model show strong correlation with corresponding histopathology. These results illustrate the potential of OCT for a wide range of basic research studies and for intra-operative image-guidance to identify foci of tumor cells within surgical margins during the surgical treatment of breast cancer.

breast cancer imaging image-guided surgery MNU-induced carcinogenesis optical coherence tomography optical imaging rat mammary tumor 


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  1. 1.
    American Cancer Society, Cancer Facts & Figures, 2003Google Scholar
  2. 2.
    American Cancer Society, Cancer Prevention & Early Detection Facts & Figures, 2003Google Scholar
  3. 3.
    Profio AE, Doiron DR: Transport of light in tissue in photodynamic therapy of cancer. Photochem Photobiol 46: 591–599, 1987Google Scholar
  4. 4.
    Yodh AG, Chance B: Spectroscopy and imaging with diffusing light. Phys Today 48: 34–40, 1995Google Scholar
  5. 5.
    Jiang H, Xu Y, Iftimia N, Eggert J, Klove K, Baron L, Fajardo L: Three-dimensional optical tomographic imaging of breast in a human subject. IEEE Trans Med Imaging 20: 1334–1340, 2001Google Scholar
  6. 6.
    Shah N, Cerussi A, Eker C, Espinoza J, Butler J, Fishkin J, Hornung R, Tromberg B: Noninvasive functional optical spectroscopy of human breast tissue. Proc Natl Acad Sci USA 98: 4420–4425, 2001Google Scholar
  7. 7.
    Huang D, Swanson EA, Lin CP, Schuman JS, Stinson WG, Chang W, Hee MR, Flotte T, Gregory K, Puliafito CA, Fujimoto JG: Optical coherence tomography. Science 254: 1178–1181, 1991Google Scholar
  8. 8.
    Bouma BE, Tearney GJ (eds.): Handbook of Optical Coherence Tomography. Marcel Dekker, New York, NY, 2002Google Scholar
  9. 9.
    Boppart SA, Bouma BE, Pitris C, Tearney GJ, Southern JF, Brezinski ME, Fujimoto JG: Intraoperative assessment of microsurgery with three-dimensional optical coherence tomography. Radiology 208: 81–86, 1998Google Scholar
  10. 10.
    Povazay B, Bizheva K, Unterhuber A, Hermann B, Sallmann H, Fercher AF, Drexler W, Apolonski A, Wadsworth WJ, Knight JC, Russell PSJ, Vetterlein M, Scherzer E: Submicrometer axial resolution optical coherence tomography. Opt Lett 27: 1800–1802, 2002Google Scholar
  11. 11.
    Tearney GJ, Brezinski ME, Bouma BE, Boppart SA, Pitris C, Southern JF, Fujimoto JG: In vivo endoscopic optical biopsy with optical coherence tomography. Science 276: 2037–2039, 1997Google Scholar
  12. 12.
    Sergeev AM, Gelikonov VM, Gelikonov GV, Feldchtein FI, Kuranov RV, Gladkova ND, Shakhova NM, Snopova LB, Shakov AV, Kuznetzova IA, Denisenko AN, Pochinko VV, Chumakov YP, Streltzova OS: In vivo endoscopic OCT imaging of precancer and cancer states of human mucosa. Opt Express 1: 432–440, 1997Google Scholar
  13. 13.
    Boppart SA, Brezinski ME, Pitris C, Fujimoto JG: Optical coherence tomography for neurosurgical imaging of human intracortical melanoma. Neurosurgery 43: 834–841, 1998Google Scholar
  14. 14.
    Li X, Chudoba C, Ko T, Pitris C, Fujimoto JG: Imaging needle for optical coherence tomography. Opt Lett 25: 1520–1522, 2000Google Scholar
  15. 15.
    Boppart SA, Bouma BE, Pitris C, Tearney GJ, Fujimoto JG: Forward-imaging instruments for optical coherence tomography. Opt Lett 22: 1618–1620, 1997Google Scholar
  16. 16.
    Holland R, Veling SH, Mravunac M, Hendriks JH: Histologic multifocality of TIS, T1-T2 breast carcinomas. Implications for clinical trails of breast-conserving surgery. Cancer 56: 979–990, 1985Google Scholar
  17. 17.
    Katz A, Strom EA, Buchholz TA, Thames HD, Smith CD, Jhingran A, Hortobagyi G, Buzdar AU, Theriault R, Singletary SE, McNeese MD: Locoregional recurrence patterns after mastectomy and doxorubicin-based chemotherapy: implications for postoperative irradiation. J Clin Oncol 18: 2817–2827, 2000Google Scholar
  18. 18.
    Schneebaum S, Even-Sapir E, Cohen M, Shacham-Lehrman H, Gat A, Brazovsky E, Livshitz G, Stadler J, Skornick Y: Clinical applications of gamma-detection probes-radioguided surgery. Eur J Nucl Med 26: S26–S35, 1999Google Scholar
  19. 19.
    Kaplan I, Oldenburg NE, Meskell P, Blake M, Church P, Holupka EJ: Real time MRI-ultrasound image guided stereotactic prostate biopsy. Magn Reson Imaging 20: 295–299, 2002Google Scholar
  20. 20.
    Puliafito CA, Hee MR, Schuman JS, Fujimoto JG: Optical Coherence Tomography of Ocular Diseases. Slack Inc., Thorofare, NJ, 1995Google Scholar
  21. 21.
    Schmitt JM, Knuttel A, Yadlowsky M, Eckhaus AA: Optical coherence tomography of a dense tissue: statistics of attenuation and backscattering. Phys Med Biol 39: 1705–1720, 1994Google Scholar
  22. 22.
    Schmitt JM, Yadlowsky MJ, Bonner RF: Subsurface imaging of living skin with optical coherence microscopy. Dermatology 191: 93–98, 1995Google Scholar
  23. 23.
    Brezinski ME, Tearney GJ, Bouma BE, Izatt JA, Hee MR, Swanson EA, Southern JF, Fujimoto JG: Optical coherence tomography for optical biopsy: properties and demonstration of vascular pathology. Circulation 93: 1206–1213, 1996Google Scholar
  24. 24.
    Tearney GJ, Brezinski ME, Southern JF, Bouma BE, Boppart SA, Fujimoto JG: Optical biopsy in human gastrointestinal tissue using optical coherence tomography. Am J Gastroenterol 92: 1800–1804, 1997Google Scholar
  25. 25.
    Tearney GJ, Brezinski ME, Southern JF, Bouma BE, Boppart SA, Fujimoto JG: Optical biopsy in human urologic tissue using optical coherence tomography. J Urol 157: 1915–1919, 1997Google Scholar
  26. 26.
    Bouma BE, Tearney GJ, Boppart SA, Hee MR, Brezinski ME, Fujimoto JG: High resolution optical coherence tomographic imaging using a modelocked Ti:Al2O3 laser. Opt Lett 20: 1486–1488, 1995Google Scholar
  27. 27.
    Drexler W, Morgner U, Kartner FX, Pitris C, Boppart SA, Li X, Ippen EP, Fujimoto JG: In vivo ultrahigh resolution optical coherence tomography. Opt Lett 24: 1221–1223, 1999Google Scholar
  28. 28.
    Tearney GJ, Bouma BE, Boppart SA, Golubovic B, Swanson EA, Fujimoto JG: Rapid acquisition of in vivo biological images using optical coherence tomography Opt Lett 21: 1408–1410, 1996Google Scholar
  29. 29.
    Ren H, Brecke KM, Ding Z, Zhao Y, Nelson JS, Chen Z: Imaging and quantifying transverse flow velocity with the Doppler bandwidth in a phase-resolved functional optical coherence tomography. Opt Lett 27: 409–411, 2002Google Scholar
  30. 30.
    Yazdanfar S, Izatt JA: Self-referenced Doppler optical coherence tomography. Opt Lett 27: 2085–2087, 2002Google Scholar
  31. 31.
    Pierce MC, Park BH, Cense B, de Boer JF: Simultaneous intensity, birefringence, and flow measurements with highspeed fiber-based optical coherence tomography. Opt Lett 27: 1534–1536, 2002Google Scholar
  32. 32.
    Tearney GJ, Boppart SA, Bouma BE, Brezinski ME, Weissman NJ, Southern JF, Fujimoto JG: Scanning singlemode fiber optic catheter-endoscope for optical coherence tomography. Opt Lett 21: 1–3, 1996Google Scholar
  33. 33.
    Pan Y, Xie H, Fedder GK: Endoscopic optical coherence tomography based on a microelectromechanical mirror. Opt Lett 26: 1966–1968, 2001Google Scholar
  34. 34.
    Bouma BE, Tearney GJ, Compton CC, Nishioka NS: Highresolution imaging of the human esophagus and stomach in vivo using optical coherence tomography. Gastrointest Endosc 51: 467–474, 2000Google Scholar
  35. 35.
    Sivak MVJr, Kobayashi K, Izatt JA, Rollins AM, Ung-Runyawee R, Chak A, Wong RC, Isenberg GA, Willis J: High-resolution endoscopic imaging of the gastrointestinal tract using optical coherence tomography. Gastrointest Endosc 51: 474–479, 2000Google Scholar
  36. 36.
    Li X, Boppart SA, Van Dam J, Mashimo H, Mutinga M, Drexler W, Klein M, Pitris C, Krinsky ML, Brezinski ME, Fujimoto JG: Optical coherence tomography: advanced technology for the endoscopic imaging of Barrett's esophagus. Endoscopy 32: 921–930, 2000Google Scholar
  37. 37.
    Jang IK, Bouma BE, Kang DH, Park SJ, Park SW, Seung KB, Choi KB, Shishkov M, Schlendorf K, Pomerantsev E, Houser SL, Aretz HT, Tearney GJ: Visualization of coronary atherosclerotic plaques in patients using optical coherence tomography: comparison with intravascular ultrasound. J Am Coll Cardiol 39: 604–609, 2002Google Scholar
  38. 38.
    Pitris C, Goodman AK, Boppart SA, Libus JJ, Fujimoto JG, Brezinski ME: High resolution imaging of gynecological neoplasms using optical coherence tomography. Obstet Gynecol 93: 135–139, 1999Google Scholar
  39. 39.
    Pitris C, Jesser C, Boppart SA, Stamper D, Brezinski ME, Fujimoto JG: Feasibility of optical coherence tomography for high resolution imaging of human gastrointestinal tract malignancies. J Gastroenterol 35: 87–92, 1999Google Scholar
  40. 40.
    Xie TQ, Zeidel ML, Pan Y: Detection of tumorgenesis in urinary bladder with optical coherence tomography: optical characterization of morphological changes. Opt Express 10: 1431–1443, 2002Google Scholar
  41. 41.
    Boppart SA, Brezinski ME, Bouma BE, Tearney GJ, Fujimoto JG: Investigation of developing embryonic morphology using optical coherence tomography. Dev Biol 177: 54–63, 1996Google Scholar
  42. 42.
    Boppart SA, Tearney GJ, Bouma BE, Southern JF, Brezinski ME, Fujimoto JG: Noninvasive assessment of the developing Xenopus cardiovascular system using optical coherence tomography. Proc Natl Acad Sci USA 94: 4256–4261, 1997Google Scholar
  43. 43.
    Boppart SA, Bouma BE, Pitris C, Southern JF, Brezinski ME, Fujimoto JG: In vivo cellular optical coherence tomography imaging. Nature Med 4: 861–864, 1998Google Scholar
  44. 44.
    Brezinski ME, Tearney GJ, Boppart SA, Swanson EA, Southern JF, Fujimoto JG: Optical biopsy with optical coherence tomography: feasibility for surgical diagnostics. J Surg Res 71: 32–40, 1997Google Scholar
  45. 45.
    Boppart SA, Herrmann JM, Pitris C, Stamper DL, Brezinski ME, Fujimoto JG: High-resolution optical coherence tomography guided laser ablation of surgical tissue. J Surg Res 82: 275–284, 1999Google Scholar
  46. 46.
    Boppart SA, Goodman AK, Pitris C, Jesser C, Libis JJ, Brezinski ME, Fujimoto JG: High-resolution imaging of endometriosis and ovarian carcinoma with optical coherence tomography: feasibility for laparoscopic-based imaging. Br J Obstet Gyn 106: 1071–1077, 1999Google Scholar
  47. 47.
    Boppart SA, Herrmann JM, Pitris C, Stamper DL, Brezinski ME, Fujimoto JG: Real-time optical coherence tomography for minimally-invasive imaging of prostate ablation. Comp Aided Surg 6: 94–103, 2001Google Scholar
  48. 48.
    Russo J, Russo I, van Zwieten M, Rogers A, Gusterson B: Classification of neoplastic and non-neoplastic lesions of the rat mammary gland. In: Jones T, Mohr U, Hunt R (eds) Integument and Mammary Glands, Monographs on Pathology of Laboratory Animals. Springer-Verlag, Berlin, 1989, pp 275–340Google Scholar
  49. 49.
    McCormick D, Adamowski C, Fiks A, Moon R: Lifetime dose-response relationships for mammary tumors induction by a single administration of N-methyl-N-nitrosourea. Cancer Res 41: 1690–1694, 1981Google Scholar
  50. 50.
    Gullino P, Pettigrew H, Grantham F: N-nitrosomethylurea as mammary gland carcinogen in rats. J Natl Cancer Inst 54: 401–409, 1975Google Scholar
  51. 51.
    Tseng M: Ultrastructure of the hormone-dependent Nnitrosomethylurea-induced mammary carcinoma of the rat. Cancer Res 40: 3112–3115, 1980Google Scholar
  52. 52.
    Arafah B, Finegan H, Roe J, Manni A, Pearson O: Hormone dependency in N-nitrosomethylurea-induced rat mammary tumors. Endocrinology 111: 584–588, 1982Google Scholar
  53. 53.
    Bigsby R: Synergistic tumor promoter effects of estrone and progesterone in methylnitrosourea-induced rat mammary cancer. Cancer Lett 179: 113–110, 2001Google Scholar
  54. 54.
    Thompson H, McGinley J, Knott K, Spoelstra N, Wolfe P: Vascular density profile of rat mammary carcinomas induced by 1-methyl-1-nitrosourea: implications for the investigation of angiogenesis. Carcinogenesis 23: 847–854, 2002Google Scholar
  55. 55.
    Dulbecco R, Armstrong B, Allen W, Bowman M: Distribution of developmental markers in rat mammary tumors induced by N-nitrosomethylurea. Cancer Res 46: 5144–5152, 1986Google Scholar
  56. 56.
    Anderson C, Beattie C: Cellular kinetics of rat mammary gland terminal end bud epithelium exposed to N-methyl-N-nitrosomethylurea in vivo. Cancer Res 52: 5076–5081, 1992Google Scholar
  57. 57.
    Singh M, McGinley J, Thompson H: A comparison of the histopathology of premalignant and malignant mammary gland lesions induced in sexually immature rats with those occurring in the human. Lab Invest 80: 221–231, 2000Google Scholar
  58. 58.
    Jin Z, Houle B, Mikheev A, Cha R, Zarbl H: Alterations in Hras 1 promoter conformation during N-nitroso-N-methylureainduced mammary carcinogenesis and pregnancy. Cancer Res 56: 4927–4935, 1996Google Scholar
  59. 59.
    Thompson H, McGinley J, Rothhammer K, Singh M: Ovarian hormone dependence of premalignant and malignant mammary gland lesions induced in pre-pubertal rats by 1-methyl-1-nitrosourea. Carcinogenesis 19: 383–386, 1998Google Scholar
  60. 60.
    Lu J, Jiang C, Mitrenga T, Cutter G, Thompson H: Pathogenetic characterization of 1-methyl-1-nitrosourea-induced mammary carcinomas in the rat. Carcinogenesis 19: 223–227, 1998Google Scholar
  61. 61.
    Thompson H, Adlaka H, Singh M: Effect of carcinogen dose and age at administration on induction of mammary carcinogenesis by 1-methyl-1-nitrosourea. Carcinogenesis 13: 1535–1539, 1992Google Scholar
  62. 62.
    Thompson H, Adlakha H: Dose-responsive induction of mammary gland carcinomas by the intraperitoneal injection of 1-methyl-1-nitrosourea. Cancer Res 51: 3411–3415, 1991Google Scholar
  63. 63.
    Thompson H, McGinely J, Rothhammer K, Singh M: Rapid induction of mammary intraductal proliferations, ductal carcinoma in situ and carcinomas by the injection of sexually immature female rats with 1-methyl-1-nitrosourea. Carcinogenesis 16: 2407–2411, 1995Google Scholar
  64. 64.
    Thordarson G, Lee AV, McCarty M, Van Horn K, Chu O, Chou Y-C, Yang J, Guzman RC, Nandi S, Talamantes F: Growth and characterization of N-methyl-N-nitrosourea-induced mammary tumors in intact and ovariectomized rats. Carcinogenesis 22: 2039–2047, 2001Google Scholar
  65. 65.
    Rose D, Fischer A, Jordan G: Activity of the antiestrogen tamoxifen against N-nitrosomethylurea-induced rat mammary carcinomas. Eur J Cancer 17: 893–898, 1981Google Scholar
  66. 66.
    Green A, Skilkaitis A, Christov K: 4-(hydroxyphenyl) retinamide selectively inhibits the development and progression of the ductal hyperplastic lesions and carcinoma in situ in mammary gland. Carcinogenesis 20: 1535–1540, 1999Google Scholar
  67. 67.
    Crist K, Chaudhuri B, Shivaram S, Chaudhuri PK: Ductal carcinoma in situ in rat's mammary gland. J Surg Res 52: 205–208, 1992Google Scholar
  68. 68.
    Thompson HJ, Singh M, McGinley J: Classification of premalignant and malignant lesions developing in the rat mammary gland after injection of sexually immature rats with 1-methyl-1-nitrosourea. J Mammary Gland Biol Neoplasia 5: 201–210, 2000Google Scholar
  69. 69.
    Thompson HJ, Singh M: Rat models of premalignant breast disease. J Mammary Gland Biol Neoplasia 5: 409–420, 2000Google Scholar
  70. 70.
    Sivaraman L, Gay J, Hilsenbeck SG, Shine HD, Conneely OM, Medina D, O'Malley BW: Effect of selective ablation of proliferating mammary epithelial cells on MNU induced rat mammary tumorgenesis. Breast Cancer Res Treat 73: 75–83, 2002Google Scholar
  71. 71.
    Marks DL, Oldenburg AL, Reynolds JJ, Boppart SA: Study of an ultrahigh numerical aperture fiber continuum generation source for optical coherence tomography. Opt Lett 27: 2010–2012, 2002Google Scholar
  72. 72.
    Oldenburg AL, Reynolds JJ, Marks DL, Boppart SA: Fast-Fourier-domain delay line for in vivo optical coherence tomography with a polygonal scanner. Appl Opt 42: 4606–4611, 2003Google Scholar
  73. 73.
    Marks DL, Oldenburg AL, Reynolds JJ, Boppart SA: Autofocus algorithm for dispersion correction in optical coherence tomography. Appl Opt 42: 3038–3046, 2003Google Scholar
  74. 74.
    Lee TM, Oldenburg AL, Sitafalwalla S, Marks DL, Luo W, Toublan FJJ, Suslick KS, Boppart SA: Engineered microsphere contrast agents for optical coherence tomography. Opt Lett 28: 1546–1548, 2003Google Scholar
  75. 75.
    Toth CA, Birngruber R, Boppart SA, Hee MR, Fujimoto JG, DiCarlo CD, Swanson EA, Cain CP, Narayan DG, Noojin GD, Roach WP: Argon laser retinal lesions evaluated in vivo by optical coherence tomography. Am J Ophthalmol 123: 188–198, 1997Google Scholar
  76. 76.
    Toth CA, Narayan DG, Boppart SA, Hee MR, Fujimoto JG, Birngruber R, Cain CP, DiCarlo CD, Roach WP: A comparison of retinal morphology viewed by optical coherence tomography and by light microscopy. Arch Ophthalmol 115: 1425–1428, 1997Google Scholar

Copyright information

© Kluwer Academic Publishers 2004

Authors and Affiliations

  • Stephen A. Boppart
    • 1
  • Wei Luo
    • 2
  • Daniel L. Marks
    • 2
  • Keith W. Singletary
    • 3
  1. 1.Department of Electrical and Computer Engineering, Bioengineering Program, Beckman Institute for Advanced Science and Technology, College of MedicineUniversity of Illinois at Urbana-ChampaignUrbanaUSA
  2. 2.Beckman Institute for Advanced Science and TechnologyUniversity of Illinois at Urbana-ChampaignUrbanaUSA
  3. 3.Department of Food Science and Human Nutrition, Functional Foods for Health ProgramUniversity of Illinois at Urbana-ChampaignUrbanaUSA

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