Skip to main content

Advertisement

SpringerLink
Log in

Optical See-Through Cancer Vision Goggles Enable Direct Patient Visualization and Real-Time Fluorescence-Guided Oncologic Surgery

  • Breast Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

The inability to visualize the patient and surgical site directly, limits the use of current near infrared fluorescence-guided surgery systems for real-time sentinel lymph node biopsy and tumor margin assessment.

Methods

We evaluated an optical see-through goggle augmented imaging and navigation system (GAINS) for near-infrared, fluorescence-guided surgery. Tumor-bearing mice injected with a near infrared cancer-targeting agent underwent fluorescence-guided, tumor resection. Female Yorkshire pigs received hind leg intradermal indocyanine green injection and underwent fluorescence-guided, popliteal lymph node resection. Four breast cancer patients received 99mTc-sulfur colloid and indocyanine green retroareolarly before undergoing sentinel lymph node biopsy using radioactive tracking and fluorescence imaging. Three other breast cancer patients received indocyanine green retroareolarly before undergoing standard-of-care partial mastectomy, followed by fluorescence imaging of resected tumor and tumor cavity for margin assessment.

Results

Using near-infrared fluorescence from the dyes, the optical see-through GAINS accurately identified all mouse tumors, pig lymphatics, and four pig popliteal lymph nodes with high signal-to-background ratio. In 4 human breast cancer patients, 11 sentinel lymph nodes were identified with a detection sensitivity of 86.67 ± 0.27% for radioactive tracking and 100% for GAINS. Tumor margin status was accurately predicted by GAINS in all three patients, including clear margins in patients 1 and 2 and positive margins in patient 3 as confirmed by paraffin-embedded section histopathology.

Conclusions

The optical see-through GAINS prototype enhances near infrared fluorescence-guided surgery for sentinel lymph node biopsy and tumor margin assessment in breast cancer patients without disrupting the surgical workflow in the operating room.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin. 2015;65(1):5–29.

    Article  PubMed  Google Scholar 

  2. Giuliano AE, Kirgan DM, Guenther JM, Morton DL. Lymphatic mapping and sentinel lymphadenectomy for breast cancer. Ann Surg. 1994;220(3):391–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Cox CE, Pendas S, Cox JM, et al. Guidelines for sentinel node biopsy and lymphatic mapping of patients with breast cancer. Ann Surg. 1998;227(5):645–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Goyal A, Newcombe RG, Chhabra A, Mansel RE, Group AT. Factors affecting failed localisation and false-negative rates of sentinel node biopsy in breast cancer: results of the ALMANAC validation phase. Breast Cancer Res Treat. 2006;99(2):203–08.

    Article  Google Scholar 

  5. Krag DN, Anderson SJ, Julian TB, et al. Technical outcomes of sentinel-lymph-node resection and conventional axillary-lymph-node dissection in patients with clinically node-negative breast cancer: results from the NSABP B-32 randomised phase III trial. Lancet Oncol. 2007;8(10):881–8.

    Article  CAS  PubMed  Google Scholar 

  6. Straver ME, Meijnen P, van Tienhoven G, et al. Sentinel node identification rate and nodal involvement in the EORTC 10981-22023 AMAROS trial. Ann Surg Oncol. 2010;17(7):1854–61.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Zavagno G, De Salvo GL, Scalco G, et al. A Randomized clinical trial on sentinel lymph node biopsy versus axillary lymph node dissection in breast cancer: results of the Sentinella/GIVOM trial. Ann Surg. 2008;247(2):207–13.

    Article  PubMed  Google Scholar 

  8. Mondal SB, Gao S, Zhu N, et al. Binocular Goggle Augmented Imaging and Navigation System provides real-time fluorescence image guidance for tumor resection and sentinel lymph node mapping. Sci Rep. 2015;5:12117.

    Article  CAS  PubMed  Google Scholar 

  9. Bézu C, Coutant C, Salengro A, Daraï E, Rouzier R, Uzan S. Anaphylactic response to blue dye during sentinel lymph node biopsy. Surg Oncol. 2011;20(1):e55–e59.

    Article  PubMed  Google Scholar 

  10. Singletary SE. Surgical margins in patients with early-stage breast cancer treated with breast conservation therapy. Am J Surg. 2002;184(5):383–93.

    Article  PubMed  Google Scholar 

  11. Moran MS, Schnitt SJ, Giuliano AE, et al. Society of Surgical Oncology-American Society for Radiation Oncology consensus guideline on margins for breast-conserving surgery with whole-breast irradiation in stages I and II invasive breast cancer. Ann Surg Oncol. 2014;21(3):704–16.

    Article  PubMed  Google Scholar 

  12. McCahill LE, Single RM, Aiello Bowles EJ, et al. Variability in reexcision following breast conservation surgery. JAMA. 2012;307(5):467–75.

    Article  PubMed  Google Scholar 

  13. Morrow M, Jagsi R, Alderman AK, et al. Surgeon recommendations and receipt of mastectomy for treatment of breast cancer. JAMA. 2009;302(14):1551–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Mullen R, Macaskill EJ, Khalil A, et al. Involved anterior margins after breast conserving surgery: is re-excision required? Eur J Surg Oncol. 2012;38(4):302–6.

    Article  CAS  PubMed  Google Scholar 

  15. Hirche C, Murawa D, Mohr Z, Kneif S, Hunerbein M. ICG fluorescence-guided sentinel node biopsy for axillary nodal staging in breast cancer. Breast Cancer Res Treat. 2010;121(2):373–8.

    Article  PubMed  Google Scholar 

  16. Hojo T, Nagao T, Kikuyama M, Akashi S, Kinoshita T. Evaluation of sentinel node biopsy by combined fluorescent and dye method and lymph flow for breast cancer. Breast. 2010;19(3):210–3.

    Article  PubMed  Google Scholar 

  17. Kitai T, Inomoto T, Miwa M, Shikayama T. Fluorescence navigation with indocyanine green for detecting sentinel lymph nodes in breast cancer. Breast Cancer. 2005;12(3):211–5.

    Article  PubMed  Google Scholar 

  18. Murawa D, Hirche C, Dresel S, Hunerbein M. Sentinel lymph node biopsy in breast cancer guided by indocyanine green fluorescence. Br J Surg. 2009;96(11):1289–94.

    Article  CAS  PubMed  Google Scholar 

  19. Sevick-Muraca EM, Sharma R, Rasmussen JC, et al. Imaging of lymph flow in breast cancer patients after microdose administration of a near-infrared fluorophore: feasibility study. Radiology. 2008;246(3):734–41.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Tagaya N, Yamazaki R, Nakagawa A, et al. Intraoperative identification of sentinel lymph nodes by near-infrared fluorescence imaging in patients with breast cancer. Am J Surg. 2008;195(6):850–3.

    Article  PubMed  Google Scholar 

  21. Troyan SL, Kianzad V, Gibbs-Strauss SL, et al. The FLARE intraoperative near-infrared fluorescence imaging system: a first-in-human clinical trial in breast cancer sentinel lymph node mapping. Ann Surg Oncol. 2009;16(10):2943–52.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Mieog JS, Troyan SL, Hutteman M, et al. Toward optimization of imaging system and lymphatic tracer for near-infrared fluorescent sentinel lymph node mapping in breast cancer. Ann Surg Oncol. 2011;18(9):2483–91.

    Article  PubMed  PubMed Central  Google Scholar 

  23. van der Vorst JR, Schaafsma BE, Verbeek FP, et al. Randomized comparison of near-infrared fluorescence imaging using indocyanine green and 99(m) technetium with or without patent blue for the sentinel lymph node procedure in breast cancer patients. Ann Surg Oncol. 2012;19(13):4104–11.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Keating J, Tchou J, Okusanya O, et al. Identification of breast cancer margins using intraoperative near-infrared imaging. J Surg Oncol. 2016;113(5):508–14.

    Article  CAS  PubMed  Google Scholar 

  25. Hirche C, Engel H, Kolios L, et al. An experimental study to evaluate the Fluobeam 800 imaging system for fluorescence-guided lymphatic imaging and sentinel node biopsy. Surg Innov. 2013;20(5):516–23.

    Article  PubMed  Google Scholar 

  26. Tobis S, Knopf JK, Silvers CR, et al. Near infrared fluorescence imaging after intravenous indocyanine green: initial clinical experience with open partial nephrectomy for renal cortical tumors. Urology. 2012;79(4):958–64.

    Article  PubMed  Google Scholar 

  27. Gotoh K, Yamada T, Ishikawa O, et al. A novel image-guided surgery of hepatocellular carcinoma by indocyanine green fluorescence imaging navigation. J Surg Oncol. 2009;100(1):75–9.

    Article  PubMed  Google Scholar 

  28. Mondal SB, Gao S, Zhu N, Liang R, Gruev V, Achilefu S. Real-time Fluorescence Image-Guided Oncologic Surgery. Adv Cancer Res. 2014;124:171–211.

    Article  PubMed  PubMed Central  Google Scholar 

  29. van den Berg NS, Miwa M, KleinJan GH, et al. (Near-infrared) fluorescence-guided surgery under ambient light conditions: a next step to embedment of the technology in clinical routine. Ann Surg Oncol. 2016;23:2586–95.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Zhu N, Huang CY, Mondal S, et al. Compact wearable dual-mode imaging system for real-time fluorescence image-guided surgery. J Biomed Opt. 2015;20(9):96010.

    Article  Google Scholar 

  31. Zhu N, Mondal S, Gao S, Achilefu S, Gruev V, Liang R. Engineering light-emitting diode surgical light for near-infrared fluorescence image-guided surgical systems. J Biomed Opt. 2014;19(7):076018.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Rua C, Lebas P, Michenet P, Ouldamer L. Evaluation of lumpectomy surgical specimen radiographs in subclinical, in situ and invasive breast cancer, and factors predicting positive margins. Diagn Intervent Imag. 2012;93(11):871–7.

    Article  CAS  Google Scholar 

  33. Judy RP, Keating JJ, DeJesus EM, et al. Quantification of tumor fluorescence during intraoperative optical cancer imaging. Sci Rep. 2015;5:16208.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Zysk AM, Chen K, Gabrielson E, et al. Intraoperative assessment of final margins with a handheld optical imaging probe during breast-conserving surgery may reduce the reoperation rate: results of a multicenter study. Ann Surg Oncol. 2015;22(10):3356–62.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Liu Y, Zhao YM, Akers W, et al. First in-human intraoperative imaging of HCC using the fluorescence goggle system and transarterial delivery of near-infrared fluorescent imaging agent: a pilot study. Transl Res. 2013;162(5):324–31.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

Funding for this project was supported primarily by funds from the U.S. National Institutes of Health (NIH) NCI (R01 CA171651) and in part by NCI grants U54 CA199092, P50 CA094056 and P30 CA091842); NIBIB (R01 EB021048, R01 EB007276 and R01 EB008111); and shared instrumentation grants (S10 OD016237 and S10 RR031625). SBM was supported in part by the Foundation for Barnes-Jewish Hospital and the Children’s Discovery Institute at St. Louis Children’s Hospital. LHB was supported in part by NCI grant U54CA199092S1. The authors thank Dr. Michael Talcott for assistance the porcine study.

Disclosure

The authors declare no commercial interest in the reported research.

Author information

Authors and Affiliations

  1. Department of Radiology, Washington University School of Medicine, St. Louis, MO, USA

    Suman B. Mondal PhD, LeMoyne Habimana-Griffin BS, Walter J. Akers PhD, DVM & Samuel Achilefu PhD

  2. Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO, USA

    Suman B. Mondal PhD, LeMoyne Habimana-Griffin BS & Samuel Achilefu PhD

  3. Department of Computer Science and Engineering, Washington University in St. Louis, St. Louis, MO, USA

    Shengkui Gao PhD & Viktor Gruev PhD

  4. College of Optical Science, The University of Arizona, Tucson, AZ, USA

    Nan Zhu PhD & Rongguang Liang PhD

  5. Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA

    Julie Margenthaler MD

  6. Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO, USA

    Samuel Achilefu PhD

  7. Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, USA

    Samuel Achilefu PhD

Authors
  1. Suman B. Mondal PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shengkui Gao PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nan Zhu PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. LeMoyne Habimana-Griffin BS
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Walter J. Akers PhD, DVM
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Rongguang Liang PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Viktor Gruev PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Julie Margenthaler MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Samuel Achilefu PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Samuel Achilefu PhD.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mondal, S.B., Gao, S., Zhu, N. et al. Optical See-Through Cancer Vision Goggles Enable Direct Patient Visualization and Real-Time Fluorescence-Guided Oncologic Surgery. Ann Surg Oncol 24, 1897–1903 (2017). https://doi.org/10.1245/s10434-017-5804-8

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1245/s10434-017-5804-8

Keywords

Search

Navigation