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Colorectal cancer presents one of the most elevated incidences of cancer worldwide. Colonoscopy relies on histopathology analysis of hematoxylin-eosin (H&E) images of the removed tissue. Novel techniques such as multi-photon microscopy (MPM) show promising results for performing real-time optical biopsies. However, clinicians are not used to this imaging modality and correlation between MPM and H&E information is not clear. The objective of this paper is to describe and make publicly available an extensive dataset of fully co-registered H&E and MPM images that allows the research community to analyze the relationship between MPM and H&E histopathological images and the effect of the semantic gap that prevents clinicians from correctly diagnosing MPM images. The dataset provides a fully scanned tissue images at 10x optical resolution (0.5 µm/px) from 50 samples of lesions obtained by colonoscopies and colectomies. Diagnostics capabilities of TPF and H&E images were compared. Additionally, TPF tiles were virtually stained into H&E images by means of a deep-learning model. A panel of 5 expert pathologists evaluated the different modalities into three classes (healthy, adenoma/hyperplastic, and adenocarcinoma). Results showed that the performance of the pathologists over MPM images was 65% of the H&E performance while the virtual staining method achieved 90%. MPM imaging can provide appropriate information for diagnosing colorectal cancer without the need for H&E staining. However, the existing semantic gap among modalities needs to be corrected. This work was supported by the PICCOLO project. This project has received funding from the European Union's Horizon 2020 Research and Innovation Programme under grant agreement No. 732111. The sole responsibility of this publication lies with the authors. The European Union is not responsible for any use that may be made of the information contained therein. This research has also been supported by the project ONKOTOOLS (KK2020/00069) funded by the Basque Government Industry Department under the ELKARTEK program.

INTRODUCTION New non-invasive technologies for improving early diagnosis of colorectal cancer (CRC) are demanded by clinicians. Optical Coherence Tomography (OCT) provides sub-surface structural information and offers diagnosis capabilities of colon polyps, further improved by machine learning methods. Databases of OCT images are necessary to facilitate algorithms development and testing. MATERIALS AND METHODS A database has been acquired from rat colonic samples with a Thorlabs OCT system with 930nm centre wavelength that provides 1.2KHz A-scan rate, 7μm axial resolution in air, 4μm lateral resolution, 1.7mm imaging depth in air, 6mm x 6mm FOV, and 107dB sensitivity. The colon from anaesthetised animals has been excised and samples have been extracted and preserved for ex-vivo analysis with the OCT equipment. RESULTS This database consists of OCT 3D volumes (C-scans) and 2D images (B-scans) of murine samples from: 1) healthy tissue, for ground-truth comparison (18 samples; 66 C-scans; 17,478 B-scans); 2) hyperplastic polyps, obtained from an induced colorectal hyperplastic murine model (47 samples; 153 C-scans; 42,450 B-scans); 3) neoplastic polyps (adenomatous and adenocarcinomatous), obtained from clinically validated Pirc F344/NTac-Apcam1137 rat model (232 samples; 564 C-scans; 158,557 B-scans); and 4) unknown tissue (polyp adjacent, presumably healthy) (98 samples; 157 C-scans; 42,070 B-scans). CONCLUSIONS A novel extensive ex-vivo OCT database of murine CRC model has been obtained and will be openly published for the research community. It can be used for classification/segmentation machine learning methods, for correlation between OCT features and histopathological structures, and for developing new non-invasive in-situ methods of diagnosis of colorectal cancer.

INTRODUCTION New endoscopic technologies developed to improve colorectal cancer diagnosis need to be validated on animal models, which already exist for neoplastic polyps, but not for hyperplasia. For that, a hyperplastic model of growth in colon has been created on murine animal. For its characterization, a first pilot study was performed, and this study aims to validate the results. MATERIALS AND METHODS 30 Pirc (Polyposis In the Rat Colon) rats, wild type strain (F344/NTac-Apcam1137), were used. The hyperplastic model was induced by laparotomy with a non-resorbable suture, not stenosing, placed through the colon wall. Then, colonic biopsies were extracted weekly from the growth around the suture. RESULTS After the second follow-up, hyperplastic growths are already found. The reproducibility of the model has been obtained and the optimal time determined, after induction of the model. According to our knowledge, this is the first induced colonic hyperplasia model in rats. It solves limitations of other traditional models that only produce hypertrophy, where hyperplasia appears when iatrogenic effects occur as undesired results in a non-standardised or reproducible form. CONCLUSIONS This work has successfully developed a preclinical model of colonic hyperplasia in rats that recreates important characteristics of human hyperplasia, such as the generation of new cells in the colonic mucosa and tissue growth, as well as the corresponding angiogenesis. The new hyperplastic model created could be used for the validation of endoscopic technology, and other studies. It would be useful to improve optical biomarkers of colorectal cancer and to discriminate between endoscopic findings.

Background The high incidence and mortality rate of colorectal cancer require new technologies to improve its early diagnosis. This study aims at extracting the medical needs related to the endoscopic technology and the colonoscopy procedure currently used for colorectal cancer diagnosis, essential for designing these demanded technologies. Methods Semi-structured interviews and an online survey were used. Results Six endoscopists were interviewed and 103 were surveyed, obtaining the demanded needs that can be divided into: a) clinical needs, for better polyp detection and classification (especially flat polyps), location, size, margins and penetration depth; b) computer-aided diagnosis (CAD) system needs, for additional visual information supporting polyp characterization and diagnosis; and c) operational/physical needs, related to limitations of image quality, colon lighting, flexibility of the endoscope tip, and even poor bowel preparation. Conclusions This study shows some undertaken initiatives to meet the detected medical needs and challenges to be solved. The great potential of advanced optical technologies suggests their use for a better polyp detection and classification since they provide additional functional and structural information than the currently used image enhancement technologies. The inspection of remaining tissue of diminutive polyps (

(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.

Background: Colorectal cancer has a high incidence rate worldwide, with over 1.8 million new cases and 880,792 deaths in 2018. Fortunately, its early detection significantly increases the survival rate, reaching a cure rate of 90% when diagnosed at a localized stage. Colonoscopy is the gold standard technique for detection and removal of colorectal lesions with potential to evolve into cancer. When polyps are found in a patient, the current procedure is their complete removal. However, in this process, gastroenterologists cannot assure complete resection and clean margins which are given by the histopathology analysis of the removed tissue, which is performed at laboratory. Aims: In this paper, we demonstrate the capabilities of multiphoton microscopy (MPM) technology to provide imaging biomarkers that can be extracted by deep learning techniques to identify malignant neoplastic colon lesions and distinguish them from healthy, hyperplastic, or benign neoplastic tissue, without the need for histopathological staining. Materials and Methods: To this end, we present a novel MPM public dataset containing 14,712 images obtained from 42 patients and grouped into 2 classes. A convolutional neural network is trained on this dataset and a spatially coherent predictions scheme is applied for performance improvement. Results: We obtained a sensitivity of 0.8228 ± 0.1575 and a specificity of 0.9114 ± 0.0814 on detecting malignant neoplastic lesions. We also validated this approach to estimate the self-confidence of the network on its own predictions, obtaining a mean sensitivity of 0.8697 and a mean specificity of 0.9524 with the 18.67% of the images classified as uncertain. Conclusions: This work lays the foundations for performing in vivo optical colon biopsies by combining this novel imaging technology together with deep learning algorithms, hence avoiding unnecessary polyp resection and allowing in situ diagnosis assessment. This work was supported by the 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 been supported by the project ONKOTOOLS (KK-2020/00069) funded by the Basque Government Industry Department under the ELKARTEK program

Although deep learning pathology diagnostic algorithms are proving comparable results with human experts in a wide variety of tasks, they still require a huge amount of well annotated data for training. Generating such extensive and well labelled datasets is time consuming and is not feasible for certain tasks and so, most of the medical datasets available are scarce in images and therefore, not enough for training. In this work we validate that the use of few shot learning techniques can transfer knowledge from a well defined source domain from Colon tissue into a more generic domain composed by Colon, Lung and Breast tissue by using very few training images. Our results show that our few-shot approach is able to obtain a balanced accuracy (BAC) of 90% with just 60 training images, even for the Lung and Breast tissues that were not present on the training set. This outperforms the finetune transfer learning approach that obtains 73% BAC with 60 images and requires 600 images to get up to 81% BAC. This study has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 732111 (PICCOLO project).