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. 2021 Mar 11;12(4):2015-2026.
doi: 10.1364/BOE.417896. eCollection 2021 Apr 1.

Clinical integration of fast Raman spectroscopy for Mohs micrographic surgery of basal cell carcinoma

Radu Boitor  1 , Coen de Wolf  2 , Frank Weesie  2 , Dustin W Shipp  1 , Sandeep Varma  3 , David Veitch  3 , Aaron Wernham  3 , Alexey Koloydenko  4 , Gerwin Puppels  5   6 , Tamar Nijsten  2 , Hywel C Williams  7 , Peter Caspers  5   6 , Ioan Notingher  1
Affiliations

Clinical integration of fast Raman spectroscopy for Mohs micrographic surgery of basal cell carcinoma

Radu Boitor et al. Biomed Opt Express. .

Abstract

We present the first clinical integration of a prototype device based on integrated auto-fluorescence imaging and Raman spectroscopy (Fast Raman device) for intra-operative assessment of surgical margins during Mohs micrographic surgery of basal cell carcinoma (BCC). Fresh skin specimens from 112 patients were used to optimise the tissue pre-processing and the Fast Raman algorithms to enable an analysis of complete Mohs layers within 30 minutes. The optimisation allowed >95% of the resection surface area to be investigated (including the deep and epidermal margins). The Fast Raman device was then used to analyse skin layers excised from the most relevant anatomical sites (nose, temple, eyelid, cheek, forehead, eyebrow and lip) and to detect the three main types of BCC (nodular, superficial and infiltrative). These results suggest that the Fast Raman technique is a promising tool to provide an objective diagnosis "tumour clear yes/no" during Mohs surgery of BCC. This clinical integration study is a key step towards a larger scale diagnosis test accuracy study to reliably determine the sensitivity and specificity in a clinical setting.

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Conflict of interest statement

I Notingher, H Williams, S Varma, A. Koloydenko hold a patent related to the Fast Raman technology. The Fast Raman device was built by RiverD International.

Figures

Fig. 1.
Fig. 1.
Integration of the Fast Raman device in the pathway of Mohs surgery. Step 1: tissue excision, mapping to maintain orientation, washing and blotting to remove superficial blood. Step 2: Analysis by Fast Raman device – output is presented as an image with BCC presented in red colour and highlighted by a green circle Step 3: Frozen section histology.
Fig. 2.
Fig. 2.
Confusion matrix for the support vector machine (SVM) classification model generated via 5-fold cross validation. The model was trained and validated with spectra acquired intra-operatively during the study. The Healthy group contains spectra of dermis, epidermis, inflamed dermis, fat and muscle. The Contaminants group contains spectra of surgical ink and substrate. Number of spectra for each group presented in parenthesis.
Fig. 3.
Fig. 3.
Typical examples of concordant BCC-negative diagnoses by Fast Raman analysis and frozen section histology. Fast Raman analysis of an: a) nose layer, b) cheek layer, c) lip layer, d) eyelid layer, e) forehead layer, f) eyebrow layer. The most relevant frozen sections, showing the majority of the resection surface are included as reference. Scalebars: 5 mm.
Fig. 4.
Fig. 4.
Typical cases of BCC-positive Fast Raman diagnoses declared negative by frozen section histology. Fast Raman analysis of tissue specimens excised from the following anatomical locations: a) lip, b) eyelid, c) nose. The most relevant frozen H&E sections are included. Tissue structures which have been incorrectly detected as BCC and are highlighted in the inset: a) incipient hair follicles; b) incipient hair follicles; c) inflammation. Scalebars: 5 mm.
Fig. 5.
Fig. 5.
Typical examples of concordant BCC-positive diagnoses by Fast Raman analysis and frozen section histology. Fast Raman analysis of an a) nodular BCC from nose, b) superficial BCC from eyelid, c) infiltrative BCC from nose. The most relevant frozen section, showing the location of the residual tumour for each Fast Raman analysis. Tumours are presented as red segments in the Fast Raman map and are highlighted by green circles. Scalebars: 5 mm.
Fig. 6.
Fig. 6.
Simulation of reduction of Fast Raman measurement time by addition of noise to Raman spectra. Representative tissue specimens: a) and b) BCC-positive; c) and d) BCC-negative. Measurement time: 30 minutes: 2s/spectrum in all rounds; 26 minutes: 1 s/spectrum in Round 1, 2 s/spectrum in Rounds 2 and 3; 21 minutes: 1 s/spectrum in Round 1 and 2, 2 s/spectrum in Round 3; 20 minutes: 1s/spectrum in all rounds. The locations of tumours are highlighted by green circles. White arrowheads highlight changes in the Fast Raman maps that are caused by the addition of noise. Scalebar: 5 mm.
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References

    1. Global Burden of Disease Cancer , “Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 29 cancer groups, 1990 to 2017: a systematic analysis for the global burden of disease study,” JAMA Oncology 5(12), 1749–1768 (2019).10.1001/jamaoncol.2019.2996 - DOI - PMC - PubMed
    1. Mosterd K., Krekels G. A., Nieman F. H., Ostertag J. U., Essers B. A., Dirksen C. D., Steijlen P. M., Vermeulen A., Neumann H., Kelleners-Smeets N. W., “Surgical excision versus Mohs’ micrographic surgery for primary and recurrent basal-cell carcinoma of the face: a prospective randomised controlled trial with 5-years’ follow-up,” Lancet Oncol. 9(12), 1149–1156 (2008).10.1016/S1470-2045(08)70260-2 - DOI - PubMed
    1. Flohil S. C., van Dorst A. M. J. M., Nijsten T., Martino Neumann H. A., Munte K., “Mohs micrographic surgery for basal cell carcinomas: appropriateness of ‘Rotterdam’ criteria and predictive factors for three or more stages,” Journal of the European Academy of Dermatology and Venereology 27(7), 907–911 (2013).10.1111/j.1468-3083.2011.04407.x - DOI - PubMed
    1. Shriner D. L., McCoy D. K., Goldberg D. J., Wagner R. F., Jr, “Mohs micrographic surgery,” J. Am. Acad. Dermatol. 39(1), 79–97 (1998).10.1016/S0190-9622(98)70405-0 - DOI - PubMed
    1. Baxter J. M., Patel A. N., Varma S., “Facial basal cell carcinoma,” BMJ 345(aug21 2), e5342 (2012).10.1136/bmj.e5342 - DOI - PubMed

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