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.     

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.     

Local contrastive loss with pseudo-label based self-training for semi-supervised medical image segmentation

Supervised deep learning-based methods yield accurate results for medical image segmentation. However, they require large labeled datasets for this, and obtaining them is a laborious task that requires clinical expertise. Semi/self-supervised learning-based approaches address this limitation by exploiting unlabeled data along with limited annotated data. Recent self-supervised learning methods use contrastive loss to learn good global level representations from unlabeled images and achieve high performance in classification tasks on popular natural image datasets like ImageNet. In pixel-level prediction tasks such as segmentation, it is crucial to also learn good local level representations along with global representations to achieve better accuracy. However, the impact of the existing local contrastive loss-based methods remains limited for learning good local representations because similar and dissimilar local regions are defined based on random augmentations and spatial proximity; not based on the semantic label of local regions due to lack of large-scale expert annotations in the semi/self-supervised setting. In this paper, we propose a local contrastive loss to learn good pixel level features useful for segmentation by exploiting semantic label information obtained from pseudo-labels of unlabeled images alongside limited annotated images with ground truth (GT) labels. In particular, we define the proposed contrastive loss to encourage similar representations for the pixels that have the same pseudo-label/GT label while being dissimilar to the representation of pixels with different pseudo-label/GT label in the dataset. We perform pseudo-label based self-training and train the network by jointly optimizing the proposed contrastive loss on both labeled and unlabeled sets and segmentation loss on only the limited labeled set. We evaluated the proposed approach on three public medical datasets of cardiac and prostate anatomies, and obtain high segmentation performance with a limited labeled set of one or two 3D volumes. Extensive comparisons with the state-of-the-art semi-supervised and data augmentation methods and concurrent contrastive learning methods demonstrate the substantial improvement achieved by the proposed method. The code is made publicly available at https://github.com/krishnabits001/pseudo_label_contrastive_training.     

DeepSMILE: Contrastive self-supervised pre-training benefits MSI and HRD classification directly from H&E whole-slide images in colorectal and breast cancer

We propose a Deep learning-based weak label learning method for analyzing whole slide images (WSIs) of Hematoxylin and Eosin (H&E) stained tumor tissue not requiring pixel-level or tile-level annotations using Self-supervised pre-training and heterogeneity-aware deep Multiple Instance LEarning (DeepSMILE). We apply DeepSMILE to the task of Homologous recombination deficiency (HRD) and microsatellite instability (MSI) prediction. We utilize contrastive self-supervised learning to pre-train a feature extractor on histopathology tiles of cancer tissue. Additionally, we use variability-aware deep multiple instance learning to learn the tile feature aggregation function while modeling tumor heterogeneity. For MSI prediction in a tumor-annotated and color normalized subset of TCGA-CRC (n=360 patients), contrastive self-supervised learning improves the tile supervision baseline from 0.77 to 0.87 AUROC, on par with our proposed DeepSMILE method. On TCGA-BC (n=1041 patients) without any manual annotations, DeepSMILE improves HRD classification performance from 0.77 to 0.81 AUROC compared to tile supervision with either a self-supervised or ImageNet pre-trained feature extractor. Our proposed methods reach the baseline performance using only 40% of the labeled data on both datasets. These improvements suggest we can use standard self-supervised learning techniques combined with multiple instance learning in the histopathology domain to improve genomic label classification performance with fewer labeled data.     

Weakly supervised segmentation on neural compressed histopathology with self-equivariant regularization

In digital pathology, segmentation is a fundamental task for the diagnosis and treatment of diseases. Existing fully supervised methods often require accurate pixel-level annotations that are both time-consuming and laborious to generate. Typical approaches first pre-process histology images into patches to meet memory constraints and later perform stitching for segmentation; at times leading to lower performance given the lack of global context. Since image level labels are cheaper to acquire, weakly supervised learning is a more practical alternative for training segmentation algorithms. In this work, we present a weakly supervised framework for histopathology segmentation using only image-level labels by refining class activation maps (CAM) with self-supervision. First, we compress gigapixel histology images with an unsupervised contrastive learning technique to retain high-level spatial context. Second, a network is trained on the compressed images to jointly predict image-labels and refine the initial CAMs via self-supervised losses. In particular, we achieve refinement via a pixel correlation module (PCM) that leverages self-attention between the initial CAM and the input to encourage fine-grained activations. Also, we introduce a feature masking technique that performs spatial dropout on the compressed input to suppress low confidence predictions. To effectively train our model, we propose a loss function that includes a classification objective with image-labels, self-supervised regularization and entropy minimization between the CAM predictions. Experimental results on two curated datasets show that our approach is comparable to fully-supervised methods and can outperform existing state-of-the-art patch-based methods. https://github.com/PhilipChicco/wsshisto     

Real-time echocardiography image analysis and quantification of cardiac indices

Deep learning has a huge potential to transform echocardiography in clinical practice and point of care ultrasound testing by providing real-time analysis of cardiac structure and function. Automated echocardiography analysis is benefited through use of machine learning for tasks such as image quality assessment, view classification, cardiac region segmentation, and quantification of diagnostic indices. By taking advantage of high-performing deep neural networks, we propose a novel and eicient real-time system for echocardiography analysis and quantification. Our system uses a self-supervised modality-specific representation trained using a publicly available large-scale dataset. The trained representation is used to enhance the learning of target echo tasks with relatively small datasets. We also present a novel Trilateral Attention Network (TaNet) for real-time cardiac region segmentation. The proposed network uses a module for region localization and three lightweight pathways for encoding rich low-level, textural, and high-level features. Feature embeddings from these individual pathways are then aggregated for cardiac region segmentation. This network is fine-tuned using a joint loss function and training strategy. We extensively evaluate the proposed system and its components, which are echo view retrieval, cardiac segmentation, and quantification, using four echocardiography datasets. Our experimental results show a consistent improvement in the performance of echocardiography analysis tasks with enhanced computational eiciency that charts a path toward its adoption in clinical practice. Specifically, our results show superior real-time performance in retrieving good quality echo from individual cardiac view, segmenting cardiac chambers with complex overlaps, and extracting cardiac indices that highly agree with the experts’ values. The source code of our implementation can be found in the project’s GitHub page.     

A dual-transformation with contrastive learning framework for lymph node metastasis prediction in pancreatic cancer

Pancreatic cancer is a malignant tumor, and its high recurrence rate after surgery is related to the lymph node metastasis status. In clinical practice, a preoperative imaging prediction method is necessary for prognosis assessment and treatment decision; however, there are two major challenges: insufficient data and difficulty in discriminative feature extraction. This paper proposed a deep learning model to predict lymph node metastasis in pancreatic cancer using multiphase CT, where a dual-transformation with contrastive learning framework is developed to overcome the challenges in fine-grained prediction with small sample sizes. Specifically, we designed a novel dynamic surface projection method to transform 3D data into 2D images for effectively using the 3D information, preserving the spatial correlation of the original texture information and reducing computational resources. Then, this dynamic surface projection was combined with the spiral transformation to establish a dual-transformation method for enhancing the diversity and complementarity of the dataset. A dual-transformation-based data augmentation method was also developed to produce numerous 2D-transformed images to alleviate the effect of insufficient samples. Finally, the dual-transformation-guided contrastive learning scheme based on intra-space-transformation consistency and inter-class specificity was designed to mine additional supervised information, thereby extracting more discriminative features. Extensive experiments have shown the promising performance of the proposed model for predicting lymph node metastasis in pancreatic cancer. Our dual-transformation with contrastive learning scheme was further confirmed on an external public dataset, representing a potential paradigm for the fine-grained classification of oncological images with small sample sizes. The code will be released at https://github.com/SJTUBME-QianLab/Dual-transformation.     

Source free domain adaptation for medical image segmentation with fourier style mining

Unsupervised domain adaptation (UDA) aims to exploit the knowledge learned from a labeled source dataset to solve similar tasks in a new unlabeled target domain. Existing UDA techniques typically assume that samples from source and target domains are freely accessible during the training. However, it may be impractical to access source images due to privacy concerns, especially in medical imaging scenarios with the patient information. To tackle this issue, we devise a novel source free domain adaptation framework with fourier style mining, where only a well-trained source segmentation model is available for the adaptation to the target domain. Our framework is composed of two stages: a generation stage and an adaptation stage. In the generation stage, we design a Fourier Style Mining (FSM) generator to inverse source-like images through statistic information of the pretrained source model and mutual Fourier Transform. These generated source-like images can provide source data distribution and benefit the domain alignment. In the adaptation stage, we design a Contrastive Domain Distillation (CDD) module to achieve feature-level adaptation, including a domain distillation loss to transfer relation knowledge and a domain contrastive loss to narrow down the domain gap by a self-supervised paradigm. Besides, a Compact-Aware Domain Consistency (CADC) module is proposed to enhance consistency learning by filtering out noisy pseudo labels with shape compactness metric, thus achieving output-level adaptation. Extensive experiments on cross-device and cross-centre datasets are conducted for polyp and prostate segmentation, and our method delivers impressive performance compared with state-of-the-art domain adaptation methods. The source code is available at https://github.com/CityU-AIM-Group/SFDA-FSM.     

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.     

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.     

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.     

‘Squeeze & excite’ guided few-shot segmentation of volumetric images

Deep neural networks enable highly accurate image segmentation, but require large amounts of manually annotated data for supervised training. Few-shot learning aims to address this shortcoming by learning a new class from a few annotated support examples. We introduce, a novel few-shot framework, for the segmentation of volumetric medical images with only a few annotated slices. Compared to other related works in computer vision, the major challenges are the absence of pre-trained networks and the volumetric nature of medical scans. We address these challenges by proposing a new architecture for few-shot segmentation that incorporates ‘squeeze & excite’ blocks. Our two-armed architecture consists of a conditioner arm, which processes the annotated support input and generates a task-specific representation. This representation is passed on to the segmenter arm that uses this information to segment the new query image. To facilitate efficient interaction between the conditioner and the segmenter arm, we propose to use ‘channel squeeze & spatial excitation’ blocks – a light-weight computational module – that enables heavy interaction between both the arms with negligible increase in model complexity. This contribution allows us to perform image segmentation without relying on a pre-trained model, which generally is unavailable for medical scans. Furthermore, we propose an efficient strategy for volumetric segmentation by optimally pairing a few slices of the support volume to all the slices of the query volume. We perform experiments for organ segmentation on whole-body contrast-enhanced CT scans from the Visceral Dataset. Our proposed model outperforms multiple baselines and existing approaches with respect to the segmentation accuracy by a significant margin. The source code is available at https://github.com/abhi4ssj/few-shot-segmentation.     

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 learning of neighborhood embedding for longitudinal MRI

In recent years, several deep learning models recommend first to represent Magnetic Resonance Imaging (MRI) as latent features before performing a downstream task of interest (such as classification or regression). The performance of the downstream task generally improves when these latent representations are explicitly associated with factors of interest. For example, we derived such a representation for capturing brain aging by applying self-supervised learning to longitudinal MRIs and then used the resulting encoding to automatically identify diseases accelerating the aging of the brain. We now propose a refinement of this representation by replacing the linear modeling of brain aging with one that is consistent in local neighborhoods in the latent space. Called Longitudinal Neighborhood Embedding (LNE), we derive an encoding so that neighborhoods are age-consistent (i.e., brain MRIs of different subjects with similar brain ages are in close proximity of each other) and progression-consistent, i.e., the latent space is defined by a smooth trajectory field where each trajectory captures changes in brain ages between a pair of MRIs extracted from a longitudinal sequence. To make the problem computationally tractable, we further propose a strategy for mini-batch sampling so that the resulting local neighborhoods accurately approximate the ones that would be defined based on the whole cohort.We evaluate LNE on three different downstream tasks: (1) to predict chronological age from T1-w MRI of 274 healthy subjects participating in a study at SRI International; (2) to distinguish Normal Control (NC) from Alzheimer’s Disease (AD) and stable Mild Cognitive Impairment (sMCI) from progressive Mild Cognitive Impairment (pMCI) based on T1-w MRI of 632 participants of the Alzheimer’s Disease Neuroimaging Initiative (ADNI); and (3) to distinguish no-to-low from moderate-to-heavy alcohol drinkers based on fractional anisotropy derived from diffusion tensor MRIs of 764 adolescents recruited by the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA). Across the three data sets, the visualization of the smooth trajectory vector fields and superior accuracy on downstream tasks demonstrate the strength of the proposed method over existing self-supervised methods in extracting information related to brain aging, which could help study the impact of substance use and neurodegenerative disorders. The code is available at https://github.com/ouyangjiahong/longitudinal-neighbourhood-embedding.     

Self-Supervised monocular depth and ego-Motion estimation in endoscopy: Appearance flow to the rescue

Recently, self-supervised learning technology has been applied to calculate depth and ego-motion from monocular videos, achieving remarkable performance in autonomous driving scenarios. One widely adopted assumption of depth and ego-motion self-supervised learning is that the image brightness remains constant within nearby frames. Unfortunately, the endoscopic scene does not meet this assumption because there are severe brightness fluctuations induced by illumination variations, non-Lambertian reflections and interreflections during data collection, and these brightness fluctuations inevitably deteriorate the depth and ego-motion estimation accuracy. In this work, we introduce a novel concept referred to as appearance flow to address the brightness inconsistency problem. The appearance flow takes into consideration any variations in the brightness pattern and enables us to develop a generalized dynamic image constraint. Furthermore, we build a unified self-supervised framework to estimate monocular depth and ego-motion simultaneously in endoscopic scenes, which comprises a structure module, a motion module, an appearance module and a correspondence module, to accurately reconstruct the appearance and calibrate the image brightness. Extensive experiments are conducted on the SCARED dataset and EndoSLAM dataset, and the proposed unified framework exceeds other self-supervised approaches by a large margin. To validate our framework’s generalization ability on different patients and cameras, we train our model on SCARED but test it on the SERV-CT and Hamlyn datasets without any fine-tuning, and the superior results reveal its strong generalization ability. Code is available at: https://github.com/ShuweiShao/AF-SfMLearner.     

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.     

DDTNet: A dense dual-task network for tumor-infiltrating lymphocyte detection and segmentation in histopathological images of breast cancer

The morphological evaluation of tumor-infiltrating lymphocytes (TILs) in hematoxylin and eosin (H& E)-stained histopathological images is the key to breast cancer (BCa) diagnosis, prognosis, and therapeutic response prediction. For now, the qualitative assessment of TILs is carried out by pathologists, and computer-aided automatic lymphocyte measurement is still a great challenge because of the small size and complex distribution of lymphocytes. In this paper, we propose a novel dense dual-task network (DDTNet) to simultaneously achieve automatic TIL detection and segmentation in histopathological images. DDTNet consists of a backbone network (i.e., feature pyramid network) for extracting multi-scale morphological characteristics of TILs, a detection module for the localization of TIL centers, and a segmentation module for the delineation of TIL boundaries, where a boundary-aware branch is further used to provide a shape prior to segmentation. An effective feature fusion strategy is utilized to introduce multi-scale features with lymphocyte location information from highly correlated branches for precise segmentation. Experiments on three independent lymphocyte datasets of BCa demonstrate that DDTNet outperforms other advanced methods in detection and segmentation metrics. As part of this work, we also propose a semi-automatic method (TILAnno) to generate high-quality boundary annotations for TILs in H& E-stained histopathological images. TILAnno is used to produce a new lymphocyte dataset that contains 5029 annotated lymphocyte boundaries, which have been released to facilitate computational histopathology in the future.     

Self-rule to multi-adapt: Generalized multi-source feature learning using unsupervised domain adaptation for colorectal cancer tissue detection

Supervised learning is constrained by the availability of labeled data, which are especially expensive to acquire in the field of digital pathology. Making use of open-source data for pre-training or using domain adaptation can be a way to overcome this issue. However, pre-trained networks often fail to generalize to new test domains that are not distributed identically due to tissue stainings, types, and textures variations. Additionally, current domain adaptation methods mainly rely on fully-labeled source datasets. In this work, we propose Self-Rule to Multi-Adapt (SRMA), which takes advantage of self-supervised learning to perform domain adaptation, and removes the necessity of fully-labeled source datasets. SRMA can effectively transfer the discriminative knowledge obtained from a few labeled source domain’s data to a new target domain without requiring additional tissue annotations. Our method harnesses both domains’ structures by capturing visual similarity with intra-domain and cross-domain self-supervision. Moreover, we present a generalized formulation of our approach that allows the framework to learn from multiple source domains. We show that our proposed method outperforms baselines for domain adaptation of colorectal tissue type classification in single and multi-source settings, and further validate our approach on an in-house clinical cohort. The code and trained models are available open-source: https://github.com/christianabbet/SRA.     

Cross-modal attention for multi-modal image registration

In the past few years, convolutional neural networks (CNNs) have been proven powerful in extracting image features crucial for medical image registration. However, challenging applications and recent advances in computer vision suggest that CNNs are limited in their ability to understand the spatial correspondence between features, which is at the core of image registration. The issue is further exaggerated when it comes to multi-modal image registration, where the appearances of input images can differ significantly. This paper presents a novel cross-modal attention mechanism for correlating features extracted from the multi-modal input images and mapping such correlation to image registration transformation. To efficiently train the developed network, a contrastive learning-based pre-training method is also proposed to aid the network in extracting high-level features across the input modalities for the following cross-modal attention learning. We validated the proposed method on transrectal ultrasound (TRUS) to magnetic resonance (MR) registration, a clinically important procedure that benefits prostate cancer biopsy. Our experimental results demonstrate that for MR-TRUS registration, a deep neural network embedded with the cross-modal attention block outperforms other advanced CNN-based networks with ten times its size. We also incorporated visualization techniques to improve the interpretability of our network, which helps bring insights into the deep learning based image registration methods. The source code of our work is available at https://github.com/DIAL-RPI/Attention-Reg.     

SRPN: similarity-based region proposal networks for nuclei and cells detection in histology images

The detection of nuclei and cells in histology images is of great value in both clinical practice and pathological studies. However, multiple reasons such as morphological variations of nuclei or cells make it a challenging task where conventional object detection methods cannot obtain satisfactory performance in many cases. A detection task consists of two sub-tasks, classification and localization. Under the condition of dense object detection, classification is a key to boost the detection performance. Considering this, we propose similarity based region proposal networks (SRPN) for nuclei and cells detection in histology images. In particular, a customised convolution layer termed as embedding layer is designed for network building. The embedding layer is added into the region proposal networks, enabling the networks to learn discriminative features based on similarity learning. Features obtained by similarity learning can significantly boost the classification performance compared to conventional methods. SRPN can be easily integrated into standard convolutional neural networks architectures such as the Faster R-CNN and RetinaNet. We test the proposed approach on tasks of multi-organ nuclei detection and signet ring cells detection in histological images. Experimental results show that networks applying similarity learning achieved superior performance on both tasks when compared to their counterparts. In particular, the proposed SRPN achieve state-of-the-art performance on the MoNuSeg benchmark for nuclei segmentation and detection while compared to previous methods, and on the signet ring cell detection benchmark when compared with baselines. The sourcecode is publicly available at: https://github.com/sigma10010/nuclei_cells_det.