Heteroscedastic Uncertainty Estimation for Probabilistic Unsupervised Registration of Noisy Medical Images

This paper proposes a heteroscedastic uncertainty estimation framework for unsupervised medical image registration. Existing methods rely on objectives (e.g. mean-squared error) that assume a uniform noise level across the image, disregarding the heteroscedastic and input-dependent characteristics of noise distribution in real-world medical images. This further introduces noisy gradients due to undesired penalization on outliers, causing unnatural deformation and performance degradation. To mitigate this, we propose an adaptive weighting scheme with a relative $\gamma$-exponentiated signal-to-noise ratio (SNR) for the displacement estimator after modeling the heteroscedastic noise using a separate variance estimator to prevent the model from being driven away by spurious gradients from error residuals, leading to more accurate displacement estimation. To illustrate the versatility and effectiveness of the proposed method, we tested our framework on two representative registration architectures across three medical image datasets. Our proposed framework consistently outperforms other baselines both quantitatively and qualitatively while also providing accurate and sensible uncertainty measures. Paired t-tests show that our improvements in registration accuracy are statistically significant. The code will be publicly available at \url{https://voldemort108x.github.io/hetero_uncertainty/}.

An Adaptive Correspondence Scoring Framework for Unsupervised Image Registration of Medical Images

We propose an adaptive training scheme for unsupervised medical image registration. Existing methods rely on image reconstruction as the primary supervision signal. However, nuisance variables (e.g. noise and covisibility) often cause the loss of correspondence between medical images, violating the Lambertian assumption in physical waves (e.g. ultrasound) and consistent imaging acquisition. As the unsupervised learning scheme relies on intensity constancy to establish correspondence between images for reconstruction, this introduces spurious error residuals that are not modeled by the typical training objective. To mitigate this, we propose an adaptive framework that re-weights the error residuals with a correspondence scoring map during training, preventing the parametric displacement estimator from drifting away due to noisy gradients, which leads to performance degradations. To illustrate the versatility and effectiveness of our method, we tested our framework on three representative registration architectures across three medical image datasets along with other baselines. Our proposed adaptive framework consistently outperforms other methods both quantitatively and qualitatively. Paired t-tests show that our improvements are statistically significant. The code will be publicly available at \url{https://voldemort108x.github.io/AdaCS/}.

Rethinking Semi-Supervised Medical Image Segmentation: A Variance-Reduction Perspective

For medical image segmentation, contrastive learning is the dominant practice to improve the quality of visual representations by contrasting semantically similar and dissimilar pairs of samples. This is enabled by the observation that without accessing ground truth label, negative examples with truly dissimilar anatomical features, if sampled, can significantly improve the performance. In reality, however, these samples may come from similar anatomical features and the models may struggle to distinguish the minority tail-class samples, making the tail classes more prone to misclassification, both of which typically lead to model collapse. In this paper, we propose ARCO, a semi-supervised contrastive learning (CL) framework with stratified group sampling theory in medical image segmentation. In particular, we first propose building ARCO through the concept of variance-reduced estimation, and show that certain variance-reduction techniques are particularly beneficial in medical image segmentation tasks with extremely limited labels. Furthermore, we theoretically prove these sampling techniques are universal in variance reduction. Finally, we experimentally validate our approaches on three benchmark datasets with different label settings, and our methods consistently outperform state-of-the-art semi- and fully-supervised methods. Additionally, we augment the CL frameworks with these sampling techniques and demonstrate significant gains over previous methods. We believe our work is an important step towards semi-supervised medical image segmentation by quantifying the limitation of current self-supervision objectives for accomplishing medical image analysis tasks.

Mine yOur owN Anatomy: Revisiting Medical Image Segmentation with Extremely Limited Labels

Recent studies on contrastive learning have achieved remarkable performance solely by leveraging few labels in the context of medical image segmentation. Existing methods mainly focus on instance discrimination and invariant mapping. However, they face three common pitfalls: (1) tailness: medical image data usually follows an implicit long-tail class distribution. Blindly leveraging all pixels in training hence can lead to the data imbalance issues, and cause deteriorated performance; (2) consistency: it remains unclear whether a segmentation model has learned meaningful and yet consistent anatomical features due to the intra-class variations between different anatomical features; and (3) diversity: the intra-slice correlations within the entire dataset have received significantly less attention. This motivates us to seek a principled approach for strategically making use of the dataset itself to discover similar yet distinct samples from different anatomical views. In this paper, we introduce a novel semi-supervised medical image segmentation framework termed Mine yOur owN Anatomy (MONA), and make three contributions. First, prior work argues that every pixel equally matters to the model training; we observe empirically that this alone is unlikely to define meaningful anatomical features, mainly due to lacking the supervision signal. We show two simple solutions towards learning invariances - through the use of stronger data augmentations and nearest neighbors. Second, we construct a set of objectives that encourage the model to be capable of decomposing medical images into a collection of anatomical features in an unsupervised manner. Lastly, our extensive results on three benchmark datasets with different labeled settings validate the effectiveness of our proposed MONA which achieves new state-of-the-art under different labeled settings.

Learning correspondences of cardiac motion from images using biomechanics-informed modeling

Learning spatial-temporal correspondences in cardiac motion from images is important for understanding the underlying dynamics of cardiac anatomical structures. Many methods explicitly impose smoothness constraints such as the $\mathcal{L}_2$ norm on the displacement vector field (DVF), while usually ignoring biomechanical feasibility in the transformation. Other geometric constraints either regularize specific regions of interest such as imposing incompressibility on the myocardium or introduce additional steps such as training a separate network-based regularizer on physically simulated datasets. In this work, we propose an explicit biomechanics-informed prior as regularization on the predicted DVF in modeling a more generic biomechanically plausible transformation within all cardiac structures without introducing additional training complexity. We validate our methods on two publicly available datasets in the context of 2D MRI data and perform extensive experiments to illustrate the effectiveness and robustness of our proposed methods compared to other competing regularization schemes. Our proposed methods better preserve biomechanical properties by visual assessment and show advantages in segmentation performance using quantitative evaluation metrics. The code is publicly available at \url{https://github.com/Voldemort108X/bioinformed_reg}.

Incremental Learning Meets Transfer Learning: Application to Multi-site Prostate MRI Segmentation

Many medical datasets have recently been created for medical image segmentation tasks, and it is natural to question whether we can use them to sequentially train a single model that (1) performs better on all these datasets, and (2) generalizes well and transfers better to the unknown target site domain. Prior works have achieved this goal by jointly training one model on multi-site datasets, which achieve competitive performance on average but such methods rely on the assumption about the availability of all training data, thus limiting its effectiveness in practical deployment. In this paper, we propose a novel multi-site segmentation framework called incremental-transfer learning (ITL), which learns a model from multi-site datasets in an end-to-end sequential fashion. Specifically, "incremental" refers to training sequentially constructed datasets, and "transfer" is achieved by leveraging useful information from the linear combination of embedding features on each dataset. In addition, we introduce our ITL framework, where we train the network including a site-agnostic encoder with pre-trained weights and at most two segmentation decoder heads. We also design a novel site-level incremental loss in order to generalize well on the target domain. Second, we show for the first time that leveraging our ITL training scheme is able to alleviate challenging catastrophic forgetting problems in incremental learning. We conduct experiments using five challenging benchmark datasets to validate the effectiveness of our incremental-transfer learning approach. Our approach makes minimal assumptions on computation resources and domain-specific expertise, and hence constitutes a strong starting point in multi-site medical image segmentation.

MyoPS: A Benchmark of Myocardial Pathology Segmentation Combining Three-Sequence Cardiac Magnetic Resonance Images

Assessment of myocardial viability is essential in diagnosis and treatment management of patients suffering from myocardial infarction, and classification of pathology on myocardium is the key to this assessment. This work defines a new task of medical image analysis, i.e., to perform myocardial pathology segmentation (MyoPS) combining three-sequence cardiac magnetic resonance (CMR) images, which was first proposed in the MyoPS challenge, in conjunction with MICCAI 2020. The challenge provided 45 paired and pre-aligned CMR images, allowing algorithms to combine the complementary information from the three CMR sequences for pathology segmentation. In this article, we provide details of the challenge, survey the works from fifteen participants and interpret their methods according to five aspects, i.e., preprocessing, data augmentation, learning strategy, model architecture and post-processing. In addition, we analyze the results with respect to different factors, in order to examine the key obstacles and explore potential of solutions, as well as to provide a benchmark for future research. We conclude that while promising results have been reported, the research is still in the early stage, and more in-depth exploration is needed before a successful application to the clinics. Note that MyoPS data and evaluation tool continue to be publicly available upon registration via its homepage (www.sdspeople.fudan.edu.cn/zhuangxiahai/0/myops20/).

Label-free virtual HER2 immunohistochemical staining of breast tissue using deep learning

The immunohistochemical (IHC) staining of the human epidermal growth factor receptor 2 (HER2) biomarker is widely practiced in breast tissue analysis, preclinical studies and diagnostic decisions, guiding cancer treatment and investigation of pathogenesis. HER2 staining demands laborious tissue treatment and chemical processing performed by a histotechnologist, which typically takes one day to prepare in a laboratory, increasing analysis time and associated costs. Here, we describe a deep learning-based virtual HER2 IHC staining method using a conditional generative adversarial network that is trained to rapidly transform autofluorescence microscopic images of unlabeled/label-free breast tissue sections into bright-field equivalent microscopic images, matching the standard HER2 IHC staining that is chemically performed on the same tissue sections. The efficacy of this virtual HER2 staining framework was demonstrated by quantitative analysis, in which three board-certified breast pathologists blindly graded the HER2 scores of virtually stained and immunohistochemically stained HER2 whole slide images (WSIs) to reveal that the HER2 scores determined by inspecting virtual IHC images are as accurate as their immunohistochemically stained counterparts. A second quantitative blinded study performed by the same diagnosticians further revealed that the virtually stained HER2 images exhibit a comparable staining quality in the level of nuclear detail, membrane clearness, and absence of staining artifacts with respect to their immunohistochemically stained counterparts. This virtual HER2 staining framework bypasses the costly, laborious, and time-consuming IHC staining procedures in laboratory, and can be extended to other types of biomarkers to accelerate the IHC tissue staining used in life sciences and biomedical workflow.

Fully Automated Left Atrium Segmentation from Anatomical Cine Long-axis MRI Sequences using Deep Convolutional Neural Network with Unscented Kalman Filter

This study proposes a fully automated approach for the left atrial segmentation from routine cine long-axis cardiac magnetic resonance image sequences using deep convolutional neural networks and Bayesian filtering. The proposed approach consists of a classification network that automatically detects the type of long-axis sequence and three different convolutional neural network models followed by unscented Kalman filtering (UKF) that delineates the left atrium. Instead of training and predicting all long-axis sequence types together, the proposed approach first identifies the image sequence type as to 2, 3 and 4 chamber views, and then performs prediction based on neural nets trained for that particular sequence type. The datasets were acquired retrospectively and ground truth manual segmentation was provided by an expert radiologist. In addition to neural net based classification and segmentation, another neural net is trained and utilized to select image sequences for further processing using UKF to impose temporal consistency over cardiac cycle. A cyclic dynamic model with time-varying angular frequency is introduced in UKF to characterize the variations in cardiac motion during image scanning. The proposed approach was trained and evaluated separately with varying amount of training data with images acquired from 20, 40, 60 and 80 patients. Evaluations over 1515 images with equal number of images from each chamber group acquired from an additional 20 patients demonstrated that the proposed model outperformed state-of-the-art and yielded a mean Dice coefficient value of 94.1%, 93.7% and 90.1% for 2, 3 and 4-chamber sequences, respectively, when trained with datasets from 80 patients.

Fully automated deep learning based segmentation of normal, infarcted and edema regions from multiple cardiac MRI sequences

Myocardial characterization is essential for patients with myocardial infarction and other myocardial diseases, and the assessment is often performed using cardiac magnetic resonance (CMR) sequences. In this study, we propose a fully automated approach using deep convolutional neural networks (CNN) for cardiac pathology segmentation, including left ventricular (LV) blood pool, right ventricular blood pool, LV normal myocardium, LV myocardial edema (ME) and LV myocardial scars (MS). The input to the network consists of three CMR sequences, namely, late gadolinium enhancement (LGE), T2 and balanced steady state free precession (bSSFP). The proposed approach utilized the data provided by the MyoPS challenge hosted by MICCAI 2020 in conjunction with STACOM. The training set for the CNN model consists of images acquired from 25 cases, and the gold standard labels are provided by trained raters and validated by radiologists. The proposed approach introduces a data augmentation module, linear encoder and decoder module and a network module to increase the number of training samples and improve the prediction accuracy for LV ME and MS. The proposed approach is evaluated by the challenge organizers with a test set including 20 cases and achieves a mean dice score of $46.8\%$ for LV MS and $55.7\%$ for LV ME+MS