Intraoperative near-infrared (NIR) fluorescence imaging using tumor-specific exogenous fluorescent agents provides whole-field images in real-time to assist the surgeon in the complete resection of tumor tissue. Although the method has high sensitivity, the specificity can sometimes be lower than expected. Raman spectroscopy can differentiate between tumor and healthy tissue with high specificity based on their molecular composition. Therefore, a combination of these modalities can be advantageous. A complication that must be addressed is that the NIR spectral region is favored by both techniques for intraoperative tissue analysis. When fluorescence and Raman emissions spectrally overlap, it becomes challenging or impossible to detect the Raman signal. Therefore, these techniques were traditionally considered mutually exclusive for clinical implementation. Here, a Raman spectroscopy setup capable of recording high-quality Raman spectra from tissue containing NIR exogenous fluorescent agents is described. In this setup, an optimal wavelength interval for Raman excitation is identified, which avoids both excitation of fluorescent agent and Raman signal self-absorption by the tissue. This combined novel setup could pave the way for clinical trials benefiting from the complementary value of intraoperative NIR fluorescence imaging and Raman spectroscopy to avoid positive margins in cancer surgery.@en

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.

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This study reports on the effects of insertion velocity, needle tip geometry and needle diameter on tissue deformation and maximum insertion force. Moreover, the effect of multiple insertions with the same needle on the maximum insertion force is reported. The tissue deformation and maximum insertion force strongly depend on the insertion velocity and the tip geometry. No correlation was found between the outer diameter and the maximum insertion force for small needles (30G – 32G). The endurance experiments showed no remarkable difference in the maximum insertion force during 100 insertions.

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We demonstrate the feasibility of short wave infrared (SWIR) spectroscopy combined with tape stripping for depth profiling of lipids and water in the stratum corneum of human skin. The proposed spectroscopic technique relies on differential detection at three wavelengths of 1720, 1750, and 1770 nm, with varying ratio of the lipid-to-water absorption coefficient and an ‘isosbestic point’. Comparison of the data acquired using SWIR spectroscopy with that obtained by a gold standard for non-invasive quantitative molecularspecific skin measurements, namely confocal Raman spectroscopy (CRS), revealed specificity of the proposed modality for water and lipid quantification. At the same time, we provide evidence showing aberrant sensitivity of Corneometer hydration read-outs to the presence of skin surface lipids, and a lack of sensitivity of the Sebumeter when attempting to measure the lipids of the cornified lipid envelope and intracellular lipid layers. We conclude that a spectroscopic SWIR-based spectroscopic method combined with tape stripping has the potential for depth profiling of the stratum corneum water and lipids, due to superior measurement sensitivity and specificity compared to the Corneometer and Sebumeter.

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