A pilot study for distinguishing basal cell carcinoma from normal human skin tissues using visible resonance Raman spectroscopy

Abstract

Aim:The aim of the study is to test visible resonance Raman (VRR) spectroscopy for rapid skin cancer diagnosis, and evaluate its effectiveness as a new optical biopsy method to distinguish basal cell carcinoma (BCC) from normal skin tissues. Methods:The VRR spectroscopic technique was undertaken using 532 nm excitation. Normal and BCC human skin tissue samples were measured in seconds. The molecular fingerprints of various native biomolecules as biomarkers were analyzed. A principal component analysis -support vector machine (PCA-SVM) statistical analysis method based on the molecular fingerprints was developed for differentiating BCC from normal skin tissues.Results: VRR provides a rapid method and enhanced Raman signals from biomolecules with resonant and nearresonant absorption bands as compared with using a near-infrared excitation light source. The VRR technique revealed chemical composition changes of native biomarkers such as tryptophan, carotenoids, lipids and proteins. The VRR spectra from BCC samples showed a strong enhancement in proteins including collagen type I combined with amide I and amino acids, and a decrease in carotenoids and lipids. The PCA-SVM statistical analysis based on the molecular fingerprints of the biomarkers yielded a 93.0% diagnostic sensitivity, 100% specificity, and 94.5% accuracy compared with histopathology reports.Conclusion: VRR can enhance molecular vibrational modes of various native biomarkers to allow for very fast display of Raman modes in seconds. It may be used as a label-free molecular pathology method for diagnosis of skin cancer and other diseases and be used for combined treatment with Mohs surgery for BCC.

Combined spatial frequency spectroscopy analysis with visible resonance Raman for optical biopsy of human brain metastases of lung cancers

“…46 These observations are in good agreement with changes of tryptophan contents in human brain malignant meningioma and gliomas tissues 10 and skin basal cell carcinoma tissues. 19 The molecular biomarker of tryptophan provides a potential approach to diagnose metastatic brain cancerous tissues and other cancers.…”

“…This result is well consistent with the previous reports of Raman spectra of glioblastoma multiforme (GBM) and basal cell carcinoma ex vivo. 10,18,19 The ratios serve as a key approach to predict the metastatic potential of brain cancer using VRR spectroscopy analysis.…”

“…VRR provides an e®ective way to enhance Raman signal from particular chemical bonds associated with key molecules and detect their changes at a molecular level, such as carotenoids, tryptophan, amides, lipids and protein in breast, skin, heart, gynecologic and brain lesions. 14,15,17 These advantages of VRR have led to a rapid progress in its applications in brain and other human cancer diagnosis 14,[17][18][19][20][21] that are di±cult to achieve by conventional nonresonance Raman method. [22][23][24][25][26][27] Recently, another new optical spatial frequency spectroscopy analysis (SFSA) method was introduced based on Fourier spatial frequency spectrum analysis of the underlying structure pattern of tissues.…”

Mammalian cell and tissue imaging using Raman and coherent Raman microscopy

“…Analysis of the fingerprint and high‐wavenumber regions (FP/HW) in the GA‐PLS‐LDA algorithm had an accuracy, sensitivity, and specificity of 96.76, 87.78, and 100%, respectively—higher than the analogous blood test which may be attributable to the simultaneous unique advantages of both FP and HW Raman tissue spectra (Žuvela et al, 2019). Recent work successfully used resonance Raman techniques (RRS) for brain tumor biopsies (Zhou et al, 2018, 2019), skin cancer detections (Liu et al, 2019), and breast cancer subtype separation (Bendau et al, 2020). Using spontaneous RS to scan colon cells from patients, a k‐means clustered image‐trained support vector machine was able to diagnose the samples as having Ulcerative Colitis, Crohn's disease, or no irritable bowel disease (IBD).…”

Introduction to this Special Issue: “Biomarker Discovery and Precision Medicine”

“…The study presented by Zaichick et al [10] showed that contents of several chemical elements were drastically different between thyroid malignant tumors and normal thyroid tissues. Finally, Liu et al [11] reported the results of using visible resonance Raman spectroscopy for rapid skin cancer diagnosis.…”