A new method using Raman spectroscopy for in vivo targeted brain cancer tissue biopsy

Abstract

Modern cancer diagnosis requires histological, molecular, and genomic tumor analyses. Tumor sampling is often achieved using a targeted needle biopsy approach. Targeting errors and cancer heterogeneity causing inaccurate sampling are important limitations of this blind technique leading to non-diagnostic or poor quality samples, and the need for repeated biopsies pose elevated patient risk. An optical technology that can analyze the molecular nature of the tissue prior to harvesting could improve cancer targeting and mitigate patient risk. Here we report on the design, development, and validation of an in situ intraoperative, label-free, cancer detection system based on high wavenumber Raman spectroscopy. This optical detection device was engineered into a commercially available biopsy system allowing tumor analysis prior to tissue harvesting without disrupting workflow. Using a dual validation approach we show that high wavenumber Raman spectroscopy can detect human dense cancer with >60% cancer cells in situ during surgery with a sensitivity and specificity of 80% and 90%, respectively. We also demonstrate for the first time the use of this system in a swine brain biopsy model. These studies set the stage for the clinical translation of this optical molecular imaging method for high yield and safe targeted biopsy.

Comparison of optically‐derived biomarkers in healthy and brain tumor tissue under one‐ and two‐photon excitation

“…For enhanced tumor visualization at the meso and microscale, other optical techniques are applied, usually through an endomicroscope . State of the art endomicroscopes can be equipped with confocal reflectance and fluorescence imaging , Raman spectroscopy and coherent anti‐Stokes Raman scattering (CARS) microscopy , fluorescence lifetime imaging (FLIM) and two‐photon microscopy . Although each modality has its own advantages and limits when utilized in the surgical field, a recent solution has been to combine two or more modalities to alleviate their limitations on one hand, and to increase the information depth retrieved enabling more differentiated diagnostics.…”

Detection of glioma by surface‐enhanced Raman scattering spectra with optimized mathematical methods

“…In previous studies, glioma detection based on mathematical analysis and Raman spectra has been reported. Desroches et al constructed a SVM model, which was evaluated by a leave‐one‐out cross‐validation approach, giving a performance with a sensitivity of 80% and a specificity of 90%. Linear discriminant analysis (LDA), which was based on Mahalanobis distances, has also been employed to predict the IDH1‐mutation status with a correct rate of 89% for the test set and 88% for the training set .…”

Raman Scattering: From Structural Biology to Medical Applications

“…Various brain tumors could be identified with the help of RS [192][193][194][195][196][197]. Gliomas of various types and one of the most malignant glioma-glioblastoma multiforme could be distinguished from other tumors.…”