Image-guided Raman spectroscopy probe-tracking for tumor margin delineation.

Conor C. Horgan,Mads S. Bergholt,Daniel J. Stuckey,Robert Kennedy,Tammy L. Kalber,Anika Nagelkerke,May Zaw Thin,Molly M. Stevens

doi:10.1117/1.jbo.26.3.036002

Abstract

.Significance: Tumor detection and margin delineation are essential for successful tumor resection. However, postsurgical positive margin rates remain high for many cancers. Raman spectroscopy has shown promise as a highly accurate clinical spectroscopic diagnostic modality, but its margin delineation capabilities are severely limited by the need for pointwise application.Aim: We aim to extend Raman spectroscopic diagnostics and develop a multimodal computer vision-based diagnostic system capable of both the detection and identification of suspicious lesions and the precise delineation of disease margins.Approach: We first apply visual tracking of a Raman spectroscopic probe to achieve real-time tumor margin delineation. We then combine this system with protoporphyrin IX fluorescence imaging to achieve fluorescence-guided Raman spectroscopic margin delineation.Results: Our system enables real-time Raman spectroscopic tumor margin delineation for both ex vivo human tumor biopsies and an in vivo tumor xenograft mouse model. We then further demonstrate that the addition of protoporphyrin IX fluorescence imaging enables fluorescence-guided Raman spectroscopic margin delineation in a tissue phantom model.Conclusions: Our image-guided Raman spectroscopic probe-tracking system enables tumor margin delineation and is compatible with both white light and fluorescence image guidance, demonstrating the potential for our system to be developed toward clinical tumor resection surgeries.

Highlights

Accurate delineation of tumor margins is essential for improving cancer survival rates, as incomplete tumor resection has been shown to significantly reduce long-term survival rates for a rangeJournal of Biomedical OpticsDownloaded From: https://www.spiedigitallibrary.org/journals/Journal-of-Biomedical-Optics on 08 Nov 2021 Terms of Use: https://www.spiedigitallibrary.org/terms-of-useMarch 2021 Vol 26(3)Horgan et al.: Image-guided Raman spectroscopy probe-tracking for tumor margin delineation of cancers.[1,2,3] the need for maximal resection needs to be balanced with the goal of healthy tissue preservation in order to minimize patient discomfort and functional impairment
Our image-guided Raman spectroscopic probe-tracking system enables tumor margin delineation and is compatible with both white light and fluorescence image guidance, demonstrating the potential for our system to be developed toward clinical tumor resection surgeries
Upon user identification of a region of interest, the system (Fig. S1, IV in the Supplemental Materials) records both the location of the probe tip and a Raman spectral signal for diagnosis. This Raman spectral signal is diagnosed in real-time through application of a previously developed diagnostic model (e.g., partial least squares-discriminant analysis (PLS-DA)) (Fig. S1, V in the Supplemental Materials) and the diagnoses displayed at the probe tip coordinates are overlaid onto the clinical imaging video

Summary

Introduction

Accurate delineation of tumor margins is essential for improving cancer survival rates, as incomplete tumor resection has been shown to significantly reduce long-term survival rates for a rangeJournal of Biomedical OpticsDownloaded From: https://www.spiedigitallibrary.org/journals/Journal-of-Biomedical-Optics on 08 Nov 2021 Terms of Use: https://www.spiedigitallibrary.org/terms-of-useMarch 2021 Vol 26(3)Horgan et al.: Image-guided Raman spectroscopy probe-tracking for tumor margin delineation of cancers.[1,2,3] the need for maximal resection needs to be balanced with the goal of healthy tissue preservation in order to minimize patient discomfort and functional impairment. Many groups have investigated the application of pointwise optical techniques such as fluorescence spectroscopy,[7,14,15] reflectance spectroscopy,[16,17,18] Raman spectroscopy,[4,19,20] optical coherence tomography,[21,22,23] and confocal endomicroscopy[24,25] for cancer detection and diagnosis These techniques probe the optical or endogenous biomolecular properties of the tissue itself, revealing differences between healthy and diseased tissue that can be used to provide accurate diagnoses. Fluorescence spectroscopy has been applied to skin cancer diagnosis[26,27] and as a quantitative adjunct to fluorescence imaging of gliomas during brain surgery.[11,15] reflectance spectroscopy has been used for the detection of cervical precancers in vivo[16] and in combination with fluorescence spectroscopy for the in vivo detection of breast, brain, and ovarian cancers.[17,18,28] Raman spectroscopy, in particular, has enabled highly accurate in vivo diagnosis of a range of cancers including breast, skin, colon, gastric, and esophageal cancers, exploiting the interaction of light with molecular bonds to identify the chemical species present in a sample.[4,19,29,30,31]

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