SAC-Net: Learning with weak and noisy labels in histopathology image segmentation

Deep convolutional neural networks have been highly effective in segmentation tasks. However, segmentation becomes more difficult when training images include many complex instances to segment, such as the task of nuclei segmentation in histopathology images. Weakly supervised learning can reduce the need for large-scale, high-quality ground truth annotations by involving non-expert annotators or algorithms to generate supervision information for segmentation. However, there is still a significant performance gap between weakly supervised learning and fully supervised learning approaches. In this work, we propose a weakly-supervised nuclei segmentation method in a two-stage training manner that only requires annotation of the nuclear centroids. First, we generate boundary and superpixel-based masks as pseudo ground truth labels to train our SAC-Net, which is a segmentation network enhanced by a constraint network and an attention network to effectively address the problems caused by noisy labels. Then, we refine the pseudo labels at the pixel level based on Confident Learning to train the network again. Our method shows highly competitive performance of cell nuclei segmentation in histopathology images on three public datasets. Code will be available at: https://github.com/RuoyuGuo/MaskGA_Net.     

Automatic Grading Assessments for Knee MRI Cartilage Defects via Self-ensembling Semi-supervised Learning with Dual-Consistency

Knee cartilage defects caused by osteoarthritis are major musculoskeletal disorders, leading to joint necrosis or even disability if not intervened at early stage. Deep learning has demonstrated its effectiveness in computer-aided diagnosis, but it is time-consuming to prepare a large set of well-annotated data by experienced radiologists for model training. In this paper, we propose a semi-supervised framework to effectively use unlabeled data for better evaluation of knee cartilage defect grading. Our framework is developed based on the widely-used mean-teacher classification model, by designing a novel dual-consistency strategy to boost the consistency between the teacher and student models. The main contributions are three-fold: (1) We define an attention loss function to make the network focus on the cartilage regions, which can both achieve accurate attention masks and boost classification performance simultaneously; (2) Besides enforcing the consistency of classification results, we further design a novel attention consistency mechanism to ensure the focusing of the student and teacher networks on the same defect regions; (3) We introduce an aggregation approach to ensemble the slice-level classification outcomes for deriving the final subject-level diagnosis. Experimental results show that our proposed method can significantly improve both classification and localization performances of knee cartilage defects. Our code is available on https://github.com/King-HAW/DC-MT.     

Dual-distribution discrepancy with self-supervised refinement for anomaly detection in medical images

Medical anomaly detection is a crucial yet challenging task aimed at recognizing abnormal images to assist in diagnosis. Due to the high-cost annotations of abnormal images, most methods utilize only known normal images during training and identify samples deviating from the normal profile as anomalies in the testing phase. Many readily available unlabeled images containing anomalies are thus ignored in the training phase, restricting the performance. To solve this problem, we introduce one-class semi-supervised learning (OC-SSL) to utilize known normal and unlabeled images for training, and propose Dual-distribution Discrepancy for Anomaly Detection (DDAD) based on this setting. Ensembles of reconstruction networks are designed to model the distribution of normal images and the distribution of both normal and unlabeled images, deriving the normative distribution module (NDM) and unknown distribution module (UDM). Subsequently, the intra-discrepancy of NDM and inter-discrepancy between the two modules are designed as anomaly scores. Furthermore, we propose a new perspective on self-supervised learning, which is designed to refine the anomaly scores rather than directly detect anomalies. Five medical datasets, including chest X-rays, brain MRIs and retinal fundus images, are organized as benchmarks for evaluation. Experiments on these benchmarks comprehensively compare a wide range of anomaly detection methods and demonstrate that our method achieves significant gains and outperforms the state-of-the-art. Code and organized benchmarks are available at https://github.com/caiyu6666/DDAD-ASR.     

Semi-supervised medical image segmentation via uncertainty rectified pyramid consistency

Despite that Convolutional Neural Networks (CNNs) have achieved promising performance in many medical image segmentation tasks, they rely on a large set of labeled images for training, which is expensive and time-consuming to acquire. Semi-supervised learning has shown the potential to alleviate this challenge by learning from a large set of unlabeled images and limited labeled samples. In this work, we present a simple yet efficient consistency regularization approach for semi-supervised medical image segmentation, called Uncertainty Rectified Pyramid Consistency (URPC). Inspired by the pyramid feature network, we chose a pyramid-prediction network that obtains a set of segmentation predictions at different scales. For semi-supervised learning, URPC learns from unlabeled data by minimizing the discrepancy between each of the pyramid predictions and their average. We further present multi-scale uncertainty rectification to boost the pyramid consistency regularization, where the rectification seeks to temper the consistency loss at outlier pixels that may have substantially different predictions than the average, potentially due to upsampling errors or lack of enough labeled data. Experiments on two public datasets and an in-house clinical dataset showed that: 1) URPC can achieve large performance improvement by utilizing unlabeled data and 2) Compared with five existing semi-supervised methods, URPC achieved better or comparable results with a simpler pipeline. Furthermore, we build a semi-supervised medical image segmentation codebase to boost research on this topic: https://github.com/HiLab-git/SSL4MIS.     

Federated learning for computational pathology on gigapixel whole slide images

Deep Learning-based computational pathology algorithms have demonstrated profound ability to excel in a wide array of tasks that range from characterization of well known morphological phenotypes to predicting non human-identifiable features from histology such as molecular alterations. However, the development of robust, adaptable and accurate deep learning-based models often rely on the collection and time-costly curation large high-quality annotated training data that should ideally come from diverse sources and patient populations to cater for the heterogeneity that exists in such datasets. Multi-centric and collaborative integration of medical data across multiple institutions can naturally help overcome this challenge and boost the model performance but is limited by privacy concerns among other difficulties that may arise in the complex data sharing process as models scale towards using hundreds of thousands of gigapixel whole slide images. In this paper, we introduce privacy-preserving federated learning for gigapixel whole slide images in computational pathology using weakly-supervised attention multiple instance learning and differential privacy. We evaluated our approach on two different diagnostic problems using thousands of histology whole slide images with only slide-level labels. Additionally, we present a weakly-supervised learning framework for survival prediction and patient stratification from whole slide images and demonstrate its effectiveness in a federated setting. Our results show that using federated learning, we can effectively develop accurate weakly-supervised deep learning models from distributed data silos without direct data sharing and its associated complexities, while also preserving differential privacy using randomized noise generation. We also make available an easy-to-use federated learning for computational pathology software package: http://github.com/mahmoodlab/HistoFL.     

Self-supervised driven consistency training for annotation efficient histopathology image analysis

Training a neural network with a large labeled dataset is still a dominant paradigm in computational histopathology. However, obtaining such exhaustive manual annotations is often expensive, laborious, and prone to inter and intra-observer variability. While recent self-supervised and semi-supervised methods can alleviate this need by learning unsupervised feature representations, they still struggle to generalize well to downstream tasks when the number of labeled instances is small. In this work, we overcome this challenge by leveraging both task-agnostic and task-specific unlabeled data based on two novel strategies: (i) a self-supervised pretext task that harnesses the underlying multi-resolution contextual cues in histology whole-slide images to learn a powerful supervisory signal for unsupervised representation learning; (ii) a new teacher-student semi-supervised consistency paradigm that learns to effectively transfer the pretrained representations to downstream tasks based on prediction consistency with the task-specific unlabeled data.We carry out extensive validation experiments on three histopathology benchmark datasets across two classification and one regression based tasks, i.e., tumor metastasis detection, tissue type classification, and tumor cellularity quantification. Under limited-label data, the proposed method yields tangible improvements, which is close to or even outperforming other state-of-the-art self-supervised and supervised baselines. Furthermore, we empirically show that the idea of bootstrapping the self-supervised pretrained features is an effective way to improve the task-specific semi-supervised learning on standard benchmarks. Code and pretrained models are made available at: https://github.com/srinidhiPY/SSL_CR_Histo.     

Adaptive convolutional neural networks for accelerating magnetic resonance imaging via k-space data interpolation

Deep learning in k-space has demonstrated great potential for image reconstruction from undersampled k-space data in fast magnetic resonance imaging (MRI). However, existing deep learning-based image reconstruction methods typically apply weight-sharing convolutional neural networks (CNNs) to k-space data without taking into consideration the k-space data's spatial frequency properties, leading to ineffective learning of the image reconstruction models. Moreover, complementary information of spatially adjacent slices is often ignored in existing deep learning methods. To overcome such limitations, we have developed a deep learning algorithm, referred to as adaptive convolutional neural networks for k-space data interpolation (ACNN-k-Space), which adopts a residual Encoder-Decoder network architecture to interpolate the undersampled k-space data by integrating spatially contiguous slices as multi-channel input, along with k-space data from multiple coils if available. The network is enhanced by self-attention layers to adaptively focus on k-space data at different spatial frequencies and channels. We have evaluated our method on two public datasets and compared it with state-of-the-art existing methods. Ablation studies and experimental results demonstrate that our method effectively reconstructs images from undersampled k-space data and achieves significantly better image reconstruction performance than current state-of-the-art techniques. Source code of the method is available at https://gitlab.com/qgpmztmf/acnn-k-space.     

Equitable modelling of brain imaging by counterfactual augmentation with morphologically constrained 3D deep generative models

We describe CounterSynth, a conditional generative model of diffeomorphic deformations that induce label-driven, biologically plausible changes in volumetric brain images. The model is intended to synthesise counterfactual training data augmentations for downstream discriminative modelling tasks where fidelity is limited by data imbalance, distributional instability, confounding, or underspecification, and exhibits inequitable performance across distinct subpopulations.Focusing on demographic attributes, we evaluate the quality of synthesised counterfactuals with voxel-based morphometry, classification and regression of the conditioning attributes, and the Fréchet inception distance. Examining downstream discriminative performance in the context of engineered demographic imbalance and confounding, we use UK Biobank and OASIS magnetic resonance imaging data to benchmark CounterSynth augmentation against current solutions to these problems. We achieve state-of-the-art improvements, both in overall fidelity and equity. The source code for CounterSynth is available at https://github.com/guilherme-pombo/CounterSynth.     

Analysis of the ISIC image datasets: Usage,benchmarks and recommendations

The International Skin Imaging Collaboration (ISIC) datasets have become a leading repository for researchers in machine learning for medical image analysis, especially in the field of skin cancer detection and malignancy assessment. They contain tens of thousands of dermoscopic photographs together with gold-standard lesion diagnosis metadata. The associated yearly challenges have resulted in major contributions to the field, with papers reporting measures well in excess of human experts. Skin cancers can be divided into two major groups - melanoma and non-melanoma. Although less prevalent, melanoma is considered to be more serious as it can quickly spread to other organs if not treated at an early stage. In this paper, we summarise the usage of the ISIC dataset images and present an analysis of yearly releases over a period of 2016 - 2020. Our analysis found a significant number of duplicate images, both within and between the datasets. Additionally, we also noted duplicates spread across testing and training sets. Due to these irregularities, we propose a duplicate removal strategy and recommend a curated dataset for researchers to use when working on ISIC datasets. Given that ISIC 2020 focused on melanoma classification, we conduct experiments to provide benchmark results on the ISIC 2020 test set, with additional analysis on the smaller ISIC 2017 test set. Testing was completed following the application of our duplicate removal strategy and an additional data balancing step. As a result of removing 14,310 duplicate images from the training set, our benchmark results show good levels of melanoma prediction with an AUC of 0.80 for the best performing model. As our aim was not to maximise network performance, we did not include additional steps in our experiments. Finally, we provide recommendations for future research by highlighting irregularities that may present research challenges. A list of image files with reference to the original ISIC dataset sources for the recommended curated training set will be shared on our GitHub repository (available at www.github.com/mmu-dermatology-research/isic_duplicate_removal_strategy).     

SSD-KD: A self-supervised diverse knowledge distillation method for lightweight skin lesion classification using dermoscopic images

Skin cancer is one of the most common types of malignancy, affecting a large population and causing a heavy economic burden worldwide. Over the last few years, computer-aided diagnosis has been rapidly developed and make great progress in healthcare and medical practices due to the advances in artificial intelligence, particularly with the adoption of convolutional neural networks. However, most studies in skin cancer detection keep pursuing high prediction accuracies without considering the limitation of computing resources on portable devices. In this case, the knowledge distillation (KD) method has been proven as an efficient tool to help improve the adaptability of lightweight models under limited resources, meanwhile keeping a high-level representation capability. To bridge the gap, this study specifically proposes a novel method, termed SSD-KD, that unifies diverse knowledge into a generic KD framework for skin disease classification. Our method models an intra-instance relational feature representation and integrates it with existing KD research. A dual relational knowledge distillation architecture is self-supervised trained while the weighted softened outputs are also exploited to enable the student model to capture richer knowledge from the teacher model. To demonstrate the effectiveness of our method, we conduct experiments on ISIC 2019, a large-scale open-accessed benchmark of skin diseases dermoscopic images. Experiments show that our distilled MobileNetV2 can achieve an accuracy as high as 85% for the classification tasks of 8 different skin diseases with minimal parameters and computing requirements. Ablation studies confirm the effectiveness of our intra- and inter-instance relational knowledge integration strategy. Compared with state-of-the-art knowledge distillation techniques, the proposed method demonstrates improved performance. To the best of our knowledge, this is the first deep knowledge distillation application for multi-disease classification on the large-scale dermoscopy database. Our codes and models are available at https://github.com/enkiwang/Portable-Skin-Lesion-Diagnosis.     

SMILE: Cost-sensitive multi-task learning for nuclear segmentation and classification with imbalanced annotations

High throughput nuclear segmentation and classification of whole slide images (WSIs) is crucial to biological analysis, clinical diagnosis and precision medicine. With the advances of CNN algorithms and the continuously growing datasets, considerable progress has been made in nuclear segmentation and classification. However, few works consider how to reasonably deal with nuclear heterogeneity in the following two aspects: imbalanced data distribution and diversified morphology characteristics. The minority classes might be dominated by the majority classes due to the imbalanced data distribution and the diversified morphology characteristics may lead to fragile segmentation results. In this study, a cost-Sensitive MultI-task LEarning (SMILE) framework is conducted to tackle the data heterogeneity problem. Based on the most popular multi-task learning backbone in nuclei segmentation and classification, we propose a multi-task correlation attention (MTCA) to perform feature interaction of multiple high relevant tasks to learn better feature representation. A cost-sensitive learning strategy is proposed to solve the imbalanced data distribution by increasing the penalization for the error classification of the minority classes. Furthermore, we propose a novel post-processing step based on the coarse-to-fine marker-controlled watershed scheme to alleviate fragile segmentation when nuclei are with large size and unclear contour. Extensive experiments show that the proposed method achieves state-of-the-art performances on CoNSeP and MoNuSAC 2020 datasets. The code is available at: https://github.com/panxipeng/nuclear_segandcls.     

Transformer-based unsupervised contrastive learning for histopathological image classification

A large-scale and well-annotated dataset is a key factor for the success of deep learning in medical image analysis. However, assembling such large annotations is very challenging, especially for histopathological images with unique characteristics (e.g., gigapixel image size, multiple cancer types, and wide staining variations). To alleviate this issue, self-supervised learning (SSL) could be a promising solution that relies only on unlabeled data to generate informative representations and generalizes well to various downstream tasks even with limited annotations. In this work, we propose a novel SSL strategy called semantically-relevant contrastive learning (SRCL), which compares relevance between instances to mine more positive pairs. Compared to the two views from an instance in traditional contrastive learning, our SRCL aligns multiple positive instances with similar visual concepts, which increases the diversity of positives and then results in more informative representations. We employ a hybrid model (CTransPath) as the backbone, which is designed by integrating a convolutional neural network (CNN) and a multi-scale Swin Transformer architecture. The CTransPath is pretrained on massively unlabeled histopathological images that could serve as a collaborative local–global feature extractor to learn universal feature representations more suitable for tasks in the histopathology image domain. The effectiveness of our SRCL-pretrained CTransPath is investigated on five types of downstream tasks (patch retrieval, patch classification, weakly-supervised whole-slide image classification, mitosis detection, and colorectal adenocarcinoma gland segmentation), covering nine public datasets. The results show that our SRCL-based visual representations not only achieve state-of-the-art performance in each dataset, but are also more robust and transferable than other SSL methods and ImageNet pretraining (both supervised and self-supervised methods). Our code and pretrained model are available at https://github.com/Xiyue-Wang/TransPath.     

Convolutional neural networks for classification of Alzheimer's disease: Overview and reproducible evaluation

Numerous machine learning (ML) approaches have been proposed for automatic classification of Alzheimer's disease (AD) from brain imaging data. In particular, over 30 papers have proposed to use convolutional neural networks (CNN) for AD classification from anatomical MRI. However, the classification performance is difficult to compare across studies due to variations in components such as participant selection, image preprocessing or validation procedure. Moreover, these studies are hardly reproducible because their frameworks are not publicly accessible and because implementation details are lacking. Lastly, some of these papers may report a biased performance due to inadequate or unclear validation or model selection procedures. In the present work, we aim to address these limitations through three main contributions. First, we performed a systematic literature review. We identified four main types of approaches: i) 2D slice-level, ii) 3D patch-level, iii) ROI-based and iv) 3D subject-level CNN. Moreover, we found that more than half of the surveyed papers may have suffered from data leakage and thus reported biased performance. Our second contribution is the extension of our open-source framework for classification of AD using CNN and T1-weighted MRI. The framework comprises previously developed tools to automatically convert ADNI, AIBL and OASIS data into the BIDS standard, and a modular set of image preprocessing procedures, classification architectures and evaluation procedures dedicated to deep learning. Finally, we used this framework to rigorously compare different CNN architectures. The data was split into training/validation/test sets at the very beginning and only the training/validation sets were used for model selection. To avoid any overfitting, the test sets were left untouched until the end of the peer-review process. Overall, the different 3D approaches (3D-subject, 3D-ROI, 3D-patch) achieved similar performances while that of the 2D slice approach was lower. Of note, the different CNN approaches did not perform better than a SVM with voxel-based features. The different approaches generalized well to similar populations but not to datasets with different inclusion criteria or demographical characteristics. All the code of the framework and the experiments is publicly available: general-purpose tools have been integrated into the Clinica software (www.clinica.run) and the paper-specific code is available at: https://github.com/aramis-lab/AD-DL.     

CaDIS: Cataract dataset for surgical RGB-image segmentation

Video feedback provides a wealth of information about surgical procedures and is the main sensory cue for surgeons. Scene understanding is crucial to computer assisted interventions (CAI) and to post-operative analysis of the surgical procedure. A fundamental building block of such capabilities is the identification and localization of surgical instruments and anatomical structures through semantic segmentation. Deep learning has advanced semantic segmentation techniques in the recent years but is inherently reliant on the availability of labelled datasets for model training. This paper introduces a dataset for semantic segmentation of cataract surgery videos complementing the publicly available CATARACTS challenge dataset. In addition, we benchmark the performance of several state-of-the-art deep learning models for semantic segmentation on the presented dataset. The dataset is publicly available at https://cataracts-semantic-segmentation2020.grand-challenge.org/.     

ClusterSeg: A crowd cluster pinpointed nucleus segmentation framework with cross-modality datasets

The detection and segmentation of individual cells or nuclei is often involved in image analysis across a variety of biology and biomedical applications as an indispensable prerequisite. However, the ubiquitous presence of crowd clusters with morphological variations often hinders successful instance segmentation. In this paper, nuclei cluster focused annotation strategies and frameworks are proposed to overcome this challenging practical problem. Specifically, we design a nucleus segmentation framework, namely ClusterSeg, to tackle nuclei clusters, which consists of a convolutional-transformer hybrid encoder and a 2.5-path decoder for precise predictions of nuclei instance mask, contours, and clustered-edges. Additionally, an annotation-efficient clustered-edge pointed strategy pinpoints the salient and error-prone boundaries, where a partially-supervised PS-ClusterSeg is presented using ClusterSeg as the segmentation backbone. The framework is evaluated with four privately curated image sets and two public sets with characteristic severely clustered nuclei across a variety range of image modalities, e.g., microscope, cytopathology, and histopathology images. The proposed ClusterSeg and PS-ClusterSeg are modality-independent and generalizable, and superior to current state-of-the-art approaches in multiple metrics empirically. Our collected data, the elaborate annotations to both public and private set, as well the source code, are released publicly at https://github.com/lu-yizhou/ClusterSeg.     

Models Genesis

Transfer learning from natural images to medical images has been established as one of the most practical paradigms in deep learning for medical image analysis. To fit this paradigm, however, 3D imaging tasks in the most prominent imaging modalities (e.g., CT and MRI) have to be reformulated and solved in 2D, losing rich 3D anatomical information, thereby inevitably compromising its performance. To overcome this limitation, we have built a set of models, called Generic Autodidactic Models, nicknamed Models Genesis, because they are created ex nihilo (with no manual labeling), self-taught (learnt by self-supervision), and generic (served as source models for generating application-specific target models). Our extensive experiments demonstrate that our Models Genesis significantly outperform learning from scratch and existing pre-trained 3D models in all five target 3D applications covering both segmentation and classification. More importantly, learning a model from scratch simply in 3D may not necessarily yield performance better than transfer learning from ImageNet in 2D, but our Models Genesis consistently top any 2D/2.5D approaches including fine-tuning the models pre-trained from ImageNet as well as fine-tuning the 2D versions of our Models Genesis, confirming the importance of 3D anatomical information and significance of Models Genesis for 3D medical imaging. This performance is attributed to our unified self-supervised learning framework, built on a simple yet powerful observation: the sophisticated and recurrent anatomy in medical images can serve as strong yet free supervision signals for deep models to learn common anatomical representation automatically via self-supervision. As open science, all codes and pre-trained Models Genesis are available at https://github.com/MrGiovanni/ModelsGenesis.     

Meta multi-task nuclei segmentation with fewer training samples

Cells/nuclei deliver massive information of microenvironment. An automatic nuclei segmentation approach can reduce pathologists’ workload and allow precise of the microenvironment for biological and clinical researches. Existing deep learning models have achieved outstanding performance under the supervision of a large amount of labeled data. However, when data from the unseen domain comes, we still have to prepare a certain degree of manual annotations for training for each domain. Unfortunately, obtaining histopathological annotations is extremely difficult. It is high expertise-dependent and time-consuming. In this paper, we attempt to build a generalized nuclei segmentation model with less data dependency and more generalizability. To this end, we propose a meta multi-task learning (Meta-MTL) model for nuclei segmentation which requires fewer training samples. A model-agnostic meta-learning is applied as the outer optimization algorithm for the segmentation model. We introduce a contour-aware multi-task learning model as the inner model. A feature fusion and interaction block (FFIB) is proposed to allow feature communication across both tasks. Extensive experiments prove that our proposed Meta-MTL model can improve the model generalization and obtain a comparable performance with state-of-the-art models with fewer training samples. Our model can also perform fast adaptation on the unseen domain with only a few manual annotations. Code is available at https://github.com/ChuHan89/Meta-MTL4NucleiSegmentation     

Rigid and non-rigid motion artifact reduction in X-ray CT using attention module

Motion artifacts are a major factor that can degrade the diagnostic performance of computed tomography (CT) images. In particular, the motion artifacts become considerably more severe when an imaging system requires a long scan time such as in dental CT or cone-beam CT (CBCT) applications, where patients generate rigid and non-rigid motions. To address this problem, we proposed a new real-time technique for motion artifacts reduction that utilizes a deep residual network with an attention module. Our attention module was designed to increase the model capacity by amplifying or attenuating the residual features according to their importance. We trained and evaluated the network by creating four benchmark datasets with rigid motions or with both rigid and non-rigid motions under a step-and-shoot fan-beam CT (FBCT) or a CBCT. Each dataset provided a set of motion-corrupted CT images and their ground-truth CT image pairs.The strong modeling power of the proposed network model allowed us to successfully handle motion artifacts from the two CT systems under various motion scenarios in real-time. As a result, the proposed model demonstrated clear performance benefits. In addition, we compared our model with Wasserstein generative adversarial network (WGAN)-based models and a deep residual network (DRN)-based model, which are one of the most powerful techniques for CT denoising and natural RGB image deblurring, respectively. Based on the extensive analysis and comparisons using four benchmark datasets, we confirmed that our model outperformed the aforementioned competitors. Our benchmark datasets and implementation code are available at https://github.com/youngjun-ko/ct_mar_attention.