Combination of High-Resolution Optical Coherence Tomography and Raman Spectroscopy for Improved Staging and Grading in Bladder Cancer

Abstract

We present a combination of optical coherence tomography (OCT) and Raman spectroscopy (RS) for improved diagnosis and discrimination of different stages and grades of bladder cancer ex vivo by linking the complementary information provided by these two techniques. Bladder samples were obtained from biopsies dissected via transurethral resection of the bladder tumor (TURBT). As OCT provides structural information rapidly, it was used as a red-flag technology to scan the bladder wall for suspicious lesions with the ability to discriminate malignant tissue from healthy urothelium. Upon identification of degenerated tissue via OCT, RS was implemented to determine the molecular characteristics via point measurements at suspicious sites. Combining the complementary information of both modalities allows not only for staging, but also for differentiation of low-grade and high-grade cancer based on a multivariate statistical analysis. OCT was able to clearly differentiate between healthy and malignant tissue by tomogram inspection and achieved an accuracy of 71% in the staging of the tumor, from pTa to pT2, through texture analysis followed by k-nearest neighbor classification. RS yielded an accuracy of 93% in discriminating low-grade from high-grade lesions via principal component analysis followed by k-nearest neighbor classification. In this study, we show the potential of a multi-modal approach with OCT for fast pre-screening and staging of cancerous lesions followed by RS for enhanced discrimination of low-grade and high-grade bladder cancer in a non-destructive, label-free and non-invasive way.

Morpho-molecular ex vivo detection and grading of non-muscle-invasive bladder cancer using forward imaging probe based multimodal optical coherence tomography and Raman spectroscopy

“…Furthermore, the sensitivity of detecting high grade lesions with RS was 99%, whereas the specificity was 87%, indicating correct detection of low grade lesions. 55 To use these techniques in vivo in the clinics, they need to be integrated into rigid or flexible cystoscopes to allow in situ assessment of the bladder wall. As a first step in this direction, we report on the development of a combined OCT-Raman system for stage and grade examination of bladder biopsies, based on fiber-optical probes.…”

Label‐free grading and staging of urothelial carcinoma through multimodal fibre‐probe spectroscopy

“…The first principal components (PCs) of a spectral data set usually represent its most relevant spectral features, which eventually can be associated to the presence of specific molecules. In particular, methods based on mixing the information provided by different PCs have already been applied to the classification of UC Raman spectra . Hence, for each spectroscopic technique, we used a classification method based on different linear combinations of the first six PCs.…”

“…Raman scattering allows to analyse the chemical composition of biological systems by probing the vibrational energy levels of molecules, hence providing highly specific information on tissue molecular composition. In particular, this technique has been used for detecting bladder cancer and for discriminating different tumour stages and grades . Finally, reflectance spectroscopy is a well‐established technology for measuring both colour and intensity of light reflected from tissues.…”

Correlated Multimodal Imaging in Life Sciences: Expanding the Biomedical Horizon

“…It relies on the effect of inelastic scattering of photons, stimulating molecular vibrations providing specific information on the chemical composition and molecular structure, and is an emerging technique in life sciences owing to its unique capability of generating spectroscopic fingerprints of cells and tissues in a nondestructive and label-free approach. It has been demonstrated that the combination OCT/RS on cancerous tissue can increase diagnostic sensitivity, specificity and accuracy compared to a single modality [57]. Two-photon excited fluorescence (TPEF) microscopy can be used to visualize endogenous fluorophores such as NADH and FAD giving information about redox states.…”

“…Advanced PHI includes R&D setups and pipelines that showcase combinations of in-vivo OI, OCT/PAI, US, MRI, CT, or PET [8,76]. Examples as outlined in section Preclinical Hybrid Imaging include label-free imaging using OCT and RS [57], or the combination of MRI and OI [77].…”