Unified Multimodal Model for Brain MRI Imputation and Understanding
Authors: Zhiyun Song, Che Liu, Tian Xia, Avinash Kori, Wenjia Bai
Organizations: Department of Computing, Imperial College London, London, UK · Department of Brain Sciences, Imperial College London, London, UK
Abstract
Multimodal large language models (MLLMs) hold great potential for medicine, as they inherit knowledge from LLM and allow multiple data modalities to be integrated, analysed and interpreted in natural language. However, the field of medical MLLMs is constrained by non-trivial challenges, notably the scarcity of high-quality training data and the frequent occurrence of missing data in the real-world clinical setting. Here, we propose a novel unified multimodal model, UniBrain, for brain magnetic resonance image (MRI) analysis. To address potential missing brain MRI modalities, we employ a unified training strategy to perform joint imaging modality imputation and brain image understanding. During training, an interleaved and description-enriched data flow is constructed to train the model in an autoregressive manner, enabling medical reasoning with generated multimodal data. A self-alignment strategy is introduced to leverage dense image embeddings to learn fine-grained anatomical features without requiring detailed image captions. Furthermore, we propose a dynamic hidden state mechanism to alleviate the exposure bias during long-context multimodal inference. Extensive experiments on multi-disease brain MRI dataset demonstrate that UniBrain achieves high performance for brain image imputation, understanding, and disease diagnosis under various extents of modality incompleteness.
Brain MRI poses a fundamental challenge for machine learning: models must learn from high-dimensional 3D data spanning multiple co-registered modalities, despite the limited sample sizes typical of neuroimaging studies relative to the diversity in anatomy, pathology, and acquisition conditions. While multimodal imaging provides complementary information critical for clinical interpretation, effectively integrating these signals remains difficult. We propose Multimodal Intra- and Cross-Context Vision Transformer (MICViT), a 3D vision transformer that explicitly models both modality-specific representations and cross-modal interactions across local and global contexts. Concretely, MICViT combines four attention mechanisms: modality-specific local and global attention for intra-modal feature learning, and cross-modal local and global attention to capture interactions between modalities. We evaluate MICViT on brain age prediction across three heterogeneous datasets (UK Biobank, n=41,404; SOOP, n=1,062; Cam-CAN, n=613) using multiple MRI modalities (e.g. T1, FLAIR, DWI, SWI). MICViT consistently outperforms state-of-the-art CNN and transformer baselines in 3D settings. Notably, it benefits more strongly from multimodal inputs, yielding larger performance gains as additional modalities are incorporated. These results demonstrate that explicitly modeling intra- and cross-modal interactions is key to unlocking the full potential of multimodal brain MRI, highlighting a promising direction for representation learning in neuroimaging.
Clinical diagnostic workups typically follow a modality escalation pathway: after initial clinical evaluation, clinicians begin with routine structural imaging (e.g., MRI), selectively add sequences such as FLAIR or T2 to refine the differential, and reserve molecular imaging (e.g., amyloid-PET) for cases that remain uncertain after standard evaluation. Consequently, patients are observed with heterogeneous and often incomplete modality subsets. However, most current AI models assume fixed data modalities as the model inputs. In this paper, we present BrainAnytime, a unified pretraining framework pretrained on 34,899 3D brain scans from five datasets that support brain image analysis under arbitrary modality availability spanning multi-sequence MRI and amyloid-PET. A single model accepts whatever imaging is available, from a lone T1 scan to a full multimodal workup. Pretraining learns structural-molecular correspondences between MRI and PET via cross-modal distillation (RCMD) and prioritizes disease-vulnerable anatomy via atlas-guided curriculum masking (PACM), all within a shared 3D masked autoencoder (Multi-MAE3D). Across four downstream tasks and five clinically motivated modality settings, BrainAnytime largely outperforms modality-specific models, missing-modality baselines, and large-scale brain MRI pretrained foundation models on most modality settings. Notably, it surpasses the strongest missing-modality baselines with relative improvements of 6.2% and 7.0% in average accuracy on CN vs. AD and CN vs. MCI classification, respectively. Code is available at https://github.com/SDH-Lab/BrainAnytime.
Multimodal MRI offers complementary information for brain tumor segmentation, but clinical scans often lack one or more modalities, which degrades segmentation performance. In this paper, we propose UniME (Uni-Encoder Meets Multi-Encoders), a two-stage heterogeneous method for brain tumor segmentation with missing modalities that reconciles the trade-offs among fine-grained structure capture, cross-modal complementarity modeling, and exploitation of available modalities. The idea is to decouple representation learning from segmentation via a two-stage heterogeneous architecture. Stage 1 pretrains a single ViT Uni-Encoder with masked image modeling to establish a unified representation robust to missing modalities. Stage 2 adds modality-specific CNN Multi-Encoders to extract high-resolution, multi-scale, fine-grained features. We fuse these features with the global representation to produce precise segmentations. Experiments on BraTS 2023 and BraTS 2024 show that UniME outperforms previous methods under incomplete multi-modal scenarios. The code is available at https://github.com/Hooorace-S/UniME