John C C Day

A miniature confocal Raman probe for endoscopic use

Raman spectroscopy is a powerful tool for studying biochemical changes in the human body. We describe a miniature, confocal fibre optic probe intended to fit within the instrument channel of a standard medical endoscope. This probe has been optimized for the study of the carcinogenesis process of oesophageal malignancy. The optical design and fabrication of this probe is described including the anisotropic wet etching technique used to make silicon motherboards and jigs. Example spectra of PTFE reference samples are shown. Spectra with acquisition times as low as 2 s from resected oesophageal tissue are presented showing identifiable biochemical changes from various pathologies.

Endoscopic Raman spectroscopy enables objective diagnosis of dysplasia in Barrett's esophagus

BACKGROUND Early detection and targeted endoscopic resection of Barretts 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 Barretts 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.

Assessment of a custom-built Raman spectroscopic probe for diagnosis of early oesophageal neoplasia

We evaluate the potential of a custom-built fiber-optic Raman probe, suitable for in vivo use, to differentiate between benign, metaplastic (Barretts oesophagus), and neoplastic (dysplastic and malignant) oesophageal tissue ex vivo on short timescales. We measured 337 Raman spectra (λ(ex)=830 nm; P(ex)=60 mW; t=1 s) using a confocal probe from fresh (298) and snap-frozen (39) oesophageal tissue collected during surgery or endoscopy from 28 patients. Spectra were correlated with histopathology and used to construct a multivariate classification model which was tested using leave one tissue site out cross-validation in order to evaluate the diagnostic accuracy of the probe system. The Raman probe system was able to differentiate, when tested with leave one site out cross-validation, between normal squamous oesophagus, Barretts oesophagus and neoplasia with sensitivities of (838% to 6%) and specificities of (89% to 99%). Analysis of a two group model to differentiate Barretts oesophagus and neoplasia demonstrated a sensitivity of 88% and a specificity of 87% for classification of neoplastic disease. This fiber-optic Raman system can provide rapid, objective, and accurate diagnosis of oesophageal pathology ex vivo. The confocal design of this probe enables superficial mucosal abnormalities (metaplasia and dysplasia) to be classified in clinically applicable timescales paving the way for an in vivo trial.

A reflectometer for the combined measurement of refractive index, microroughness, macroroughness and gloss of low-extinction surfaces

Roughness, porosity and gloss are important properties of many surfaces including coated and printed paper, paints and mineral-filled plastics. A visible light reflectometer is described for essentially simultaneous measurement of refractive index, gloss, microroughness (rms amplitude in the sub-wavelength region) and the two-dimensional forward scattering pattern (yielding the surface slope distribution and associated statistics) of glossy or semi-glossy low-extinction surfaces. The principal novelty is the ability to obtain this useful combination of data in a single measurement. In combination with an x?y stage, the reflectometer can readily produce surface maps of the various measurement parameters and it is expected that the data should offer improved insights into cause and effect in paper and other surfaces, for example to identify causes of gloss and print mottle. Illustrative experimental data are provided and some comparisons made between data obtained by reflectometry and by alternative techniques such as spectroscopic ellipsometry and atomic force microscopy.

Evaluation of a Confocal Raman Probe for Pathological Diagnosis during Colonoscopy

Raman spectroscopy of human tissue can provide a unique biochemical ‘fingerprint’ that alters with disease progression. Light incident on tissue is scattered and may be altered in wavelength, which can be represented as a Raman spectrum. A confocal fibreoptic Raman probe designed to fit down the accessory channel of a colonoscope has been constructed. This in‐vitro study evaluated the accuracy of pathological diagnosis in the colon using probe‐based Raman spectroscopy.

Ultra-low spatial resolution Raman mapping using a novel fibre optic probe

Ultra-low spatial resolution Raman (ULSRR) mapping using fibre probes has been performed on mammalian and human tissues. This will provide an understanding of the potential for in vivo surveillance of the lining of organs using such a technique and for identifying abnormal tissues such as residual tumours within a surgical field. The aim of the study was to create Raman probe map images of excised oesophageal specimens following radical and palliative oesophagectomy procedures. A reproducible mapping grid was placed over the excised tissue surface and Raman mapping at 830nm performed at regular intervals to provide images of 200 pixels over the region of interest. Principal component analysis was used to create pseudocolour score images of both porcine phantoms and a human resected oesophagus. A principal component fed linear discriminant (LD) classification model of 72 biopsy samples from 35 patients was created using a novel single fibre Raman probe. A subset of the training dataset was used to populate a matrix of 200 pixels to simulate a Raman probe map. Spectra from the simulated map were then projected onto the LD model and a pseudocolour LD pathology map created. Delineation of clinically significant pathology groups was demonstrated therefore this study has shown the feasibility of in vivo ULSRR for margin assessment using a Raman probe.

Evaluation of a multi-fibre needle Raman probe for tissue analysis

Raman spectroscopy is a rapid technique for the identification of cancers. Its coupling with a hypodermic needle provides a minimally invasive instrument with the potential to aid real time assessment of suspicious lesions in vivo and guide surgery. A fibre optic Raman needle probe was utilised in this study to evaluate the classification ability of the instrument as a diagnostic tool together with multivariate analysis, through measurements of tissues from different animal species as well as various different porcine tissue types. Cross validation was performed and preliminary classification accuracies were calculated as 100% for the identification of tissue type and 97.5% for the identification of animal species. A lymph node sample was also measured using the needle probe to assess the use of the technique for human tissue and hence its efficiency as a clinical instrument. This needle probe has been demonstrated to have the capabilities to classify tissue samples based on their biochemical components. The Raman needle probe also has the potential to act as a diagnostic and surgical tool to delineate cancerous from non-cancerous cells in real time, thus assisting complete removal of a tumour.

TOWARDS REAL-TIME 'BIOCHEMICAL ENDOSCOPY' FOR DIAGNOSIS OF EARLY BARRETT'S NEOPLASIA

Introduction Raman spectroscopy is a powerful analytical technique that can rapidly and accurately identify biochemical changes in cells that have become neoplastic. We aim to transfer this laboratory based technique to the bedside in order to identify high-grade dysplasia and early malignant change within Barretts oesophagus. Here we demonstrate the feasibility of a novel fibre-optic Raman probe to map the pathology encountered in a resected human distal oesophagus. Methods A novel Raman probe1 2 designed to fit through the 2.8 mm instrument channel of a standard endoscope was used to map a distal oesophagus ex vivo. Following Ivor-Lewis oesophagectomy (with curative intent in patients with oesophageal adenocarcinoma), a reproducible mapping grid was placed over the distal oesophagus and Raman spectra were measured at specified grid positions using 1 and 5 s acquisition times (Figure 1). A monochromatic 830 nm laser was used for excitation and a Renishaw system 100 spectrometer for the measurement of Raman spectra. Figure 1 PWE-093 Mapping of a distal oesophagus using a perspex grid for probe positioning Results Laboratory based Raman systems can delineate eight pathological groups in the distal oesophagus with sensitivities between 73% and 100%.3 To date we have measured 76 spectra from 3 oesophageal specimens using the novel endoscopic probe and data collection and analysis is currently on-going (Figure 2). Histopathological diagnosis has been confirmed by expert pathologists following point biopsy at each grid position in order to correlate the Raman signal with the gold standard. Multivariate analysis will be used to extract subtle spectral features to evaluate the accuracy of the probe for delineating between pathological groups. Figure 2 PWE-093 Example mean Raman probe spectra measured on normal squamous, Barretts and neoplastic oesophageal tissue Conclusion Further data collection (currently on-going) is needed to generate a robust classification algorithm in order to delineate between Barretts metaplasia, low/high-grade dysplasia and cancer in the distal oesophagus. Preliminary spectra obtained using a novel endoscopic probe are consistent with laboratory data and suggest profound potential for in vivo endoscopic diagnosis using Raman spectroscopy.

High power laser with integrated lens using focused ion beam etching

Control of the optical mode in high power lasers is essential for a range of high brightness optical pumping applications. The inclusion of a lens within the cavity of a semiconductor laser is desirable not only to increase the proportion of light coupled back into the optical waveguide for improved efficiency, but also in the reduction of the divergence in the far field emission for higher brightness operation. In this work, a collimating lens is introduced at the output facet of a tapered waveguide laser to compensate for the divergence of the optical mode. This in turn is shown to enhance the laser efficiency while simultaneously reducing the far field divergence. Tapered waveguide lasers are considered in this work which operate at a wavelength of 980 nm with a well defined single lobed far field and up to 54 % wall plug efficiency. The lens has been formed by focused ion beam etching to leave a parabolic region of higher refractive index near the output facet. The lens design is computer generated and transferred to the laser using focused ion beam etching running under custom software.

Autonomous vehicles for ore prospecting: robots in the air and water

A rapidly developing field of autonomous technology for commercial applications is that of unmanned mobile robotic systems. The major enabling technology for this development is the micro-computer; developed for mobile phones and following a trend of becoming increasingly more powerful while maintaining low cost. Robotic systems in the air are more commonly referred to as unmanned aerial vehicles (UAVs) and in the sea – autonomous underwater vehicles (AUVs). Both types of system offer a major opportunity for international mining industry by providing a means of prospecting for valuable ores over large often remote areas without significant ‘on the ground’ involvement of human staff. Such systems are terrain independent, may be loaded with multiple different light-weight sensors (LiDAR, Thermal/visual imaging, radiation etc.) and provide a complimentary follow-on from satellitebased surveying to investigate interest areas at a higher spatial resolution. The present talk will provide details of two specific areas of technology development at the University of Bristol: (i) aerial radiation mapping using UAVs and (ii) deep sea prospecting using low-cost observation class AUVs/ROVs. Radiation mapping UAVs have been deployed on multiple occasions over the past decade (Kurvinen et al. 2005; Pöllänen et al. 2009). However, major technology acceleration within the field has been evident since the incident at the Fukushima Daiichi Nuclear Power Plant (FDNPP) in March 2011 (Boudergui et al. 2011; Towler et al. 2012; Han et al. 2013; Han & Chen 2014; MacFarlane et al. 2014; Cao et al. 2015; Martin et al. 2015; Sanada & Torii, 2015; Furutani et al. n.d.). There can be no doubt that the use of UAVs to carry out radiation surveys is an invaluable tool in furthering the efficiency of the response to future nuclear accidents and disasters but the same technology may be exploited to prospect for valuable ore bodies (uranium, thorium, REE, gold, coal, evaporates). UAVs have the capability to produce high-resolution maps without the need to enlist a large workforce or incur great expense. Radiation surveying is much more difficult under the sea due to the efficient attenuation of radiation by the water. Radiation mapping is only possible when operating extremely close (or in contact) with the ocean floor. Such a capability may be provided by ROV platforms but supplemented by other techniques such as micro-gravity mapping and fluorescence imaging photogrammetry. In the near future, valuable deposits such as cobalt crusts and seafloor massive sulphides (SMS) will be the target of such robotic surveying systems, marking a new era for deep sea prospecting.