Annals of Surgical Oncology

, Volume 20, Issue 11, pp 3685–3693

Three-dimensional Optical Coherence Tomography for Optical Biopsy of Lymph Nodes and Assessment of Metastatic Disease

  • Renu John
  • Steven G. Adie
  • Eric J. Chaney
  • Marina Marjanovic
  • Krishnarao V. Tangella
  • Stephen A. Boppart
Translational Research and Biomarkers



Numerous techniques have been developed for localizing lymph nodes before surgical resection and for their histological assessment. Nondestructive high-resolution transcapsule optical imaging of lymph nodes offers the potential for in situ assessment of metastatic involvement, potentially during surgical procedures.


Three-dimensional optical coherence tomography (3-D OCT) was used for imaging and assessing resected popliteal lymph nodes from a preclinical rat metastatic tumor model over a 9-day time-course study after tumor induction. The spectral-domain OCT system utilized a center wavelength of 800 nm, provided axial and transverse resolutions of 3 and 12 μm, respectively, and performed imaging at 10,000 axial scans per second.


OCT is capable of providing high-resolution label-free images of intact lymph node microstructure based on intrinsic optical scattering properties with penetration depths of ~1–2 mm. The results demonstrate that OCT is capable of differentiating normal, reactive, and metastatic lymph nodes based on microstructural changes. The optical scattering and structural changes revealed by OCT from day 3 to day 9 after the injection of tumor cells into the lymphatic system correlate with inflammatory and immunological changes observed in the capsule, precortical regions, follicles, and germination centers found during histopathology.


We report for the first time a longitudinal study of 3-D transcapsule OCT imaging of intact lymph nodes demonstrating microstructural changes during metastatic infiltration. These results demonstrate the potential of OCT as a technique for intraoperative, real-time in situ 3-D optical biopsy of lymph nodes for the intraoperative staging of cancer.


  1. 1.
    Willard-Mack CL. Normal structure, function, and histology of lymph nodes. Toxicol Pathol. 2006;34:409–24.PubMedCrossRefGoogle Scholar
  2. 2.
    Torabi M, Aquino SL, Harisinghani MG. Current concepts in lymph node imaging. J Nucl Med. 2004;45:1509–18.PubMedGoogle Scholar
  3. 3.
    Gadd M. Sentinel lymph node biopsy for staging early breast cancer: minimizing the trade-off by maximizing the accuracy. Ann Oncol. 2009;20:973–5.PubMedCrossRefGoogle Scholar
  4. 4.
    Quan ML, McCready D. The evolution of lymph node assessment in breast cancer. J Surg Oncol. 2009;99:194–8.PubMedCrossRefGoogle Scholar
  5. 5.
    Szabo BK, Aspelin P, Kristoffersen WM, Tot T, Bone B. Invasive breast cancer: correlation of dynamic mr features with prognostic factors. Eur Radiol. 2003;13:2425–35.PubMedCrossRefGoogle Scholar
  6. 6.
    Fischbein NJ, Noworolski SM, Henry RG, Kaplan MJ, Dillon WP, Nelson SJ. Assessment of metastatic cervical adenopathy using dynamic contrast-enhanced MR imaging. Am J Neuroradiol. 2003;24:301–11.PubMedGoogle Scholar
  7. 7.
    Kim SH, Kim SC, Choi BI, Han MC. Uterine cervical carcinoma: evaluation of pelvic lymph node metastasis with MR imaging. Radiology. 1994;190:807–11.PubMedGoogle Scholar
  8. 8.
    Harisinghani MG, Barentsz J, Hahn PF, et al. Noninvasive detection of clinically occult lymph node metastases in prostate cancer. N Engl J Med. 2003;348:2491–9.PubMedCrossRefGoogle Scholar
  9. 9.
    Anzai Y, Blackwell KE, Hirschowitz SL, et al. Initial clinical experience with dextran-coated superparamagnetic iron oxide for detection of lymph node metastases in patients with head and neck cancer. Radiology. 1994;192:709–15.PubMedGoogle Scholar
  10. 10.
    Krag D, Weaver D, Ashikaga T, et al. The sentinel node in breast cancer—a multicenter validation study. N Engl J Med. 1998;339:941–6.PubMedCrossRefGoogle Scholar
  11. 11.
    Blessing WD, Stolier AJ, Teng SC, Bolton JS, Fuhrman GM. A comparison of methylene blue and lymphazurin in breast cancer sentinel node mapping. Am J Surg. 2002;184:341–5.PubMedCrossRefGoogle Scholar
  12. 12.
    Schaafsma BE, Mieog JS, Hutteman M, et al. The clinical use of indocyanine green as a near-infrared fluorescent contrast agent for image-guided oncologic surgery. J Surg Oncol. 2011;104:323–32.PubMedCrossRefGoogle Scholar
  13. 13.
    Sampath L, Wang W, Sevick-Muraca EM. Near-infrared fluorescent optical imaging for nodal staging. J Biomed Opt. 2008;13:041312.PubMedCrossRefGoogle Scholar
  14. 14.
    Rosbach KJ, Shin D, Muldoon TJ, et al. High-resolution fiber optic microscopy with fluorescent contrast enhancement for the identification of axillary lymph node metastases in breast cancer: a pilot study. Biomed Opt Express. 2010;1:911–22.PubMedCrossRefGoogle Scholar
  15. 15.
    Nguyen NQ, Biankin AV, Leong RW, et al. Real time intraoperative confocal laser microscopy-guided surgery. Ann Surg. 2009;249:735–7.PubMedCrossRefGoogle Scholar
  16. 16.
    Fujimoto JG, Brezinski ME, Tearney GJ, et al. Optical biopsy and imaging using optical coherence tomography. Nat Med. 1995:1:970–2.PubMedCrossRefGoogle Scholar
  17. 17.
    Tearney GJ, Brezinski ME, Bouma BE, Boppart SA, Pitris C, Southern JF, Fujimoto JG. In vivo endoscopic optical biopsy with optical coherence tomography. Science. 1997;276:2037–9.PubMedCrossRefGoogle Scholar
  18. 18.
    Boppart SA, Bouma BE, Pitris C, Southern JF, Brezinski ME, Fujimoto JG. In vivo cellular optical coherence tomography imaging. Nat Med. 1998;4:861–5.PubMedCrossRefGoogle Scholar
  19. 19.
    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. 1997;71:32–40.PubMedCrossRefGoogle Scholar
  20. 20.
    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. 1999;82:275–84.PubMedCrossRefGoogle Scholar
  21. 21.
    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. 1998;208:81–6.PubMedGoogle Scholar
  22. 22.
    Nguyen FT, Zysk AM, Chaney EJ, et al. Intraoperative evaluation of breast tumor margins with optical coherence tomography. Cancer Res. 2009;69:8790–6.PubMedCrossRefGoogle Scholar
  23. 23.
    Luo W, Nguyen FT, Zysk AM, et al. Optical biopsy of lymph node morphology using optical coherence tomography. Tech Cancer Res Treat. 2005;4:539–47.Google Scholar
  24. 24.
    McLaughlin RA, Scolaro L, Robbins P, Hamza S, Saunders C, Sampson DD. Imaging of human lymph nodes using optical coherence tomography: potential for staging cancer. Cancer Res. 2010;70:2579–84.PubMedCrossRefGoogle Scholar
  25. 25.
    Nguyen FT, Zysk AM, Chaney EJ, et al. Optical coherence tomography: the intraoperative assessment of lymph nodes in breast cancer. IEEE Eng Med Biol. 2010;29:63–70.CrossRefGoogle Scholar
  26. 26.
    Taback B, Hashimoto K, Kuo CT, Chan A, Giuliano AE, Hoon DS. Molecular lymphatic mapping of the sentinel lymph node. Am J Pathol. 2002;161:1153–61.PubMedCrossRefGoogle Scholar
  27. 27.
    Klein T, Wieser W, Eigenwillig CM, Biedermann BR, Huber R. Megahertz OCT for ultrawide-field retinal imaging with a 1050 nm Fourier domain mode-locked laser. Opt Express. 2011;19:3044–62.PubMedCrossRefGoogle Scholar
  28. 28.
    Tsai TH, Zhou C, Adler DC, Fujimoto JG. Frequency comb swept lasers. Opt Express. 2009;17:21257–70.PubMedCrossRefGoogle Scholar
  29. 29.
    de Boer M, van Deurzen CHM, van Dijck JAAM, et al. Micrometastases or isolated tumor cells and the outcome of breast cancer. N Engl J Med. 2009;361:653–63.PubMedCrossRefGoogle Scholar
  30. 30.
    Boppart SA, Bouma BE, Pitris C, Tearney GJ, Brezinski ME, Fujimoto JG. Forward-imaging instruments for optical coherence tomographic imaging. Opt Lett. 1997;22:1618–20.PubMedCrossRefGoogle Scholar
  31. 31.
    Jung W, Kim J, Jeon M, Chaney EJ, Stewart CJ, Boppart SA. Handheld optical coherence tomography scanner for primary care diagnostics. IEEE Trans Biomed Eng. 2011;58:741–4.PubMedCrossRefGoogle Scholar
  32. 32.
    Zysk AM, Nguyen FT, Chaney EJ, et al. Clinical feasibility of microscopically-guided breast needle biopsy using a fiber optic probe with computer-aided detection. Tech Cancer Res Treat. 2009;8:315–22.Google Scholar
  33. 33.
    Li X, Chudoba C, Ko T, Pitris C, Fujimoto JG. Imaging needle for optical coherence tomography. Opt Lett. 2000;25:1520–2.PubMedCrossRefGoogle Scholar

Copyright information

© Society of Surgical Oncology 2012

Authors and Affiliations

  • Renu John
    • 1
  • Steven G. Adie
    • 1
  • Eric J. Chaney
    • 1
  • Marina Marjanovic
    • 1
  • Krishnarao V. Tangella
    • 2
  • Stephen A. Boppart
    • 1
    • 3
  1. 1.Beckman Institute for Advanced Science and TechnologyUniversity of Illinois at Urbana-ChampaignUrbanaUSA
  2. 2.Department of PathologyCollege of Medicine, University of Illinois at Urbana-ChampaignUrbanaUSA
  3. 3.Departments of Bioengineering, Electrical and Computer Engineering, and MedicineUniversity of Illinois at Urbana-ChampaignUrbanaUSA

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