Raman spectroscopy of bladder tissue in the presence of 5-aminolevulinic acid
ABSTRACT Raman spectroscopy has the ability to provide differential diagnosis of different cancers with high sensitivity and specificity. A major limitation in its clinical application is the weak nature of Raman signal, which inhibits scanning large surface areas of tissues. In bladder cancer diagnosis, fluorescence-guided endoscopy with 5-aminolevulinic acid (5-ALA) has gained interest as a technique that can provide such spatial differentiation, thus improving early detection and more complete removal of superficial tumors. However, several studies have demonstrated the poor specificity of this modality. Combining fluorescence with Raman spectroscopy could improve its diagnostic capability. However, little is known about the effect of agents such as 5-ALA on Raman spectra of tissue. In this paper, we present measuring Raman spectroscopy from benign and malignant bladder tissues in the presence of 5-ALA and attempt to evaluate the potential to discriminate between different pathologies. Raman spectra were recorded from 92 bladder biopsies without 5-ALA and 38 biopsies with 5-ALA using a Raman microspectrometer system at 830nm excitation. Empirical and multivariate statistical techniques were used for data analysis. Algorithms were developed to determine the effect of 5-ALA on tissue and its influence on the prediction ability of a preliminary benign/malignant prediction model. In samples with 5-ALA, an overall decrease in Raman intensity was observed when compared to the Raman spectra from samples without 5-ALA. Additionally, differences in relative intensities at 1270 and 1330cm(-1) were also noted. However, significant differences were observed in the Raman spectra of benign and malignant samples with 5-ALA indicating the potential of using Raman spectroscopy for discriminating bladder cancer in the presence of 5-ALA. The Principal-Component fed Linear-Discriminant Analysis (PCA/LDA) algorithm derived from biopsies in the absence of 5-ALA used to predict biopsies in the presence of 5-ALA resulted in an overall sensitivity and specificity of 42.6% and 71.1%, respectively. This suggests the presence of 5-ALA in tissue affects the Raman spectra. A PCA/LDA algorithm based on fluorescence information (i.e. PpIX fluorescence positive or negative) and the Raman spectrum of 5-ALA biopsies, had a sensitivity and specificity of 100% and 80.8%, respectively. This study demonstrates that applying 5-ALA affects the Raman spectra of bladder tissues. However, benign/malignant differentiation can be accomplished with a preliminary PCA/LDA algorithm, suggesting the potential of a combined diagnostic modality in vivo.
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ABSTRACT: Biomolecular changes associated with cancer progression can be identified using Raman spectroscopy, allowing for this technique to be utilized as a non-invasive tool for the diagnosis of bladder cancer. Applications of Raman spectroscopy for diagnostics in real-time have consistently produced higher sensitivities and specificities than current clinical methods. This technique can be applied in vivo during bladder visualization (cystoscopic) procedures as an “optical biopsy” or in vitro to cells obtained from urine cytology specimens. This review follows the evolution of studies in this field from the first in vitro experiment to the most recent in vivo application, identifies how diagnostic algorithms are developed, and provides molecular information associated with the etiology of the biochemical continuum of disease progression. Future prospects for the application of Raman spectroscopy in bladder cancer diagnostics are also discussed.05/2014; 3(3):2193-0643. DOI:10.1515/plm-2014-0004
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ABSTRACT: The molecular changes that occur with cervical remodelling during pregnancy are not completely understood. This paper reviews Raman spectroscopy, an optical technique for detecting changes in the pregnant cervix, and reports preliminary studies on cervical remodelling in mice that suggest that the technique provides advantages over other methods. Conclusion. Raman spectroscopy is sensitive to biochemical changes in the pregnant cervix and has high potential as a tool for detecting premature cervical remodelling in pregnant women.This article is protected by copyright. All rights reserved.Acta Paediatrica 03/2014; 103(7). DOI:10.1111/apa.12630 · 1.84 Impact Factor
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ABSTRACT: The use of vibrational spectroscopy for diagnosis and staging of cancer is extremely attractive, promising many benefits over the currently used histopathology methods. The hypothesis underlying this approach is that cancers have characteristic biochemical fingerprints that can be captured using spectroscopy. To relate complex multivariate spectra to disease state, machine-learning methods are typically used to recognize diagnostic spectral patterns. This article provides an extensive review of this field. The average diagnostic performance of the reviewed studies is impressive (>90% sensitivity and specificity) but most studies were small (<40 samples). Furthermore, diagnostic performance has often been calculated using methods now known to be overoptimistic. We conclude that, if the combination of spectroscopy and machine learning is to translate into clinical practice, larger studies are needed and researchers should routinely provide spectral data in support of their publications so that the data can be reanalyzed by other groups.TrAC Trends in Analytical Chemistry 07/2014; 59. DOI:10.1016/j.trac.2014.02.016 · 6.61 Impact Factor