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Near-infrared intraoperative molecular imaging with conventional neurosurgical microscope can be improved with narrow band “boost” excitation

  • Technical Note - Brain Tumors
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Abstract

Background

Intraoperative visualization of brain tumors with near-infrared (NIR)-fluorescent dyes is an emerging method for tumor margin approximation but are limited by existing fluorescence detection platforms. We previously showed that a dedicated NIR imaging platform outperformed a state-of-the-art neurosurgical microscope in fluorescence signal characteristics. This study examined whether conventional neurosurgical microscope NIR signal could be improved with the addition of a narrow wavelength excitation source.

Methods

Imaging was conducted with a broad-spectrum neurosurgical microscope and commercial near-infrared module. Addition of an 805-nm laser was used to “boost” NIR excitation of indocyanine green (ICG). In vitro quantification was performed on serial dilutions of ICG. Patients underwent tumor resection with delayed 24-h imaging of ICG infusion. NIR fluorescence of dura, cortex, or tumor was quantified from images prior to (pre-boost) and following added excitation with the laser (post-boost). Signal to background ratio (SBR) of pre- and post-boost was calculated as a readout of image enhancement.

Results

In vitro, excitation boost effected a 29% increase in mean SBR in six serial dilutions of ICG. Intraoperative boost was performed in 11 patients including meningioma, glioblastoma multiforme, and metastases. Increase in tumor fluorescence was pronounced under direct tumor visualization. Across all patients, boost excitation resulted in 35% mean improvement from pre-boost SBR (p < 0.001).

Conclusion

Neurosurgical microscopes remain the preferred method of visualizing tumor during intracranial surgery. However, current modalities for NIR signal detection are suboptimal. We demonstrate that augmentation of a fluorescence microscope module with a focused excitation source is a simple mechanism of improving NIR tumor visualization.

Clinical trial registration

NCT03262636

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References

  1. Cho SS, Zeh R, Pierce J et al (2018) Comparison of near-infrared imaging camera systems for intracranial tumor detection. Mol Imaging Biol 20(2):213–220. https://doi.org/10.1007/s11307-017-1107-5

    Article  CAS  PubMed  Google Scholar 

  2. DSouza AV, Lin H, Henderson E et al (2016) Review of fluorescence guided surgery systems: identification of key performance capabilities beyond indocyanine green imaging. J Biomed Opt 21(8):080901. https://doi.org/10.1117/1.JBO.21.8.080901

    Article  PubMed Central  Google Scholar 

  3. Jiang JX, Keating JJ, Jesus E et al (2015) Optimization of the enhanced permeability and retention effect for near-infrared imaging of solid tumors with indocyanine green. Am J Nucl Med Mol Imaging 5(4):390–400 Available at: http://www.ncbi.nlm.nih.gov/pubmed/26269776 (Accessed: 20 Aug 2018)

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Kovar JL, Curtis E, Othman S et al (2013) Characterization of IRDye 800CW chlorotoxin as a targeting agent for brain tumors. Anal Biochem 440(2):212–219. https://doi.org/10.1016/j.ab.2013.05.013

    Article  CAS  PubMed  Google Scholar 

  5. Lee JYK, Thawani JP, Pierce J et al (2016) Intraoperative near-infrared optical imaging can localize gadolinium-enhancing gliomas during surgery. Neurosurgery 79(6):856–871. https://doi.org/10.1227/NEU.0000000000001450

    Article  PubMed  PubMed Central  Google Scholar 

  6. Lee JYK, Pierce JT, Zeh R et al (2017) Intraoperative near-infrared optical contrast can localize brain metastases. World Neurosurgery 106:120–130. https://doi.org/10.1016/j.wneu.2017.06.128

    Article  PubMed  Google Scholar 

  7. Lee JYK, Pierce JT, Thawani J et al (2018) Near-infrared fluorescent image-guided surgery for intracranial meningioma. J Neurosurg 128(2):380–390. https://doi.org/10.3171/2016.10.JNS161636

    Article  CAS  PubMed  Google Scholar 

  8. Miller SE, Tummers W, Theraphongphom N et al (2018) First-in-human intraoperative near-infrared fluorescence imaging of glioblastoma using cetuximab-IRDye800. J Neuro-Oncol 139(1):135–143. https://doi.org/10.1007/s11060-018-2854-0

    Article  CAS  Google Scholar 

  9. Warram, J. M. , de Boer E., Korb M. et al. (2015) ‘Fluorescence-guided resection of experimental malignant glioma using cetuximab-IRDye 800CW’, Br J Neurosurg. 29(6), pp. 850–858. doi: https://doi.org/10.3109/02688697.2015.1056090

    Article  Google Scholar 

  10. Zeh R, Sheikh S, Xia L et al (2017) The second window ICG technique demonstrates a broad plateau period for near infrared fluorescence tumor contrast in glioblastoma. PLOS ONE Edited by M Bogyo 12(7):e0182034. https://doi.org/10.1371/journal.pone.0182034

    Article  CAS  Google Scholar 

  11. Zhang DY, Singhal S, Lee JYK (2018) Optical principles of fluorescence-guided brain tumor surgery: a practical primer for the neurosurgeon. Neurosurgery. https://doi.org/10.1093/neuros/nyy315

    Article  Google Scholar 

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Funding

Research reported in this publication was funded by the National Center for Advancing Translational Sciences of the National Institutes of Health under Award Number UL1TR001878. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Additional financial support was received from the Institute for Translational Medicine and Therapeutics of the University of Pennsylvania. Funding sources had no role in the design or conduct of this research.

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Correspondence to Carrie Li.

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The authors declare that they have no conflict of interest.

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All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional research committee of the Hospital of the University of Pennsylvania and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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This article is part of the Topical Collection on Brain Tumors

Presentations

• Digital Poster Presentation: Pennsylvania Neurosurgical Society’s (PNS) 105th Scientific Meeting, July 21, 2018 in Hershey, Pennsylvania

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Li, C., Buch, L., Cho, S. et al. Near-infrared intraoperative molecular imaging with conventional neurosurgical microscope can be improved with narrow band “boost” excitation. Acta Neurochir 161, 2311–2318 (2019). https://doi.org/10.1007/s00701-019-04054-5

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  • DOI: https://doi.org/10.1007/s00701-019-04054-5

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