Diagnosing diseases through histopathology whole slide images (WSIs) is fundamental in modern pathology but is challenged by the gigapixel scale and complexity of WSIs. Trained histopathologists overcome this challenge by navigating the WSI, looking for relevant patches, taking notes, and compiling them to produce a final holistic diagnostic. Traditional AI approaches, such as multiple instance learning and transformer-based models, fail short of such a holistic, iterative, multi-scale diagnostic procedure, limiting their adoption in the real-world. We introduce PathFinder, a multi-modal, multi-agent framework that emulates the decision-making process of expert pathologists. PathFinder integrates four AI agents, the Triage Agent, Navigation Agent, Description Agent, and Diagnosis Agent, that collaboratively navigate WSIs, gather evidence, and provide comprehensive diagnoses with natural language explanations. The Triage Agent classifies the WSI as benign or risky; if risky, the Navigation and Description Agents iteratively focus on significant regions, generating importance maps and descriptive insights of sampled patches. Finally, the Diagnosis Agent synthesizes the findings to determine the patient's diagnostic classification. Our Experiments show that PathFinder outperforms state-of-the-art methods in skin melanoma diagnosis by 8% while offering inherent explainability through natural language descriptions of diagnostically relevant patches. Qualitative analysis by pathologists shows that the Description Agent's outputs are of high quality and comparable to GPT-4o. PathFinder is also the first AI-based system to surpass the average performance of pathologists in this challenging melanoma classification task by 9%, setting a new record for efficient, accurate, and interpretable AI-assisted diagnostics in pathology. Data, code and models available at https://pathfinder-dx.github.io/

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.

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 slowed 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 $802, 144$ 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.