The complementary value of intraoperative fluorescence imaging and Raman spectroscopy for cancer surgery: combining the incompatibles

L. J. Lauwerends, H. Abbasi, T. C. Bakker Schut, P. B.A.A. Van Driel, J. A.U. Hardillo, I. P. Santos, E. M. Barroso, S. Koljenović, A. L. Vahrmeijer, R. J. Baatenburg de Jong, G. J. Puppels, S. Keereweer*

*Corresponding author for this work

Research output: Contribution to journalReview articleAcademicpeer-review

13 Citations (Scopus)
30 Downloads (Pure)


A clear margin is an important prognostic factor for most solid tumours treated by surgery. Intraoperative fluorescence imaging using exogenous tumour-specific fluorescent agents has shown particular benefit in improving complete resection of tumour tissue. However, signal processing for fluorescence imaging is complex, and fluorescence signal intensity does not always perfectly correlate with tumour location. Raman spectroscopy has the capacity to accurately differentiate between malignant and healthy tissue based on their molecular composition. In Raman spectroscopy, specificity is uniquely high, but signal intensity is weak and Raman measurements are mainly performed in a point-wise manner on microscopic tissue volumes, making whole-field assessment temporally unfeasible. In this review, we describe the state-of-the-art of both optical techniques, paying special attention to the combined intraoperative application of fluorescence imaging and Raman spectroscopy in current clinical research. We demonstrate how these techniques are complementary and address the technical challenges that have traditionally led them to be considered mutually exclusive for clinical implementation. Finally, we present a novel strategy that exploits the optimal characteristics of both modalities to facilitate resection with clear surgical margins.

Original languageEnglish
Pages (from-to)2364-2376
Number of pages13
JournalEuropean Journal of Nuclear Medicine and Molecular Imaging
Issue number7
Early online date1 Feb 2022
Publication statusPublished - Jun 2022

Bibliographical note

Funding Information:
This work was supported by the Dutch Cancer Society KWF [Research Grant: 12175] and the Daniel den Hoed Fonds.

Publisher Copyright:
© 2022, The Author(s).


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