Frequency-Disentangled Multi-Phase Breast DCE-MRI Synthesis from Pre-Contrast MRI

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) captures spatially heterogeneous and temporally evolving tumor enhancement. Synthesizing multi-phase DCE-MRI from pre-contrast MRI therefore requires recovering patient-specific enhancement patterns rather than merely generating realistic images. However, existing methods often oversmooth intratumoral heterogeneity and introduce spurious enhancement outside lesions. We propose Freq-Syn, a frequency-disentangled framework that synthesizes multi-phase breast DCE-MRI from a pre-contrast 3D volume and target acquisition times. Unlike whole-image prediction, Freq-Syn represents enhancement as a progressive Gaussian scale-space hierarchy of global contrast, regional uptake, lesion morphology, and fine texture. Cross-phase interaction jointly models their temporal evolution, while synthesis-guided localization constrains where heterogeneous enhancement is generated. Lesion annotations provide targeted supervision during training but are not required at inference. On the internal and external test sets, Freq-Syn achieves SSIM scores of 0.83 and 0.81, respectively. Compared with the best-performing comparison methods, Freq-Syn reduces the false enhancement rate from 40.47% to 16.93% internally and from 37.49% to 19.59% externally. For downstream lesion segmentation, Freq-Syn consistently achieves higher Dice scores than all comparison synthesis methods on both test sets, demonstrating that the synthesized images preserve task-relevant tumor information. These results highlight the effectiveness of explicitly modeling spatial and temporal enhancement patterns for faithful multi-phase DCE-MRI synthesis. These results demonstrate the effectiveness of explicitly modeling spatial and temporal enhancement patterns for faithful multi-phase DCE-MRI synthesis.