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.
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.
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.