Few Shot Learning in Histopathological Images:Reducing the Need of Labeled Data on Biological Datasets

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)

MRI Deep Learning-Based Solution for Alzheimer’s Disease Prediction

Background: Alzheimer’s is a degenerative dementing disorder that starts with a mild memory impairment and progresses to a total loss of mental and physical faculties. The sooner the diagnosis is made, the better for the patient, as preventive actions and treatment can be started. Al though tests such as the Mini-Mental State Tests Examination are usually used for early identification, diagnosis relies on magnetic resonance imaging (MRI) brain analysis. Methods: Public initiatives such as the OASIS (Open Access Series of Imaging Studies) collection provide neuroimaging datasets openly available for research purposes. In this work, a new method based on deep learning and image processing techniques for MRI-based Alzheimer’s diagnosis is proposed and compared with previous literature works. Results: Our method achieves a balance accuracy (BAC) up to 0.93 for image-based automated diagnosis of the disease, and a BAC of 0.88 for the establishment of the disease stage (healthy tissue, very mild and severe stage). Conclusions: Results obtained surpassed the state-of-the-art proposals using the OASIS collection. This demonstrates that deep learning-based strategies are an effective tool for building a robust solution for Alzheimer’s-assisted diagnosis based on MRI data.This work was partially supported by the SUPREME project. This project has received funding from the Basque Government’s Industry Department HAZITEK program under agreement ZE-2019/00022. This research has also received funding from the Basque Government’s Industry Department under the ELKARTEK program’s project ONKOTOOLS under agreement KK-2020/0006

Autofluorescence image reconstruction and virtual staining for in-vivo optical biopsying

Modern photonic technologies are emerging, allowing the acquisition of in-vivo endoscopic tissue imaging at a microscopic scale, with characteristics comparable to traditional histological slides, and with a label-free modality. This raises the possibility of an ‘optical biopsy’ to aid clinical decision making. This approach faces barriers for being incorporated into clinical practice, including the lack of existing images for training, unfamiliarity of clinicians with the novel image domains and the uncertainty of trusting ‘black-box’ machine learned image analysis, where the decision making remains inscrutable. In this paper, we propose a new method to transform images from novel photonics techniques (e.g. autofluorescence microscopy) into already established domains such as Hematoxilyn-Eosin (H-E) microscopy through virtual reconstruction and staining. We introduce three main innovations: 1) we propose a transformation method based on a Siamese structure that simultaneously learns the direct and inverse transformation ensuring domain back-transformation quality of the transformed data. 2) We also introduced an embedding loss term that ensures similarity not only at pixel level, but also at the image embedding description level. This drastically reduces the perception distortion trade-off problem existing in common domain transfer based on generative adversarial networks. These virtually stained images can serve as reference standard images for comparison with the already known H-E images. 3) We also incorporate an uncertainty margin concept that allows the network to measure its own confidence, and demonstrate that these reconstructed and virtually stained images can be used on previously-studied classification models of H-E images that have been computationally degraded and de-stained. The three proposed methods can be seamlessly incorporated on any existing architectures. We obtained balanced accuracies of 0.95 and negative predictive values of 1.00 over the reconstructed and virtually stained image-set on the detection of color-rectal tumoral tissue. This is of great importance as we reduce the need for extensive labeled datasets for training, which are normally not available on the early studies of a new imaging technology.The authors would like to thank all pathologists that generated the BIOPOOL dataset (FP7-ICT-296162) that has been used for this work and specially to M. Saiz, A. Gaafar, S. Fernandez, A. Saiz, E. de Miguel, B. Catón, J. J. Aguirre, R. Ruiz, Ma A. Viguri, and R. Rezola

Medical needs related to the endoscopic technology and colonoscopy for colorectal cancer diagnosis

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.This work is part of the PICCOLO project, which has received funding from the European Union’s Horizon 2020 research and innovation Programme under grant agreement No. 732111. GR18199, funded by “Consejería de Economía, Ciencia y Agenda Digital, Junta de Extremadura” and co-funded by European Union (ERDF “A way to make Europe”). The funding bodies did not play any roles in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript

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

PICCOLO White-Light and Narrow-Band Imaging Colonoscopic Dataset: A Performance Comparative of Models and Datasets

Colorectal cancer is one of the world leading death causes. Fortunately, an early diagnosis allows for e_ective treatment, increasing the survival rate. Deep learning techniques have shown their utility for increasing the adenoma detection rate at colonoscopy, but a dataset is usually required so the model can automatically learn features that characterize the polyps. In this work, we present the PICCOLO dataset, that comprises 3433 manually annotated images (2131 white-light images 1302 narrow-band images), originated from 76 lesions from 40 patients, which are distributed into training (2203), validation (897) and test (333) sets assuring patient independence between sets. Furthermore, clinical metadata are also provided for each lesion. Four di_erent models, obtained by combining two backbones and two encoder–decoder architectures, are trained with the PICCOLO dataset and other two publicly available datasets for comparison. Results are provided for the test set of each dataset. Models trained with the PICCOLO dataset have a better generalization capacity, as they perform more uniformly along test sets of all datasets, rather than obtaining the best results for its own test set. This dataset is available at the website of the Basque Biobank, so it is expected that it will contribute to the further development of deep learning methods for polyp detection, localisation and classification, which would eventually result in a better and earlier diagnosis of colorectal cancer, hence improving patient outcomes.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. Furthermore, this publication has also been partially supported by GR18199 from Consejería de Economía, Ciencia y Agenda Digital of Junta de Extremadura (co-funded by European Regional Development Fund–ERDF. “A way to make Europe”/ “Investing in your future”. This work has been performed by the ICTS “NANBIOSIS” at the Jesús Usón Minimally Invasive Surgery Centre

Melanoma and nevi subtype histopathological characterization with optical coherence tomography

Background: Melanoma incidence has continued to rise in the latest decades, and the forecast is not optimistic. Non-invasive diagnostic imaging techniques such as optical coherence tomography (OCT) are largely studied; however, there is still no agreement on its use for the diagnosis of melanoma. For dermatologists, the differentiation of non-invasive (junctional nevus, compound nevus, intradermal nevus, and melanoma in-situ) versus invasive (superficial spreading melanoma and nodular melanoma) lesions is the key issue in their daily routine. Methods: This work performs a comparative analysis of OCT images using haematoxylin-eosin (HE) and anatomopathological features identified by a pathologist. Then, optical and textural properties are extracted from OCT images with the aim to identify subtle features that could potentially maximize the usefulness of the imaging technique in the identification of the lesion?s potential invasiveness. Results: Preliminary features reveal differences discriminating melanoma in-situ from superficial spreading melanoma and also between melanoma and nevus subtypes that pose a promising baseline for further research. Conclusions: Answering the final goal of diagnosing non-invasive versus invasive lesions with OCT does not seem feasible in the short term, but the obtained results demonstrate a step forward to achieve this.This work has been funded by the Department of Economic Development, Sustainability and the Environment of the Basque Government (Spain) ELKARTEK projects ONKOTOOLS with grant numbers KK-2020/00069, the Spanish Ministry of Science and Education CERVERA project AI4ES with grant numbers CER-20211030, and by the ECSEL JU European project ASTONISH with the grant number 692470, UC Industrial Doctorate DI14

Novel Pixelwise Co-Registered Hematoxylin-Eosin and Multiphoton Microscopy Image Dataset for Human Colon Lesion Diagnosis

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

Clinical Validation Benchmark Dataset and Expert Performance Baseline for Colorectal Polyp Localization Methods

Colorectal cancer is one of the leading death causes worldwide, but, fortunately, early detection highly increases survival rates, with the adenoma detection rate being one surrogate marker for colonoscopy quality. Artificial intelligence and deep learning methods have been applied with great success to improve polyp detection and localization and, therefore, the adenoma detection rate. In this regard, a comparison with clinical experts is required to prove the added value of the systems. Nevertheless, there is no standardized comparison in a laboratory setting before their clinical validation. The ClinExpPICCOLO comprises 65 unedited endoscopic images that represent the clinical setting. They include white light imaging and narrow band imaging, with one third of the images containing a lesion but, differently to another public datasets, the lesion does not appear well-centered in the image. Together with the dataset, an expert clinical performance baseline has been established with the performance of 146 gastroenterologists, who were required to locate the lesions in the selected images. Results shows statistically significant differences between experience groups. Expert gastroenterologists’ accuracy was 77.74, while sensitivity and specificity were 86.47 and 74.33, respectively. These values can be established as minimum values for a DL method before performing a clinical trial in the hospital setting