Multimodal Whole Slide Foundation Model for Pathology

The field of computational pathology has been transformed with recent advances in foundation models that encode histopathology region-of-interests (ROIs) into versatile and transferable feature representations via self-supervised learning (SSL). However, translating these advancements to address complex clinical challenges at the patient and slide level remains constrained by limited clinical data in disease-specific cohorts, especially for rare clinical conditions. We propose TITAN, a multimodal whole slide foundation model pretrained using 335,645 WSIs via visual self-supervised learning and vision-language alignment with corresponding pathology reports and 423,122 synthetic captions generated from a multimodal generative AI copilot for pathology. Without any finetuning or requiring clinical labels, TITAN can extract general-purpose slide representations and generate pathology reports that generalize to resource-limited clinical scenarios such as rare disease retrieval and cancer prognosis. We evaluate TITAN on diverse clinical tasks and find that TITAN outperforms both ROI and slide foundation models across machine learning settings such as linear probing, few-shot and zero-shot classification, rare cancer retrieval and cross-modal retrieval, and pathology report generation.

Tree of Attributes Prompt Learning for Vision-Language Models

Prompt learning has proven effective in adapting vision language models for downstream tasks. However, existing methods usually append learnable prompt tokens solely with the category names to obtain textual features, which fails to fully leverage the rich context indicated in the category name. To address this issue, we propose the Tree of Attributes Prompt learning (TAP), which first instructs LLMs to generate a tree of attributes with a "concept - attribute - description" structure for each category, and then learn the hierarchy with vision and text prompt tokens. Unlike existing methods that merely augment category names with a set of unstructured descriptions, our approach essentially distills structured knowledge graphs associated with class names from LLMs. Furthermore, our approach introduces text and vision prompts designed to explicitly learn the corresponding visual attributes, effectively serving as domain experts. Additionally, the general and diverse descriptions generated based on the class names may be wrong or absent in the specific given images. To address this misalignment, we further introduce a vision-conditional pooling module to extract instance-specific text features. Extensive experimental results demonstrate that our approach outperforms state-of-the-art methods on the zero-shot base-to-novel generalization, cross-dataset transfer, as well as few-shot classification across 11 diverse datasets.

Morphological Prototyping for Unsupervised Slide Representation Learning in Computational Pathology

Representation learning of pathology whole-slide images (WSIs) has been has primarily relied on weak supervision with Multiple Instance Learning (MIL). However, the slide representations resulting from this approach are highly tailored to specific clinical tasks, which limits their expressivity and generalization, particularly in scenarios with limited data. Instead, we hypothesize that morphological redundancy in tissue can be leveraged to build a task-agnostic slide representation in an unsupervised fashion. To this end, we introduce PANTHER, a prototype-based approach rooted in the Gaussian mixture model that summarizes the set of WSI patches into a much smaller set of morphological prototypes. Specifically, each patch is assumed to have been generated from a mixture distribution, where each mixture component represents a morphological exemplar. Utilizing the estimated mixture parameters, we then construct a compact slide representation that can be readily used for a wide range of downstream tasks. By performing an extensive evaluation of PANTHER on subtyping and survival tasks using 13 datasets, we show that 1) PANTHER outperforms or is on par with supervised MIL baselines and 2) the analysis of morphological prototypes brings new qualitative and quantitative insights into model interpretability.

A Structure-Guided Gauss-Newton Method for Shallow ReLU Neural Network

In this paper, we propose a structure-guided Gauss-Newton (SgGN) method for solving least squares problems using a shallow ReLU neural network. The method effectively takes advantage of both the least squares structure and the neural network structure of the objective function. By categorizing the weights and biases of the hidden and output layers of the network as nonlinear and linear parameters, respectively, the method iterates back and forth between the nonlinear and linear parameters. The nonlinear parameters are updated by a damped Gauss-Newton method and the linear ones are updated by a linear solver. Moreover, at the Gauss-Newton step, a special form of the Gauss-Newton matrix is derived for the shallow ReLU neural network and is used for efficient iterations. It is shown that the corresponding mass and Gauss-Newton matrices in the respective linear and nonlinear steps are symmetric and positive definite under reasonable assumptions. Thus, the SgGN method naturally produces an effective search direction without the need of additional techniques like shifting in the Levenberg-Marquardt method to achieve invertibility of the Gauss-Newton matrix. The convergence and accuracy of the method are demonstrated numerically for several challenging function approximation problems, especially those with discontinuities or sharp transition layers that pose significant challenges for commonly used training algorithms in machine learning.

A Foundational Multimodal Vision Language AI Assistant for Human Pathology

The field of computational pathology has witnessed remarkable progress in the development of both task-specific predictive models and task-agnostic self-supervised vision encoders. However, despite the explosive growth of generative artificial intelligence (AI), there has been limited study on building general purpose, multimodal AI assistants tailored to pathology. Here we present PathChat, a vision-language generalist AI assistant for human pathology using an in-house developed foundational vision encoder pretrained on 100 million histology images from over 100,000 patient cases and 1.18 million pathology image-caption pairs. The vision encoder is then combined with a pretrained large language model and the whole system is finetuned on over 250,000 diverse disease agnostic visual language instructions. We compare PathChat against several multimodal vision language AI assistants as well as GPT4V, which powers the commercially available multimodal general purpose AI assistant ChatGPT-4. When relevant clinical context is provided with the histology image, PathChat achieved a diagnostic accuracy of 87% on multiple-choice questions based on publicly available cases of diverse tissue origins and disease models. Additionally, using open-ended questions and human expert evaluation, we found that overall PathChat produced more accurate and pathologist-preferable responses to diverse queries related to pathology. As an interactive and general vision language AI assistant that can flexibly handle both visual and natural language inputs, PathChat can potentially find impactful applications in pathology education, research, and human-in-the-loop clinical decision making.

A General-Purpose Self-Supervised Model for Computational Pathology

Tissue phenotyping is a fundamental computational pathology (CPath) task in learning objective characterizations of histopathologic biomarkers in anatomic pathology. However, whole-slide imaging (WSI) poses a complex computer vision problem in which the large-scale image resolutions of WSIs and the enormous diversity of morphological phenotypes preclude large-scale data annotation. Current efforts have proposed using pretrained image encoders with either transfer learning from natural image datasets or self-supervised pretraining on publicly-available histopathology datasets, but have not been extensively developed and evaluated across diverse tissue types at scale. We introduce UNI, a general-purpose self-supervised model for pathology, pretrained using over 100 million tissue patches from over 100,000 diagnostic haematoxylin and eosin-stained WSIs across 20 major tissue types, and evaluated on 33 representative CPath clinical tasks in CPath of varying diagnostic difficulties. In addition to outperforming previous state-of-the-art models, we demonstrate new modeling capabilities in CPath such as resolution-agnostic tissue classification, slide classification using few-shot class prototypes, and disease subtyping generalization in classifying up to 108 cancer types in the OncoTree code classification system. UNI advances unsupervised representation learning at scale in CPath in terms of both pretraining data and downstream evaluation, enabling data-efficient AI models that can generalize and transfer to a gamut of diagnostically-challenging tasks and clinical workflows in anatomic pathology.

Towards a Visual-Language Foundation Model for Computational Pathology

The accelerated adoption of digital pathology and advances in deep learning have enabled the development of powerful models for various pathology tasks across a diverse array of diseases and patient cohorts. However, model training is often difficult due to label scarcity in the medical domain and the model's usage is limited by the specific task and disease for which it is trained. Additionally, most models in histopathology leverage only image data, a stark contrast to how humans teach each other and reason about histopathologic entities. We introduce CONtrastive learning from Captions for Histopathology (CONCH), a visual-language foundation model developed using diverse sources of histopathology images, biomedical text, and notably over 1.17 million image-caption pairs via task-agnostic pretraining. Evaluated on a suite of 13 diverse benchmarks, CONCH can be transferred to a wide range of downstream tasks involving either or both histopathology images and text, achieving state-of-the-art performance on histology image classification, segmentation, captioning, text-to-image and image-to-text retrieval. CONCH represents a substantial leap over concurrent visual-language pretrained systems for histopathology, with the potential to directly facilitate a wide array of machine learning-based workflows requiring minimal or no further supervised fine-tuning.

Visual Language Pretrained Multiple Instance Zero-Shot Transfer for Histopathology Images

Contrastive visual language pretraining has emerged as a powerful method for either training new language-aware image encoders or augmenting existing pretrained models with zero-shot visual recognition capabilities. However, existing works typically train on large datasets of image-text pairs and have been designed to perform downstream tasks involving only small to medium sized-images, neither of which are applicable to the emerging field of computational pathology where there are limited publicly available paired image-text datasets and each image can span up to 100,000 x 100,000 pixels. In this paper we present MI-Zero, a simple and intuitive framework for unleashing the zero-shot transfer capabilities of contrastively aligned image and text models on gigapixel histopathology whole slide images, enabling multiple downstream diagnostic tasks to be carried out by pretrained encoders without requiring any additional labels. MI-Zero reformulates zero-shot transfer under the framework of multiple instance learning to overcome the computational challenge of inference on extremely large images. We used over 550k pathology reports and other available in-domain text corpora to pre-train our text encoder. By effectively leveraging strong pre-trained encoders, our best model pretrained on over 33k histopathology image-caption pairs achieves an average median zero-shot accuracy of 70.2% across three different real-world cancer subtyping tasks. Our code is available at: https://github.com/mahmoodlab/MI-Zero.

IUP: An Intelligent Utility Prediction Scheme for Solid-State Fermentation in 5G IoT

At present, SOILD-STATE Fermentation (SSF) is mainly controlled by artificial experience, and the product quality and yield are not stable. Accurately predicting the quality and yield of SSF is of great significance for improving human food security and supply. In this paper, we propose an Intelligent Utility Prediction (IUP) scheme for SSF in 5G Industrial Internet of Things (IoT), including parameter collection and utility prediction of SSF process. This IUP scheme is based on the environmental perception and intelligent learning algorithms of the 5G Industrial IoT. We build a workflow model based on rewritable petri net to verify the correctness of the system model function and process. In addition, we design a utility prediction model for SSF based on the Generative Adversarial Networks (GAN) and Fully Connected Neural Network (FCNN). We design a GAN with constraint of mean square error (MSE-GAN) to solve the problem of few-shot learning of SSF, and then combine with the FCNN to realize the utility prediction (usually use the alcohol) of SSF. Based on the production of liquor in laboratory, the experiments show that the proposed method is more accurate than the other prediction methods in the utility prediction of SSF, and provide the basis for the numerical analysis of the proportion of preconfigured raw materials and the appropriate setting of cellar temperature.