Abstract
We assess the clinical utility of a unique simultaneous fingerprint (FP) (i.e., 800-1800 cm-1) and high-wavenumber (HW) (i.e., 2800-3600 cm-1) fiber-optic Raman spectroscopy for in vivo diagnosis of laryngeal cancer at endoscopy. A total of 2124 high-quality in vivo FP/HW Raman spectra (normal = 1321; cancer = 581) were acquired from 101 tissue sites (normal = 71; cancer = 30) of 60 patients (normal = 44; cancer = 16) undergoing routine endoscopic examination. FP/HW Raman spectra differ significantly between normal and cancerous laryngeal tissue that could be attributed to changes of proteins, lipids, nucleic acids, and the bound water content in the larynx. Partial least squares-discriminant analysis and leave-one tissue site-out, cross-validation were employed on the in vivo FP/HW tissue Raman spectra acquired, yielding a diagnostic accuracy of 91.1% (sensitivity: 93.3% (28/30); specificity: 90.1% (64/71)) for laryngeal cancer identification, which is superior to using either FP (accuracy: 86.1%; sensitivity: 86.7% (26/30); specificity: 85.9% (61/71)) or HW (accuracy: 84.2%; sensitivity: 76.7% (23/30); specificity: 87.3% (62/71)) Raman technique alone. Further receiver operating characteristic analysis reconfirms the best performance of the simultaneous FP/HW Raman technique for laryngeal cancer diagnosis. We demonstrate for the first time that the simultaneous FP/HW Raman spectroscopy technique can be used for improving real-time in vivo diagnosis of laryngeal carcinoma during endoscopic examination.
Highlights
Laryngeal cancer is one of the most common malignancies in the head and neck, accounting for 30% to 40% of head and neck cancer [1]
With our successful development of a rapid fiber-optic Raman spectroscopy system capable of simultaneously acquiring both the fingerprint (FP) (i.e., 800-1800 cm−1) and highwavenumber (HW) (i.e., 2800-3600 cm−1) tissue Raman spectra in vivo at endoscopy [30, 31], in this work, we aim to assess the clinical utility of the rapid FP and HW Raman spectroscopy system for real-time in vivo diagnosis of cancerous tissue in the larynx
At the proximal ends of the Raman probe, the excitation and emission fibers were coupled into two separate in-line filter modules: one integrated with a narrow band-pass filter (LL01-785, Semrock, Inc.) for suppressing laser noise, and the other integrated with an edge long-pass filter (LP02-785RU, Semrock, Inc.) for further reduction of the scattered laser light while permitting the emitted tissue Raman photons to transmit into the Raman spectrograph
Summary
Laryngeal cancer is one of the most common malignancies in the head and neck, accounting for 30% to 40% of head and neck cancer [1]. Smoking tobacco and excess alcohol consumption could be one of the major risk factors for developing laryngeal cancer [2, 3]. Well-performed but randomized endoscopic biopsies followed by hematoxylin and eosin staining and microscopic viewing by the pathologists remains the gold standard for cancer diagnosis, but it is invasive and impractical for screening high risk patients with multiple suspicious lesions, which might affect the quality of life due to multiple biopsies [3, 4]. Conventional white-light reflectance (WLR) endoscopy suffers from limited diagnostic accuracy due to the lack of obvious morphological changes of early neoplastic lesions on the tissue surface. There is of great clinical needs to develop rapid, objective and minimally invasive or non-invasive diagnostic techniques for real-time diagnosis and characterization of laryngeal cancer with biomolecular specificity
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