Domain-adversarial neural networks to address the appearance variability of histopathology images

Preparing and scanning histopathology slides consists of several steps, each with a multitude of parameters. The parameters can vary between pathology labs and within the same lab over time, resulting in significant variability of the tissue appearance that hampers the generalization of automatic image analysis methods. Typically, this is addressed with ad-hoc approaches such as staining normalization that aim to reduce the appearance variability. In this paper, we propose a systematic solution based on domain-adversarial neural networks. We hypothesize that removing the domain information from the model representation leads to better generalization. We tested our hypothesis for the problem of mitosis detection in breast cancer histopathology images and made a comparative analysis with two other approaches. We show that combining color augmentation with domain-adversarial training is a better alternative than standard approaches to improve the generalization of deep learning methods.Comment: MICCAI 2017 Workshop on Deep Learning in Medical Image Analysi

Inferring a Third Spatial Dimension from 2D Histological Images

Histological images are obtained by transmitting light through a tissue specimen that has been stained in order to produce contrast. This process results in 2D images of the specimen that has a three-dimensional structure. In this paper, we propose a method to infer how the stains are distributed in the direction perpendicular to the surface of the slide for a given 2D image in order to obtain a 3D representation of the tissue. This inference is achieved by decomposition of the staining concentration maps under constraints that ensure realistic decomposition and reconstruction of the original 2D images. Our study shows that it is possible to generate realistic 3D images making this method a potential tool for data augmentation when training deep learning models.Comment: IEEE International Symposium on Biomedical Imaging (ISBI), 201

Effect of latent space distribution on the segmentation of images with multiple annotations

We propose the Generalized Probabilistic U-Net, which extends the Probabilistic U-Net by allowing more general forms of the Gaussian distribution as the latent space distribution that can better approximate the uncertainty in the reference segmentations. We study the effect the choice of latent space distribution has on capturing the variation in the reference segmentations for lung tumors and white matter hyperintensities in the brain. We show that the choice of distribution affects the sample diversity of the predictions and their overlap with respect to the reference segmentations. We have made our implementation available at https://github.com/ishaanb92/GeneralizedProbabilisticUNetComment: Accepted for publication at the Journal of Machine Learning for Biomedical Imaging (MELBA) https://melba-journal.org/2023:005. arXiv admin note: text overlap with arXiv:2207.1287

Roto-Translation Equivariant Convolutional Networks: Application to Histopathology Image Analysis

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

Automated measurement of brain and white matter lesion volume in type 2 diabetes mellitus

Aims/hypothesis: Type 2 diabetes mellitus has been associated with brain atrophy and cognitive decline, but the association with ischaemic white matter lesions is unclear. Previous neuroimaging studies have mainly used semiquantitative rating scales to measure atrophy and white matter lesions (WMLs). In this study we used an automated segmentation technique to investigate the association of type 2 diabetes, several diabetes-related risk factors and cognition with cerebral tissue and WML volumes. Subjects and methods: Magnetic resonance images of 99 patients with type 2 diabetes and 46 control participants from a population-based sample were segmented using a k-nearest neighbour classifier trained on ten manually segmented data sets. White matter, grey matter, lateral ventricles, cerebrospinal fluid not including lateral ventricles, and WML volumes were assessed. Analyses were adjusted for age, sex, level of education and intracranial volume. Results: Type 2 diabetes was associated with a smaller volume of grey matter (-21.8 ml; 95% CI -34.2, -9.4) and with larger lateral ventricle volume (7.1 ml; 95% CI 2.3, 12.0) and with larger white matter lesion volume (56.5%; 95% CI 4.0, 135.8), whereas white matter volume was not affected. In separate analyses for men and women, the effects of diabetes were only significant in women. Conclusions/interpretation: The combination of atrophy with larger WML volume indicates that type 2 diabetes is associated with mixed pathology in the brain. The observed sex differences were unexpected and need to be addressed in further studies. © 2007 Springer-Verlag

Adaptive stochastic gradient descent optimisation for image registration.

Abstract We present a stochastic gradient descent optimisation method for image registration with adaptive step size prediction. The method is based on the theoretical work by Plakhov and Cruz (J. Math. Sci. 120(1): [964][965][966][967][968][969][970][971][972][973] 2004). Our main methodological contribution is the derivation of an image-driven mechanism to select proper values for the most important free parameters of the method. The selection mechanism employs general characteristics of the cost functions that commonly occur in intensity-based image registration. Also, the theoretical convergence conditions of the optimisation method are taken into account. The proposed adaptive stochastic gradient descent (ASGD) method is compared to a standard, non-adaptive RobbinsMonro (RM) algorithm. Both ASGD and RM employ a stochastic subsampling technique to accelerate the optimisation process. Registration experiments were performed on 3D CT and MR data of the head, lungs, and prostate, using various similarity measures and transformation models. The results indicate that ASGD is robust to these variations in the registration framework and is less sensitive to the settings of the user-defined parameters than RM. The main disadvantage of RM is the need for a predetermined step size function. The ASGD method provides a solution for that issue

Deep Learning-Based Grading of Ductal Carcinoma In Situ in Breast Histopathology Images

Ductal carcinoma in situ (DCIS) is a non-invasive breast cancer that can progress into invasive ductal carcinoma (IDC). Studies suggest DCIS is often overtreated since a considerable part of DCIS lesions may never progress into IDC. Lower grade lesions have a lower progression speed and risk, possibly allowing treatment de-escalation. However, studies show significant inter-observer variation in DCIS grading. Automated image analysis may provide an objective solution to address high subjectivity of DCIS grading by pathologists. In this study, we developed a deep learning-based DCIS grading system. It was developed using the consensus DCIS grade of three expert observers on a dataset of 1186 DCIS lesions from 59 patients. The inter-observer agreement, measured by quadratic weighted Cohen's kappa, was used to evaluate the system and compare its performance to that of expert observers. We present an analysis of the lesion-level and patient-level inter-observer agreement on an independent test set of 1001 lesions from 50 patients. The deep learning system (dl) achieved on average slightly higher inter-observer agreement to the observers (o1, o2 and o3) ($\kappa_{o1,dl}=0.81, \kappa_{o2,dl}=0.53, \kappa_{o3,dl}=0.40$) than the observers amongst each other ($\kappa_{o1,o2}=0.58, \kappa_{o1,o3}=0.50, \kappa_{o2,o3}=0.42$) at the lesion-level. At the patient-level, the deep learning system achieved similar agreement to the observers ($\kappa_{o1,dl}=0.77, \kappa_{o2,dl}=0.75, \kappa_{o3,dl}=0.70$) as the observers amongst each other ($\kappa_{o1,o2}=0.77, \kappa_{o1,o3}=0.75, \kappa_{o2,o3}=0.72$). In conclusion, we developed a deep learning-based DCIS grading system that achieved a performance similar to expert observers. We believe this is the first automated system that could assist pathologists by providing robust and reproducible second opinions on DCIS grade