A conditional generative model for T2-weighted prostate MRI with downstream evaluation in clinically significant cancer classificatio
Authors: Xavier Rafael-Palou, Alejandro Vergara-Richart, Ignacio Iborra Roncales, Carmen Prieto-de-la-Lastra, Andreu Antolin-Redondo, Juan Morote, Ana Jimenez-Pastor
Organizations: Quantitative Imaging Biomarkers in Medicine · Quantitative Imaging Biomarkers in Medicine (Quibim S.L.), Valencia, Spain · Universitat Politècnica de València, València, Spain · Universitat Polit`ecnica de Val`encia, Val`encia, Spain · Department of Radiology, Institut de Diagnòstic per la Imatge · Department of Surgery, Universitat Autònoma de Barcelona, Bellaterra, Spain · Department of Radiology, Institut de Diagn`ostic per la Imatge (IDI), Hospital Universitari Vall d’Hebron, Barcelona, Spain · Department of Surgery, Universitat Aut`onoma de Barcelona, Bellaterra, Spain
Scarce and unrepresentative training data limit the performance of prostate MRI prediction models. Synthetic T2-weighted (T2W) MRI may augment training data containing clinically significant prostate cancer (csPCa) and transition zone (TZ) lesions. In this retrospective, single-center, ethics-committee-approved study, we developed a conditional generative model for T2W prostate MRI extending MAISI-v2 with csPCa class, zonal, and lesion-mask-guided conditioning, incorporating a relative advantage weighted loss fine-tuned on 1,303 patients (1,654 lesions). Fidelity was assessed by incremental ablation, and downstream utility was evaluated with T2W-based csPCa classifiers across five simulated training-data scenarios, each testing 18 synthetic-data configurations. The proposed model reduced Fréchet inception distance (FID) from 13.28 (pretrained MAISI-v2) to 2.04±0.06 internally (PI-CAI: 3.83±0.51). Synthetic augmentation significantly increased AUC in all five scenarios (+0.027 to +0.088; adjusted p=0.016--0.043), though cross-institutional augmentation of PI-CAI yielded a non-significant gain (+0.013; p=0.397). Overall, our model improved T2W MRI fidelity, and synthetic images improved csPCa classification under simulated data constraints, although benefit did not transfer significantly across institutions.
Figures & tables
Abbreviation
Definition
ADC
Apparent diffusion coefficient
AUC
Area under the receiver operating characteristic curve
BH
Benjamini–Hochberg
CNet
ControlNet
csPCa
Clinically significant prostate cancer
CV
Cross-validation
Table 1
Train
Validation
Test
Lesion level
Patient level
Lesion level
Patient level
Lesion level
Patient level
Cases
1,335
1,047
159
126
160
130
csPCa − (csPCa+)
855 (480)
609 (438)
112 (47)
84 (42)
106 (54)
81 (49)
Lesion PZ (TZ)
877 (458)
683 (364)
110 (49)
90 (36)
100 (60)
83 (47)
Prostate vol. (mL)
53.0 (40.0, 73.0)
53.0 (40.0, 74.0)
60.0 (42.0, 87.0)
59.5 (40.0, 84.8)
52.0 (35.0, 78.3)
52.5 (37.0, 79.0)
Spacing XY (mm)
0.625 (0.56, 0.63)
0.625 (0.56, 0.63)
0.625 (0.56, 0.63)
0.625 (0.56, 0.63)
0.625 (0.56, 0.63)
0.625 (0.56, 0.63)
Table 1: Cohort characteristics of the training, validation, and test partitions, reported at the lesion level and patient level. Continuous variables are reported as median (interquartile range, 25th–75th percentiles). csPCa − (csPCa+), cases without (with) clinically significant prostate cancer; Lesion PZ (TZ), cases with the lesion in the peripheral (transition) zone; FoV, field of view.
Figure 1: Study flowchart. Left, in-house cohort: exclusions, patient-level partitions for generative model development and csPCa classification, and the five training scenarios augmented with the proposed generative model. Right, PI-CAI cohort: patient-level split, 5-fold cross-validation for configuration and threshold selection, external generative fidelity evaluation, and cross-institutional classification with in-house synthetic subsets. PCa, prostate cancer; csPCa, clinically significant PCa; PZ, peripheral zone; TZ, transition zone; CV, cross-validation; R, real-only; R+S, real plus synthetic.
Figure 2: Overview of the proposed generative model, comprising three networks: variational autoencoder (VAE), latent diffusion model (LDM) and ControlNet (CNET). The ControlNet receives the multi-class zone and lesion mask, the noisy latent ( xt ), and the timestep ( t ), modality and csPCa embedding, and injects its features into the frozen LDM U-Net, which also receives the voxel spacing; the frozen VAE decoder maps the generated latent ( z ) to the synthetic T2-weighted image. csPCa, clinically significant prostate cancer.
Scenario training set (real data)
Scenario
Constraint applied
Total
csPCa+
csPCa −
TZ Lesions
PZ Lesions
csPCa+ & TZ
Full data
None. All downstream training set
968
394
574
345
623
147
Low data
30% of downstream training set
290
118
172
103
187
49
csPCa+ imbal.
30% of csPCa+ lesions from downstream train
693
119
574
247
446
49
TZ imbal.
30% of TZ lesions from downstream train
727
296
431
104
623
49
csPCa+/TZ imbal.
30% of csPCa+ TZ lesions from downstream train
866
292
574
243
623
45
Table 2: Simulated training-data scenarios and characteristics of their real training sets (patient level). csPCa, clinically significant prostate cancer; PZ, peripheral zone; TZ, transition zone.
Factor
Levels
Description
Synthetic size
10%, 20%, 30%
Proportion of synthetic images relative to the real training set of each scenario.
Class proportion
Balanced, TR-ratio, TR-inv
csPCa+/csPCa − ratio of synthetic subset. Balanced : equal csPCa+/csPCa − . TR-ratio : same ratio as real training set. TR-inv : inverse ratio (e.g., 30:70 becomes 70:30) to counterbalance imbalance.
Case selection
Fixed, Bounded
Selection criterion from generated pool. Fixed : first N images without filtering. Bounded : uncertainty-guided, retaining images with predicted csPCa+ probability between 0.40 and 0.60.
Table 3: Design of synthetic augmentation configurations (18 configurations; 3×3×2 ). csPCa, clinically significant prostate cancer; TR, real training set.
ID
Main components
N Test
FID
KID
Prec
Rec
M0 (MAISI-v2)
LDM
130
13.28±2.01
0.0093±4.7×10−4
0.302±0.06
0.014±0.01
M1
LDM
130
3.587±0.37
0.0027±5.2×10−4
0.514±0.08
0.287±0.09
M2
LDM + csPCa
130
3.173±0.31
0.0023±4.4×10−4
0.558±0.07
0.315±0.09
M3
LDM + csPCa + EMA
130
2.789±0.27
0.0019±3.8×10−4
0.531±0.07
0.354±0.09
M4
CNet + LDM (M3)
160
2.653±0.08
0.0019±9.4×10−4
0.559±0.08
0.385±0.10
M5
CNet + LDM (M3) + relLoss
160
2.439±0.08
0.0017±8.1×10−4
0.574±0.08
0.390±0.10
Table 4: Quantitative test-set ablation results. LDM models were trained and tested on patient-level dataset, whereas CNet-based models used the lesion-level dataset. Values are mean ± SD across the three orthogonal planes. M0 is the pretrained MAISI-v2 model without fine-tuning. CNet, ControlNet; csPCa, clinically significant prostate cancer class conditioning; EMA, exponential moving average; FID, Fréchet inception distance; KID, kernel inception distance; LDM, latent diffusion model; Prec, precision; Rec, recall; relLoss, relative advantage loss; relWLoss, relative advantage weighted loss; wLoss, region-weighted loss.
Figure 3: Generative ablation results on the in-house test set: Fréchet inception distance (FID; left, log scale; values above bars are means) and precision and recall (right) for the pretrained baseline (M0), latent diffusion model (LDM) ablations (M1–M3), ControlNet and loss ablations (M4–M6), and the proposed model (M7, Ours). Error bars represent SD across the three orthogonal planes.
Figure 4: Representative axial T2-weighted slices of four cases (rows): real image (first column) and synthetic images from M3 (best LDM without mask conditioning; second column), M5 (ControlNet with relative advantage loss; third column), M6 (ControlNet with region-weighted loss; fourth column), and M7 (proposed model, ControlNet with relative advantage weighted loss; last column).
Synthetic criteria
Test results
Scenario
Data
Sz
Prop
Sel
AUC
F1
Prec
Sens
Spec
Full data
R
–
–
–
0.673±0.01
0.561±0.05
0.487±0.02
0.669±0.12
0.576±0.06
R+S
10
TR-inv
Bound
0.705±0.01
0.582±0.05
0.485±0.01
0.743±0.15
0.523±0.07
Low data
R
–
–
–
0.616±0.08
0.552±0.01
0.452±0.04
0.721±0.06
0.457±0.13
R+S
20
TR-ratio
Bound
0.704±0.02
0.578±0.02
0.493±0.06
0.739±0.16
0.502±0.26
csPCa+ imbal.
R
–
–
–
0.590±0.02
0.516±0.03
0.414±0.02
0.700±0.12
0.394±0.15
Table 5: csPCa test-set results of the best configurations trained with real data only (R) and with synthetic augmentation (R+S) in each scenario. Synthetic criteria apply only to R+S: Sz, synthetic size (% of the real training set); Prop, class proportion; Sel, case selection (Table 3 ). Values are mean ± SD across five seeds. AUC, area under the curve; Bound, uncertainty-bounded selection; csPCa, clinically significant prostate cancer; TR-inv, inverse ratio; TR-ratio, real ratio; TZ, transition zone.
Figure 5: Effect of synthetic T2-weighted (T2W) augmentation (R+S) versus real data only (R) in the five training scenarios: test AUC (A) and F1-score (B), shown as mean and SD across five seeds with the R+S − R difference above each pair, and heatmap of the R+S − R differences for all test metrics (C). AUC, area under the receiver operating characteristic curve; csPCa, clinically significant prostate cancer; imbal., imbalance; TZ, transition zone.
The development of AI systems for tumor-specific applications is limited by the scarcity of labeled data. Synthetic tumor inpainting offers a promising approach but faces challenges for prostate cancer MRI which contains high-resolution multi-sequence data. Although methods leveraging latent diffusion models (LDMs) enable large-volume synthesis, they are prone to shortcut learning, simply reproducing the condition image created by masking the lesion region. In this work, we introduce PCaPaint, a prostate cancer inpainting method based on LDMs that explicitly addresses this failure mode. To overcome shortcut learning that compromises synthetic tumor texture, we propose a simple yet efficient conditioning strategy in which the condition image is filled with Gaussian noise, and we provide theoretical justification. In addition, we propose a novel training objective for LDM that emphasizes the error within the lesion region. Furthermore, we introduce a multi-sequence latent design, in which T2w scans and DWI&ADC scans are compressed using two separate autoencoders to preserve their distinct frequency characteristics. Extensive experiments demonstrate that the generated synthetic data improves downstream performance in prostate lesion segmentation, patient-level classification and lesion-level detection. Furthermore, our method significantly outperforms a recent state-of-the-art LDM-based tumor inpainting method both in downstream performance and in synthetic image quality.
Generative augmentation is often proposed as a remedy for small medical-image datasets, but synthetic images are only useful when they improve downstream task performance. "Augmentation" here means synthetic supplementation: GAN-generated samples added to the real training pool, not geometric or photometric transforms of existing images. Twelve class-plane StyleGAN2-ADA generators were trained on constrained BRISC 2025 partitions to test whether their output, with or without InceptionV3 feature-space filtering, improves held-out tumour classification across three classifier families: a random forest (RF) on InceptionV3 features, a compact two-headed convolutional neural network (CNN), and MobileViTV2, a mobile hybrid convolutional-transformer. Each was evaluated at 1:1 and 1:2 real-to-synthetic ratios. An independent GPT-5.5 blind test placed gated real-versus-synthetic discrimination at 57.73% (95% CI: 54.48--60.92%) on the model-legible subset -- modestly above chance. The RF classifier did not benefit from the synthetic MRIs. The CNN showed consistent mean gains that did not survive Holm correction. MobileViTV2 showed the clearest benefit: filtered 1:1 augmentation improved tumour classification accuracy by 1.02% absolute (95% CI: 0.54--1.54%; Holm-corrected p = 0.0104). A secondary efficiency analysis found that every augmented CNN condition selected its checkpoint 42--64% earlier than baseline, while compute-matched MobileViTV2 runs reached selection after 50--67% fewer real-data epochs. Overall, augmentation utility was found to be architecture- and ratio-dependent, not guaranteed by visual fidelity alone.
Synthetic biparametric MRI (bpMRI) may help alleviate the limited availability of large and representative prostate MRI datasets for deep learning applications. In this work, we present a conditional 3D diffusion framework for anatomy-conditioned synthesis of complete prostate bpMRI from anatomical masks. The framework supports sequential synthesis, in which T2w and diffusion modalities are generated by separately trained models, and joint synthesis, in which all bpMRI modalities are generated simultaneously within a single model. Five configurations were trained using PI-CAI, FastMRI Prostate, and PROSTATEx datasets to investigate different conditioning schemes, target modalities, and synthesis strategies. Evaluation using distribution-based metrics, paired-image similarity, and qualitative assessment demonstrated the feasibility of both synthesis pathways. Joint synthesis achieved competitive distributional fidelity while generating complete bpMRI, whereas direct synthesis of ADC and computed high-b-value DWI outperformed their derivation from synthetic diffusion-weighted images.