Precise Location Matching Improves Dense Contrastive Learning in Digital Pathology

Dense prediction tasks such as segmentation and detection of pathological entities hold crucial clinical value in the digital pathology workflow. However, obtaining dense annotations on large cohorts is usually tedious and expensive. Contrastive learning (CL) is thus often employed to leverage large volumes of unlabeled data to pre-train the backbone network. To boost CL for dense prediction, some studies have proposed variations of dense matching objectives in pre-training. However, our analysis shows that employing existing dense matching strategies on histopathology images enforces invariance among incorrect pairs of dense features and, thus, is imprecise. To address this, we propose a precise location-based matching mechanism that utilizes the overlapping information between geometric transformations to precisely match regions in two augmentations. Extensive experiments on two pretraining datasets (TCGA-BRCA, NCT-CRC-HE) and three downstream datasets (GlaS, CRAG, BCSS) highlight the superiority of our method in semantic and instance segmentation tasks. Our method outperforms previous dense matching methods by up to 7.2 % in average precision for detection and 5.6 % in average precision for instance segmentation tasks. Additionally, by using our matching mechanism in the three popular contrastive learning frameworks, MoCo-v2, VICRegL and ConCL, the average precision in detection is improved by 0.7 % to 5.2 % and the average precision in segmentation is improved by 0.7 % to 4.0 %, demonstrating its generalizability.

Patch-level Gaze Distribution Prediction for Gaze Following

Gaze following aims to predict where a person is looking in a scene, by predicting the target location, or indicating that the target is located outside the image. Recent works detect the gaze target by training a heatmap regression task with a pixel-wise mean-square error (MSE) loss, while formulating the in/out prediction task as a binary classification task. This training formulation puts a strict, pixel-level constraint in higher resolution on the single annotation available in training, and does not consider annotation variance and the correlation between the two subtasks. To address these issues, we introduce the patch distribution prediction (PDP) method. We replace the in/out prediction branch in previous models with the PDP branch, by predicting a patch-level gaze distribution that also considers the outside cases. Experiments show that our model regularizes the MSE loss by predicting better heatmap distributions on images with larger annotation variances, meanwhile bridging the gap between the target prediction and in/out prediction subtasks, showing a significant improvement in performance on both subtasks on public gaze following datasets.

Taking a Respite from Representation Learning for Molecular Property Prediction

Artificial intelligence (AI) has been widely applied in drug discovery with a major task as molecular property prediction. Despite the boom of AI techniques in molecular representation learning, some key aspects underlying molecular property prediction haven't been carefully examined yet. In this study, we conducted a systematic comparison on three representative models, random forest, MolBERT and GROVER, which utilize three major molecular representations, extended-connectivity fingerprints, SMILES strings and molecular graphs, respectively. Notably, MolBERT and GROVER, are pretrained on large-scale unlabelled molecule corpuses in a self-supervised manner. In addition to the commonly used MoleculeNet benchmark datasets, we also assembled a suite of opioids-related datasets for downstream prediction evaluation. We first conducted dataset profiling on label distribution and structural analyses; we also examined the activity cliffs issue in the opioids-related datasets. Then, we trained 4,320 predictive models and evaluated the usefulness of the learned representations. Furthermore, we explored into the model evaluation by studying the effect of statistical tests, evaluation metrics and task settings. Finally, we dissected the chemical space generalization into inter-scaffold and intra-scaffold generalization and measured prediction performance to evaluate model generalizbility under both settings. By taking this respite, we reflected on the key aspects underlying molecular property prediction, the awareness of which can, hopefully, bring better AI techniques in this field.

Gigapixel Whole-Slide Images Classification using Locally Supervised Learning

Histopathology whole slide images (WSIs) play a very important role in clinical studies and serve as the gold standard for many cancer diagnoses. However, generating automatic tools for processing WSIs is challenging due to their enormous sizes. Currently, to deal with this issue, conventional methods rely on a multiple instance learning (MIL) strategy to process a WSI at patch level. Although effective, such methods are computationally expensive, because tiling a WSI into patches takes time and does not explore the spatial relations between these tiles. To tackle these limitations, we propose a locally supervised learning framework which processes the entire slide by exploring the entire local and global information that it contains. This framework divides a pre-trained network into several modules and optimizes each module locally using an auxiliary model. We also introduce a random feature reconstruction unit (RFR) to preserve distinguishing features during training and improve the performance of our method by 1% to 3%. Extensive experiments on three publicly available WSI datasets: TCGA-NSCLC, TCGA-RCC and LKS, highlight the superiority of our method on different classification tasks. Our method outperforms the state-of-the-art MIL methods by 2% to 5% in accuracy, while being 7 to 10 times faster. Additionally, when dividing it into eight modules, our method requires as little as 20% of the total gpu memory required by end-to-end training. Our code is available at https://github.com/cvlab-stonybrook/local_learning_wsi.

Target-absent Human Attention

The prediction of human gaze behavior is important for building human-computer interactive systems that can anticipate a user's attention. Computer vision models have been developed to predict the fixations made by people as they search for target objects. But what about when the image has no target? Equally important is to know how people search when they cannot find a target, and when they would stop searching. In this paper, we propose the first data-driven computational model that addresses the search-termination problem and predicts the scanpath of search fixations made by people searching for targets that do not appear in images. We model visual search as an imitation learning problem and represent the internal knowledge that the viewer acquires through fixations using a novel state representation that we call Foveated Feature Maps (FFMs). FFMs integrate a simulated foveated retina into a pretrained ConvNet that produces an in-network feature pyramid, all with minimal computational overhead. Our method integrates FFMs as the state representation in inverse reinforcement learning. Experimentally, we improve the state of the art in predicting human target-absent search behavior on the COCO-Search18 dataset

Diffusion models as plug-and-play priors

We consider the problem of inferring high-dimensional data $\mathbf{x}$ in a model that consists of a prior $p(\mathbf{x})$ and an auxiliary constraint $c(\mathbf{x},\mathbf{y})$. In this paper, the prior is an independently trained denoising diffusion generative model. The auxiliary constraint is expected to have a differentiable form, but can come from diverse sources. The possibility of such inference turns diffusion models into plug-and-play modules, thereby allowing a range of potential applications in adapting models to new domains and tasks, such as conditional generation or image segmentation. The structure of diffusion models allows us to perform approximate inference by iterating differentiation through the fixed denoising network enriched with different amounts of noise at each step. Considering many noised versions of $\mathbf{x}$ in evaluation of its fitness is a novel search mechanism that may lead to new algorithms for solving combinatorial optimization problems.

Learning Probabilistic Structural Representation for Biomedical Image Segmentation

Accurate segmentation of various fine-scale structures from biomedical images is a very important yet challenging problem. Existing methods use topological information as an additional training loss, but are ultimately learning a pixel-wise representation. In this paper, we propose the first deep learning method to learn a structural representation. We use discrete Morse theory and persistent homology to construct an one-parameter family of structures as the structural representation space. Furthermore, we learn a probabilistic model that can do inference tasks on such a structural representation space. We empirically demonstrate the strength of our method, i.e., generating true structures rather than pixel-maps with better topological integrity, and facilitating a human-in-the-loop annotation pipeline using the sampling of structures and structure-aware uncertainty.

A Novel Framework for Characterization of Tumor-Immune Spatial Relationships in Tumor Microenvironment

Understanding the impact of tumor biology on the composition of nearby cells often requires characterizing the impact of biologically distinct tumor regions. Biomarkers have been developed to label biologically distinct tumor regions, but challenges arise because of differences in the spatial extent and distribution of differentially labeled regions. In this work, we present a framework for systematically investigating the impact of distinct tumor regions on cells near the tumor borders, accounting their cross spatial distributions. We apply the framework to multiplex immunohistochemistry (mIHC) studies of pancreatic cancer and show its efficacy in demonstrating how biologically different tumor regions impact the immune response in the tumor microenvironment. Furthermore, we show that the proposed framework can be extended to largescale whole slide image analysis.