Generating Seamless Virtual Immunohistochemical Whole Slide Images with Content and Color Consistency

Immunohistochemical (IHC) stains play a vital role in a pathologist's analysis of medical images, providing crucial diagnostic information for various diseases. Virtual staining from hematoxylin and eosin (H&E)-stained whole slide images (WSIs) allows the automatic production of other useful IHC stains without the expensive physical staining process. However, current virtual WSI generation methods based on tile-wise processing often suffer from inconsistencies in content, texture, and color at tile boundaries. These inconsistencies lead to artifacts that compromise image quality and potentially hinder accurate clinical assessment and diagnoses. To address this limitation, we propose a novel consistent WSI synthesis network, CC-WSI-Net, that extends GAN models to produce seamless synthetic whole slide images. Our CC-WSI-Net integrates a content- and color-consistency supervisor, ensuring consistency across tiles and facilitating the generation of seamless synthetic WSIs while ensuring Sox10 immunohistochemistry accuracy in melanocyte detection. We validate our method through extensive image-quality analyses, objective detection assessments, and a subjective survey with pathologists. By generating high-quality synthetic WSIs, our method opens doors for advanced virtual staining techniques with broader applications in research and clinical care.

Bayesian Intrinsic Groupwise Image Registration: Unsupervised Disentanglement of Anatomy and Geometry

This article presents a general Bayesian learning framework for multi-modal groupwise registration on medical images. The method builds on probabilistic modelling of the image generative process, where the underlying common anatomy and geometric variations of the observed images are explicitly disentangled as latent variables. Thus, groupwise registration is achieved through the solution to Bayesian inference. We propose a novel hierarchical variational auto-encoding architecture to realize the inference procedure of the latent variables, where the registration parameters can be calculated in a mathematically interpretable fashion. Remarkably, this new paradigm can learn groupwise registration in an unsupervised closed-loop self-reconstruction process, sparing the burden of designing complex intensity-based similarity measures. The computationally efficient disentangled architecture is also inherently scalable and flexible, allowing for groupwise registration on large-scale image groups with variable sizes. Furthermore, the inferred structural representations from disentanglement learning are capable of capturing the latent anatomy of the observations with visual semantics. Extensive experiments were conducted to validate the proposed framework, including four datasets from cardiac, brain and abdominal medical images. The results have demonstrated the superiority of our method over conventional similarity-based approaches in terms of accuracy, efficiency, scalability and interpretability.

Quilt-LLaVA: Visual Instruction Tuning by Extracting Localized Narratives from Open-Source Histopathology Videos

The gigapixel scale of whole slide images (WSIs) poses a challenge for histopathology multi-modal chatbots, requiring a global WSI analysis for diagnosis, compounding evidence from different WSI patches. Current visual instruction datasets, generated through large language models, focus on creating question/answer pairs for individual image patches, which may lack diagnostic capacity on their own in histopathology, further complicated by the absence of spatial grounding in histopathology image captions. To bridge this gap, we introduce Quilt-Instruct, a large-scale dataset of 107,131 histopathology-specific instruction question/answer pairs, that is collected by leveraging educational histopathology videos from YouTube, which provides spatial localization of captions by automatically extracting narrators' cursor movements. In addition, we provide contextual reasoning by extracting diagnosis and supporting facts from the entire video content to guide the extrapolative reasoning of GPT-4. Using Quilt-Instruct, we train Quilt-LLaVA, which can reason beyond the given single image patch, enabling diagnostic reasoning and the capability of spatial awareness. To evaluate Quilt-LLaVA, we propose a comprehensive evaluation dataset created from 985 images and 1283 human-generated question-answers. We also thoroughly evaluate Quilt-LLaVA using public histopathology datasets, where Quilt-LLaVA significantly outperforms SOTA by over 10% on relative GPT-4 score and 4% and 9% on open and closed set VQA. Our code, data, and model are publicly available at quilt-llava.github.io.

Quilt-1M: One Million Image-Text Pairs for Histopathology

Recent accelerations in multi-modal applications have been made possible with the plethora of image and text data available online. However, the scarcity of analogous data in the medical field, specifically in histopathology, has halted comparable progress. To enable similar representation learning for histopathology, we turn to YouTube, an untapped resource of videos, offering $1,087$ hours of valuable educational histopathology videos from expert clinicians. From YouTube, we curate Quilt: a large-scale vision-language dataset consisting of $768,826$ image and text pairs. Quilt was automatically curated using a mixture of models, including large language models, handcrafted algorithms, human knowledge databases, and automatic speech recognition. In comparison, the most comprehensive datasets curated for histopathology amass only around $200$K samples. We combine Quilt with datasets from other sources, including Twitter, research papers, and the internet in general, to create an even larger dataset: Quilt-1M, with $1$M paired image-text samples, marking it as the largest vision-language histopathology dataset to date. We demonstrate the value of Quilt-1M by fine-tuning a pre-trained CLIP model. Our model outperforms state-of-the-art models on both zero-shot and linear probing tasks for classifying new histopathology images across $13$ diverse patch-level datasets of $8$ different sub-pathologies and cross-modal retrieval tasks.

Multi-modal Masked Autoencoders Learn Compositional Histopathological Representations

Self-supervised learning (SSL) enables learning useful inductive biases through utilizing pretext tasks that require no labels. The unlabeled nature of SSL makes it especially important for whole slide histopathological images (WSIs), where patch-level human annotation is difficult. Masked Autoencoders (MAE) is a recent SSL method suitable for digital pathology as it does not require negative sampling and requires little to no data augmentations. However, the domain shift between natural images and digital pathology images requires further research in designing MAE for patch-level WSIs. In this paper, we investigate several design choices for MAE in histopathology. Furthermore, we introduce a multi-modal MAE (MMAE) that leverages the specific compositionality of Hematoxylin & Eosin (H&E) stained WSIs. We performed our experiments on the public patch-level dataset NCT-CRC-HE-100K. The results show that the MMAE architecture outperforms supervised baselines and other state-of-the-art SSL techniques for an eight-class tissue phenotyping task, utilizing only 100 labeled samples for fine-tuning. Our code is available at https://github.com/wisdomikezogwo/MMAE_Pathology

Brain-Aware Replacements for Supervised Contrastive Learning

We propose a novel framework for Alzheimer's disease (AD) detection using brain MRIs. The framework starts with a data augmentation method called Brain-Aware Replacements (BAR), which leverages a standard brain parcellation to replace medically-relevant 3D brain regions in an anchor MRI from a randomly picked MRI to create synthetic samples. Ground truth "hard" labels are also linearly mixed depending on the replacement ratio in order to create "soft" labels. BAR produces a great variety of realistic-looking synthetic MRIs with higher local variability compared to other mix-based methods, such as CutMix. On top of BAR, we propose using a soft-label-capable supervised contrastive loss, aiming to learn the relative similarity of representations that reflect how mixed are the synthetic MRIs using our soft labels. This way, we do not fully exhaust the entropic capacity of our hard labels, since we only use them to create soft labels and synthetic MRIs through BAR. We show that a model pre-trained using our framework can be further fine-tuned with a cross-entropy loss using the hard labels that were used to create the synthetic samples. We validated the performance of our framework in a binary AD detection task against both from-scratch supervised training and state-of-the-art self-supervised training plus fine-tuning approaches. Then we evaluated BAR's individual performance compared to another mix-based method CutMix by integrating it within our framework. We show that our framework yields superior results in both precision and recall for the AD detection task.

Learning Oculomotor Behaviors from Scanpath

Identifying oculomotor behaviors relevant for eye-tracking applications is a critical but often challenging task. Aiming to automatically learn and extract knowledge from existing eye-tracking data, we develop a novel method that creates rich representations of oculomotor scanpaths to facilitate the learning of downstream tasks. The proposed stimulus-agnostic Oculomotor Behavior Framework (OBF) model learns human oculomotor behaviors from unsupervised and semi-supervised tasks, including reconstruction, predictive coding, fixation identification, and contrastive learning tasks. The resultant pre-trained OBF model can be used in a variety of applications. Our pre-trained model outperforms baseline approaches and traditional scanpath methods in autism spectrum disorder and viewed-stimulus classification tasks. Ablation experiments further show our proposed method could achieve even better results with larger model sizes and more diverse eye-tracking training datasets, supporting the model's potential for future eye-tracking applications. Open source code: http://github.com/BeibinLi/OBF.

Semi-supervised Synthesis of High-Resolution Editable Textures for 3D Humans

We introduce a novel approach to generate diverse high fidelity texture maps for 3D human meshes in a semi-supervised setup. Given a segmentation mask defining the layout of the semantic regions in the texture map, our network generates high-resolution textures with a variety of styles, that are then used for rendering purposes. To accomplish this task, we propose a Region-adaptive Adversarial Variational AutoEncoder (ReAVAE) that learns the probability distribution of the style of each region individually so that the style of the generated texture can be controlled by sampling from the region-specific distributions. In addition, we introduce a data generation technique to augment our training set with data lifted from single-view RGB inputs. Our training strategy allows the mixing of reference image styles with arbitrary styles for different regions, a property which can be valuable for virtual try-on AR/VR applications. Experimental results show that our method synthesizes better texture maps compared to prior work while enabling independent layout and style controllability.

HATNet: An End-to-End Holistic Attention Network for Diagnosis of Breast Biopsy Images

Training end-to-end networks for classifying gigapixel size histopathological images is computationally intractable. Most approaches are patch-based and first learn local representations (patch-wise) before combining these local representations to produce image-level decisions. However, dividing large tissue structures into patches limits the context available to these networks, which may reduce their ability to learn representations from clinically relevant structures. In this paper, we introduce a novel attention-based network, the Holistic ATtention Network (HATNet) to classify breast biopsy images. We streamline the histopathological image classification pipeline and show how to learn representations from gigapixel size images end-to-end. HATNet extends the bag-of-words approach and uses self-attention to encode global information, allowing it to learn representations from clinically relevant tissue structures without any explicit supervision. It outperforms the previous best network Y-Net, which uses supervision in the form of tissue-level segmentation masks, by 8%. Importantly, our analysis reveals that HATNet learns representations from clinically relevant structures, and it matches the classification accuracy of human pathologists for this challenging test set. Our source code is available at \url{https://github.com/sacmehta/HATNet}

Personalized Face Modeling for Improved Face Reconstruction and Motion Retargeting

Traditional methods for image-based 3D face reconstruction and facial motion retargeting fit a 3D morphable model (3DMM) to the face, which has limited modeling capacity and fail to generalize well to in-the-wild data. Use of deformation transfer or multilinear tensor as a personalized 3DMM for blendshape interpolation does not address the fact that facial expressions result in different local and global skin deformations in different persons. Moreover, existing methods learn a single albedo per user which is not enough to capture the expression-specific skin reflectance variations. We propose an end-to-end framework that jointly learns a personalized face model per user and per-frame facial motion parameters from a large corpus of in-the-wild videos of user expressions. Specifically, we learn user-specific expression blendshapes and dynamic (expression-specific) albedo maps by predicting personalized corrections on top of a 3DMM prior. We introduce novel constraints to ensure that the corrected blendshapes retain their semantic meanings and the reconstructed geometry is disentangled from the albedo. Experimental results show that our personalization accurately captures fine-grained facial dynamics in a wide range of conditions and efficiently decouples the learned face model from facial motion, resulting in more accurate face reconstruction and facial motion retargeting compared to state-of-the-art methods.