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Hughes O.R.,Royal National Throat | Stone N.,Biophotonics Research Unit | Kraft M.,Kantonsspital Aarau | Arens C.,University Hospital Magdeburg | Birchall M.A.,Royal National Throat
Head and Neck | Year: 2010

Failure to remove tumor cells from the larynx significantly increases the risk of local recurrence following surgical excision. Healthy tissue must be preserved to optimize long-term vocal and swallowing function. It is essential to accurately distinguish between healthy mucosa, dysplasia, and invasive carcinoma. Optical and molecular examining technologies have been developed to improve tumor margin identification in vivo. We aimed to review the efficacy of these technologies. Published articles were identified using MEDLINE, EMBASE, and Cochrane central register of controlled trials (CENTRAL). Randomized clinical trials are required to establish the benefit to patients and cost to the health service of using 5-aminolevulinic acid (ALA)-induced fluorescent imaging, contact endoscopy, and optical coherence tomography (OCT). Furthermore, primary research is required to validate other techniques, such as confocal endomicroscopy and Raman spectroscopy, and to develop their clinical applications in the larynx. © 2010 Wiley Periodicals, Inc. Source

Brereton R.G.,University of Bristol | Lloyd G.R.,Biophotonics Research Unit
Journal of Chemometrics | Year: 2014

Partial least squares discriminant analysis (PLS-DA) has been available for nearly 20years yet is poorly understood by most users. By simple examples, it is shown graphically and algebraically that for two equal class sizes, PLS-DA using one partial least squares (PLS) component provides equivalent classification results to Euclidean distance to centroids, and by using all nonzero components to linear discriminant analysis. Extensions where there are unequal class sizes and more than two classes are discussed including common pitfalls and dilemmas. Finally, the problems of overfitting and PLS scores plots are discussed. It is concluded that for classification purposes, PLS-DA has no significant advantages over traditional procedures and is an algorithm full of dangers. It should not be viewed as a single integrated method but as step in a full classification procedure. However, despite these limitations, PLS-DA can provide good insight into the causes of discrimination via weights and loadings, which gives it a unique role in exploratory data analysis, for example in metabolomics via visualisation of significant variables such as metabolites or spectroscopic peaks. © 2014 John Wiley & Sons, Ltd. Source

Stone N.,Biophotonics Research Unit | Faulds K.,University of Strathclyde | Graham D.,University of Strathclyde | Matousek P.,Rutherford Appleton Laboratory
Analytical Chemistry | Year: 2010

This letter discusses the potential of deep Raman spectroscopy, surface enhanced spatially offset Raman spectroscopy (SESORS and its variants), for noninvasively detecting small, deeply buried lesions using surface enhanced resonance Raman scattering (SERRS) active nanoparticles. An experimental demonstration of this concept is performed in transmission Raman geometry. This method opens prospects for in vivo, noninvasive, specific detection of molecular changes associated with disease up to depths of several centimeters representing significant improvement over traditionally detected Raman signals by 2 orders of magnitude. The disease specific signals can be achieved using uniquely tagged nanoparticles conjugated to target molecules, e.g., antibodies for production of the SERRS signal. This provides the molecular specific signal which is many orders of magnitude greater than normal biological Raman signals and can be easily multiplexed. To date, there have been no studies demonstrating the viability of deep Raman spectroscopy coupled to surface enhanced techniques for detecting low concentrations of molecules of interest at depths of greater than 5.5 mm in tissue. Such a breakthrough would open a host of new applications in medical diagnoses. Here we propose to facilitate such capability by combining SERRS (as a probe for disease specific changes) with deep Raman spectroscopy techniques. This permits noninvasive measurement of Raman signatures from conjugated SERRS nanoparticles at clinically relevant concentrations through tissues of between 15 and 25 mm thick. © 2010 American Chemical Society. Source

Baker R.,Biophotonics Research Unit | Baker R.,Cranfield University | Rogers K.D.,Cranfield University | Shepherd N.,Cranfield University | And 2 more authors.
British Journal of Cancer | Year: 2010

Background:Breast microcalcifications are key diagnostically significant radiological features for localisation of malignancy. This study explores the hypothesis that breast calcification composition is directly related to the local tissue pathological state.Methods:A total of 236 human breast calcifications from 110 patients were analysed by mid-Fouries transform infrared (FTIR) spectroscopy from three different pathology types (112 invasive carcinoma (IC), 64 in-situ carcinomas and 60 benign). The biochemical composition and the incorporation of carbonate into the hydroxyapatite lattice of the microcalcifications were studied by infrared microspectroscopy. This allowed the spectrally identified composition to be directly correlated with the histopathology grading of the surrounding tissue.Results:The carbonate content of breast microcalcifications was shown to significantly decrease when progressing from benign to malignant disease. In this study, we report significant correlations (P0.001) between microcalcification chemical composition (carbonate content and protein matrix: mineral ratios) and distinct pathology grades (benign, in-situ carcinoma and ICs). Furthermore, a significant correlation (P0.001) was observed between carbonate concentrations and carcinoma in-situ sub-grades. Using the two measures of pathology-specific calcification composition (carbonate content and protein matrix: mineral ratios) as the inputs to a two-metric discriminant model sensitivities of 79, 84 and 90% and specificities of 98, 82 and 96% were achieved for benign, ductal carcinoma in situ and invasive malignancies, respectively.Conclusions:We present the first demonstration of a direct link between the chemical nature of microcalcifications and the grade of the pathological breast disease. This suggests that microcalcifications have a significant association with cancer progression, and could be used for future objective analytical classification of breast pathology. A simple two-metric model has been demonstrated, more complex spectral analysis may yeild greater discrimination performance. Furthermore there appears to be a sequential progression of calcification composition. © 2010 Cancer Research UK. All rights reserved. Source

Almond L.M.,Biophotonics Research Unit | Hutchings J.,Biophotonics Research Unit | Lloyd G.,Biophotonics Research Unit | Barr H.,Biophotonics Research Unit | And 7 more authors.
Gastrointestinal Endoscopy | Year: 2014

Background Early detection and targeted endoscopic resection of Barrett's esophagus-associated high-grade dysplasia (HGD) can prevent progression to invasive esophageal malignancy. Raman spectroscopy, a highly sophisticated analytical technique, has been translated into an endoscopic tool to facilitate rapid, objective diagnosis of dysplasia in the esophagus. Objective To evaluate the ability of endoscopic Raman spectroscopy (ERS) to objectively detect esophageal HGD and adenocarcinoma. Design A total of 798 one-second spectra were measured from 673 ex vivo esophageal tissue samples, collected from patients with Barrett's esophagus by using a novel endoscopic Raman probe. Spectra were correlated with consensus histopathology. Multivariate analysis was used to evaluate the classification accuracy of ERS ex vivo. Setting Probe measurements were conducted in the laboratory. Tissue specimens were collected from the operating theatre and endoscopy unit. Patients Tissue from 62 patients was included in the study. Interventions Endoscopic biopsy/resection or esophagectomy was performed where indicated clinically. Main Outcome Measurement Diagnostic performance of ERS for detection of HGD and esophageal adenocarcinoma. Results ERS demonstrated a sensitivity of 86% and a specificity of 88% for detecting HGD and adenocarcinoma. The ability to grade dysplasia and differentiate intestinal metaplasia from nonintestinal metaplasia columnar-lined esophagus was also demonstrated. Diagnostic classification was based on objective measurement of the biochemical profile of different tissue types. The potential for combination ERS and narrow-band imaging was also demonstrated. Limitations Measurements were taken from ex vivo tissue. Conclusion ERS enables rapid, accurate, objective diagnosis of superficial esophageal disease (metaplasia, dysplasia, intramucosal cancer) in clinically applicable time scales. Copyright © 2014 by the American Society for Gastrointestinal Endoscopy. Source

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