PathSegDiff: Pathology Segmentation using Diffusion model representations

Image segmentation is crucial in many computational pathology pipelines, including accurate disease diagnosis, subtyping, outcome, and survivability prediction. The common approach for training a segmentation model relies on a pre-trained feature extractor and a dataset of paired image and mask annotations. These are used to train a lightweight prediction model that translates features into per-pixel classes. The choice of the feature extractor is central to the performance of the final segmentation model, and recent literature has focused on finding tasks to pre-train the feature extractor. In this paper, we propose PathSegDiff, a novel approach for histopathology image segmentation that leverages Latent Diffusion Models (LDMs) as pre-trained featured extractors. Our method utilizes a pathology-specific LDM, guided by a self-supervised encoder, to extract rich semantic information from H\&E stained histopathology images. We employ a simple, fully convolutional network to process the features extracted from the LDM and generate segmentation masks. Our experiments demonstrate significant improvements over traditional methods on the BCSS and GlaS datasets, highlighting the effectiveness of domain-specific diffusion pre-training in capturing intricate tissue structures and enhancing segmentation accuracy in histopathology images.

Pathology Image Compression with Pre-trained Autoencoders

The growing volume of high-resolution Whole Slide Images in digital histopathology poses significant storage, transmission, and computational efficiency challenges. Standard compression methods, such as JPEG, reduce file sizes but often fail to preserve fine-grained phenotypic details critical for downstream tasks. In this work, we repurpose autoencoders (AEs) designed for Latent Diffusion Models as an efficient learned compression framework for pathology images. We systematically benchmark three AE models with varying compression levels and evaluate their reconstruction ability using pathology foundation models. We introduce a fine-tuning strategy to further enhance reconstruction fidelity that optimizes a pathology-specific learned perceptual metric. We validate our approach on downstream tasks, including segmentation, patch classification, and multiple instance learning, showing that replacing images with AE-compressed reconstructions leads to minimal performance degradation. Additionally, we propose a K-means clustering-based quantization method for AE latents, improving storage efficiency while maintaining reconstruction quality. We provide the weights of the fine-tuned autoencoders at https://huggingface.co/collections/StonyBrook-CVLab/pathology-fine-tuned-aes-67d45f223a659ff2e3402dd0.

Gen-SIS: Generative Self-augmentation Improves Self-supervised Learning

Self-supervised learning (SSL) methods have emerged as strong visual representation learners by training an image encoder to maximize similarity between features of different views of the same image. To perform this view-invariance task, current SSL algorithms rely on hand-crafted augmentations such as random cropping and color jittering to create multiple views of an image. Recently, generative diffusion models have been shown to improve SSL by providing a wider range of data augmentations. However, these diffusion models require pre-training on large-scale image-text datasets, which might not be available for many specialized domains like histopathology. In this work, we introduce Gen-SIS, a diffusion-based augmentation technique trained exclusively on unlabeled image data, eliminating any reliance on external sources of supervision such as text captions. We first train an initial SSL encoder on a dataset using only hand-crafted augmentations. We then train a diffusion model conditioned on embeddings from that SSL encoder. Following training, given an embedding of the source image, this diffusion model can synthesize its diverse views. We show that these `self-augmentations', i.e. generative augmentations based on the vanilla SSL encoder embeddings, facilitate the training of a stronger SSL encoder. Furthermore, based on the ability to interpolate between images in the encoder latent space, we introduce the novel pretext task of disentangling the two source images of an interpolated synthetic image. We validate Gen-SIS's effectiveness by demonstrating performance improvements across various downstream tasks in both natural images, which are generally object-centric, as well as digital histopathology images, which are typically context-based.

ZoomLDM: Latent Diffusion Model for multi-scale image generation

Diffusion models have revolutionized image generation, yet several challenges restrict their application to large-image domains, such as digital pathology and satellite imagery. Given that it is infeasible to directly train a model on 'whole' images from domains with potential gigapixel sizes, diffusion-based generative methods have focused on synthesizing small, fixed-size patches extracted from these images. However, generating small patches has limited applicability since patch-based models fail to capture the global structures and wider context of large images, which can be crucial for synthesizing (semantically) accurate samples. In this paper, to overcome this limitation, we present ZoomLDM, a diffusion model tailored for generating images across multiple scales. Central to our approach is a novel magnification-aware conditioning mechanism that utilizes self-supervised learning (SSL) embeddings and allows the diffusion model to synthesize images at different 'zoom' levels, i.e., fixed-size patches extracted from large images at varying scales. ZoomLDM achieves state-of-the-art image generation quality across all scales, excelling particularly in the data-scarce setting of generating thumbnails of entire large images. The multi-scale nature of ZoomLDM unlocks additional capabilities in large image generation, enabling computationally tractable and globally coherent image synthesis up to $4096 \times 4096$ pixels and $4\times$ super-resolution. Additionally, multi-scale features extracted from ZoomLDM are highly effective in multiple instance learning experiments. We provide high-resolution examples of the generated images on our website https://histodiffusion.github.io/docs/publications/zoomldm/.

Fast constrained sampling in pre-trained diffusion models

Diffusion models have dominated the field of large, generative image models, with the prime examples of Stable Diffusion and DALL-E 3 being widely adopted. These models have been trained to perform text-conditioned generation on vast numbers of image-caption pairs and as a byproduct, have acquired general knowledge about natural image statistics. However, when confronted with the task of constrained sampling, e.g. generating the right half of an image conditioned on the known left half, applying these models is a delicate and slow process, with previously proposed algorithms relying on expensive iterative operations that are usually orders of magnitude slower than text-based inference. This is counter-intuitive, as image-conditioned generation should rely less on the difficult-to-learn semantic knowledge that links captions and imagery, and should instead be achievable by lower-level correlations among image pixels. In practice, inverse models are trained or tuned separately for each inverse problem, e.g. by providing parts of images during training as an additional condition, to allow their application in realistic settings. However, we argue that this is not necessary and propose an algorithm for fast-constrained sampling in large pre-trained diffusion models (Stable Diffusion) that requires no expensive backpropagation operations through the model and produces results comparable even to the state-of-the-art \emph{tuned} models. Our method is based on a novel optimization perspective to sampling under constraints and employs a numerical approximation to the expensive gradients, previously computed using backpropagation, incurring significant speed-ups.

$\infty$-Brush: Controllable Large Image Synthesis with Diffusion Models in Infinite Dimensions

Synthesizing high-resolution images from intricate, domain-specific information remains a significant challenge in generative modeling, particularly for applications in large-image domains such as digital histopathology and remote sensing. Existing methods face critical limitations: conditional diffusion models in pixel or latent space cannot exceed the resolution on which they were trained without losing fidelity, and computational demands increase significantly for larger image sizes. Patch-based methods offer computational efficiency but fail to capture long-range spatial relationships due to their overreliance on local information. In this paper, we introduce a novel conditional diffusion model in infinite dimensions, $\infty$-Brush for controllable large image synthesis. We propose a cross-attention neural operator to enable conditioning in function space. Our model overcomes the constraints of traditional finite-dimensional diffusion models and patch-based methods, offering scalability and superior capability in preserving global image structures while maintaining fine details. To our best knowledge, $\infty$-Brush is the first conditional diffusion model in function space, that can controllably synthesize images at arbitrary resolutions of up to $4096\times4096$ pixels. The code is available at https://github.com/cvlab-stonybrook/infinity-brush.

Diffusion-Refined VQA Annotations for Semi-Supervised Gaze Following

Training gaze following models requires a large number of images with gaze target coordinates annotated by human annotators, which is a laborious and inherently ambiguous process. We propose the first semi-supervised method for gaze following by introducing two novel priors to the task. We obtain the first prior using a large pretrained Visual Question Answering (VQA) model, where we compute Grad-CAM heatmaps by `prompting' the VQA model with a gaze following question. These heatmaps can be noisy and not suited for use in training. The need to refine these noisy annotations leads us to incorporate a second prior. We utilize a diffusion model trained on limited human annotations and modify the reverse sampling process to refine the Grad-CAM heatmaps. By tuning the diffusion process we achieve a trade-off between the human annotation prior and the VQA heatmap prior, which retains the useful VQA prior information while exhibiting similar properties to the training data distribution. Our method outperforms simple pseudo-annotation generation baselines on the GazeFollow image dataset. More importantly, our pseudo-annotation strategy, applied to a widely used supervised gaze following model (VAT), reduces the annotation need by 50%. Our method also performs the best on the VideoAttentionTarget dataset.

Learned representation-guided diffusion models for large-image generation

To synthesize high-fidelity samples, diffusion models typically require auxiliary data to guide the generation process. However, it is impractical to procure the painstaking patch-level annotation effort required in specialized domains like histopathology and satellite imagery; it is often performed by domain experts and involves hundreds of millions of patches. Modern-day self-supervised learning (SSL) representations encode rich semantic and visual information. In this paper, we posit that such representations are expressive enough to act as proxies to fine-grained human labels. We introduce a novel approach that trains diffusion models conditioned on embeddings from SSL. Our diffusion models successfully project these features back to high-quality histopathology and remote sensing images. In addition, we construct larger images by assembling spatially consistent patches inferred from SSL embeddings, preserving long-range dependencies. Augmenting real data by generating variations of real images improves downstream classifier accuracy for patch-level and larger, image-scale classification tasks. Our models are effective even on datasets not encountered during training, demonstrating their robustness and generalizability. Generating images from learned embeddings is agnostic to the source of the embeddings. The SSL embeddings used to generate a large image can either be extracted from a reference image, or sampled from an auxiliary model conditioned on any related modality (e.g. class labels, text, genomic data). As proof of concept, we introduce the text-to-large image synthesis paradigm where we successfully synthesize large pathology and satellite images out of text descriptions.

PathLDM: Text conditioned Latent Diffusion Model for Histopathology

To achieve high-quality results, diffusion models must be trained on large datasets. This can be notably prohibitive for models in specialized domains, such as computational pathology. Conditioning on labeled data is known to help in data-efficient model training. Therefore, histopathology reports, which are rich in valuable clinical information, are an ideal choice as guidance for a histopathology generative model. In this paper, we introduce PathLDM, the first text-conditioned Latent Diffusion Model tailored for generating high-quality histopathology images. Leveraging the rich contextual information provided by pathology text reports, our approach fuses image and textual data to enhance the generation process. By utilizing GPT's capabilities to distill and summarize complex text reports, we establish an effective conditioning mechanism. Through strategic conditioning and necessary architectural enhancements, we achieved a SoTA FID score of 7.64 for text-to-image generation on the TCGA-BRCA dataset, significantly outperforming the closest text-conditioned competitor with FID 30.1.

Conditional Generation from Unconditional Diffusion Models using Denoiser Representations

Denoising diffusion models have gained popularity as a generative modeling technique for producing high-quality and diverse images. Applying these models to downstream tasks requires conditioning, which can take the form of text, class labels, or other forms of guidance. However, providing conditioning information to these models can be challenging, particularly when annotations are scarce or imprecise. In this paper, we propose adapting pre-trained unconditional diffusion models to new conditions using the learned internal representations of the denoiser network. We demonstrate the effectiveness of our approach on various conditional generation tasks, including attribute-conditioned generation and mask-conditioned generation. Additionally, we show that augmenting the Tiny ImageNet training set with synthetic images generated by our approach improves the classification accuracy of ResNet baselines by up to 8%. Our approach provides a powerful and flexible way to adapt diffusion models to new conditions and generate high-quality augmented data for various conditional generation tasks.