Anatomy-aware Sketch-guided Latent Diffusion Model for Orbital Tumor Multi-Parametric MRI Missing Modalities Synthesis

Synthesizing missing modalities in multi-parametric MRI (mpMRI) is vital for accurate tumor diagnosis, yet remains challenging due to incomplete acquisitions and modality heterogeneity. Diffusion models have shown strong generative capability, but conventional approaches typically operate in the image domain with high memory costs and often rely solely on noise-space supervision, which limits anatomical fidelity. Latent diffusion models (LDMs) improve efficiency by performing denoising in latent space, but standard LDMs lack explicit structural priors and struggle to integrate multiple modalities effectively. To address these limitations, we propose the anatomy-aware sketch-guided latent diffusion model (ASLDM), a novel LDM-based framework designed for flexible and structure-preserving MRI synthesis. ASLDM incorporates an anatomy-aware feature fusion module, which encodes tumor region masks and edge-based anatomical sketches via cross-attention to guide the denoising process with explicit structure priors. A modality synergistic reconstruction strategy enables the joint modeling of available and missing modalities, enhancing cross-modal consistency and supporting arbitrary missing scenarios. Additionally, we introduce image-level losses for pixel-space supervision using L1 and SSIM losses, overcoming the limitations of pure noise-based loss training and improving the anatomical accuracy of synthesized outputs. Extensive experiments on a five-modality orbital tumor mpMRI private dataset and a four-modality public BraTS2024 dataset demonstrate that ASLDM outperforms state-of-the-art methods in both synthesis quality and structural consistency, showing strong potential for clinically reliable multi-modal MRI completion.