Automated nuclei segmentation and classification are the keys to analyze and understand the cellular characteristics and functionality, supporting computer-aided digital pathology in disease diagnosis. However, the task still remains challenging due to the intrinsic variations in size, intensity, and morphology of different types of nuclei. Herein, we propose a self-guided ordinal regression neural network for simultaneous nuclear segmentation and classification that can exploit the intrinsic characteristics of nuclei and focus on highly uncertain areas during training. The proposed network formulates nuclei segmentation as an ordinal regression learning by introducing a distance decreasing discretization strategy, which stratifies nuclei in a way that inner regions forming a regular shape of nuclei are separated from outer regions forming an irregular shape. It also adopts a self-guided training strategy to adaptively adjust the weights associated with nuclear pixels, depending on the difficulty of the pixels that is assessed by the network itself. To evaluate the performance of the proposed network, we employ large-scale multi-tissue datasets with 276349 exhaustively annotated nuclei. We show that the proposed network achieves the state-of-the-art performance in both nuclei segmentation and classification in comparison to several methods that are recently developed for segmentation and/or classification.
In this paper, we present a new neural architectural block for the vision domain, named Mixing Regionally and Locally (MRL), developed with the aim of effectively and efficiently mixing the provided input features. We bifurcate the input feature mixing task as mixing at a regional and local scale. To achieve an efficient mix, we exploit the domain-wide receptive field provided by self-attention for regional-scale mixing and convolutional kernels restricted to local scale for local-scale mixing. More specifically, our proposed method mixes regional features associated with local features within a defined region, followed by a local-scale features mix augmented by regional features. Experiments show that this hybridization of self-attention and convolution brings improved capacity, generalization (right inductive bias), and efficiency. Under similar network settings, MRL outperforms or is at par with its counterparts in classification, object detection, and segmentation tasks. We also show that our MRL-based network architecture achieves state-of-the-art performance for H&E histology datasets. We achieved DICE of 0.843, 0.855, and 0.892 for Kumar, CoNSep, and CPM-17 datasets, respectively, while highlighting the versatility offered by the MRL framework by incorporating layers like group convolutions to improve dataset-specific generalization.
Automatic nuclei segmentation and classification play a vital role in digital pathology. However, previous works are mostly built on data with limited diversity and small sizes, making the results questionable or misleading in actual downstream tasks. In this paper, we aim to build a reliable and robust method capable of dealing with data from the 'the clinical wild'. Specifically, we study and design a new method to simultaneously detect, segment, and classify nuclei from Haematoxylin and Eosin (H&E) stained histopathology data, and evaluate our approach using the recent largest dataset: PanNuke. We address the detection and classification of each nuclei as a novel semantic keypoint estimation problem to determine the center point of each nuclei. Next, the corresponding class-agnostic masks for nuclei center points are obtained using dynamic instance segmentation. Meanwhile, we proposed a novel Joint Pyramid Fusion Module (JPFM) to model the cross-scale dependencies, thus enhancing the local feature for better nuclei detection and classification. By decoupling two simultaneous challenging tasks and taking advantage of JPFM, our method can benefit from class-aware detection and class-agnostic segmentation, thus leading to a significant performance boost. We demonstrate the superior performance of our proposed approach for nuclei segmentation and classification across 19 different tissue types, delivering new benchmark results.
Histology images are inherently symmetric under rotation, where each orientation is equally as likely to appear. However, this rotational symmetry is not widely utilised as prior knowledge in modern Convolutional Neural Networks (CNNs), resulting in data hungry models that learn independent features at each orientation. Allowing CNNs to be rotation-equivariant removes the necessity to learn this set of transformations from the data and instead frees up model capacity, allowing more discriminative features to be learned. This reduction in the number of required parameters also reduces the risk of overfitting. In this paper, we propose Dense Steerable Filter CNNs (DSF-CNNs) that use group convolutions with multiple rotated copies of each filter in a densely connected framework. Each filter is defined as a linear combination of steerable basis filters, enabling exact rotation and decreasing the number of trainable parameters compared to standard filters. We also provide the first in-depth comparison of different rotation-equivariant CNNs for histology image analysis and demonstrate the advantage of encoding rotational symmetry into modern architectures. We show that DSF-CNNs achieve state-of-the-art performance, with significantly fewer parameters, when applied to three different tasks in the area of computational pathology: breast tumour classification, colon gland segmentation and multi-tissue nuclear segmentation.
Rotation-invariance is a desired property of machine-learning models for medical image analysis and in particular for computational pathology applications. We propose a framework to encode the geometric structure of the special Euclidean motion group SE(2) in convolutional networks to yield translation and rotation equivariance via the introduction of SE(2)-group convolution layers. This structure enables models to learn feature representations with a discretized orientation dimension that guarantees that their outputs are invariant under a discrete set of rotations. Conventional approaches for rotation invariance rely mostly on data augmentation, but this does not guarantee the robustness of the output when the input is rotated. At that, trained conventional CNNs may require test-time rotation augmentation to reach their full capability. This study is focused on histopathology image analysis applications for which it is desirable that the arbitrary global orientation information of the imaged tissues is not captured by the machine learning models. The proposed framework is evaluated on three different histopathology image analysis tasks (mitosis detection, nuclei segmentation and tumor classification). We present a comparative analysis for each problem and show that consistent increase of performances can be achieved when using the proposed framework.
Accurate segmenting nuclei instances is a crucial step in computer-aided image analysis to extract rich features for cellular estimation and following diagnosis as well as treatment. While it still remains challenging because the wide existence of nuclei clusters, along with the large morphological variances among different organs make nuclei instance segmentation susceptible to over-/under-segmentation. Additionally, the inevitably subjective annotating and mislabeling prevent the network learning from reliable samples and eventually reduce the generalization capability for robustly segmenting unseen organ nuclei. To address these issues, we propose a novel deep neural network, namely Contour-aware Informative Aggregation Network (CIA-Net) with multi-level information aggregation module between two task-specific decoders. Rather than independent decoders, it leverages the merit of spatial and texture dependencies between nuclei and contour by bi-directionally aggregating task-specific features. Furthermore, we proposed a novel smooth truncated loss that modulates losses to reduce the perturbation from outliers. Consequently, the network can focus on learning from reliable and informative samples, which inherently improves the generalization capability. Experiments on the 2018 MICCAI challenge of Multi-Organ-Nuclei-Segmentation validated the effectiveness of our proposed method, surpassing all the other 35 competitive teams by a significant margin.
Nuclear segmentation and classification within Haematoxylin & Eosin stained histology images is a fundamental prerequisite in the digital pathology work-flow. The development of automated methods for nuclear segmentation and classification enables the quantitative analysis of tens of thousands of nuclei within a whole-slide pathology image, opening up possibilities of further analysis of large-scale nuclear morphometry. However, automated nuclear segmentation and classification is faced with a major challenge in that there are several different types of nuclei, some of them exhibiting large intra-class variability such as the tumour cells. Additionally, some of the nuclei are often clustered together. To address these challenges, we present a novel convolutional neural network for simultaneous nuclear segmentation and classification that leverages the instance-rich information encoded within the vertical and horizontal distances of nuclear pixels to their centres of mass. These distances are then utilised to separate clustered nuclei, resulting in an accurate segmentation, particularly in areas with overlapping instances. Then for each segmented instance, the network predicts the type of nucleus via a devoted up-sampling branch. We demonstrate state-of-the-art performance compared to other methods on multiple independent multi-tissue histology image datasets. As part of this work, we introduce a new dataset of Haematoxylin & Eosin stained colorectal adenocarcinoma image tiles, containing 24,319 exhaustively annotated nuclei with associated class labels.
Convolutional networks are powerful visual models that yield hierarchies of features. We show that convolutional networks by themselves, trained end-to-end, pixels-to-pixels, exceed the state-of-the-art in semantic segmentation. Our key insight is to build "fully convolutional" networks that take input of arbitrary size and produce correspondingly-sized output with efficient inference and learning. We define and detail the space of fully convolutional networks, explain their application to spatially dense prediction tasks, and draw connections to prior models. We adapt contemporary classification networks (AlexNet, the VGG net, and GoogLeNet) into fully convolutional networks and transfer their learned representations by fine-tuning to the segmentation task. We then define a novel architecture that combines semantic information from a deep, coarse layer with appearance information from a shallow, fine layer to produce accurate and detailed segmentations. Our fully convolutional network achieves state-of-the-art segmentation of PASCAL VOC (20% relative improvement to 62.2% mean IU on 2012), NYUDv2, and SIFT Flow, while inference takes one third of a second for a typical image.
There is large consent that successful training of deep networks requires many thousand annotated training samples. In this paper, we present a network and training strategy that relies on the strong use of data augmentation to use the available annotated samples more efficiently. The architecture consists of a contracting path to capture context and a symmetric expanding path that enables precise localization. We show that such a network can be trained end-to-end from very few images and outperforms the prior best method (a sliding-window convolutional network) on the ISBI challenge for segmentation of neuronal structures in electron microscopic stacks. Using the same network trained on transmitted light microscopy images (phase contrast and DIC) we won the ISBI cell tracking challenge 2015 in these categories by a large margin. Moreover, the network is fast. Segmentation of a 512x512 image takes less than a second on a recent GPU. The full implementation (based on Caffe) and the trained networks are available at http://lmb.informatik.uni-freiburg.de/people/ronneber/u-net .
We introduce Group equivariant Convolutional Neural Networks (G-CNNs), a natural generalization of convolutional neural networks that reduces sample complexity by exploiting symmetries. G-CNNs use G-convolutions, a new type of layer that enjoys a substantially higher degree of weight sharing than regular convolution layers. G-convolutions increase the expressive capacity of the network without increasing the number of parameters. Group convolution layers are easy to use and can be implemented with negligible computational overhead for discrete groups generated by translations, reflections and rotations. G-CNNs achieve state of the art results on CIFAR10 and rotated MNIST.
In many computer vision tasks, we expect a particular behavior of the output with respect to rotations of the input image. If this relationship is explicitly encoded, instead of treated as any other variation, the complexity of the problem is decreased, leading to a reduction in the size of the required model. In this paper, we propose the Rotation Equivariant Vector Field Networks (RotEqNet), a Convolutional Neural Network (CNN) architecture encoding rotation equivariance, invariance and covariance. Each convolutional filter is applied at multiple orientations and returns a vector field representing magnitude and angle of the highest scoring orientation at every spatial location. We develop a modified convolution operator relying on this representation to obtain deep architectures. We test RotEqNet on several problems requiring different responses with respect to the inputs' rotation: image classification, biomedical image segmentation, orientation estimation and patch matching. In all cases, we show that RotEqNet offers extremely compact models in terms of number of parameters and provides results in line to those of networks orders of magnitude larger.
We present a conceptually simple, flexible, and general framework for object instance segmentation. Our approach efficiently detects objects in an image while simultaneously generating a high-quality segmentation mask for each instance. The method, called Mask R-CNN, extends Faster R-CNN by adding a branch for predicting an object mask in parallel with the existing branch for bounding box recognition. Mask R-CNN is simple to train and adds only a small overhead to Faster R-CNN, running at 5 fps. Moreover, Mask R-CNN is easy to generalize to other tasks, e.g., allowing us to estimate human poses in the same framework. We show top results in all three tracks of the COCO suite of challenges, including instance segmentation, bounding-box object detection, and person keypoint detection. Without bells and whistles, Mask R-CNN outperforms all existing, single-model entries on every task, including the COCO 2016 challenge winners. We hope our simple and effective approach will serve as a solid baseline and help ease future research in instance-level recognition. Code has been made available at: https://github.com/facebookresearch/Detectron
In many machine learning tasks it is desirable that a model's prediction transforms in an equivariant way under transformations of its input. Convolutional neural networks (CNNs) implement translational equivariance by construction; for other transformations, however, they are compelled to learn the proper mapping. In this work, we develop Steerable Filter CNNs (SFCNNs) which achieve joint equivariance under translations and rotations by design. The proposed architecture employs steerable filters to efficiently compute orientation dependent responses for many orientations without suffering interpolation artifacts from filter rotation. We utilize group convolutions which guarantee an equivariant mapping. In addition, we generalize He's weight initialization scheme to filters which are defined as a linear combination of a system of atomic filters. Numerical experiments show a substantial enhancement of the sample complexity with a growing number of sampled filter orientations and confirm that the network generalizes learned patterns over orientations. The proposed approach achieves state-of-the-art on the rotated MNIST benchmark and on the ISBI 2012 2D EM segmentation challenge.
Object segmentation and structure localization are important steps in automated image analysis pipelines for microscopy images. We present a convolution neural network (CNN) based deep learning architecture for segmentation of objects in microscopy images. The proposed network can be used to segment cells, nuclei and glands in fluorescence microscopy and histology images after slight tuning of input parameters. The network trains at multiple resolutions of the input image, connects the intermediate layers for better localization and context and generates the output using multi-resolution deconvolution filters. The extra convolutional layers which bypass the max-pooling operation allow the network to train for variable input intensities and object size and make it robust to noisy data. We compare our results on publicly available data sets and show that the proposed network outperforms recent deep learning algorithms.