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Kuangyu Shi

Publications and source records attributed to Kuangyu Shi.

At least 19 recordsLinked to original sources

Voxel-wise Bayesian Estimation for Multi-Population Positronium Lifetime Imaging

Positronium lifetime imaging (PLI) provides local annihilation environment data beyond conventional activity imaging. Existing approaches, however, often estimate lifetime parameters over predefined regions, neglecting multiple lifetime populations within the same location. We present a 3D, population-specific Bayesian framework for fast voxel-wise PLI. A partial system matrix describes the spatial probability of detected events, while measured lifetimes provide soft assignments to slow, fast, and noise populations. These event responsibilities are used to estimate a decay-rate posterior independently for each voxel, preserving local lifetime variation and statistical uncertainty. In simulations, our formulation recovered spatially varying slow-population decay rates and a common fast-population rate, whereas a single-population model produced systematic bias. Slow-population two-standard-deviation coverage ranged from 93.8% to 98.1%. Experimental validation using 124I triple-coincidence data from a Siemens Biograph Vision Quadra scanner produced separate slow- and fast-population maps for aluminum, nickel, copper, and quartz. The long-lived quartz component matched ortho-positronium, while the fast population showed material-dependent differences among metals. Fast-population coverage was lower (69.1%), indicating underestimated uncertainty. The method is highly efficient, requiring only seconds to minutes per population on a single CPU core. This framework provides fast, population-specific PLI with Bayesian uncertainty quantification, making spatially resolved statistical inference feasible and practical for volumetric applications.

stat.AP

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.

eess.IV

TheraAgent: Multi-Agent Framework with Self-Evolving Memory and Evidence-Calibrated Reasoning for PET Theranostics

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.

cs.AI

CT-Conditioned Diffusion Prior with Physics-Constrained Sampling for PET Super-Resolution

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.

cs.CV

Developing Foundation Models for Universal Segmentation from 3D Whole-Body Positron Emission Tomography

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.

cs.CV

DECADE: A Temporally-Consistent Unsupervised Diffusion Model for Enhanced Rb-82 Dynamic Cardiac PET Image Denoising

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.

cs.CV

Feasibility study of the positronium lifetime imaging with the Biograph Vision Quadra and J-PET tomographs

Background: After its first ex-vivo and in-vivo demonstration, Positronium Lifetime Imaging (PLI) has received considerable interest as a potential new diagnostic biomarker. High sensitivity Positron Emission Tomography (PET) systems are needed for PLI since it requires simultaneous registration of annihilation photons and prompt gamma. In this simulation-based study, a~feasibility of PLI with the long axial field-of-view Biograph Vision Quadra (Quadra) and the Total Body J-PET scanner was investigated. Methods: The study was performed using the GATE software. Background radiation, present within the Quadra tomograph, was added to the simulation. First, the optimal placement of the energy window for the registration of the prompt gamma was investigated. Next, the organ-wise sensitivity of Quadra was calculated for the $^{68}$Ga, $^{44}$Sc, $^{22}$Na and $^{124}$I radioisotopes. Finally, the sensitivity for the scandium isotope was compared to the sensitivities obtainable with the Total Body J-PET scanner, as well as with the modular J-PET prototype. Results: The PLI sensitivities for the Quadra with the background radiation are estimated to 9.22(3), 10.46(4), 5.91(3), and 15.39(4) cps/kBq for the $^{44}$Sc, $^{68}$Ga, $^{22}$Na and $^{124}$I radioisotopes, respectively. The highest sensitivity was obtained when the energy window for the deexcitation photon is adjacent to the energy window for the annihilation photons. The determined PLI sensitivities with Quadra and the Total Body J-PET are in the order of sensitivities of standard PET imaging with the short axial field-of-view ($\sim$20 cm) PET scanners. Conclusion: The organ-wise PLI sensitivity of Quadra has been computed for the $^{68}$Ga, $^{44}$Sc, $^{22}$Na and $^{124}$I radioisotopes. A sensitivity gain by a factor of 150 was estimated relative to the modular J-PET system previously used for the first in-vivo PLI.

physics.med-ph

First Positronium Lifetime Imaging using $^{52}$Mn and $^{55}$Co with a plastic-based PET scanner

Positronium Lifetime Imaging (PLI) extends positron emission tomography by using the lifetime of positronium atoms as a probe of tissue molecular architecture. In this work, we report the first PLI measurements performed with $^{52}$Mn and $^{55}$Co using the modular J-PET. Four samples were studied in each experiment: two Certified Reference Materials (polycarbonate and fused silica) and two human tissues (cardiac myxoma and adipose). The selection of PLI events was based on the registration of two 511~keV annihilation photons and one prompt gamma in triple coincidence. From the resulting lifetime spectra we extracted the mean ortho-positronium lifetime $\tau_{\text{oPs}}$ and the mean positron lifetime $\Delta T_{\text{mean}}$ for each sample. The measured values of $\tau_{\text{oPs}}$ in polycarbonate using both isotopes matches well with the certified reference values. Furthermore, $^{55}$Co reproduced identical results for fused-silica measurements at their respective uncertainty levels. In contrast, measurements with $^{52}$Mn in fused silica show a minor deviation, which could be caused by the Parafilm spacer. In myxoma and adipose tissue, the reduced $\tau_{\text{oPs}}$ values are mainly linked to the long storage history of the samples rather than to the choice of isotope. Comparing peak-to-background ratios and spectral purity, $^{55}$Co provides cleaner PLI data under the same experimental conditions. Although $^{52}$Mn offers a longer half-life and a multi gamma cascade enhancing $\beta^{+}$ + $\gamma$ coincidences, but at the expense of higher background. In this study, we demonstrate that the applied selection criteria on the data measured with the modular J-PET can be used for PLI studies even with radionuclides with complex decay patterns.

physics.med-ph

A Brief History of Digital Twin Technology

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.

cs.AI

Mathematical and Computational Nuclear Oncology: Toward Optimized Radiopharmaceutical Therapy via Digital Twins

This article presents the general framework of theranostic digital twins (TDTs) in computational nuclear medicine, designed to support clinical decision-making and improve cancer patient prognosis through personalized radiopharmaceutical therapies (RPTs). It outlines potential clinical applications of TDTs and proposes a roadmap for successful implementation. Additionally, the chapter provides a conceptual overview of the current state of the art in the mathematical and computational modeling of RPTs, highlighting key challenges and the strategies being pursued to address them.

q-bio.OT

Patient-specific AI for generation of 3D dosimetry imaging from two 2D-planar measurements

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.

physics.med-ph

Artificial intelligence for simplified patient-centered dosimetry in radiopharmaceutical therapies

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.

physics.med-ph

An Overview of Physiologically Based Pharmacokinetic (PBPK) and Population Pharmacokinetic (PopPK) Models

This review discusses the current applications, advantages, and limitations of PBPK and PopPK models in radiopharmaceutical therapy (RPT). PBPK models simulate radiopharmaceutical kinetics by integrating prior physiological and drug parameter information, whereas PopPK models leverage population data to enhance individual dose estimation accuracy. Future directions include developing hybrid models, incorporating artificial intelligence, and establishing regulatory guidelines to promote their clinical adoption. Ultimately, these modeling strategies aim to enable precise, personalized RPT dosing, thereby improving therapeutic outcomes and safety.

physics.med-ph

First Positronium Lifetime Imaging with Scandium-44 on a Long Axial Field-of-view PET/CT

Purpose: 44Sc has been successfully produced, synthesized, labeled and first-in-human studies were conducted some years ago. The decay properties of 44Sc, together with being close to a clinical implementation, make it an ideal candidate for in vivo positronium lifetime measurements. In this study, we investigate the count statistics for ortho-positronium (oPs) measurements with 44Sc. Method: A NEMA image quality phantom was filled with 41.7 MBq of 44Sc dissolved in water and scanned on a commercial long-axial field-of-view PET/CT. Three-photon events were identified using a prototype feature of the scanner and dedicated software. The lifetime of oPs was determined in the phantom spheres and in 4x4x4 mm^3 voxels. Results: All measured oPs lifetimes are compatible, within the uncertainties, with the literature values for water. The oPs lifetime is 2.65+-0.50, 1.39+-0.20 and 1.76+-0.18 ns in the three smallest spheres of the phantom and 1.79+-0.57 ns for a single voxel in the central region of the largest sphere. The relative standard deviation in the background regions of the time difference distributions, i.e., for time differences smaller than -2.7 ns, is above 20% - even for voxels inside the phantom spheres. Conclusions: Despite the favorable physical properties of 44Sc, the count statistics of three-photon events remains a challenge. The high prompt-photon energy causes a significant amount of random three-photon coincidences with the given methodology and, therefore, increases the statistical uncertainties on the measured oPs lifetime.

physics.med-ph

First positronium imaging using $^{44}$Sc with the J-PET scanner: a case study on the NEMA-Image Quality phantom

Positronium Lifetime Imaging (PLI), an emerging extension of conventional positron emission tomography (PET) imaging, offers a novel window for probing the submolecular properties of biological tissues by imaging the mean lifetime of the positronium atom. Currently, the method is under rapid development in terms of reconstruction and detection systems. Recently, the first in vivo PLI of the human brain was performed using the J-PET scanner utilizing the $^{68}$Ga isotope. However, this isotope has limitations due to its comparatively low prompt gamma yields, which is crucial for positronium lifetime measurement. Among alternative radionuclides, $^{44}$Sc stands out as a promising isotope for PLI, characterized by a clinically suitable half-life (4.04 hours) emitting 1157 keV prompt gamma in 100% cases after the emission of the positron. This study reports the first experimental demonstration of PLI with $^{44}$Sc, carried out on a NEMA-Image Quality (IQ) phantom using the Modular J-PET tomograph-the first plastic scintillators-based PET scanner.

physics.med-ph

Fed-NDIF: A Noise-Embedded Federated Diffusion Model For Low-Count Whole-Body PET Denoising

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.

eess.IV

Positronium Imaging: History, Current Status, and Future Perspectives

Positronium imaging was recently proposed to image the properties of positronium atoms in the patient body. Positronium properties depend on the size of intramolecular voids and oxygen concentration; therefore, they deliver information different and complementary to the anatomic, morphological, and metabolic images. Thus far, the mean ortho-positronium lifetime imaging has been at the center of research interest. The first ex vivo and in vivo positronium lifetime images of humans have been demonstrated with the dedicated J-PET scanner enabling simultaneous registration of annihilation photons and prompt gamma from ${\beta^{+} \gamma}$ emitters. Annihilation photons are used to reconstruct the annihilation place and time while prompt gamma is used to reconstruct the time of positronium formation. This review describes recent achievements in the translation of positronium imaging into clinics. The first measurements of positronium lifetime in humans with commercial PET scanners modernized to register triple coincidences are reported. The in vivo observations of differences in ortho-positronium lifetime between tumor and healthy tissues and between different oxygen concentrations are discussed. So far, the positronium lifetime measurements in humans were completed with clinically available ${^{68}\text{Ga}}$, ${^{82}\text{Rb}}$, and ${^{124}\text{I}}$ radionuclides. Status and challenges in developing positronium imaging on a way to a clinically useful procedure are presented and discussed.

physics.med-ph

Semi-Supervised Learning for Dose Prediction in Targeted Radionuclide: A Synthetic Data Study

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.

physics.med-ph