Characterization of Optical Coherence Tomography Images for Colon Lesion Differentiation under Deep Learning

(1) Background: Clinicians demand new tools for early diagnosis and improved detection of colon lesions that are vital for patient prognosis. Optical coherence tomography (OCT) allows microscopical inspection of tissue and might serve as an optical biopsy method that could lead to in-situ diagnosis and treatment decisions; (2) Methods: A database of murine (rat) healthy, hyperplastic and neoplastic colonic samples with more than 94,000 images was acquired. A methodology that includes a data augmentation processing strategy and a deep learning model for automatic classification (benign vs. malignant) of OCT images is presented and validated over this dataset. Comparative evaluation is performed both over individual B-scan images and C-scan volumes; (3) Results: A model was trained and evaluated with the proposed methodology using six different data splits to present statistically significant results. Considering this, 0.9695 (_0.0141) sensitivity and 0.8094 (_0.1524) specificity were obtained when diagnosis was performed over B-scan images. On the other hand, 0.9821 (_0.0197) sensitivity and 0.7865 (_0.205) specificity were achieved when diagnosis was made considering all the images in the whole C-scan volume; (4) Conclusions: The proposed methodology based on deep learning showed great potential for the automatic characterization of colon polyps and future development of the optical biopsy paradigm.This work was partially supported by PICCOLO project. This project has received funding from the European Union’s Horizon2020 Research and Innovation Programme under grant agreement No. 732111. This research has also received funding from the Basque Government’s Industry Department under the ELKARTEK program’s project ONKOTOOLS under agreement KK-2020/00069 and the industrial doctorate program UC- DI14 of the University of Cantabria

High Resolution Infrared Spectroscopic Analysis Of Human Colorectal Pathology

Epithelial misplacement is a benign pathology of the intestines that mimics invasive carcinoma and leads to a high degree of diagnostic difficulty in the discrimination between the two by pathologists. Particular difficulties are associated with the diagnosis between the two, and currently a National Expert Board of specialist pathologists delivers a second opinion for equivocal cases referred from local Hospitals. Novel analysis techniques to assist the diagnosis of epithelial misplacement vs. Cancer would not only aid the Board in the diagnosis, but speed up time taken to diagnosis for future patient management, and therefore increase overall patient satisfaction. This research aims to define the use of high resolution spectroscopy in the colon and assess its use in analysis of formalin-fixed paraffin-embedded tissue that has been routinely processed by the pathology laboratory. It is predicted that it will be an accurate, rapid and non-destructive novel diagnostic technique, and particularly useful in difficult cases such as in the discrimination of epithelial misplacement from cancer, making it a useful addition to the diagnostic process to improve efficiency of the patient diagnostic and treatment pathway. 65 colonic samples were analysed from a total of 58 patients diagnosed with various colonic pathologies and spectra measured in high resolution using the Agilent® 620 FTIR microscope coupled to a 670 Agilent spectrometer in transmission mode. Spectra were then fed into a specialist computer software programme, analysed using principal component-fed linear discriminant analysis model and tested with a leave one sample out cross validation method. The ‘Two Group’ Model defined the ability of the high resolution spectral analysis to discriminate between epithelial misplacement and cancer with a sensitivity of 74.6% and specificity of 82.3%. These results are excellent and have never been recorded previously in the literature. However, further research is required to assess its role in the discrimination of various other colonic pathologies, and the model needs independent testing with new cases of both epithelial misplacement and cancer to continue the assessment of the novel high resolution technique

An Investigation of the Diagnostic Potential of Autofluorescence Lifetime Spectroscopy and Imaging for Label-Free Contrast of Disease

The work presented in this thesis aimed to study the application of fluorescence lifetime spectroscopy (FLS) and fluorescence lifetime imaging microscopy (FLIM) to investigate their potential for diagnostic contrast of diseased tissue with a particular emphasis on autofluorescence (AF) measurements of gastrointestinal (GI) disease. Initially, an ex vivo study utilising confocal FLIM was undertaken with 420 nm excitation to characterise the fluorescence lifetime (FL) images obtained from 71 GI samples from 35 patients. A significant decrease in FL was observed between normal colon and polyps (p = 0.024), and normal colon and inflammatory bowel disease (IBD) (p = 0.015). Confocal FLIM was also performed on 23 bladder samples. A longer, although not significant, FL for cancer was observed, in paired specimens (n = 5) instilled with a photosensitizer. The first in vivo study was a clinical investigation of skin cancer using a fibre-optic FL spectrofluorometer and involved the interrogation of 27 lesions from 25 patients. A significant decrease in the FL of basal cell carcinomas compared to healthy tissue was observed (p = 0.002) with 445 nm excitation. A novel clinically viable FLS fibre-optic probe was then applied ex vivo to measure 60 samples collected from 23 patients. In a paired analysis of neoplastic polyps and normal colon obtained from the same region of the colon in the same patient (n = 12), a significant decrease in FL was observed (p = 0.021) with 435 nm excitation. In contrast, with 375 nm excitation, the mean FL of IBD specimens (n = 4) was found to be longer than that of normal tissue, although not statistically significant. Finally, the FLS system was applied in vivo in 17 patients, with initial data indicating that 435 nm excitation results in AF lifetimes that are broadly consistent with ex vivo studies, although no diagnostically significant differences were observed in the signals obtained in vivo.Open Acces

State of the art in advanced endoscopic imaging for the detection and evaluation of dysplasia and early cancer of the gastrointestinal tract

Ideally, endoscopists should be able to detect, characterize, and confirm the nature of a lesion at the bedside, minimizing uncertainties and targeting biopsies and resections only where necessary. However, under conventional white-light inspection – at present, the sole established technique available to most of humanity – premalignant conditions and early cancers can frequently escape detection. In recent years, a range of innovative techniques have entered the endoscopic arena due to their ability to enhance the contrast of diseased tissue regions beyond what is inherently possible with standard white-light endoscopy equipment. The aim of this review is to provide an overview of the state-of-the-art advanced endoscopic imaging techniques available for clinical use that are impacting the way precancerous and neoplastic lesions of the gastrointestinal tract are currently detected and characterized at endoscopy. The basic instrumentation and the physics behind each method, followed by the most influential clinical experience, are described. High-definition endoscopy, with or without optical magnification, has contributed to higher detection rates compared with white-light endoscopy alone and has now replaced ordinary equipment in daily practice. Contrast-enhancement techniques, whether dye-based or computed, have been combined with white-light endoscopy to further improve its accuracy, but histology is still required to clarify the diagnosis. Optical microscopy techniques such as confocal laser endomicroscopy and endocytoscopy enable in vivo histology during endoscopy; however, although of invaluable assistance for tissue characterization, they have not yet made transition between research and clinical use. It is still unknown which approach or combination of techniques offers the best potential. The optimal method will entail the ability to survey wide areas of tissue in concert with the ability to obtain the degree of detailed information provided by microscopic techniques. In this respect, the challenging combination of autofluorescence imaging and confocal endomicroscopy seems promising, and further research is awaited

Using Fluorescence – Polarization Endoscopy in Detection of Precancerous and Cancerous Lesions in Colon and Pancreatic Cancer

Colitis-associated cancer (CAC) arises from premalignant flat lesions of the colon, which are difficult to detect with current endoscopic screening approaches. We have developed a complementary fluorescence and polarization reporting strategy that combines the unique biochemical and physical properties of dysplasia and cancer for real time detection of these lesions. Utilizing a new thermoresponsive sol-gel formulation with targeted molecular probe allowed topical application and detection of precancerous and cancerous lesions during endoscopy. Incorporation of nanowire-filtered polarization imaging into NIR fluorescence endoscopy served as a validation strategy prior to obtaining biopsies. In order to reduce repeat surgeries arising from incomplete tumor resection, we demonstrated the efficacy of the targeted molecular probe towards margins of sporadic colorectal cancer (SCC). Fluorescence-polarization microscopy using circular polarized (CP) light served as a rapid, supplementary tool for assessment and validation of excised tissue to ensure complete tumor resection for examining tumor margins prior to H&E-based pathological diagnosis. We extended our platform towards non-invasive directed detection of pancreatic cancer utilizing fluorescence molecular tomography (FMT) and NIR laparoscopy using identified targeted molecular probe. We were able to non-invasively distinguished between pancreatitis and pancreatic cancer and guide pancreatic tumor resection using NIR laparoscopy

Novel developments in endoscopic mucosal imaging

Endoscopic techniques such as High-definition and optical-chromoendoscopy have had enormous impact on endoscopy practice. Since these techniques allow assessment of most subtle morphological mucosal abnormalities, further improvements in endoscopic practice lay in increasing the detection efficacy of endoscopists. Several new developments could assist in this. First, web based training tools could improve the skills of the endoscopist for enhancing the detection and classification of lesions. Secondly, incorporation of computer aided detection will be the next step to raise endoscopic quality of the captured data. These systems will aid the endoscopist in interpreting the increasing amount of visual information in endoscopic images providing real-time objective second reading. In addition, developments in the field of molecular imaging open opportunities to add functional imaging data, visualizing biological parameters, of the gastrointestinal tract to white-light morphology imaging. For the successful implementation of abovementioned techniques, a true multi-disciplinary approach is of vital importance

The role of Raman Spectroscopy in the detection of dysplasia in Barrett’s oesophagus

Introduction The incidence of oesophageal adenocarcinoma is increasing. Although improvements have been seen, the overall 5 year survival rate remains poor, at 15.1%. As with other cancers, the survival rate is highest when the disease is confined to the oesophagus. Barrett’s oesophagus is an acquired condition, characterised by the replacement of the normal distal squamous epithelial lining of the oesophagus with columnar epithelium. Oesophageal adenocarcinoma develops, in most instances, along a pathway of increasing dysplasia in the sections of Barrett’s oesophagus. If dysplasia can be diagnosed accurately, then this would permit treatment prior to the development of adenocarcinoma. Methods Samples of Barrett’s oesophagus with varying degrees of dysplasia and adenocarcinoma were measured with Raman point and mapping spectroscopy. Analysis was performed using Matlab®. Results Samples of squamous epithelia, Barrett’s oesophagus without dysplasia, with low-grade dysplasia, with high-grade dysplasia and oesophageal adenocarcinoma were measured and analysed. 2078 point spectra measurements and 117 map regions were analysed. Raman point spectra measurements and Raman mapping differentiated samples without dysplasia from those with dysplasia, and differentiated samples of low-grade dysplasia from those of high-grade dysplasia and adenocarcinoma. The specificity and sensitivity were, however, low. Conclusion This research has illustrated the ability of Raman spectroscopy to discern samples of Barrett’s oesophagus with low-grade dysplasia from those with higher grades of dysplasia. This capability could be utilised clinically with in- vivo measurements to identify the areas requiring detailed surveillance and biopsies. The majority of patients with Barrett’s oesophagus and low-grade dysplasia will never progress to adenocarcinoma. There is currently no means, either via histopathology or via a biomarker, to identify the minority who will develop high- grade dysplasia or adenocarcinoma. Raman spectroscopy may have the ability to do this and I believe this is the path that this technology should pursue

Detection and classification of gastrointestinal cancer and other pathologies through quantitative analysis of optical coherence tomography data and goniophotometry

The changes in light interaction between healthy and diseased tissues have been investigated as a potential diagnostic application. Here we attempt to differentiate between healthy and pathological gastrointestinal tissues using quantitative analysis of optical coherence tomography (OCT) data and goniophotometry. A goniophotometer was constructed and calibrated using titanium oxide and microsphere phantoms. Measurements were carried out on human gastrointestinal tissue sections collected using the methodology described below. The anisotropy factor g was extracted from the scattering curves by fitting the Henyey-Greenstein function. Measurements on human samples were in the forward scattering range with g 0.6-0.7, in agreement with the literature. Optical coherence tomography imaging was carried out on gastrointestinal tissues collected from patients undergoing elective surgery or endoscopy at St. Mary’s Hospital, London. In total 146 patients were included. Data was processed using gradient analysis of signal attenuation and morphological analysis with kNN classification. Results were correlated with histological diagnoses. Gradient analysis results were statistically significant across most categories, showing particularly good differences in the gradient distributions between healthy and diseased oesophageal tissues. Morphological analysis and kNN classification produced sensitivity and specificity values for healthy oesophagus and cancer in surgical specimens reaching 100% / 97.87% and 99.99% / 99.91% respectively and high accuracy in detecting Barrett's oesophagus in endoscopic specimens, with sensitivity and specificity values of 99.80% and 99.02%. Results in rectal tissue where also noteworthy, with detection of dysplasia reaching a sensitivity and specificity of 99.55% / 96.01%. Despite limitations in our work, we have shown that the detection of gastrointestinal pathologies using quantitative analysis of OCT data is a promising technique with good ex vivo results. Transferring the methodology to the in vivo domain holds a lot of potential as a future quick and reliable diagnostic technique.Open Acces

New Techniques in Gastrointestinal Endoscopy

As result of progress, endoscopy has became more complex, using more sophisticated devices and has claimed a special form. In this moment, the gastroenterologist performing endoscopy has to be an expert in macroscopic view of the lesions in the gut, with good skills for using standard endoscopes, with good experience in ultrasound (for performing endoscopic ultrasound), with pathology experience for confocal examination. It is compulsory to get experience and to have patience and attention for the follow-up of thousands of images transmitted during capsule endoscopy or to have knowledge in physics necessary for autofluorescence imaging endoscopy. Therefore, the idea of an endoscopist has changed. Examinations mentioned need a special formation, a superior level of instruction, accessible to those who have already gained enough experience in basic diagnostic endoscopy. This is the reason for what these new issues of endoscopy are presented in this book of New techniques in Gastrointestinal Endoscopy