A generalized deep learning framework for whole-slide image segmentation and analysis.

Histopathology tissue analysis is considered the gold standard in cancer diagnosis and prognosis. Whole-slide imaging (WSI), i.e., the scanning and digitization of entire histology slides, are now being adopted across the world in pathology labs. Trained histopathologists can provide an accurate diagnosis of biopsy specimens based on WSI data. Given the dimensionality of WSIs and the increase in the number of potential cancer cases, analyzing these images is a time-consuming process. Automated segmentation of tumorous tissue helps in elevating the precision, speed, and reproducibility of research. In the recent past, deep learning-based techniques have provided state-of-the-art results in a wide variety of image analysis tasks, including the analysis of digitized slides. However, deep learning-based solutions pose many technical challenges, including the large size of WSI data, heterogeneity in images, and complexity of features. In this study, we propose a generalized deep learning-based framework for histopathology tissue analysis to address these challenges. Our framework is, in essence, a sequence of individual techniques in the preprocessing-training-inference pipeline which, in conjunction, improve the efficiency and the generalizability of the analysis. The combination of techniques we have introduced includes an ensemble segmentation model, division of the WSI into smaller overlapping patches while addressing class imbalances, efficient techniques for inference, and an efficient, patch-based uncertainty estimation framework. Our ensemble consists of DenseNet-121, Inception-ResNet-V2, and DeeplabV3Plus, where all the networks were trained end to end for every task. We demonstrate the efficacy and improved generalizability of our framework by evaluating it on a variety of histopathology tasks including breast cancer metastases (CAMELYON), colon cancer (DigestPath), and liver cancer (PAIP). Our proposed framework has state-of-the-art performance across all these tasks and is ranked within the top 5 currently for the challenges based on these datasets. The entire framework along with the trained models and the related documentation are made freely available at GitHub and PyPi. Our framework is expected to aid histopathologists in accurate and efficient initial diagnosis. Moreover, the estimated uncertainty maps will help clinicians to make informed decisions and further treatment planning or analysis.

PAIP 2019: Liver cancer segmentation challenge.

Pathology Artificial Intelligence Platform (PAIP) is a free research platform in support of pathological artificial intelligence (AI). The main goal of the platform is to construct a high-quality pathology learning data set that will allow greater accessibility. The PAIP Liver Cancer Segmentation Challenge, organized in conjunction with the Medical Image Computing and Computer Assisted Intervention Society (MICCAI 2019), is the first image analysis challenge to apply PAIP datasets. The goal of the challenge was to evaluate new and existing algorithms for automated detection of liver cancer in whole-slide images (WSIs). Additionally, the PAIP of this year attempted to address potential future problems of AI applicability in clinical settings. In the challenge, participants were asked to use analytical data and statistical metrics to evaluate the performance of automated algorithms in two different tasks. The participants were given the two different tasks: Task 1 involved investigating Liver Cancer Segmentation and Task 2 involved investigating Viable Tumor Burden Estimation. There was a strong correlation between high performance of teams on both tasks, in which teams that performed well on Task 1 also performed well on Task 2. After evaluation, we summarized the top 11 team's algorithms. We then gave pathological implications on the easily predicted images for cancer segmentation and the challenging images for viable tumor burden estimation. Out of the 231 participants of the PAIP challenge datasets, a total of 64 were submitted from 28 team participants. The submitted algorithms predicted the automatic segmentation on the liver cancer with WSIs to an accuracy of a score estimation of 0.78. The PAIP challenge was created in an effort to combat the lack of research that has been done to address Liver cancer using digital pathology. It remains unclear of how the applicability of AI algorithms created during the challenge can affect clinical diagnoses. However, the results of this dataset and evaluation metric provided has the potential to aid the development and benchmarking of cancer diagnosis and segmentation.

Segmentation and Classification in Digital Pathology for Glioma Research: Challenges and Deep Learning Approaches.

Biomedical imaging Is an important source of information in cancer research. Characterizations of cancer morphology at onset, progression, and in response to treatment provide complementary information to that gleaned from genomics and clinical data. Accurate extraction and classification of both visual and latent image features Is an increasingly complex challenge due to the increased complexity and resolution of biomedical image data. In this paper, we present four deep learning-based image analysis methods from the Computational Precision Medicine (CPM) satellite event of the 21st International Medical Image Computing and Computer Assisted Intervention (MICCAI 2018) conference. One method Is a segmentation method designed to segment nuclei in whole slide tissue images (WSIs) of adult diffuse glioma cases. It achieved a Dice similarity coefficient of 0.868 with the CPM challenge datasets. Three methods are classification methods developed to categorize adult diffuse glioma cases into oligodendroglioma and astrocytoma classes using radiographic and histologic image data. These methods achieved accuracy values of 0.75, 0.80, and 0.90, measured as the ratio of the number of correct classifications to the number of total cases, with the challenge datasets. The evaluations of the four methods indicate that (1) carefully constructed deep learning algorithms are able to produce high accuracy in the analysis of biomedical image data and (2) the combination of radiographic with histologic image information improves classification performance.

Fully convolutional multi-scale residual DenseNets for cardiac segmentation and automated cardiac diagnosis using ensemble of classifiers.

Deep fully convolutional neural network (FCN) based architectures have shown great potential in medical image segmentation. However, such architectures usually have millions of parameters and inadequate number of training samples leading to over-fitting and poor generalization. In this paper, we present a novel DenseNet based FCN architecture for cardiac segmentation which is parameter and memory efficient. We propose a novel up-sampling path which incorporates long skip and short-cut connections to overcome the feature map explosion in conventional FCN based architectures. In order to process the input images at multiple scales and view points simultaneously, we propose to incorporate Inception module's parallel structures. We propose a novel dual loss function whose weighting scheme allows to combine advantages of cross-entropy and Dice loss leading to qualitative improvements in segmentation. We demonstrate computational efficacy of incorporating conventional computer vision techniques for region of interest detection in an end-to-end deep learning based segmentation framework. From the segmentation maps we extract clinically relevant cardiac parameters and hand-craft features which reflect the clinical diagnostic analysis and train an ensemble system for cardiac disease classification. We validate our proposed network architecture on three publicly available datasets, namely: (i) Automated Cardiac Diagnosis Challenge (ACDC-2017), (ii) Left Ventricular segmentation challenge (LV-2011), (iii) 2015 Kaggle Data Science Bowl cardiac challenge data. Our approach in ACDC-2017 challenge stood second place for segmentation and first place in automated cardiac disease diagnosis tasks with an accuracy of 100% on a limited testing set (n=50). In the LV-2011 challenge our approach attained 0.74 Jaccard index, which is so far the highest published result in fully automated algorithms. In the Kaggle challenge our approach for LV volume gave a Continuous Ranked Probability Score (CRPS) of 0.0127, which would have placed us tenth in the original challenge. Our approach combined both cardiac segmentation and disease diagnosis into a fully automated framework which is computationally efficient and hence has the potential to be incorporated in computer-aided diagnosis (CAD) tools for clinical application.

Deep Learning Techniques for Automatic MRI Cardiac Multi-Structures Segmentation and Diagnosis: Is the Problem Solved?

Delineation of the left ventricular cavity, myocardium, and right ventricle from cardiac magnetic resonance images (multi-slice 2-D cine MRI) is a common clinical task to establish diagnosis. The automation of the corresponding tasks has thus been the subject of intense research over the past decades. In this paper, we introduce the "Automatic Cardiac Diagnosis Challenge" dataset (ACDC), the largest publicly available and fully annotated dataset for the purpose of cardiac MRI (CMR) assessment. The dataset contains data from 150 multi-equipments CMRI recordings with reference measurements and classification from two medical experts. The overarching objective of this paper is to measure how far state-of-the-art deep learning methods can go at assessing CMRI, i.e., segmenting the myocardium and the two ventricles as well as classifying pathologies. In the wake of the 2017 MICCAI-ACDC challenge, we report results from deep learning methods provided by nine research groups for the segmentation task and four groups for the classification task. Results show that the best methods faithfully reproduce the expert analysis, leading to a mean value of 0.97 correlation score for the automatic extraction of clinical indices and an accuracy of 0.96 for automatic diagnosis. These results clearly open the door to highly accurate and fully automatic analysis of cardiac CMRI. We also identify scenarios for which deep learning methods are still failing. Both the dataset and detailed results are publicly available online, while the platform will remain open for new submissions.