Raman spectroscopy for identification of epithelial cancers

Abstract

There is a real need for improvements in cancer detection. Significant problems are encountered when utilising the gold standard of excisional biopsy combined with histopathology. This can include missed lesions, perforation and high levels of inter- and intra-observer discrepancies. The clinical requirements for an objective, non-invasive real time probe for accurate and repeatable measurement of tissue pathological state are overwhelming. This study has evaluated the potential for Raman spectroscopy to achieve this goal. The technique measures the molecular specific inelastic scattering of laser light within tissue, thus enabling the analysis of biochemical changes that precede and accompany disease processes. Initial work has been carried out to optimise a commercially available Raman microspectrometer for tissue measurements; to target potential malignancies with a clinical need for diagnostic improvements (oesophagus. colon, breast, andd prostate) and to build and test spectral libraries and prediction algorithms for tissue types and pathologies. This study has followed rigorous sample collection protocols and histopathological analysis using a board of expert pathologists. Only the data from samples with full agreement of a homogeneous pathology have been used to construct a training data set of Raman spectra. Measurements of tissue specimens from the full spectrum of different pathological groups found in each tissue have been made. Diagnostic predictive models have been constructed and optimised using multivariate analysis techniques. They have been tested using cross-validation or leave-one-out and demonstrated high levels of discrimination between pathology groups (greater than 90% sensitivity and specificity for all tissues). However larger sample numbers are required for further evaluation. The discussions outline the likely work required for successful implementation of in vivo Raman detection of early malignancies.

Raman spectroscopy can differentiate malignant tumors from normal breast tissue and detect early neoplastic changes in a mouse model

“…8,11,[34][35][36][37][38][39][40][41][42][43][44] Our data is confirmatory, and, in addition, demonstrates changes in the tumor bed, which probably represent the detection of chemical signs of preneoplastic changes.…”

Molecular characterization of reconstructed skin model by Raman microspectroscopy: Comparison with excised human skin

“…The phenylalanine also contributes to the 1175 and 1339 cm 21 vibrations. 19,25,[38][39][40][41][42][43][44] The presence of tyrosine (Tyr) is highlighted by the 643 cm 21 band (ring breathing) and the Raman doublet at 829 and 851 cm 21 , this doublet is due to Fermi resonance between the ring breathing vibration, and the overtone of the nonplanar ring vibration at 413 cm 21 . The intensity ratio I 829 /I 851 is related to the state of the phenolic hydroxyl group.…”

“…15 The potential of Raman spectroscopy to discriminate pathologic from healthy skin structures and to classify different types and grades of cutaneous lesions has been demonstrated by several studies. [16][17][18][19][20][21][22][23][24] Other research works studied the molecular composition of the skin, 25,26 followed the effects induced by different types of drugs, 25,27 and established in depth concentration profiles (starting from the surface and going deeper into the skin) of different molecules (water and endogenous molecules). [27][28][29][30][31][32][33][34] The follow-up, in real-time analysis, of the diffusion of the exogenous products through skin layers has also been performed.…”

Direct observation of spectral differences between normal and basal cell carcinoma (BCC) tissues using confocal Raman microscopy

“…Technologies such as Fourier transform infrared (FTIR), Raman, and confocal fluorescence microscopy have been used to elucidate the origin and progression of cancer. [1][2][3][4][5][6] These technologies have also been used for the early detection of cancer and biochemical changes in cells and tissues causing cancer. 7,8 Among these spectroscopic techniques, Raman spectroscopy has attracted considerable attention for medical diagnosis since it is nondestructive, does not require a sample preparation process, and provides detailed information about the molecular structure of normal and diseased tissues.…”