K. Pohl
Famous AuthorPublications
GeoSAE: Geometric Prior-Guided Layer-Wise Sparse Autoencoder Annotation of Brain MRI Foundation Models
Brain MRI foundation models learn rich representations of anatomy, but interpreting what clinical information they encode remains an open problem. Standard sparse autoencoders (SAEs) suffer from severe feature collapse in deep transformer layers, and in Alzheimer's disease (AD) research, aging confounds nearly every clinical variable, making naive annotation unreliable. We propose GeoSAE, a geometry-guided SAE framework that uses the foundation model's learned manifold structure to prevent feature collapse and annotates each surviving feature via age-deconfounded partial correlations. Applied to ~14k T1-weighted MRI scans from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and the Australian Imaging biomarkers and Lifestyle (AIBL) datasets, GeoSAE identifies a compact, fully interpretable feature set that predicts mild cognitive impairment (MCI)-to-AD conversion (AUC 0.746) using only 2% of the embedding dimensions, while comorbidity-annotated features achieve only chance-level performance. The identified features replicate across cohorts without retraining (r=0.97) and localize to neuroanatomically distinct regions consistent with Braak staging. This shows that geometry-guided SAEs can extract interpretable, biomarkers from frozen brain MRI foundation models.
Modality-Aware and Anatomical Vector-Quantized Autoencoding for Multimodal Brain MRI
Learning a robust Variational Autoencoder (VAE) is a fundamental step for many deep learning applications in medical image analysis, such as MRI synthesizes. Existing brain VAEs predominantly focus on single-modality data (i.e., T1-weighted MRI), overlooking the complementary diagnostic value of other modalities like T2-weighted MRIs. Here, we propose a modality-aware and anatomically grounded 3D vector-quantized VAE (VQ-VAE) for reconstructing multi-modal brain MRIs. Called NeuroQuant, it first learns a shared latent representation across modalities using factorized multi-axis attention, which can capture relationships between distant brain regions. It then employs a dual-stream 3D encoder that explicitly separates the encoding of modality-invariant anatomical structures from modality-dependent appearance. Next, the anatomical encoding is discretized using a shared codebook and combined with modality-specific appearance features via Feature-wise Linear Modulation (FiLM) during the decoding phase. This entire approach is trained using a joint 2D/3D strategy in order to account for the slice-based acquisition of 3D MRI data. Extensive experiments on two multi-modal brain MRI datasets demonstrate that NeuroQuant achieves superior reconstruction fidelity compared to existing VAEs, enabling a scalable foundation for downstream generative modeling and cross-modal brain image analysis.
A Generative Foundation Model for Multimodal Histopathology
Accurate diagnosis and treatment of complex diseases require integrating histological, molecular, and clinical data, yet in practice these modalities are often incomplete owing to tissue scarcity, assay cost, and workflow constraints. Existing computational approaches attempt to impute missing modalities from available data but rely on task-specific models trained on narrow, single source-target pairs, limiting their generalizability. Here we introduce MuPD (Multimodal Pathology Diffusion), a generative foundation model that embeds hematoxylin and eosin (H&E)-stained histology, molecular RNA profiles, and clinical text into a shared latent space through a diffusion transformer with decoupled cross-modal attention. Pretrained on 100 million histology image patches, 1.6 million text-histology pairs, and 10.8 million RNA-histology pairs spanning 34 human organs, MuPD supports diverse cross-modal synthesis tasks with minimal or no task-specific fine-tuning. For text-conditioned and image-to-image generation, MuPD synthesizes histologically faithful tissue architectures, reducing Fréchet inception distance (FID) scores by 50% relative to domain-specific models and improving few-shot classification accuracy by up to 47% through synthetic data augmentation. For RNA-conditioned histology generation, MuPD reduces FID by 23% compared with the next-best method while preserving cell-type distributions across five cancer types. As a virtual stainer, MuPD translates H&E images to immunohistochemistry and multiplex immunofluorescence, improving average marker correlation by 37% over existing approaches. These results demonstrate that a single, unified generative model pretrained across heterogeneous pathology modalities can substantially outperform specialized alternatives, providing a scalable computational framework for multimodal histopathology.