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The VRR method has a high S/N ratio, and provides visually intuitive results for inspection. Even the raw
RR spectra can be used for a direct comparison between cancerous and normal tissues. In contrast, it is
much more difficult to inspect the raw Raman data acquired using NIR such as 785 nm excitation, because
of the much lower S/N ratio. In fact, the raw Raman spectra are rarely provided in the literature [81,82] . The
VRR system also uses less power and shorter integration time to collect signals [28,29,31,32] , thus providing a
safer and more suitable method for in vivo and real-time in-situ skin cancer diagnosis compared with other
NIR or FT-Raman system. We believe we cannot obtain Raman spectra fast and at a local spot in a skin
tissue to get cancer margins without using the 532 nm RR.

This pilot study shows that VRR technology may have broad clinical applications for real-time, and label-free
detection of skin lesions and other human tumors such as breast and brain [37-42,83,84] . A most recent reference
[85]
to salient features of VRR in carotene in solution is given by Lu et al. .

DECLARATIONS
Acknowledgments
The authors are grateful to Dr. K. Sutkus for his assistance to manuscript preparation and submission.

Authors’ contributions
Read and revised the manuscript: All authors
Performed experiments, initiated the manuscript and performed data analysis: Liu CH
Performed the PCA-SVM analysis and wrote part of the manuscript: Wu B
Revised the manuscript: Sordillo LA
Performed experiments: Boydston-White S
Prepared the samples: Sriramoju V
Performed data analysis: Zhang C
Financially supported the study, participated in discussions and revised the manuscript: Beckman H
Participated in discussions and revised the manuscript: Zhang L, Pei Z, Shi LY
Is the principal investigator of the project, and supervised the entire study: Alfano RR

Availability of data and materials
The data that support the findings of this study are available from the corresponding author upon reasonable
request.

Financial support and sponsorship
This preliminary work was supported in part by a seed grant from Sinai hospital of Detroit medical staff
foundation.

Conflicts of interest
All authors declared that there are no conflicts of interest.

Ethical approval and consent to participate
In this study, the human skin normal and BCC specimens were obtained from the NDRI (Philadelphia, PA).
The experimental procedures were approved by the City College of the City University of New York, IRB office.

Consent for publication
Not applicable.

Copyright
© The Author(s) 2019.