VLM- and LLM-Driven Multi-Agent System for PET Image Denoising

Positron emission tomography (PET) imaging suffers from limited spatial resolution and low signal-to-noise ratio, which can compromise quantitative accuracy and lesion detectability. Deep learning-based denoising methods have demonstrated strong potential for improving PET image quality. However, their practical deployment in real-world settings remains challenging, often requiring multiple specialized models and expert interventions, such as identifying motion-induced misregistration artifacts, estimating noise levels to select an appropriate denoiser, and performing lesion-focused quantitative assessment after denoising. Recent advances in vision-language models (VLMs) for image quality understanding and large language models (LLMs) for contextual reasoning provide new opportunities for automated, decision-driven workflows. Inspired by expert workflows for PET image quality enhancement, we propose an VLM- and LLM-driven multi-agent PET denoising framework that dynamically assesses image quality and lesion status, autonomously selects optimal denoising models and parameters, and enables closed-loop feedback with rollback mechanisms. Experiments were conducted on Siemens Biograph Vision Quadra PET/CT data with 1/20 and 1/50 low-dose settings. Individual module evaluations demonstrated the reliability of the agentic components, while the complete framework achieved higher PSNR and SSIM than UNet, GAN, and DDPM baselines at both dose levels. These preliminary results demonstrate the feasibility of using a closed-loop multi-agent framework to adapt PET denoising strategies to different image conditions.

ENCORE: Efficient Noise Context-Aware Representation for Low-Dose CT Denoising

While deep learning-based denoising has become widely adopted in low-dose CT, conventional models use generic architectures designed for natural images, failing to account for non-stationary and spatially correlated CT noise characteristics. To address this, we propose an Efficient Noise COntext-aware REpresentation (ENCORE) framework that explicitly leverages CT noise characteristics and anatomical features. First, we reformulate the noise synthesis procedure based on a realistic noise distribution beyond the conventional Gaussian approximation, establishing a rigorous foundation for training pair generation. Next, we extract local noise power and correlation contexts to guide the denoising process. To fully leverage the potential of noise context, we propose a FlyingConv module, which adaptively changes convolution weights for each local image region. Notably, our approach demonstrates substantial gains in both denoising quality and computational efficiency. Furthermore, manipulating the intensity of the noise context maps at inference time enables zero-shot conditional denoising, allowing for dynamic control over the output image texture. The entire pipeline is available at https://github.com/minwoo-yu/ENCORE.git

HDDPM: Heteroscedastic Denoising Diffusion Probabilistic Model for Quantitative Low-Count Brain PET Recovery

Positron emission tomography (PET) seeks to balance diagnostic quality with ra-diation dose. Low-count PET noise is non-Gaussian, non-stationary, and spatial-ly dependent. It scales directly with local activity and is shaped by iterative recon-struction and physical corrections. Standard denoising diffusion probabilistic models (DDPMs) ignore these PET properties. Their forward process adds iso-tropic, homoscedastic Gaussian noise to the target. Such an approach fails to cap-ture the realistic physical degradation generated by the imaging system. To ad-dress the above limitations, this study introduces a heteroscedastic residual diffu-sion model (HDDPM) for low-count brain PET recovery in which the forward corruption is itself intensity-aware. We designed a fixed, Poisson-based variance module to generate voxel-wise noise maps. These maps naturally place stronger noise perturbation on low-activity regions than high-activity ones, meanwhile the network predicts the low-to-standard-count residual under explicit dose-fraction conditioning. We evaluated our proposed model (HDDPM) alongside generative frameworks across three different scanners, using both internal and external da-tasets at various simulated dose levels (1% to 50%). HDDPM and isotropic DDPM showed comparable overall image quality, but HDDPM stood out in the lowest-dose (1%) external scans. It is highly reliable and significantly reduces measurement errors in both high- and low-activity regions, compared to the standard model. These results support that heteroscedastic noising with the pro-posed HDDPM is feasible, and it provides a physically motivated inductive bias for quantitative low-count PET recovery by reflecting the activity-dependent noise structure of PET.

A Zero-Shot Deep Image Prior Framework for Denoising and Deconvolution in Fluorescence Microscopy

Fluorescence microscopy images are degraded by noise and diffraction-induced blur, which compromise structural fidelity and limit quantitative analysis. Supervised deep learning methods achieve impressive restoration performance but require large-scale paired datasets that are difficult to obtain in practice. To address this issue, we propose SDIP, a zero-shot deep image prior (DIP) framework that sequentially performs denoising and deconvolution without external training data. An aSeqDIP-based module first suppresses noise while preserving fine structures through sequential autoencoding regularization. In the deconvolution stage, a wavelet-based background correction step is incorporated before the proposed RLG-DIP module performs artifact-reduced deconvolution. RLG-DIP uses the Richardson-Lucy deconvolution result as a physically consistent guidance prior, integrating the imaging model with the implicit prior of DIP to stabilize the ill-posed deconvolution process. Experiments on the BioSR dataset across multiple cellular structures demonstrate that SDIP improves both signal-to-noise ratio and resolution, achieving superior visual quality and improved quantitative performance on most evaluated structures. The proposed framework may also provide useful insights for designing physically guided DIP methods for other inverse problems.

UniPET: a universal network for high-quality PET image denoising across varied dose reduction factors

Most existing deep learning-based PET image denoising methods assume a fixed and known dose reduction factor (DRF) for low-dose PET images. However, these methods encounter significant performance degradation when the DRF varies beyond the assumed one in practical applications. To address the challenge posed by varied DRFs, several preliminary studies focus on the task of universal PET image denoising, aiming to train a universal model over low-dose data across DRFs. Nonetheless, these vanilla universal models often struggle with misaligned styles present in different DRF data, leading to the \textit{style elimination issue} with a significant over-smoothing effect. To deal with this issue, we innovatively introduce domain generalization to PET image denoising and propose a universal PET image denoising network (UniPET) to achieve high-quality PET image denoising across diverse DRFs. UniPET comprises two primary innovations: a style alignment network (SAN) and a region-aware learning strategy (RALS). Specifically, SAN utilizes style alignment techniques derived from domain generalization to align and recover styles across different DRFs, ensuring the model's generalizability across various DRFs while effectively preserving styles. Furthermore, to enhance style recovery, RALS distinguishes between flat and stylized regions, exclusively conducting adversarial learning on the latter, thereby more effectively guiding the model's focus towards learning stylized regions. It is demonstrated that our proposed UniPET can adaptively recover different DRF styles and achieve high-quality PET image denoising across DRFs. Comprehensive experiments show that UniPET exhibits comparable performance to individual DRF-specific models at specific DRFs and realizes state-of-the-art performance in universal PET image denoising quantitatively, perceptually, and clinically.

U-TTT: Towards Generalizable PET Image Denoising via Test-Time Training

Existing deep learning models for Positron Emission Tomography (PET) image denoising often suffer from severe performance degradation under distribution shifts, fundamentally restricting their robust clinical deployment. This lack of generalization stems from the conventional paradigm of fixed-parameter models that cannot adapt to variations in test data (e.g., dose levels or scanner types) after training. To overcome this limitation and achieve robust generalization, we introduce U-TTT, a novel U-shaped model that integrates Test-Time Training (TTT) layers to dynamically adjust model parameters during inference through self-supervision, thereby adapting to the specific characteristics of each test instance. Furthermore, to comprehensively capture the complex degradations of 3D PET data, U-TTT features a dual-domain adaptation mechanism comprising a Spatial Test-Time Training (S-TTT) layer and a Frequency Test-Time Training (F-TTT) layer. The S-TTT layer captures and corrects spatial structural degradations, while the F-TTT layer suppresses global noise spectra and restores delicate high-frequency details. Extensive experiments demonstrate that U-TTT achieves state-of-the-art PET denoising performance and exhibits superior generalization under challenging distribution shifts, including both unseen dose levels and unseen scanners. Our code will be available at https://github.com/Yaziwel/U-TTT.