State Space Models (SSMs) with selective scan (Mamba) have been adapted into efficient vision models. Mamba, unlike Vision Transformers, achieves linear complexity for token interactions through a recurrent hidden state process. This sequential processing is enhanced by a parallel scan algorithm, which reduces the computational time of recurrent steps from L sequential steps to log(L) parallel steps with respect to the number of input tokens (L). In this work, we propose Fast Vision Mamba (FastVim), that further reduces the computational time of the SSM block by reducing the number of recurrent steps in Vision Mamba models while still retaining model performance. By alternately pooling tokens along image dimensions across Mamba blocks, we obtain a 2× reduction in the number of parallel steps in SSM block. Our model offers up to 72.5% speedup in inference speed compared to baseline Vision Mamba models on high resolution (2048×2048) images. Our experiments demonstrate state-of-the-art performance with dramatically improved throughput in a range of tasks such as image classification, cell perturbation prediction, segmentation, and object detection. Code is made available at github.com/insitro/FastVim

Integrating histopathology with spatial transcriptomics (ST) provides a powerful opportunity to link tissue morphology with molecular function. Yet most existing multimodal approaches rely on a small set of highly variable genes, which limits predictive scope and overlooks the coordinated biological programs that shape tissue phenotypes. We present PEaRL (Pathway Enhanced Representation Learning), a multimodal framework that represents transcriptomics through pathway activation scores computed with ssGSEA. By encoding biologically coherent pathway signals with a transformer and aligning them with histology features via contrastive learning, PEaRL reduces-dimensionality, improves interpretability, and strengthens cross-modal correspondence. Across three cancer ST datasets—breast, skin, and lymph node—PEaRL consistently outperforms SOTA methods, yielding higher accuracy for both gene- and pathway-level expression prediction (up to 58.9% and 20.4% increase in Pearson correlation coefficient compared to SOTA). These results demonstrate that grounding transcriptomic representation in pathways produces more biologically faithful and interpretable multi-modal models, advancing computational pathology beyond gene-level embeddings.

Pretraining a Multiple Instance Learning (MIL) aggregator enables the derivation of Whole Slide Image (WSI)-level embeddings from patch-level representations without supervision. While recent multimodal MIL pretraining approaches leveraging auxiliary modalities have demonstrated performance gains over unimodal WSI pretraining, the acquisition of these additional modalities necessitates extensive clinical profiling. This requirement increases costs and limits scalability in existing WSI datasets lacking such paired modalities. To address this, we propose Gigapixel Vision-Concept Knowledge Contrastive pretraining (GECKO), which aligns WSIs with a Concept Prior derived from the available WSIs. First, we derive an inherently interpretable concept prior by computing the similarity between each WSI patch and textual descriptions of predefined pathology concepts. GECKO then employs a dual-branch MIL network: one branch aggregates patch embeddings into a WSI-level deep embedding, while the other aggregates the concept prior into a corresponding WSI-level concept embedding. Both aggregated embeddings are aligned using a contrastive objective, thereby pretraining the entire dual-branch MIL model. Moreover, when auxiliary modalities such as transcriptomics data are available, GECKO seamlessly integrates them. Across five diverse tasks, GECKO consistently outperforms prior unimodal and multimodal pretraining approaches while also delivering clinically meaningful interpretability that bridges the gap between computational models and pathology expertise. Code is made available at https://github.com/bmi-imaginelab/GECKO

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.

Introducing interpretability and reasoning into Multiple Instance Learning (MIL) methods for Whole Slide Image (WSI) analysis is challenging, given the complexity of gigapixel slides. Traditionally, MIL interpretability is limited to identifying salient regions deemed pertinent for downstream tasks, offering little insight to the end-user (pathologist) regarding the rationale behind these selections. To address this, we propose Self-Interpretable MIL (SI-MIL), a method intrinsically designed for interpretability from the very outset. SI-MIL employs a deep MIL framework to guide an interpretable branch grounded on handcrafted pathological features, facilitating linear predictions. Beyond identifying salient regions, SI-MIL uniquely provides feature-level interpretations rooted in pathological insights for WSIs. Notably, SI-MIL, with its linear prediction constraints, challenges the prevalent myth of an inevitable trade-off between model interpretability and performance, demonstrating competitive results compared to state-of-the-art methods on WSI-level prediction tasks across three cancer types. In addition, we thoroughly benchmark the local-and global-interpretability of SI-MIL in terms of statistical analysis, a domain expert study, and desiderata of interpretability, namely, user-friendliness and faithfulness.