Mingjie Li
Publications
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.
Redefining the Down-Sampling Scheme of U-Net for Precision Biomedical Image Segmentation
U-Net architectures have been instrumental in advancing biomedical image segmentation (BIS) but often struggle with capturing long-range information. One reason is the conventional down-sampling techniques that prioritize computational efficiency at the expense of information retention. This paper introduces a simple but effective strategy, we call it Stair Pooling, which moderates the pace of down-sampling and reduces information loss by leveraging a sequence of concatenated small and narrow pooling operations in varied orientations. Specifically, our method modifies the reduction in dimensionality within each 2D pooling step from $\frac{1}{4}$ to $\frac{1}{2}$. This approach can also be adapted for 3D pooling to preserve even more information. Such preservation aids the U-Net in more effectively reconstructing spatial details during the up-sampling phase, thereby enhancing its ability to capture long-range information and improving segmentation accuracy. Extensive experiments on three BIS benchmarks demonstrate that the proposed Stair Pooling can increase both 2D and 3D U-Net performance by an average of 3.8\% in Dice scores. Moreover, we leverage the transfer entropy to select the optimal down-sampling paths and quantitatively show how the proposed Stair Pooling reduces the information loss.