A cross-modal generative model for incomplete and degraded prostate MRI with multicentre clinical validation
Authors: Siyuan Ma, Liang He, Mengying Zhu, Yi Chai, Mengyao Lyu, Haowei Wang, Qizhen Lan, HaoBo Sun, +9 more
Organizations: College of Computing and Data Science, Nanyang Technological University, Singapore · School of Computer Science and Technology, Tongji University, Shanghai, China · Department of Radiology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China · National University of Singapore, Singapore · Department of Medical Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China · McWilliams School of Biomedical Informatics, The University of Texas Health Science Center at Houston (UTHealth Houston), Houston, Texas, USA · Jiangsu Key Laboratory of Urban ITS, Jiangsu Province Collaborative Innovation Center of Modern Urban Traffic Technologies, School of Transportation, Southeast University, Nanjing 210096, China · Department of Radiology, Ningbo Hangzhou Bay Hospital, Ningbo, Zhejiang, China · Department of Radiology, Changhai Hospital, Naval Medical University, Shanghai, China
Missing or degraded sequences can limit prostate multiparametric MRI. We developed MSCNet, a sequence-conditioned cross-modal generative framework for reconstructing unavailable contrasts and restoring degraded acquisitions. Across ten completion tasks, task-specific MSCNet achieved mean structural similarity of 0.818 versus 0.798 for the strongest task-matched comparators; matched-capacity analyses showed larger differences in lesion fidelity and boundary preservation. In a blinded 1,000-case reader study, overall image quality met the prespecified non-inferiority criterion for DWI, ADC and T2W completion, but not T1W. In a separate 200-case diagnostic assessment, AUCs for clinically significant cancer were 0.860 with acquired images, 0.841 with MSCNet and 0.797 with baseline-generated images. A locked 186-case three-hospital cohort supported multicentre transportability. These retrospective results support quality-controlled cross-modal reconstruction as an adjunct to acquired prostate MRI.
Figures & tables
Figure 1: Study overview, cohorts, completion tasks and MSCNet framework. A, Clinical motivation and workflow for incomplete or degraded prostate mpMRI, cross-modal completion or enhancement, and radiologist review. B, Public, institutional, artefact and reader-study cohorts. C, Matrix of 2-to-1 and 3-to-1 completion tasks. D, MSCNet architecture, synthesis outputs and optimization objectives, including modality-specific encoders, multi-scale cross-modal gated fusion, global-context modelling, attention-gated decoding, deep supervision and edge-aware reconstruction.
Figure 2: Visual and spatial behaviour of multi-sequence prostate MRI completion. A, Input sequences, acquired reference targets, baseline outputs, MSCNet outputs, residual maps and enlarged regions. B, Residual decomposition in the gland, boundary ring and peri-gland regions. C, Local structural similarity, residual error and boundary error at the apex, mid-gland and base. D, Adjacent-slice consistency, slice-to-slice variation, volumetric smoothness and z-trend correlation. E, Edge preservation, boundary SSIM, gradient similarity and capsule sharpness.
Figure 3: Optimized quantitative performance and clinical-anatomical effect size. A, Task-level SSIM for MSCNet and the strongest task-specific non-MSCNet comparator. B, Absolute SSIM gain for each completion task. C, Grouped macro SSIM for physical-coupling, cross-contrast and T1W tasks. D, Task-level LPIPS for MSCNet and the strongest task-specific comparator. E, Matched-capacity analysis on the locked subset, showing whole-image SSIM, lesion fidelity and boundary SSIM. F, Internal and external-hospital SSIM, including the three external sites and pooled estimate.
Figure 4: Clinical artefact transfer and virtual enhancement. A, Workflow from clinical artefact collection and pattern extraction to cross-domain transfer, strict pairing, restoration and safety review. B, Representative susceptibility, motion, banding, Gibbs-ringing and chemical-shift cases before and after restoration. C, Before-and-after image-quality distributions by artefact type. D, Correlation among distortion, structural and perceptual metrics. E, Comparison with baseline restoration models. F, Artefact-type and severity distribution in the clinical cohort.
Figure 5: Blinded radiologist reader study. A, Sampling, task strata, anonymization, block randomization, reader experience, Likert endpoints and statistical plan. B, Mean scores for five clinical dimensions across four completion tasks. C, Overall image-quality distributions. D, Diagnostic-confidence distributions. E, Task-level lesion-conspicuity scores. F, Reference and MSCNet score distributions relative to the prespecified reference-minus-0.5 margin. G, Improvement of MSCNet over the baseline across tasks and clinical dimensions.
Figure 6: Diagnostic validation and clinical usability. A, Separate diagnostic cohort, image conditions, blinded reading and pathology or clinical follow-up reference standard. Summary values in the endpoint panel correspond to the MSCNet condition and match the quantitative results in B. B, AUC, sensitivity, specificity, positive predictive value, negative predictive value and AUC difference for acquired, MSCNet and baseline images. C, Lesion Dice, centre-distance error, volume overlap and boundary-distance error. D, PI-RADS agreement matrix in the 1,000-case reader-study set. E, Paired reading time and diagnostic confidence before and after AI assistance. F, Retrospective usability categories after AI assistance.
Cohort
Source
Sequences
Size or split
Primary role
PI-CAI
Public, multicentre
T2W, ADC, high-b-value DWI
1,476; 1,000/200/276
Public-domain development and held-out evaluation of 2-to-1 tasks
Controlled artefact transfer, same-patient repeat-scan validation and safety evaluation
Reader study
Ren Ji Hospital held-out cohort
Four representative tasks
1,000; 250 per task
Three-reader blinded assessment
Extended Data Table 1: Study cohorts and analytical roles. Splits were defined at the patient level. PROSTATEx was treated as a vendor-specific public cohort rather than independent external validation.
Dataset
Task
Input → target
PSNR
SSIM
LPIPS
MAE
PI-CAI
P1
T2W + ADC → high-b DWI
25.91 (+0.53)
0.8600 (+0.0180)
0.0890 ( − 0.0100)
0.0384 ( − 0.0036)
PI-CAI
P2
T2W + high-b DWI → ADC
28.43 (+0.48)
0.8890 (+0.0170)
0.0700 ( − 0.0110)
0.0261 ( − 0.0029)
PI-CAI
P3
ADC + high-b DWI → T2W
23.07 (+0.66)
0.7300 (+0.0240)
0.1480 ( − 0.0160)
0.0573 ( − 0.0047)
Institutional
A
T2W + ADC → DWI
24.17 (+0.46)
0.8460 (+0.0180)
0.0950 ( − 0.0110)
0.0621 ( − 0.0039)
Institutional
B
T2W + DWI → ADC
27.46 (+0.44)
0.8660 (+0.0180)
0.0830 ( − 0.0100)
0.0382 ( − 0.0038)
Institutional
C
ADC + DWI → T2W
21.59 (+0.61)
0.7140 (+0.0240)
0.1620 ( − 0.0160)
0.0662 ( − 0.0048)
Extended Data Table 2: Main quantitative performance of MSCNet. Values in parentheses are absolute changes relative to the strongest non-MSCNet baseline. PSNR and SSIM are higher-is-better; LPIPS and MAE are lower-is-better.
Extended Data Table 3: Clinical reader-study and diagnostic-validation summary. Reader scores were obtained in 1,000 held-out cases; diagnostic discrimination was evaluated in a separate 200-case set.
Magnetic resonance imaging comes in various modality contrasts that provide complementary anatomical and pathological information. Complete multimodal acquisitions are often unavailable due to time and protocol constraints. This leads to real-world datasets with missing modalities, where conventional medical image translation methods are typically limited to fixed source-target settings or require retraining for each observed source-target pair. We propose a unified framework that formulates missing-modality generation as a linear inverse problem under a joint distribution and solves it via posterior sampling with a flow matching model. By learning a joint prior over the complete modality set, our method can reconstruct arbitrary missing modalities at inference time by guiding the sampling trajectory to enforce measurement consistency with observed modalities. We further mitigate inter-modality error propagation in multi-target generation by adopting a many-to-one sampling strategy. Experiments on BraTS and IXI datasets show that our method achieves the best performance over baselines across most missing-modality scenarios. In downstream tumor segmentation, synthesized images from our method result in higher segmentation performance, indicating better preservation of clinically relevant structures.
Jonghun Kim
Department of Electrical and Computer Engineering, Sungkyunkwan University, Suwon, Korea
Robust segmentation of clinically significant prostate cancer (csPCa) on multi-parametric MRI must tolerate frequent degradation of its most informative diffusion sequences. Multi-modal fusion commonly employs learned modality gating under the assumption that gates implement per-sample modality quality routing -- rarely tested directly. We ask how gating behaves across backbone architectures. We systematically analyze modality-isolated gated fusion (MIGF) for csPCa segmentation on two backbones (nnU-Net and Mamba) using PI-CAI (n=1500), with cross-cohort validation on Prostate158 (n=158): a factorial ablation over gating, modality dropout, and deep supervision under 5-fold cross-validation (180 trained models), plus a gate-weight and counterfactual analysis of 30 trained gating models. Modality gating is backbone-conditional. On nnU-Net, adding gating reduces the ranking score (marginal effect -0.037; gating configurations p<0.05), whereas on Mamba the gating-plus-dropout configuration improves it (+0.024, p=0.037). Gate-weight analysis explains this: nnU-Net gates collapse into a near-static modality prior (across-case SD 0.0033), while Mamba gates retain sample-dependent variation (0.0365, ~11x larger, non-overlapping); replacing per-sample gates with their training-set mean leaves nnU-Net unchanged but degrades Mamba. Modality dropout is the only component beneficial on both backbones. Under cross-cohort shift, convolutional backbones collapse to case-level specificity near zero, whereas Mamba retains it (MIGF-Mamba highest, 0.31). Learned modality gates do not universally perform per-sample quality routing; their effective behavior is conditional on the backbone's inherent modality awareness. Among tested configurations, MIGF-Mamba is the most cross-cohort robust, and training-time modality dropout is the only component beneficial across both backbones.
Yongbo Shu, Wenzhao Xie, Shanhu Yao +4
The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, China · School of Life Sciences, Central South University, Changsha, 410013, Hunan, China · Hunan Provincial Key Laboratory of Medical Information Research (Central South University), Changsha, 410011, Hunan, China +2
Zero-shot MRI reconstruction relies on generative priors, but single-modality unconditional priors produce hallucinations under severe ill-posedness. In many clinical workflows, complementary MRI acquisitions (e.g. high-quality structural scans) are routinely available, yet existing reconstruction methods lack mechanisms to leverage this additional information. We propose MPFlow, a zero-shot multi-modal reconstruction framework built on rectified flow that incorporates auxiliary MRI modalities at inference time without retraining the generative prior to improve anatomical fidelity. Cross-modal guidance is enabled by our proposed self-supervised pretraining strategy, Patch-level Multi-modal MR Image Pretraining (PAMRI), which learns shared representations across modalities. Sampling is jointly guided by data consistency and cross-modal feature alignment using pre-trained PAMRI, systematically suppressing intrinsic and extrinsic hallucinations. Extensive experiments on HCP and BraTS show that MPFlow matches diffusion baselines on image quality using only 20% of sampling steps while reducing tumor hallucinations by more than 15% (segmentation dice score). This demonstrates that cross-modal guidance enables more reliable and efficient zero-shot MRI reconstruction.
Seunghoi Kim, Chen Jin, Henry F. J. Tregidgo +2
University College London, UK · Centre for AI, DS&AI, AstraZeneca, UK