TransNSNet: A Transformer-Enhanced Multi-Scale Adversarial Framework for CT-to-PET Image Synthesis

Positron Emission Tomography (PET) provides important metabolic information for tumor detection and staging but remains significantly less accessible than Computed Tomography (CT) due to its high cost, infrastructure requirements, and reliance on injected radioactive tracers. CT-to-PET image translation using generative models aims to address this disparity, yet state-of-the-art diffusion-based methods are limited by the scarcity of paired training data. To overcome this, we propose a domain-adapted latent diffusion framework that transfers natural-image priors using a relatively small dataset of 21,930 paired CT/PET slices, incorporating a signed power transform to resolve extreme intensity sparsity in PET data. Compared to CPDM, a state-ofthe-art baseline for CT-to-PET image translation, our approach yields superior performance in pixel-wise reconstruction and localized tumor fidelity, demonstrating effective transfer of natural-image priors to the medical domain. We further provide a systematic analysis of evaluation metric reliability for sparse PET data, showing that standard full-image metrics can be misleading indicators of translated image quality, and propose background-filtered and mask-restricted metrics as more clinically meaningful alternatives.

Magnetic Resonance Imaging (MRI), Computed Tomography (CT), and Positron Emission Tomography (PET) provide complementary information about tissues. Medical image-to-image (I2I) translation enables virtual scanning by synthesizing a target modality from a source one without requiring an additional acquisition. Despite growing interest, many methods operate on 2D slices, are evaluated on isolated tasks under different experimental settings, and lack clinically oriented assessment. This work presents a reproducible benchmark for 3D I2I translation in oncological imaging that compares seven generative models: three Generative Adversarial Networks (Pix2Pix, CycleGAN, and SRGAN) and four latent models (Latent Diffusion Model, Latent Diffusion Model+ControlNet, Brownian Bridge, and Flow Matching). The benchmark comprises 77 experiments across eleven configurations drawn from five datasets, covering three anatomical regions (head/neck, lung, and pelvis) and four translation directions (cone-beam CT to CT, MRI to CT, CT to PET, and T2-weighted MRI to T2-FLAIR). Under the evaluated configurations, SRGAN achieves the highest quantitative image fidelity across all tasks, while latent models perform less well, due to information loss introduced by the variational autoencoder. A tumor-level analysis reveals that all models struggle with small lesions and that, in CT to PET synthesis, models reproduce tumor shape more reliably than tracer uptake values. A Visual Turing test involving 17 physicians, including 15 radiologists, shows near-chance classification accuracy (56.7%), suggesting that experts struggle to distinguish real from synthetic volumes under the viewing conditions of the study. Expert preferences do not follow quantitative rankings, exposing a dissociation between quantitative metrics and clinical preference.

Although self-supervised pretraining is expected to learn broadly transferable representations, its effectiveness across imaging modalities substantially different from the pretraining domain, and on complex tumor-segmentation tasks, remains understudied. Evaluating CT-pretrained transformers on MRI rectal cancer segmentation, we identified two interacting failure modes in CT-to-MRI transfer: (a) inefficient token usage caused by zero-padding to match pretrained input dimensions, and (b) ineffective feature adaptation. We investigated these vulnerabilities using two primary CT-pretrained hierarchical shifted-window transformer backbones, SMIT and Swin UNETR, together with VoCo as a large-scale-pretrained supporting benchmark; these models differ in pretraining objectives and datasets. Mechanistic analysis leveraged an attention dilution index (ADI), an entropy-based metric quantifying attention diverted toward uninformative padding tokens, and centered kernel alignment (CKA) to measure feature reuse during MRI adaptation. ADI increased with zero-padding, while high feature reuse did not necessarily translate to improved downstream accuracy. To mitigate these issues, we introduced two interventions: a tumor-aware augmentation strategy to expand tumor appearance heterogeneity coverage, and an anisotropic cropping strategy to restore token efficiency. Fine-tuning with these strategies on identical rectal MRI datasets yielded detection rates of 91.1% (225/247) and 88.7% (219/247) for the primary SMIT and Swin UNETR backbones, with the supporting VoCo benchmark reaching 90.3% (223/247), demonstrating significantly improved robustness under CT-to-MRI transfer. This study is among the first to examine when pretrained transformers fail to transfer across imaging modalities and demonstrates how targeted mitigation strategies can systematically overcome cross-modality transfer limitations.