Domain-Adapted Latent Diffusion Models for CT-to-PET Image Translation

Computed tomography (CT) and positron emission tomography (PET) provide complementary anatomical and functional information for cancer diagnosis and treatment planning. However, the widespread use of PET is limited by high radiation exposure, elevated costs, and restricted availability. To address these limitations, deep learning-based CT-to-PET translation has emerged as a promising approach for synthesizing PET-like information directly from CT images, although accurately modeling the large cross-modal gap remains challenging. In this work, we propose a 3D CT-to-PET translation framework based on latent Brownian Bridge Diffusion (BBDM). The method consists of two stages. First, a Variational Autoencoder (VAE) is trained on paired CT-PET patches, integrating contrastive learning to improve latent alignment between anatomical and metabolic representations. Second, a BBDM is trained in the latent space to translate CT latent representations into their corresponding PET counterparts. The translated PET latents are then decoded and stitched to reconstruct the final 3D PET volume. We evaluate the proposed approach on two publicly available datasets. Quantitative results based on image fidelity and lesion-level PET-specific metrics demonstrate improved performance compared with competing methods. In particular, the proposed approach improves PET signal fidelity, better preserves clinically relevant uptake patterns, and shows improved performance in preserving small-lesion metabolic activation, paving the way for virtual imaging applications.

Synthetic PET images are valuable for quantitative imaging workflow development, scalable virtual imaging trials, and deep learning model training, but conventional physics-based simulation approaches are computationally intensive, limited in anatomical variability, and often fail to capture heterogeneous PET uptake. This study developed a pretrained domain-adapted diffusion (PAD) model for anatomy-conditioned PET synthesis from uniform organ activity maps. PAD adopts a natural-image pretrained text-to-image decoder with an upstream conditioning encoder and a downstream PET-domain adapter. A two-phase training strategy was used, with the first phase learning coarse uptake distributions and the second refining local image details. Uniform organ activity maps were generated from CT-based segmentations by assigning each organ its mean uptake from the paired PET image. Evaluation included quantitative accuracy, noise assessment, radiomic analysis, tumor segmentation performance, and a human observer study. PAD-generated images achieved high quantitative accuracy, with concordance correlation coefficients above 0.92 between organ mean SUVs and assigned activity values. The synthesized images showed noise levels and texture characteristics similar to target PET images and produced comparable tumor segmentation performance. In a two-alternative forced-choice observer study, four readers achieved approximately 50% accuracy, indicating visual indistinguishability between synthesized and target images. PAD also generated realistic PET images from XCAT-derived activity maps, demonstrating compatibility with phantom-based anatomical priors. Overall, PAD provides a diffusion-based framework for generating clinically relevant heterogeneous PET images from uniform organ activity maps derived from clinical segmentations or digital phantoms, supporting data augmentation and downstream imaging studies.

This study investigates CT-to-PET image synthesis using TransNSNet, a Transformer-enhanced multi-scale adversarial framework. A paired CT-PET dataset was curated from the public non-small cell lung cancer (NSCLC) Radiogenomics collection through patient screening, slice-level matching, preprocessing, and patient-level train-test separation. The proposed framework generates PET-like predictions at multiple spatial scales and applies coarse-to-fine reconstruction supervision, while TransPatchGAN introduces contextual feature interaction into adversarial evaluation. A progressive ablation study compares Pix2Pix, NSNet-Base, NSNet-D, and TransNSNet. Image-level performance was summarized over a fixed convergence window (epochs 80-101) from one training run per model. TransNSNet achieved the best mean value in nine of ten metrics, whereas NSNet-Base achieved the highest visual saliency-induced index. For fixed-fraction high-intensity regions, NSNet-D was marginally higher in slice-level recall and balanced accuracy, but the equal-weight patient-level values were nearly identical and the highest Dice values shifted to TransNSNet. These differences were small relative to between-patient variability. In the separate adaptive patient-level analysis (n=10), no pairwise model difference remained statistically significant after Holm correction. TransNSNet also had a substantially smaller parameter footprint than the original next-scale models. These findings indicate promising image-quality trends, but they do not establish statistical superiority or clinical validity; synthesized PET-like images should not be interpreted as substitutes for clinically acquired PET.