Development and preliminary results of an endoscopic Raman probe for potential in vivo diagnosis of lung cancers

Short, Michael; Lam, Stephen; McWilliams, Annette; Zhao, Jianhua; Lui, Harvey; Zeng, Haishan

doi:10.1364/ol.33.000711

Cited by 134 publications

(132 citation statements)

References 9 publications

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“…Endoscopic Raman probes are currently being developed to overcome these limitations while maintaining its ultrasensitive and multiplexing properties (32,33).…”

Section: Discussionmentioning

confidence: 99%

Multiplexed imaging of surface enhanced Raman scattering nanotags in living mice using noninvasive Raman spectroscopy

Zavaleta

Walton

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

656

665

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Raman spectroscopy is a newly developed, noninvasive preclinical imaging technique that offers picomolar sensitivity and multiplexing capabilities to the field of molecular imaging. In this study, we demonstrate the ability of Raman spectroscopy to separate the spectral fingerprints of up to 10 different types of surface enhanced Raman scattering (SERS) nanoparticles in a living mouse after s.c. injection. Based on these spectral results, we simultaneously injected the five most intense and spectrally unique SERS nanoparticles i.v. to image their natural accumulation in the liver. All five types of SERS nanoparticles were successfully identified and spectrally separated using our optimized noninvasive Raman imaging system. In addition, we were able to linearly correlate Raman signal with SERS concentration after injecting four spectrally unique SERS nanoparticles either s.c. (R 2 ‫؍‬ 0.998) or i.v. (R 2 ‫؍‬ 0.992). These results show great potential for multiplexed imaging in living subjects in cases in which several targeted SERS probes could offer better detection of multiple biomarkers associated with a specific disease.imaging in vivo ͉ multiplex ͉ SERS ͉ nanoparticles I n recent years, the biomedical research community has come to realize that no single targeting agent is likely to provide sufficient information needed to characterize or detect a specific disease process. As a result, several efforts have been made toward the discovery of multiple biomarkers and targeting ligands in the hope of improving earlier detection and management of specific diseases. The ability to simultaneously detect multiple targets, sensitively and in vivo, is an attractive feat; but it is a task often difficult to accomplish. Thus far, nanoparticles have played an important role in this endeavor; however most nanostructure-based platforms for multiplex detection methods have been tailored for in vitro applications (1-6), leading to little progress in the field of in vivo multiplex imaging.Recently, there has been an overwhelming interest in sensitive imaging of nanoparticles for both diagnostic and therapeutic applications (7-11). As a result, new preclinical imaging modalities optimized for nanoparticle imaging have been developed, further expanding the field of molecular imaging. Thus far, fluorescence and Raman spectroscopy, in conjunction with quantum dots and surface enhanced Raman scattering (SERS) nanoparticles, respectively, have been the predominant imaging modalities to evaluate in vivo multiplex imaging (12)(13)(14). Raman imaging, in particular, has generated quite a bit of interest recently; we have demonstrated its ability to detect picomolar concentrations in vivo along with its unique ability to multiplex using SERS nanoparticles and others have developed novel Raman nanoparticles with the potential to be used in vivo as well (14-17).Both quantum dots and SERS nanoparticles have shown great potential as multiplexed imaging probes ex vivo, whether for cellular imaging or for biosensor applications; however, seve...

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“…Endoscopic Raman probes are currently being developed to overcome these limitations while maintaining its ultrasensitive and multiplexing properties (32,33).…”

Section: Discussionmentioning

confidence: 99%

Multiplexed imaging of surface enhanced Raman scattering nanotags in living mice using noninvasive Raman spectroscopy

Zavaleta

Walton

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

656

665

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“…[4][5][6][7][8][9][10][11][12][13][14] These investigations show that specific spectral features of Raman spectra could be used to correlate with the molecular and structural changes of tissue associated with neoplastic trans-formation. Diagnostic sensitivities of ϳ85 to 95% and specificities of ϳ90 to 98% have been reported for differentiation between normal and pathological ͑e.g., dysplasia, adenocarcinoma͒ gastric tissues in vitro using Raman spectroscopic technique.…”

Section: Introductionmentioning

confidence: 99%

“…[4][5][6] The fabrication of a millimeter-scaled or even smaller flexible fiber optic Raman probe with abilities of efficient fiber fluorescence/Raman background rejections while having high tissue Raman signal collection efficiency renders another technical challenge for clinical Raman endoscopic examinations. 6,8,15 Very recently, we have successfully developed a high throughput Raman endoscopy system integrated with trimodal wide-field endoscopic imaging for rapid in vivo gastric tissue Raman measurements at gastroscopy. 16 With the unique image-guided Raman endoscopy technique developed, we aim, in this work, to evaluate the clinical utility of Raman spectroscopy for in vivo diagnosis and detection of gastric dysplasia during clinical gastroscopic examination.…”

Section: Introductionmentioning

confidence: 99%

In vivo early diagnosis of gastric dysplasia using narrow-band image-guided Raman endoscopy

et al. 2010

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Abstract. We first report on the implementation of a novel narrowband image-guided Raman endoscopy technique for in vivo diagnosis of gastric dysplasia. High-quality in vivo Raman spectra can be acquired from normal and dysplastic gastric mucosal tissue within 0.5 sec under narrow-band image ͑NBI͒ guidance at gastroscopy. Significant differences are observed in in vivo Raman spectra between normal ͑n =54͒ and dysplastic ͑n =18͒ gastric tissue from 30 gastric patients, particularly in the spectral ranges of 825 to 950, 1000 to 1100, 1250 to 1500, and 1600 to 1800 cm −1 , which primarily contain signals related to proteins, nucleic acids, and lipids. The multivariate analysis ͓i.e., principal components analysis ͑PCA͒ and linear discriminant analysis ͑LDA͔͒, together with the leave-one tissue siteout, cross validation on in vivo gastric Raman spectra yields a diagnostic sensitivity of 94.4% ͑17/ 18͒ and specificity of 96.3% ͑52/ 54͒ for distinction of gastric dysplastic tissue. This study suggests that narrowband image-guided Raman endoscopy associated with PCA-LDA diagnostic algorithms has potential for the noninvasive, in vivo early diagnosis and detection of gastric precancer during clinical gastroscopic examination.

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“…Raman spectroscopy is an inelastic light scattering technique capable of non-destructively providing detailed quantitative chemical information on tissues at the molecular level, while the spectral signatures may unambiguously be assigned to the intra-and intercellular constituents (e.g., proteins, lipids and nucleic acids) of tissues. Compared to other optical spectroscopic techniques, such as fluorescence spectroscopy and infrared absorption spectroscopy, Raman spectroscopy is particularly amenable to in vivo measurements, as the excitation wavelengths and laser (14) and skin (15,16). A number of these Raman spectroscopic investigations have been limited to micro-Raman spectroscopy and off-line post-processing.…”

Section: Introductionmentioning

confidence: 99%

Rapid detection of nasopharyngeal cancer using Raman spectroscopy and multivariate statistical analysis

Huang²,

Pan

et al. 2014

Molecular and Clinical Oncology

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Abstract. Optical spectroscopic techniques, including Raman spectroscopy, have shown promise for in vivo cancer diagnostics in a variety of organs. In this study, the potential use of a home-made Raman spectral system with a millimeter order excitation laser spot size combined with a multivariate statistical analysis for the rapid detection and discrimination of nasopharyngeal cancer from normal nasopharyngeal tissue was evaluated. Raman scattering signals were acquired from 16 normal and 32 nasopharyngeal carcinoma tissue samples. Linear discriminant analysis (LDA) based on principal component analysis (PCA) and partial least squares (PLS) were employed to generate diagnostic algorithms for the classification of different nasopharyngeal tissue types. Spectral differences in Raman spectra between the two types of tissues were revealed; the normalized intensities of Raman peaks at 1,001, 1,207 and 1,658 cm -1 were more intense for nasopharyngeal carcinoma tissue compared to normal tissue, while Raman bands at 848, 936 and 1,446 cm -1 were stronger in normal nasopharyngeal samples. The PCA-LDA algorithm together with leave-one-out cross validation yields a diagnostic sensitivity of 81% and a specificity of 87%, while the PLS method coupled with subwindow permutation analysis improves the diagnostic sensitivity and specificity to 85 and 88%, respectively. Therefore, Raman spectroscopy combined with PCA-LDA/PLS demonstrated good potential for improving the clinical diagnosis of nasopharyngeal cancers. IntroductionNasopharyngeal cancer is a squamous cell carcinoma that develops in the epithelial lining of the nasopharynx and has the highest incidence rates in East Asia, particularly in the Southeastern region of China, where the age-standardized incidence rate reaches 26.9/100,000 in males (1,2). Early diagnosis and adequate treatment of nasopharyngeal cancer is crucial to increase the survival rate of the patients. Current diagnostics rely on the visualization of gross morphological changes (e.g., irregularity, modularity and anatomical location) associated with neoplastic transformation, using routine white-light reflectance endoscopy. The definitive diagnosis and staging of patients with neoplastic diseases usually requires surgical removal of tissue for histological review. It is usually difficult to identify nasopharyngeal cancer in its early stages (3,4). Therefore, there is an urgent need to develop a fast and non-destructive technique to aid the clinical identification of early-stage nasopharyngeal cancer.A variety of optical imaging and spectroscopic techniques, including Raman spectroscopy, are currently being investigated with the aim to improve cancer diagnosis and treatment (5-7). These techniques have the potential to provide chemical as well as morphological information and are less invasive compared to the currently available diagnostic procedures. Raman spectroscopy is an inelastic light scattering technique capable of non-destructively providing detailed quantitative chemical information on tissues ...

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Development and preliminary results of an endoscopic Raman probe for potential in vivo diagnosis of lung cancers

Cited by 134 publications

References 9 publications

Multiplexed imaging of surface enhanced Raman scattering nanotags in living mice using noninvasive Raman spectroscopy

Multiplexed imaging of surface enhanced Raman scattering nanotags in living mice using noninvasive Raman spectroscopy

In vivo early diagnosis of gastric dysplasia using narrow-band image-guided Raman endoscopy

Rapid detection of nasopharyngeal cancer using Raman spectroscopy and multivariate statistical analysis

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