Controllable Latent Space Augmentation for Digital Pathology

Whole slide image (WSI) analysis in digital pathology presents unique challenges due to the gigapixel resolution of WSIs and the scarcity of dense supervision signals. While Multiple Instance Learning (MIL) is a natural fit for slide-level tasks, training robust models requires large and diverse datasets. Even though image augmentation techniques could be utilized to increase data variability and reduce overfitting, implementing them effectively is not a trivial task. Traditional patch-level augmentation is prohibitively expensive due to the large number of patches extracted from each WSI, and existing feature-level augmentation methods lack control over transformation semantics. We introduce HistAug, a fast and efficient generative model for controllable augmentations in the latent space for digital pathology. By conditioning on explicit patch-level transformations (e.g., hue, erosion), HistAug generates realistic augmented embeddings while preserving initial semantic information. Our method allows the processing of a large number of patches in a single forward pass efficiently, while at the same time consistently improving MIL model performance. Experiments across multiple slide-level tasks and diverse organs show that HistAug outperforms existing methods, particularly in low-data regimes. Ablation studies confirm the benefits of learned transformations over noise-based perturbations and highlight the importance of uniform WSI-wise augmentation. Code is available at https://github.com/MICS-Lab/HistAug.

On the Risk of Misleading Reports: Diagnosing Textual Biases in Multimodal Clinical AI

Clinical decision-making relies on the integrated analysis of medical images and the associated clinical reports. While Vision-Language Models (VLMs) can offer a unified framework for such tasks, they can exhibit strong biases toward one modality, frequently overlooking critical visual cues in favor of textual information. In this work, we introduce Selective Modality Shifting (SMS), a perturbation-based approach to quantify a model's reliance on each modality in binary classification tasks. By systematically swapping images or text between samples with opposing labels, we expose modality-specific biases. We assess six open-source VLMs-four generalist models and two fine-tuned for medical data-on two medical imaging datasets with distinct modalities: MIMIC-CXR (chest X-ray) and FairVLMed (scanning laser ophthalmoscopy). By assessing model performance and the calibration of every model in both unperturbed and perturbed settings, we reveal a marked dependency on text input, which persists despite the presence of complementary visual information. We also perform a qualitative attention-based analysis which further confirms that image content is often overshadowed by text details. Our findings highlight the importance of designing and evaluating multimodal medical models that genuinely integrate visual and textual cues, rather than relying on single-modality signals.

THUNDER: Tile-level Histopathology image UNDERstanding benchmark

Progress in a research field can be hard to assess, in particular when many concurrent methods are proposed in a short period of time. This is the case in digital pathology, where many foundation models have been released recently to serve as feature extractors for tile-level images, being used in a variety of downstream tasks, both for tile- and slide-level problems. Benchmarking available methods then becomes paramount to get a clearer view of the research landscape. In particular, in critical domains such as healthcare, a benchmark should not only focus on evaluating downstream performance, but also provide insights about the main differences between methods, and importantly, further consider uncertainty and robustness to ensure a reliable usage of proposed models. For these reasons, we introduce THUNDER, a tile-level benchmark for digital pathology foundation models, allowing for efficient comparison of many models on diverse datasets with a series of downstream tasks, studying their feature spaces and assessing the robustness and uncertainty of predictions informed by their embeddings. THUNDER is a fast, easy-to-use, dynamic benchmark that can already support a large variety of state-of-the-art foundation, as well as local user-defined models for direct tile-based comparison. In this paper, we provide a comprehensive comparison of 23 foundation models on 16 different datasets covering diverse tasks, feature analysis, and robustness. The code for THUNDER is publicly available at https://github.com/MICS-Lab/thunder.

Full Conformal Adaptation of Medical Vision-Language Models

Vision-language models (VLMs) pre-trained at large scale have shown unprecedented transferability capabilities and are being progressively integrated into medical image analysis. Although its discriminative potential has been widely explored, its reliability aspect remains overlooked. This work investigates their behavior under the increasingly popular split conformal prediction (SCP) framework, which theoretically guarantees a given error level on output sets by leveraging a labeled calibration set. However, the zero-shot performance of VLMs is inherently limited, and common practice involves few-shot transfer learning pipelines, which cannot absorb the rigid exchangeability assumptions of SCP. To alleviate this issue, we propose full conformal adaptation, a novel setting for jointly adapting and conformalizing pre-trained foundation models, which operates transductively over each test data point using a few-shot adaptation set. Moreover, we complement this framework with SS-Text, a novel training-free linear probe solver for VLMs that alleviates the computational cost of such a transductive approach. We provide comprehensive experiments using 3 different modality-specialized medical VLMs and 9 adaptation tasks. Our framework requires exactly the same data as SCP, and provides consistent relative improvements of up to 27% on set efficiency while maintaining the same coverage guarantees.

BayesAdapter: enhanced uncertainty estimation in CLIP few-shot adaptation

The emergence of large pre-trained vision-language models (VLMs) represents a paradigm shift in machine learning, with unprecedented results in a broad span of visual recognition tasks. CLIP, one of the most popular VLMs, has exhibited remarkable zero-shot and transfer learning capabilities in classification. To transfer CLIP to downstream tasks, adapters constitute a parameter-efficient approach that avoids backpropagation through the large model (unlike related prompt learning methods). However, CLIP adapters have been developed to target discriminative performance, and the quality of their uncertainty estimates has been overlooked. In this work we show that the discriminative performance of state-of-the-art CLIP adapters does not always correlate with their uncertainty estimation capabilities, which are essential for a safe deployment in real-world scenarios. We also demonstrate that one of such adapters is obtained through MAP inference from a more general probabilistic framework. Based on this observation we introduce BayesAdapter, which leverages Bayesian inference to estimate a full probability distribution instead of a single point, better capturing the variability inherent in the parameter space. In a comprehensive empirical evaluation we show that our approach obtains high quality uncertainty estimates in the predictions, standing out in calibration and selective classification. Our code is publicly available at: https://github.com/pablomorales92/BayesAdapter.

Are foundation models for computer vision good conformal predictors?

Recent advances in self-supervision and constrastive learning have brought the performance of foundation models to unprecedented levels in a variety of tasks. Fueled by this progress, these models are becoming the prevailing approach for a wide array of real-world vision problems, including risk-sensitive and high-stakes applications. However, ensuring safe deployment in these scenarios requires a more comprehensive understanding of their uncertainty modeling capabilities, which has been barely explored. In this work, we delve into the behavior of vision and vision-language foundation models under Conformal Prediction (CP), a statistical framework that provides theoretical guarantees of marginal coverage of the true class. Across extensive experiments including popular vision classification benchmarks, well-known foundation vision models, and three CP methods, our findings reveal that foundation models are well-suited for conformalization procedures, particularly those integrating Vision Transformers. Furthermore, we show that calibrating the confidence predictions of these models leads to efficiency degradation of the conformal set on adaptive CP methods. In contrast, few-shot adaptation to downstream tasks generally enhances conformal scores, where we identify Adapters as a better conformable alternative compared to Prompt Learning strategies. Our empirical study identifies APS as particularly promising in the context of vision foundation models, as it does not violate the marginal coverage property across multiple challenging, yet realistic scenarios.

On the detection of Out-Of-Distribution samples in Multiple Instance Learning

The deployment of machine learning solutions in real-world scenarios often involves addressing the challenge of out-of-distribution (OOD) detection. While significant efforts have been devoted to OOD detection in classical supervised settings, the context of weakly supervised learning, particularly the Multiple Instance Learning (MIL) framework, remains under-explored. In this study, we tackle this challenge by adapting post-hoc OOD detection methods to the MIL setting while introducing a novel benchmark specifically designed to assess OOD detection performance in weakly supervised scenarios. Extensive experiments based on diverse public datasets do not reveal a single method with a clear advantage over the others. Although DICE emerges as the best-performing method overall, it exhibits significant shortcomings on some datasets, emphasizing the complexity of this under-explored and challenging topic. Our findings shed light on the complex nature of OOD detection under the MIL framework, emphasizing the importance of developing novel, robust, and reliable methods that can generalize effectively in a weakly supervised context. The code for the paper is available here: https://github.com/loic-lb/OOD_MIL.

Spatio-Temporal Analysis of Patient-Derived Organoid Videos Using Deep Learning for the Prediction of Drug Efficacy

Over the last ten years, Patient-Derived Organoids (PDOs) emerged as the most reliable technology to generate ex-vivo tumor avatars. PDOs retain the main characteristics of their original tumor, making them a system of choice for pre-clinical and clinical studies. In particular, PDOs are attracting interest in the field of Functional Precision Medicine (FPM), which is based upon an ex-vivo drug test in which living tumor cells (such as PDOs) from a specific patient are exposed to a panel of anti-cancer drugs. Currently, the Adenosine Triphosphate (ATP) based cell viability assay is the gold standard test to assess the sensitivity of PDOs to drugs. The readout is measured at the end of the assay from a global PDO population and therefore does not capture single PDO responses and does not provide time resolution of drug effect. To this end, in this study, we explore for the first time the use of powerful large foundation models for the automatic processing of PDO data. In particular, we propose a novel imaging-based high-throughput screening method to assess real-time drug efficacy from a time-lapse microscopy video of PDOs. The recently proposed SAM algorithm for segmentation and DINOv2 model are adapted in a comprehensive pipeline for processing PDO microscopy frames. Moreover, an attention mechanism is proposed for fusing temporal and spatial features in a multiple instance learning setting to predict ATP. We report better results than other non-time-resolved methods, indicating that the temporality of data is an important factor for the prediction of ATP. Extensive ablations shed light on optimizing the experimental setting and automating the prediction both in real-time and for forecasting.

Structured State Space Models for Multiple Instance Learning in Digital Pathology

Multiple instance learning is an ideal mode of analysis for histopathology data, where vast whole slide images are typically annotated with a single global label. In such cases, a whole slide image is modelled as a collection of tissue patches to be aggregated and classified. Common models for performing this classification include recurrent neural networks and transformers. Although powerful compression algorithms, such as deep pre-trained neural networks, are used to reduce the dimensionality of each patch, the sequences arising from whole slide images remain excessively long, routinely containing tens of thousands of patches. Structured state space models are an emerging alternative for sequence modelling, specifically designed for the efficient modelling of long sequences. These models invoke an optimal projection of an input sequence into memory units that compress the entire sequence. In this paper, we propose the use of state space models as a multiple instance learner to a variety of problems in digital pathology. Across experiments in metastasis detection, cancer subtyping, mutation classification, and multitask learning, we demonstrate the competitiveness of this new class of models with existing state of the art approaches. Our code is available at https://github.com/MICS-Lab/s4_digital_pathology.

Artifact Removal in Histopathology Images

In the clinical setting of histopathology, whole-slide image (WSI) artifacts frequently arise, distorting regions of interest, and having a pernicious impact on WSI analysis. Image-to-image translation networks such as CycleGANs are in principle capable of learning an artifact removal function from unpaired data. However, we identify a surjection problem with artifact removal, and propose an weakly-supervised extension to CycleGAN to address this. We assemble a pan-cancer dataset comprising artifact and clean tiles from the TCGA database. Promising results highlight the soundness of our method.