Water Concentration Analysis by Raman Spectroscopy to Determine the Location of the Tumor Border in Oral Cancer Surgery

Abstract

Adequate resection of oral cavity squamous cell carcinoma (OCSCC) means complete tumor removal with a clear margin of more than 5 mm. For OCSCC, 85% of the surgical resections appear inadequate. Raman spectroscopy is an objective and fast tool that can provide real-time information about the molecular composition of tissue and has the potential to provide an objective and fast intraoperative assessment of the entire resection surface. A previous study demonstrated that OCSCC can be discriminated from healthy surrounding tissue based on the higher water concentration in tumor. In this study, we investigated how the water concentration changes across the tumor border toward the healthy surrounding tissue on freshly excised specimens from the oral cavity. Experiments were performed on tissue sections from 20 patients undergoing surgery for OCSCC. A transition from a high to a lower water concentration, from tumor (76% ± 8% of water) toward healthy surrounding tissue (54% ± 24% of water), takes place over a distance of about 4 to 6 mm across the tumor border. This was accompanied by an increase of the heterogeneity of the water concentration in the surrounding healthy tissue. The water concentration distributions between the regions were significantly different (P < 0.0001). This new finding highlights the potential of Raman spectroscopy for objective intraoperative assessment of the resection margins. Cancer Res; 76(20); 5945-53. ©2016 AACR.

Clinical applications of infrared and Raman spectroscopy: state of play and future challenges

“…In the field of oral cancer, Barroso et al [23] have demonstrated discrimination between oral cancer and healthy tissue based on water content of freshly excised tongue specimens, determined by Raman spectroscopy in the high wavenumber region. This dramatic signature difference can be used to determine the location of the tumor border in oral cancer surgery [24].…”

In vivo Raman spectroscopy–assisted early identification of potential second primary/recurrences in oral cancers: An exploratory study

“…In a recent pilot study for differentiating normal and benign from premalignant and malignant conditions, premalignant and malignant lesions could be predicted with 100% sensitivity and 77% specificity . Even the surgical demarcation studies could successfully differentiate tumor and nontumor tissue with an accuracy of either 86% or in the range of 75%‐100% . The majority of the oral cancer studies have shown high accuracy, sensitivity, and specificity values for oral cancer diagnosis, or specifically identifying normal, benign, and premalignant from malignant conditions.…”

“…29 Even the surgical demarcation studies could successfully differentiate tumor and nontumor tissue with an accuracy of either 86% or in the range of 75%-100%. [30][31][32] The majority of the oral cancer studies have shown high accuracy, sensitivity, and specificity values for oral cancer diagnosis, or specifically identifying normal, benign, and premalignant from malignant conditions. Several of these studies have also reported misclassifications between contralateral normal mucosa (clinically normal appearing areas in subjects with tumor) and tumor site.…”

“…28,29 The potential of Raman spectroscopy in surgical demarcations has also been successfully explored in recent years. [30][31][32] Further, another study has identified cancer field effects/malignancy-associated changes in the normal mucosa of patients with oral cancer, 33 these are the earliest events in oral carcinogenesis. Hamster buccal pouch (animal model) is very similar to human buccal mucosa and mimics oral carcinogenesis.…”

Advancing Raman microspectroscopy for cellular and subcellular analysis: towards in vitro high-content spectralomic analysis

“…The application of Raman spectroscopy to biomolecules and even tissues was first demonstrated as early as the 1960s [1][2][3] and by the mid-1970s biomedical applications were explored [4]. Whole cell and tissue studies have been carried out on a range of pathologies [5][6][7][8][9] and in vivo studies [10][11][12] have demonstrated the prospective for diagnostic applications. The potential of vibrational spectroscopy in conjunction with multivariate analysis techniques as a diagnostic tool has thus been well demonstrated and the concept of Spectral Cytopathology has been coined [13].…”