Alzheimer's disease (AD) is a heterogeneous neurodegenerative disorder in which tau neurofibrillary tangles are a pathological hallmark closely associated with cognitive dysfunction and neurodegeneration. In this study, we used brain tau data to investigate AD heterogeneity by identifying and characterizing the subpopulations among patients. We included 615 cognitively normal and 159 AD brain ¹⁸F-flortaucipr PET scans, along with T1-weighted MRI from the Alzheimer Disease Neuroimaging Initiative database. A three dimensional-convolutional neural network model was employed for AD detection using standardized uptake value ratio (SUVR) images. The model-derived saliency maps were generated and employed as informative image features for clustering AD participants. Among the identified subpopulations, statistical analysis of demographics, neuropsychological measures, and SUVR were compared. Correlations between neuropsychological measures and regional SUVRs were assessed. A generalized linear model was utilized to investigate the sex and APOE ε4 interaction effect on regional SUVRs. Two distinct subpopulations of AD patients were revealed, denoted as S_Hi and S_Lo. Compared to the S_Lo group, the S_Hi group exhibited a significantly higher global tau burden in the brain, but both groups showed similar cognition distribution levels. In the S_Hi group, the associations between the neuropsychological measurements and regional tau deposition were weakened. Moreover, a significant interaction effect of sex and APOE ε4 on tau deposition was observed in the S_Lo group, but no such effect was found in the S_Hi group. Our results suggest that tau tangles, as shown by SUVR, continue to accumulate even when cognitive function plateaus in AD patients, highlighting the advantages of PET in later disease stages. The differing relationships between cognition and tau deposition, and between gender, APOE4, and tau deposition, provide potential for subtype-specific treatments. Targeting gender-specific and genetic factors influencing tau deposition, as well as interventions aimed at tau's impact on cognition, may be effective.

To accelerate optical photon transport simulations in the GATE medical physics framework using a Generative Adversarial Network (GAN), while ensuring high modeling accuracy. Traditionally, detailed optical Monte Carlo methods have been the gold standard for modeling photon interactions in detectors, but their high computational cost remains a challenge. This study explores the integration of optiGAN, a Generative Adversarial Network (GAN) model into GATE 10, the new Python-based version of the GATE medical physics simulation framework released in November 2024.
Approach: The goal of optiGAN is to accelerate optical photon transport simulations while maintaining modelling accuracy. The optiGAN model, based on a GAN architecture, was integrated into GATE 10 as a computationally efficient alternative to traditional optical Monte Carlo simulations. To ensure consistency, optical photon transport modules were implemented in GATE 10 and validated against GATE v9.3 under identical simulation conditions. Subsequently, simulations using full Monte Carlo tracking in GATE 10 were compared to those using GATE 10-optiGAN.
Main results: Validation studies confirmed that GATE 10 produces results consistent with GATE v9.3. Simulations using GATE 10-optiGAN showed over 92% similarity to Monte Carlo-based GATE 10 results, based on the Jensen-Shannon distance across multiple photon transport parameters. optiGAN successfully captured multimodal distributions of photon position, direction, and energy at the photodetector face. Simulation time analysis revealed a reduction of approximately 50% in execution time with GATE 10-optiGAN compared to full Monte Carlo simulations.
Significance: The study confirms both the fidelity of optical photon transport modeling in GATE 10 and the effective integration of deep learning-based acceleration through optiGAN. This advancement enables large-scale, high-fidelity optical simulations with significantly reduced computational cost, supporting broader applications in medical imaging and detector design.

To investigate the effects of the deep learning model RaDynPET on fourfold reduced-count whole-body PET examinations. A total of 120 patients (84 internal cohorts and 36 external cohorts) undergoing ¹⁸F-FDG PET/CT examinations were enrolled. PET images were reconstructed using OSEM algorithm with 120-s (G120) and 30-s (G30) list-mode data. RaDynPET was developed to generate enhanced images (R30) from G30. Two experienced nuclear medicine physicians independently evaluated subjective image quality using a 5-point Likert scale. Standardized uptake values (SUV), standard deviations, liver signal-to-noise ratio (SNR), lesion tumor-to-background ratio (TBR), and contrast-to-noise ratio (CNR) were compared. Subgroup analyses evaluated performance across demographics, and lesion detectability were evaluated using external datasets. RaDynPET was also compared to other deep learning methods. In internal cohorts, R30 demonstrated significantly higher image quality scores than G30 and G120. R30 showed excellent agreement with G120 for liver and lesion SUV values and surpassed G120 in liver SNR and CNR. Liver SNR and CNR of R30 were comparable to G120 in thin group, and the CNR of R30 was comparable to G120 in young age group. In external cohorts, R30 maintained strong SUV agreement with G120, with lesion-level sensitivity and specificity of 95.45% and 98.41%, respectively. There was no statistical difference in lesion detection between R30 and G120. RaDynPET achieved the highest PSNR and SSIM among deep learning methods. The RaDynPET model effectively restored high image quality while maintaining SUV agreement for ¹⁸F-FDG PET scans acquired in 25% of the standard acquisition time.

Recent work has shown improved lesion detectability and flexibility to reconstruction hyperparameters (e.g. scanner geometry or dose level) when PET images are reconstructed by leveraging pre-trained diffusion models. Such methods train a diffusion model (without sinogram data) on high-quality, but still noisy, PET images. In this work, we propose a simple method for generating subject-specific PET images from a dataset of multi-subject PET-MR scans, synthesizing "pseudo-PET" images by transforming between different patients' anatomy using image registration. The images we synthesize retain information from the subject's MR scan, leading to higher resolution and the retention of anatomical features compared to the original set of PET images. With simulated and real [$^{18}$F]FDG datasets, we show that pre-training a personalized diffusion model with subject-specific "pseudo-PET" images improves reconstruction accuracy with low-count data. In particular, the method shows promise in combining information from a guidance MR scan without overly imposing anatomical features, demonstrating an improved trade-off between reconstructing PET-unique image features versus features present in both PET and MR. We believe this approach for generating and utilizing synthetic data has further applications to medical imaging tasks, particularly because patient-specific PET images can be generated without resorting to generative deep learning or large training datasets.

This study evaluated the relationship between 18F-fluorodeoxyglucose PET/computed tomography (18F-FDG PET/CT) radiomic features and clinical parameters, including tumor localization, histopathological subtype, lymph node metastasis, mortality, and treatment response, in esophageal cancer (EC) patients undergoing chemoradiotherapy and the predictive performance of various machine learning (ML) models. In this retrospective study, 39 patients with EC who underwent pretreatment 18F-FDG PET/CT and received concurrent chemoradiotherapy were analyzed. Texture features were extracted using LIFEx software. Logistic regression, Naive Bayes, random forest, extreme gradient boosting (XGB), and support vector machine classifiers were applied to predict clinical outcomes. Cox regression and Kaplan-Meier analyses were used to evaluate overall survival (OS), and the accuracy of ML algorithms was quantified using the area under the receiver operating characteristic curve. Radiomic features showed significant associations with several clinical parameters. Lymph node metastasis, tumor localization, and treatment response emerged as predictors of OS. Among the ML models, XGB demonstrated the most consistent and highest predictive performance across clinical outcomes. Radiomic features extracted from 18F-FDG PET/CT, when combined with ML approaches, may aid in predicting treatment response and clinical outcomes in EC. Radiomic features demonstrated value in assessing tumor heterogeneity; however, clinical parameters retained a stronger prognostic value for OS.

To develop and validate a novel nomogram combining multi-organ PET metabolic metrics for major pathological response (MPR) prediction in resectable non-small cell lung cancer (rNSCLC) patients receiving neoadjuvant immunochemotherapy. This retrospective cohort included rNSCLC patients who underwent baseline [¹⁸F]F-FDG PET/CT prior to neoadjuvant immunochemotherapy at Xiangya Hospital from April 2020 to April 2024. Patients were randomly stratified into training (70%) and validation (30%) cohorts. Using deep learning-based automated segmentation, we quantified metabolic parameters (SUV_mean, SUV_max, SUV_peak, MTV, TLG) and their ratio to liver metabolic parameters for primary tumors and nine key organs. Feature selection employed a tripartite approach: univariate analysis, LASSO regression, and random forest optimization. The final multivariable model was translated into a clinically interpretable nomogram, with validation assessing discrimination, calibration, and clinical utility. Among 115 patients (MPR rate: 63.5%, n = 73), five metabolic parameters emerged as predictive biomarkers for MPR: Spleen_SUV_mean, Colon_SUV_peak, Spine_TLG, Lesion_TLG, and Spleen-to-Liver SUV_max ratio. The nomogram demonstrated consistent performance across cohorts (training AUC = 0.78 [95%CI 0.67-0.88]; validation AUC = 0.78 [95%CI 0.62-0.94]), with robust calibration and enhanced clinical net benefit on decision curve analysis. Compared to tumor-only parameters, the multi-organ model showed higher specificity (100% vs. 92%) and positive predictive value (100% vs. 90%) in the validation set, maintaining 76% overall accuracy. This first-reported multi-organ metabolic nomogram noninvasively predicts MPR in rNSCLC patients receiving neoadjuvant immunochemotherapy, outperforming conventional tumor-centric approaches. By quantifying systemic host-tumor metabolic crosstalk, this tool could help guide personalized therapeutic decisions while mitigating treatment-related risks, representing a paradigm shift towards precision immuno-oncology management.

This study aims to develop a CycleGAN based denoising model to enhance the quality of low-dose PET (LDPET) images, making them as close as possible to standard-dose PET (SDPET) images. Using a Philips Vereos PET/CT system, whole-body PET images of fluorine-18 fluorodeoxyglucose (18F-FDG) were acquired from 37 patients to facilitate the development of the UR-CycleGAN model. In this model, low-dose data were simulated by reconstructing PET images with a 30-s acquisition time, while standard-dose data were reconstructed from a 2.5-min acquisition. The network was trained in a supervised manner on 13 210 pairs of PET images, and the quality of the images was objectively evaluated using peak signal-to-noise ratio (PSNR) and structural similarity index (SSIM). Compared to simulated low-dose data, the denoised PET images generated by our model showed significant improvement, with a clear trend toward SDPET image quality. The proposed method reduces acquisition time by 80% compared to standard-dose imaging, while achieving image quality close to SDPET images. It also enhances visual detail fidelity, demonstrating the feasibility and practical utility of the model for significantly reducing imaging time while maintaining high image quality.

Multiple parametric imaging in positron emission tomography (PET) is challenging due to the noisy dynamic data and the complex mapping to kinetic parameters. Although methods like direct parametric reconstruction have been proposed to improve the image quality, limitations persist, particularly for nonlinear and small-value micro-parameters (e.g., k₂, k₃). This study presents a novel unsupervised deep learning approach to reconstruct and improve the quality of these micro-parameters. We proposed a direct parametric image reconstruction model, DIP-PM, integrating deep image prior (DIP) with a parameter magnification (PM) strategy. The model employs a U-Net generator to predict multiple parametric images using a CT image prior, with each output channel subsequently magnified by a factor to adjust the intensity. The model was optimized with a log-likelihood loss computed between the measured projection data and forward projected data. Two tracer datasets were simulated for evaluation: ⁸²Rb data using the 1-tissue compartment (1 TC) model and ¹⁸F-FDG data using the 2-tissue compartment (2 TC) model, with 10-fold magnification applied to the 1 TC k₂ and the 2 TC k₃, respectively. DIP-PM was compared to the indirect method, direct algorithm (OTEM) and the DIP method without parameter magnification (DIP-only). Performance was assessed on phantom data using peak signal-to-noise ratio (PSNR), normalized root mean square error (NRMSE) and structural similarity index (SSIM), as well as on real ¹⁸F-FDG scan from a male subject. For the 1 TC model, OTEM performed well in K₁ reconstruction, but both indirect and OTEM methods showed high noise and poor performance in k₂. The DIP-only method suppressed noise in k₂, but failed to reconstruct fine structures in the myocardium. DIP-PM outperformed other methods with well-preserved detailed structures, particularly in k₂, achieving the best metrics (PSNR: 19.00, NRMSE: 0.3002, SSIM: 0.9289). For the 2 TC model, traditional methods exhibited high noise and blurred structures in estimating all nonlinear parameters (K₁, k₂, k₃), while DIP-based methods significantly improved image quality. DIP-PM outperformed all methods in k₃ (PSNR: 21.89, NRMSE: 0.4054, SSIM: 0.8797), and consequently produced the most accurate 2 TC K_i images (PSNR: 22.74, NRMSE: 0.4897, SSIM: 0.8391). On real FDG data, DIP-PM also showed evident advantages in estimating K₁, k₂ and k₃ while preserving myocardial structures. The results underscore the efficacy of the DIP-based direct parametric imaging in generating and improving quality of PET parametric images. This study suggests that the proposed DIP-PM method with the parameter magnification strategy can enhance the fidelity of nonlinear micro-parameter images.

The potential of Large Language Models (LLMs) in enhancing a variety of natural language tasks in clinical fields includes medical imaging reporting. This pilot study examines the efficacy of a retrieval-augmented generation (RAG) LLM system considering zero-shot learning capability of LLMs, integrated with a comprehensive database of PET reading reports, in improving reference to prior reports and decision making. We developed a custom LLM framework with retrieval capabilities, leveraging a database of over 10 years of PET imaging reports from a single center. The system uses vector space embedding to facilitate similarity-based retrieval. Queries prompt the system to generate context-based answers and identify similar cases or differential diagnoses. From routine clinical PET readings, experienced nuclear medicine physicians evaluated the performance of system in terms of the relevance of queried similar cases and the appropriateness score of suggested potential diagnoses. The system efficiently organized embedded vectors from PET reports, showing that imaging reports were accurately clustered within the embedded vector space according to the diagnosis or PET study type. Based on this system, a proof-of-concept chatbot was developed and showed the framework's potential in referencing reports of previous similar cases and identifying exemplary cases for various purposes. From routine clinical PET readings, 84.1% of the cases retrieved relevant similar cases, as agreed upon by all three readers. Using the RAG system, the appropriateness score of the suggested potential diagnoses was significantly better than that of the LLM without RAG. Additionally, it demonstrated the capability to offer differential diagnoses, leveraging the vast database to enhance the completeness and precision of generated reports. The integration of RAG LLM with a large database of PET imaging reports suggests the potential to support clinical practice of nuclear medicine imaging reading by various tasks of AI including finding similar cases and deriving potential diagnoses from them. This study underscores the potential of advanced AI tools in transforming medical imaging reporting practices.

Lung adenocarcinoma (LUAD) constitutes a major cause of cancer-related fatalities worldwide. Early identification of malignant pulmonary nodules constitutes the most effective approach to reducing the mortality of LUAD. Despite the wide application of low-dose computed tomography (LDCT) in the early screening of LUAD, the identification of malignant pulmonary nodules by it remains a challenge. In this study, CEACAM6 (also called CD66c) as a potential biomarker is investigated for differentiating malignant lung nodules. Then, the CEACAM6-targeting monoclonal antibody (mAb, tinurilimab) is radiolabeled with ⁸⁹Zr and ¹³¹I for theranostic applications. In terms of diagnosis, machine learning confirms CEACAM6 as a specific extracellular marker for discrimination between LUAD and benign nodules. The ⁸⁹Zr-labeled mAb is highly specific uptake in CEACAM6-positive LUAD via positron emission tomography (PET) imaging, and its ability to distinguish in malignant pulmonary nodules are significantly higher than that of ¹⁸F Fluorodeoxyglucose (FDG) by positron emission tomography/magnetic resonance (PET/MR) imaging. While the ¹³¹I-labeled mAb serving as the therapeutic aspect has significantly suppressed tumor growth after a single treatment. These results proves that ⁸⁹Zr/¹³¹I-labeled tinurilimab facilitates the differential capacity of malignant pulmonary nodules and radioimmunotherapy of LUAD in preclinical models. Further clinical evaluation and translation of this CEACAM6-targeted theranostics may be significant help in diagnosis and treatment of LUAD.