Pretreatment DCE-MRI Resolves Response Quality Within Pathologic Endpoints in Neoadjuvant Breast Cancer

Pathologic complete response (pCR) is a strong neoadjuvant endpoint, yet 5-15% of complete responders recur and clinical/genomic variables do not reliably identify them. We tested whether pretreatment dynamic contrast-enhanced MRI entropy - intratumoral enhancement heterogeneity - resolves response quality hidden within pCR and residual cancer burden (RCB). Across four cohorts (1,200 patients), a prespecified entropy threshold defined favorable and adverse structural states. Crossing structure with pathology yielded a four-tier framework spanning 4.1-fold recurrence in I-SPY1 and 7.7-fold at response extremes. In I-SPY2, 55 of 219 complete responders (25.1%) were structurally adverse, pretreatment. In an external HER2-positive responder synthesis (I-SPY1 pathology-confirmed pCR plus UCSF best-response proxy; n = 33, 10 events), adverse structure was associated with higher recurrence risk (HR = 2.87, 95% CI 1.38-5.96) capturing 7 of 10 recurrences, enriching rather than determining risk. In a HER2-positive RCB-0 subset, recurrence was 12.5% with favorable and 80.0% with adverse structure; Firth Cox regression preserved the association (HR = 8.13, 95% CI 1.71-49.21; n = 21, 6 events). In Duke (n = 908; 76 events), favorable structure remained independently associated with lower distant-recurrence risk (adjusted HR = 0.61, 95% CI 0.41-0.91). RNA linked favorable structure to a directionally reproduced immune-architecture program among non-overlapping patients within ISPY2; EMT-pathway enrichment was favorable-side, while the adverse tier contained a broadly immune-depleted substate. Yet full-cohort RNA models weakly discriminated structural state and did not recover continuous entropy. Pretreatment MRI therefore does not replace pCR or RCB; it reveals response-quality differences that these endpoints compress and identifies a recurrence-enriched group for prospective validation.

Pre- to Post-Contrast Synthesis of Breast DCE-MRI using Latent Bridge Matching

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is central to breast cancer imaging, but gadolinium administration increases scan burden and motivates contrast-reduced alternatives, including synthetic contrast generation. We propose a latent bridge matching (LBM) framework for synthesizing peak-enhanced breast DCE-MRI from pre-contrast images in the MAMA-SYNTH challenge setting. Instead of starting from Gaussian noise as in conventional latent diffusion models (LDMs), the proposed model learns a conditional bridge between paired pre-contrast and peak-enhanced VAE latents. A latent UNet predicts the remaining correction from intermediate bridge states to the peak-enhanced latent, enabling iterative refinement while keeping the trajectory anchored to patient-specific anatomy. We evaluated two LBM conditioning variants on 91 DUKE validation cases. For the tumor-conditioned variant, tumor masks were used as conditioning inputs. Tumor-conditioning improved performance compared with pre-contrast conditioning, reducing MSE from 1.023 to 0.940 and FRD from 7.523 to 4.716, while increasing tumor SSIM from 0.355 to 0.429. The tumor-conditioned LBM also outperformed the evaluated LDM baseline on this validation cohort. These results suggest that latent bridge matching is a promising pre-contrast-anchored formulation for virtual contrast enhancement, while further work is needed to validate generalization and remove dependence on ground-truth tumor masks at inference.

Longitudinal 3D Foundation Modeling for Neoadjuvant Breast Cancer Response Prediction from Serial DCE-MRI

Pathologic complete response (pCR) is an important endpoint in neoadjuvant chemotherapy (NAC) for breast cancer, and predicting pCR from imaging during treatment could support treatment response assessment. Many existing imaging-based approaches rely on a single static timepoint, which fails to capture changes that occur during treatment. In this work, we present a longitudinal framework that combines a frozen 3D foundation encoder (Pillar-0) with our Temporal Dynamics Network (TDN) to predict treatment response from serial Dynamic Contrast-Enhanced (DCE) MRI acquired across four clinical timepoints from pre-treatment to pre-surgery. The TDN combines time-aware volumetric embeddings with clinical and treatment data to predict pCR. Evaluated on 982 patients from the combined I-SPY2 and ACRIN-6698 cohort, the proposed model achieves strong performance across all reported metrics when longitudinal 3D imaging is fused with clinical data (test AUROC: 73.6%, balanced accuracy: 69.1%). While clinical variables provide the strongest individual predictive signal, longitudinal 3D imaging contributes complementary information when fused with clinical data, improving pCR prediction. Our source code is available at: https://github.com/omarftt/longitudinal_temporal_pillar.

Dense Temporal Contrast Synthesis via Conditioned Latent Transport

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is essential for breast cancer management, but reliance on gadolinium-based contrast agents (GBCAs) restricts use in contraindicated populations, prolongs scan protocols, and presents environmental toxicity concerns. Contrast synthesis offers a non-invasive alternative; however, existing approaches struggle to balance spatial realism with temporal continuity, suffer from slow iterative sampling, underutilize structural priors, and lack clinical validation. We propose a novel conditioned latent transport framework that predicts contrast enhancement in a single forward pass. By anchoring the latent trajectory to the pre-contrast anatomy and applying continuous time conditioning, the model synthesizes patient-specific contrast evolution at any acquisition time. The proposed approach outperforms baseline and the state-of-the-art models across spatial, perceptual, temporal, and distributional metrics. Evaluated on an independent external cohort, the method demonstrates robustness to domain shifts induced by scanner noise as well as differing acquisition protocol. Furthermore, our synthetic contrast enhancement significantly improved downstream tumor segmentation performance, yielding a 22.4% relative increase in Dice coefficient (0.60 vs. 0.49 baseline pre-contrast, p < 0.01), reducing boundary segmentation error by over 39%, while outperforming all other generative model baselines. Finally, a reader study involving four breast radiologists evaluated the image quality, kinetic fidelity, and diagnostic viability of our synthesized sequences across 40 randomly selected cases. The results demonstrated that in 70% of cases, synthesized images provided sufficient clinical information to support the same management decisions as real DCE-MRI, suggesting a path toward safer and faster contrast-free or contrast-reduced imaging workflows.

Spatio-Temporal Mixture-of-Modality-Experts Diffusion for Quantitative DCE-MRI Synthesis from Incomplete MR Sequences

Quantitative maps from dynamic contrast-enhanced MRI (DCE-MRI) are essential for tumor assessment but are often unavailable due to contrast-agent risks and protocol variability. Prior methods predict these maps from other MRI modalities, yet most assume fixed, fully observed inputs and fail under realistic missingness. We present Spatio-Temporal Mixture-of-Modality-Experts (ST-MoME), a conditional diffusion framework that synthesizes 3D DCE parameter maps from diverse subsets of multimodal MRI. ST-MoME fuses modality-specific expert features through a spatio-temporal gating network that produces voxel-wise, timestep-dependent weights, forming a conditioning tensor that guides denoising. To preserve quantitative fidelity, ST-MoME performs diffusion directly in image space with 3D patch-based training and a Swin-based backbone. On a clinical brain-tumor cohort of 386 patients, we evaluate ST-MoME across 16 controlled modality-availability scenarios. It achieves the lowest mean Normalized Mean Square Error (NMSE) aggregated across all three DCE parameters, with leading performance on $v_p$ and $v_e$, competitive results on $K^{\mathrm{trans}}$, and the lowest reconstruction error within the clinically critical tumor region. A post-hoc analysis of the learned gating dynamics shows a structural-early, physiological-late fusion schedule consistent with clinical intuition.