Latent Space Is Not Flat: Rethinking Latent Structure for 3D Medical Image Synthesis

High-fidelity 3D MRI synthesis requires both globally coherent anatomy and fine-grained voxel-level detail. Although latent diffusion makes volumetric generation tractable, its image autoencoder introduces a reconstruction bottleneck that can limit the fine detail recoverable in the final volume. We present VoxStruct3D, a voxel-space flow-matching framework that directly models full-resolution MRI volumes using a clean-data prediction objective. Its Volumetric Voxel Generator (VVG) combines factorized 3D patch embedding with overlapping upsampling, time-modulated residual refinement, and skip fusion, enabling neighboring tokens to jointly reconstruct shared voxel regions and suppress patch-boundary artifacts. To complement direct voxel-space modeling with an explicit anatomical prior, we further introduce a Structure-First, Image-Follows (SFIF) strategy. A frozen pretrained 3D medical encoder and a StructVAE extract compact structure tokens that preserve dominant anatomy, while a structure-leading schedule keeps their trajectory ahead of the image trajectory. Patch-Aligned RoPE spatially aligns the unequal token grids, and asymmetric attention enforces one-way guidance from structure to image. Experiments on pathological and healthy T1-weighted brain MRI datasets show that VoxStruct3D achieves the strongest overall performance across feature-distribution alignment, sample diversity, and perceptual quality, producing anatomically coherent and visually realistic volumes.

Multi-contrast magnetic resonance imaging (MRI) provides complementary information for clinical diagnosis. However, acquiring all MRI sequences is often time-consuming and costly. Recent generative models perform cross-contrast synthesis to address this issue by inferring absent contrasts from the available ones. Nevertheless, synthesizing 3D MRI presents significant challenges. Due to the massive volume sizes, operating directly in the pixel space is computationally prohibitive; therefore, a common approach is to first compress the 3D volumes into a latent space and subsequently train generative models in that space. We observe that existing compression architectures face several critical issues: they under-preserve long-range anatomical coherence, discard clinically meaningful semantics, and rely on optimization objectives that lead to over-smoothed reconstructions. Ultimately, these shortcomings compromise the performance of subsequent generative models. In this work, we propose a semantics-first latent modeling framework for 3D MRI reconstruction and cross-contrast synthesis. Specifically, we introduce a Latent Harmonization Encoder (LHE) to capture global anatomical dependencies, ensuring coherent volumetric representations. To mitigate semantic degradation during latent compression, we further design a Semantic Recovery Block (SRB) that injects high-level priors from a self-supervised semantic teacher, enhancing contrast-aware separability in the latent space. Additionally, we propose an Anatomy-aware Frequency Loss (AFL) to adaptively preserve diagnostically relevant high-frequency structures. Extensive experiments on two public multi-contrast MRI datasets demonstrate consistent improvements in reconstruction fidelity and cross-contrast synthesis quality. Our code is available at https://github.com/script-Yang/RSF.

High-resolution 3D medical image generation remains challenging because fully volumetric models are computationally expensive, while efficient 2D slice generators often fail to preserve anatomical consistency across the third dimension. We propose LiFT, a framework for Lifted inter-slice Feature Trajectories that factorizes 3D volume synthesis into per-slice image generation and inter-slice trajectory learning. Rather than modeling the volumetric distribution end-to-end, LiFT treats a volume as an ordered trajectory in feature space, capturing how anatomical structures appear, transform, and disappear across depth. A tri-planar drifting loss aligns the trajectory of generated slices with the trajectories of real volumes, enabling distributional learning over inter-slice progressions in unconditional generation; in paired translation, a bidirectional $z$-context mixer trained against the registered target supplies through-plane coherence while preserving per-slice fidelity. We evaluate LiFT on BraTS 2023 (unconditional and missing-modality MR) and SynthRAD2023 (MR-to-CT). Across these settings, LiFT preserves per-slice quality, approaches the reported cWDM missing-MR reconstruction quality at \sim$$135\times lower inference cost (without formal equivalence testing), and improves through-plane coherence on MR-to-CT relative to a no-mapper ablation, demonstrating that lightweight inter-slice trajectory learning is a viable route to high-resolution 3D medical synthesis.