Kuangyu Shi

Matteo Ferrante, Lisa Rinaldi, Francesca Botta et al.

Lesion segmentation is a crucial step of the radiomic workflow. Manual segmentation requires long execution time and is prone to variability, impairing the realisation of radiomic studies and their robustness. In this study, a deep-learning automatic segmentation method was applied on computed tomography images of non-small-cell lung cancer patients. The use of manual vs automatic segmentation in the performance of survival radiomic models was assessed, as well. METHODS A total of 899 NSCLC patients were included (2 proprietary: A and B, 1 public datasets: C). Automatic segmentation of lung lesions was performed by training a previously developed architecture, the nnU-Net, including 2D, 3D and cascade approaches. The quality of automatic segmentation was evaluated with DICE coefficient, considering manual contours as reference. The impact of automatic segmentation on the performance of a radiomic model for patient survival was explored by extracting radiomic hand-crafted and deep-learning features from manual and automatic contours of dataset A, and feeding different machine learning algorithms to classify survival above/below median. Models' accuracies were assessed and compared. RESULTS The best agreement between automatic and manual contours with DICE=0.78 +(0.12) was achieved by averaging predictions from 2D and 3D models, and applying a post-processing technique to extract the maximum connected component. No statistical differences were observed in the performances of survival models when using manual or automatic contours, hand-crafted, or deep features. The best classifier showed an accuracy between 0.65 and 0.78. CONCLUSION The promising role of nnU-Net for automatic segmentation of lung lesions was confirmed, dramatically reducing the time-consuming physicians' workload without impairing the accuracy of survival predictive models based on radiomics.

Bo Zhou, Huidong Xie, Qiong Liu et al.

Low-count PET is an efficient way to reduce radiation exposure and acquisition time, but the reconstructed images often suffer from low signal-to-noise ratio (SNR), thus affecting diagnosis and other downstream tasks. Recent advances in deep learning have shown great potential in improving low-count PET image quality, but acquiring a large, centralized, and diverse dataset from multiple institutions for training a robust model is difficult due to privacy and security concerns of patient data. Moreover, low-count PET data at different institutions may have different data distribution, thus requiring personalized models. While previous federated learning (FL) algorithms enable multi-institution collaborative training without the need of aggregating local data, addressing the large domain shift in the application of multi-institutional low-count PET denoising remains a challenge and is still highly under-explored. In this work, we propose FedFTN, a personalized federated learning strategy that addresses these challenges. FedFTN uses a local deep feature transformation network (FTN) to modulate the feature outputs of a globally shared denoising network, enabling personalized low-count PET denoising for each institution. During the federated learning process, only the denoising network's weights are communicated and aggregated, while the FTN remains at the local institutions for feature transformation. We evaluated our method using a large-scale dataset of multi-institutional low-count PET imaging data from three medical centers located across three continents, and showed that FedFTN provides high-quality low-count PET images, outperforming previous baseline FL reconstruction methods across all low-count levels at all three institutions.

Zhihao Chen, Jiahui Wang, Yizhou Chen et al.

PET theranostics is transforming precision oncology, yet treatment response varies substantially; many patients receiving 177Lu-PSMA radioligand therapy (RLT) for metastatic castration-resistant prostate cancer (mCRPC) fail to respond, demanding reliable pre-therapy prediction. While LLM-based agents have shown remarkable potential in complex medical diagnosis, their application to PET theranostic outcome prediction remains unexplored, which faces three key challenges: (1) data and knowledge scarcity: RLT was only FDA-approved in 2022, yielding few training cases and insufficient domain knowledge in general LLMs; (2) heterogeneous information integration: robust prediction hinges on structured knowledge extraction from PET/CT, laboratory tests, and free-text clinical documentation; (3) evidence-grounded reasoning: clinical decisions must be anchored in trial evidence rather than LLM hallucinations. In this paper, we present TheraAgent, to our knowledge, the first agentic framework for PET theranostics, with three core innovations: (1) Multi-Expert Feature Extraction with Confidence-Weighted Consensus, where three specialized experts process heterogeneous inputs with uncertainty quantification; (2) Self-Evolving Agentic Memory (SEA-Mem), which learns prognostic patterns from accumulated cases, enabling case-based reasoning from limited data; (3) Evidence-Calibrated Reasoning, integrating a curated theranostics knowledge base to ground predictions in VISION/TheraP trial evidence. Evaluated on 35 real patients and 400 synthetic cases, TheraAgent achieves 75.7% overall accuracy on real patients and 87.0% on synthetic cases, outperforming MDAgents and MedAgent-Pro by over 20%. These results highlight a promising blueprint for trustworthy AI agents in PET theranostics, enabling trial-calibrated, multi-source decision support. Code will be released upon acceptance.

Liutao Yang, Zi Wang, Peiyuan Jing et al.

PET super-resolution is highly under-constrained because paired multi-resolution scans from the same subject are rarely available, and effective resolution is determined by scanner-specific physics (e.g., PSF, detector geometry, and acquisition settings). This limits supervised end-to-end training and makes purely image-domain generative restoration prone to hallucinated structures when anatomical and physical constraints are weak. We formulate PET super-resolution as posterior inference under heterogeneous system configurations and propose a CT-conditioned diffusion framework with physics-constrained sampling. During training, a conditional diffusion prior is learned from high-quality PET/CT pairs using cross-attention for anatomical guidance, without requiring paired LR--HR PET data. During inference, measurement consistency is enforced through a scanner-aware forward model with explicit PSF effects and gradient-based data-consistency refinement. Under both standard and OOD settings, the proposed method consistently improves experimental metrics and lesion-level clinical relevance indicators over strong baselines, while reducing hallucination artifacts and improving structural fidelity.

Yichi Zhang, Le Xue, Wenbo Zhang et al.

Positron emission tomography (PET) is a key nuclear medicine imaging modality that visualizes radiotracer distributions to quantify in vivo physiological and metabolic processes, playing an irreplaceable role in disease management. Despite its clinical importance, the development of deep learning models for quantitative PET image analysis remains severely limited, driven by both the inherent segmentation challenge from PET's paucity of anatomical contrast and the high costs of data acquisition and annotation. To bridge this gap, we develop generalist foundational models for universal segmentation from 3D whole-body PET imaging. We first build the largest and most comprehensive PET dataset to date, comprising 11041 3D whole-body PET scans with 59831 segmentation masks for model development. Based on this dataset, we present SegAnyPET, an innovative foundational model with general-purpose applicability to diverse segmentation tasks. Built on a 3D architecture with a prompt engineering strategy for mask generation, SegAnyPET enables universal and scalable organ and lesion segmentation, supports efficient human correction with minimal effort, and enables a clinical human-in-the-loop workflow. Extensive evaluations on multi-center, multi-tracer, multi-disease datasets demonstrate that SegAnyPET achieves strong zero-shot performance across a wide range of segmentation tasks, highlighting its potential to advance the clinical applications of molecular imaging.

Jing Zhang, Alexandre Bousse, Chi-Hieu Pham et al.

Targeted Radionuclide Therapy (TRT) is a modern strategy in radiation oncology that aims to administer a potent radiation dose specifically to cancer cells using cancer-targeting radiopharmaceuticals. Accurate radiation dose estimation tailored to individual patients is crucial. Deep learning, particularly with pre-therapy imaging, holds promise for personalizing TRT doses. However, current methods require large time series of SPECT imaging, which is hardly achievable in routine clinical practice, and thus raises issues of data availability. Our objective is to develop a semi-supervised learning (SSL) solution to personalize dosimetry using pre-therapy images. The aim is to develop an approach that achieves accurate results when PET/CT images are available, but are associated with only a few post-therapy dosimetry data provided by SPECT images. In this work, we introduce an SSL method using a pseudo-label generation approach for regression tasks inspired by the FixMatch framework. The feasibility of the proposed solution was preliminarily evaluated through an in-silico study using synthetic data and Monte Carlo simulation. Experimental results for organ dose prediction yielded promising outcomes, showing that the use of pseudo-labeled data provides better accuracy compared to using only labeled data.

Alejandro Lopez-Montes, Robert Seifert, Astrid Delker et al.

In this work we explored the use of patient specific reinforced learning to generate 3D activity maps from two 2D planar images (anterior and posterior). The solution of this problem remains unachievable using conventional methodologies and is of particular interest for dosimetry in nuclear medicine where approaches for post-therapy distribution of radiopharmaceuticals such as 177Lu-PSMA are typically done via either expensive and long 3D SPECT acquisitions or fast, yet only 2D, planar scintigraphy. Being able to generate 3D activity maps from planar scintigraphy opens the gate for new dosimetry applications removing the need for SPECT and facilitating multi-time point dosimetry studies. Our solution comprises the generation of a patient specific dataset with possible 3D uptake maps of the radiopharmaceuticals withing the anatomy of the individual followed by an AI approach (we explored both the use of 3DUnet and diffusion models) able to generate 3D activity maps from 2D planar images. We have validated our method both in simulation and real planar acquisitions. We observed enhanced results using patient specific reinforcement learning (~20% reduction on MAE and ~5% increase in SSIM) and better organ delineation and patient anatomy especially when combining diffusion models with patient specific training yielding a SSIM=0.89 compared to the ground truth for simulations and 0.73 when compared to a SPECT acquisition performed half an hour after the planar. We believe that our methodology can set a change of paradigm for nuclear medicine dosimetry allowing for 3D quantification using only planar scintigraphy without the need of expensive and time-consuming SPECT leveraging the pre-therapy information of the patients.

Yujin Oh, Robert Seifert, Yihan Cao et al.

In oncology, Positron Emission Tomography-Computed Tomography (PET/CT) is widely used in cancer diagnosis, staging, and treatment monitoring, as it combines anatomical details from CT with functional metabolic activity and molecular marker expression information from PET. However, existing artificial intelligence-driven PET/CT analyses rely predominantly on task-specific models trained from scratch or on limited datasets, limiting their generalizability and robustness. To address this, we propose a foundation model approach specifically designed for multimodal PET/CT imaging. We introduce the Cross-Fraternal Twin Masked Autoencoder (FratMAE), a novel framework that effectively integrates whole-body anatomical and functional or molecular information. FratMAE employs separate Vision Transformer (ViT) encoders for PET and CT scans, along with cross-attention decoders that enable synergistic interactions between modalities during masked autoencoder training. Additionally, it incorporates textual metadata to enhance PET representation learning. By pre-training on PET/CT datasets, FratMAE captures intricate cross-modal relationships and global uptake patterns, achieving superior performance on downstream tasks and demonstrating its potential as a generalizable foundation model.

Yinchi Zhou, Liang Guo, Huidong Xie et al.

Rb-82 dynamic cardiac PET imaging is widely used for the clinical diagnosis of coronary artery disease (CAD), but its short half-life results in high noise levels that degrade dynamic frame quality and parametric imaging. The lack of paired clean-noisy training data, rapid tracer kinetics, and frame-dependent noise variations further limit the effectiveness of existing deep learning denoising methods. We propose DECADE (A Temporally-Consistent Unsupervised Diffusion model for Enhanced Rb-82 CArdiac PET DEnoising), an unsupervised diffusion framework that generalizes across early- to late-phase dynamic frames. DECADE incorporates temporal consistency during both training and iterative sampling, using noisy frames as guidance to preserve quantitative accuracy. The method was trained and evaluated on datasets acquired from Siemens Vision 450 and Siemens Biograph Vision Quadra scanners. On the Vision 450 dataset, DECADE consistently produced high-quality dynamic and parametric images with reduced noise while preserving myocardial blood flow (MBF) and myocardial flow reserve (MFR). On the Quadra dataset, using 15%-count images as input and full-count images as reference, DECADE outperformed UNet-based and other diffusion models in image quality and K1/MBF quantification. The proposed framework enables effective unsupervised denoising of Rb-82 dynamic cardiac PET without paired training data, supporting clearer visualization while maintaining quantitative integrity.

Yunqi Zhang, Kuangyu Shi, Biao Li

Emerging from NASA's spacecraft simulations in the 1960s, digital twin technology has advanced through industrial adoption to spark a healthcare transformation. A digital twin is a dynamic, data-driven virtual counterpart of a physical system, continuously updated through real-time data streams and capable of bidirectional interaction. In medicine, digital twin integrates imaging, biosensors, and computational models to generate patient-specific simulations that support diagnosis, treatment planning, and drug development. Representative applications include cardiac digital twin for predicting arrhythmia treatment outcomes, oncology digital twin for tracking tumor progression and optimizing radiotherapy, and pharmacological digital twin for accelerating drug discovery. Despite rapid progress, major challenges, including interoperability, data privacy, and model fidelity, continue to limit widespread clinical integration. Emerging solutions such as explainable AI, federated learning, and harmonized regulatory frameworks offer promising pathways forward. Looking ahead, advances in multi-organ digital twin, genomics integration, and ethical governance will be essential to ensure that digital twin shifts healthcare from reactive treatment to predictive, preventive, and truly personalized medicine.

Alejandro Lopez-Montes, Fereshteh Yousefirizi, Yizhou Chen et al.

KEY WORDS: Artificial Intelligence (AI), Theranostics, Dosimetry, Radiopharmaceutical Therapy (RPT), Patient-friendly dosimetry KEY POINTS - The rapid evolution of radiopharmaceutical therapy (RPT) highlights the growing need for personalized and patient-centered dosimetry. - Artificial Intelligence (AI) offers solutions to the key limitations in current dosimetry calculations. - The main advances on AI for simplified dosimetry toward patient-friendly RPT are reviewed. - Future directions on the role of AI in RPT dosimetry are discussed.

Yinchi Zhou, Huidong Xie, Menghua Xia et al.

Low-count positron emission tomography (LCPET) imaging can reduce patients' exposure to radiation but often suffers from increased image noise and reduced lesion detectability, necessitating effective denoising techniques. Diffusion models have shown promise in LCPET denoising for recovering degraded image quality. However, training such models requires large and diverse datasets, which are challenging to obtain in the medical domain. To address data scarcity and privacy concerns, we combine diffusion models with federated learning -- a decentralized training approach where models are trained individually at different sites, and their parameters are aggregated on a central server over multiple iterations. The variation in scanner types and image noise levels within and across institutions poses additional challenges for federated learning in LCPET denoising. In this study, we propose a novel noise-embedded federated learning diffusion model (Fed-NDIF) to address these challenges, leveraging a multicenter dataset and varying count levels. Our approach incorporates liver normalized standard deviation (NSTD) noise embedding into a 2.5D diffusion model and utilizes the Federated Averaging (FedAvg) algorithm to aggregate locally trained models into a global model, which is subsequently fine-tuned on local datasets to optimize performance and obtain personalized models. Extensive validation on datasets from the University of Bern, Ruijin Hospital in Shanghai, and Yale-New Haven Hospital demonstrates the superior performance of our method in enhancing image quality and improving lesion quantification. The Fed-NDIF model shows significant improvements in PSNR, SSIM, and NMSE of the entire 3D volume, as well as enhanced lesion detectability and quantification, compared to local diffusion models and federated UNet-based models.

Francesca De Benetti, Walter Simson, Magdalini Paschali et al.

Dynamic positron emission tomography imaging (dPET) provides temporally resolved images of a tracer enabling a quantitative measure of physiological processes. Voxel-wise physiologically-based pharmacokinetic (PBPK) modeling of the time activity curves (TAC) can provide relevant diagnostic information for clinical workflow. Conventional fitting strategies for TACs are slow and ignore the spatial relation between neighboring voxels. We train a spatio-temporal UNet to estimate the kinetic parameters given TAC from F-18-fluorodeoxyglucose (FDG) dPET. This work introduces a self-supervised loss formulation to enforce the similarity between the measured TAC and those generated with the learned kinetic parameters. Our method provides quantitatively comparable results at organ-level to the significantly slower conventional approaches, while generating pixel-wise parametric images which are consistent with expected physiology. To the best of our knowledge, this is the first self-supervised network that allows voxel-wise computation of kinetic parameters consistent with a non-linear kinetic model. The code will become publicly available upon acceptance.

Shubham Kumar, Abhijit Guha Roy, Ping Wu et al.

Several diseases of parkinsonian syndromes present similar symptoms at early stage and no objective widely used diagnostic methods have been approved until now. Positron emission tomography (PET) with $^{18}$F-FDG was shown to be able to assess early neuronal dysfunction of synucleinopathies and tauopathies. Tensor factorization (TF) based approaches have been applied to identify characteristic metabolic patterns for differential diagnosis. However, these conventional dimension-reduction strategies assume linear or multi-linear relationships inside data, and are therefore insufficient to distinguish nonlinear metabolic differences between various parkinsonian syndromes. In this paper, we propose a Deep Projection Neural Network (DPNN) to identify characteristic metabolic pattern for early differential diagnosis of parkinsonian syndromes. We draw our inspiration from the existing TF methods. The network consists of a (i) compression part: which uses a deep network to learn optimal 2D projections of 3D scans, and a (ii) classification part: which maps the 2D projections to labels. The compression part can be pre-trained using surplus unlabelled datasets. Also, as the classification part operates on these 2D projections, it can be trained end-to-end effectively with limited labelled data, in contrast to 3D approaches. We show that DPNN is more effective in comparison to existing state-of-the-art and plausible baselines.

Deepa Gunashekar, Sailesh Conjeti, Abhijit Guha Roy et al.

Cross modal image syntheses is gaining significant interests for its ability to estimate target images of a different modality from a given set of source images,like estimating MR to MR, MR to CT, CT to PET etc, without the need for an actual acquisition.Though they show potential for applications in radiation therapy planning,image super resolution, atlas construction, image segmentation etc.The synthesis results are not as accurate as the actual acquisition.In this paper,we address the problem of multi modal image synthesis by proposing a fully convolutional deep learning architecture called the SynNet.We extend the proposed architecture for various input output configurations. And finally, we propose a structure preserving custom loss function for cross-modal image synthesis.We validate the proposed SynNet and its extended framework on BRATS dataset with comparisons against three state-of-the art methods.And the results of the proposed custom loss function is validated against the traditional loss function used by the state-of-the-art methods for cross modal image synthesis.

Hongwei Li, Kanru Lin, Maximilian Reichert et al.

The lethal nature of pancreatic ductal adenocarcinoma (PDAC) calls for early differential diagnosis of pancreatic cysts, which are identified in up to 16% of normal subjects, and some of which may develop into PDAC. Previous computer-aided developments have achieved certain accuracy for classification on segmented cystic lesions in CT. However, pancreatic cysts have a large variation in size and shape, and the precise segmentation of them remains rather challenging, which restricts the computer-aided interpretation of CT images acquired for differential diagnosis. We propose a computer-aided framework for early differential diagnosis of pancreatic cysts without pre-segmenting the lesions using densely-connected convolutional networks (Dense-Net). The Dense-Net learns high-level features from whole abnormal pancreas and builds mappings between medical imaging appearance to different pathological types of pancreatic cysts. To enhance the clinical applicability, we integrate saliency maps in the framework to assist the physicians to understand the decision of the deep learning method. The test on a cohort of 206 patients with 4 pathologically confirmed subtypes of pancreatic cysts has achieved an overall accuracy of 72.8%, which is significantly higher than the baseline accuracy of 48.1%, which strongly supports the clinical potential of our developed method.