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Differentiated thyroid cancer and positron emission computed tomography: when, how and why?

Coca Pelaz A, Rodrigo JP, Zafereo M, Nixon I, Guntinas-Lichius O, Randolph G, Civantos FJ, Pace-Asciak P, Jara MA, Kuker R, Ferlito A

pubmed logopapersJul 3 2025
Fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) has become an indispensable tool in oncology, offering both metabolic and anatomical insights into tumor behavior. Most differentiated thyroid carcinomas (DTC) are indolent and therefore FDG PET/CT is not routinely incorporated into management. However, in biologically aggressive DTCs, FDG PET/CT plays a crucial role in detecting recurrence and metastases. This narrative review with articles from the last 25 years from PubMed database, explores the evolving role of FDG PET/CT, focusing on its utility in recurrence detection, staging, and follow-up of radioactive iodine (RAI)-refractory cases. Current guidelines recommend FDG PET/CT primarily for high-risk patients with elevated thyroglobulin levels and negative RAI scans (TENIS syndrome). We also examine advancements in PET imaging, novel radiotracers and theragnostic approaches that enhance diagnostic accuracy and treatment monitoring. While FDG PET/CT has proven valuable in biologically aggressive DTC, its routine use remains limited by cost, accessibility, and concerns regarding radiation exposure in younger patients requiring repeated imaging studies. Future developments in molecular imaging, including novel tracers and artificial intelligence-driven analysis, are expected to refine its role, leading to more personalized and effective management, though economic and reimbursement challenges remain important considerations for broader adoption.

Prediction of PD-L1 expression in NSCLC patients using PET/CT radiomics and prognostic modelling for immunotherapy in PD-L1-positive NSCLC patients.

Peng M, Wang M, Yang X, Wang Y, Xie L, An W, Ge F, Yang C, Wang K

pubmed logopapersJul 1 2025
To develop a positron emission tomography/computed tomography (PET/CT)-based radiomics model for predicting programmed cell death ligand 1 (PD-L1) expression in non-small cell lung cancer (NSCLC) patients and estimating progression-free survival (PFS) and overall survival (OS) in PD-L1-positive patients undergoing first-line immunotherapy. We retrospectively analysed 143 NSCLC patients who underwent pretreatment <sup>18</sup>F-fluorodeoxyglucose (<sup>18</sup>F-FDG) PET/CT scans, of whom 86 were PD-L1-positive. Clinical data collected included gender, age, smoking history, Tumor-Node-Metastases (TNM) staging system, pathologic types, laboratory parameters, and PET metabolic parameters. Four machine learning algorithms-Bayes, logistic, random forest, and Supportsupport vector machine (SVM)-were used to build models. The predictive performance was validated using receiver operating characteristic (ROC) curves. Univariate and multivariate Cox analyses identified independent predictors of OS and PFS in PD-L1-positive expression patients undergoing immunotherapy, and a nomogram was created to predict OS. A total of 20 models were built for predicting PD-L1 expression. The clinical combined PET/CT radiomics model based on the SVM algorithm performed best (area under curve for training and test sets: 0.914 and 0.877, respectively). The Cox analyses showed that smoking history independently predicted PFS. SUVmean, monocyte percentage and white blood cell count were independent predictors of OS, and the nomogram was created to predict 1-year, 2-year, and 3-year OS based on these three factors. We developed PET/CT-based machine learning models to help predict PD-L1 expression in NSCLC patients and identified independent predictors of PFS and OS in PD-L1-positive patients receiving immunotherapy, thereby aiding precision treatment.

Development and validation of a nomogram for predicting bone marrow involvement in lymphoma patients based on <sup>18</sup>F-FDG PET radiomics and clinical factors.

Lu D, Zhu X, Mu X, Huang X, Wei F, Qin L, Liu Q, Fu W, Deng Y

pubmed logopapersJul 1 2025
This study aimed to develop and validate a nomogram combining <sup>18</sup>F-FDG PET radiomics and clinical factors to non-invasively predict bone marrow involvement (BMI) in patients with lymphoma. A radiomics nomogram was developed using monocentric data, randomly divided into a training set (70%) and a test set (30%). Bone marrow biopsy (BMB) served as the gold standard for BMI diagnosis. Independent clinical risk factors were identified through univariate and multivariate logistic regression analyses to construct a clinical model. Radiomics features were extracted from PET and CT images and selected using least absolute shrinkage and selection operator (LASSO) regression, yielding a radiomics score (Rad<sub>score</sub>) for each patient. Models based on clinical factors, CT Rad<sub>score</sub>, and PET Rad<sub>score</sub> were established and evaluated using eight machine learning algorithms to identify the optimal prediction model. A combined model was constructed and presented as a nomogram. Model performance was assessed using the area under the receiver operating characteristic curve (AUC), calibration curves, and decision curve analysis (DCA). A total of 160 patients were included, of whom 70 had BMI based on BMB results. The training group comprised 112 patients (BMI: 56, without BMI: 56), while the test group included 48 patients (BMI: 14, without BMI: 34). Independent risk factors, including the number of extranodal involvements and B symptoms, were incorporated into the clinical model. In the clinical model, CT Rad<sub>score</sub>, and PET Rad<sub>score</sub>, the AUCs in the test set were 0.820 (95% CI: 0.705-0.935), 0.538 (95% CI: 0.351-0.723), and 0.836 (95% CI: 0.686-0.986). Due to the limited diagnostic performance of CT Rad<sub>score</sub>, the nomogram was constructed using PET Rad<sub>score</sub> and the clinical model. The radiomics nomogram achieved AUCs of 0.916 (95% CI: 0.865-0.967) in the training set and 0.863 (95% CI: 0.763-0.964) in the test set. Calibration curves and DCA confirmed the nomogram's discrimination, calibration, and clinical utility in both sets. By integrating PET Rad<sub>score</sub>, the number of extranodal involvements, and B symptoms, this <sup>18</sup>F-FDG PET radiomics-based nomogram offers a non-invasive method to predict bone marrow status in lymphoma patients, providing nuclear medicine physicians with valuable decision support for pre-treatment evaluation.

Dynamic frame-by-frame motion correction for 18F-flurpiridaz PET-MPI using convolution neural network

Urs, M., Killekar, A., Builoff, V., Lemley, M., Wei, C.-C., Ramirez, G., Kavanagh, P., Buckley, C., Slomka, P. J.

medrxiv logopreprintJul 1 2025
PurposePrecise quantification of myocardial blood flow (MBF) and flow reserve (MFR) in 18F-flurpiridaz PET significantly relies on motion correction (MC). However, the manual frame-by-frame correction leads to significant inter-observer variability, time-consuming, and requires significant experience. We propose a deep learning (DL) framework for automatic MC of 18F-flurpiridaz PET. MethodsThe method employs a 3D ResNet based architecture that takes 3D PET volumes and outputs motion vectors. It was validated using 5-fold cross-validation on data from 32 sites of a Phase III clinical trial (NCT01347710). Manual corrections from two experienced operators served as ground truth, and data augmentation using simulated vectors enhanced training robustness. The study compared the DL approach to both manual and standard non-AI automatic MC methods, assessing agreement and diagnostic accuracy using minimal segmental MBF and MFR. ResultsThe area under the receiver operating characteristic curves (AUC) for significant CAD were comparable between DL-MC MBF, manual-MC MBF from Operators (AUC=0.897,0.892 and 0.889, respectively; p>0.05), standard non-AI automatic MC (AUC=0.877; p>0.05) and significantly higher than No-MC (AUC=0.835; p<0.05). Similar findings were observed with MFR. The 95% confidence limits for agreement with the operator were {+/-}0.49ml/g/min (mean difference = 0.00) for MFR and {+/-}0.24ml/g/min (mean difference = 0.00) for MBF. ConclusionDL-MC is significantly faster but diagnostically comparable to manual-MC. The quantitative results obtained with DL-MC for MBF and MFR are in excellent agreement with those manually corrected by experienced operators compared to standard non-AI automatic MC in patients undergoing 18F-flurpiridaz PET-MPI.

Robust and generalizable artificial intelligence for multi-organ segmentation in ultra-low-dose total-body PET imaging: a multi-center and cross-tracer study.

Wang H, Qiao X, Ding W, Chen G, Miao Y, Guo R, Zhu X, Cheng Z, Xu J, Li B, Huang Q

pubmed logopapersJul 1 2025
Positron Emission Tomography (PET) is a powerful molecular imaging tool that visualizes radiotracer distribution to reveal physiological processes. Recent advances in total-body PET have enabled low-dose, CT-free imaging; however, accurate organ segmentation using PET-only data remains challenging. This study develops and validates a deep learning model for multi-organ PET segmentation across varied imaging conditions and tracers, addressing critical needs for fully PET-based quantitative analysis. This retrospective study employed a 3D deep learning-based model for automated multi-organ segmentation on PET images acquired under diverse conditions, including low-dose and non-attenuation-corrected scans. Using a dataset of 798 patients from multiple centers with varied tracers, model robustness and generalizability were evaluated via multi-center and cross-tracer tests. Ground-truth labels for 23 organs were generated from CT images, and segmentation accuracy was assessed using the Dice similarity coefficient (DSC). In the multi-center dataset from four different institutions, our model achieved average DSC values of 0.834, 0.825, 0.819, and 0.816 across varying dose reduction factors and correction conditions for FDG PET images. In the cross-tracer dataset, the model reached average DSC values of 0.737, 0.573, 0.830, 0.661, and 0.708 for DOTATATE, FAPI, FDG, Grazytracer, and PSMA, respectively. The proposed model demonstrated effective, fully PET-based multi-organ segmentation across a range of imaging conditions, centers, and tracers, achieving high robustness and generalizability. These findings underscore the model's potential to enhance clinical diagnostic workflows by supporting ultra-low dose PET imaging. Not applicable. This is a retrospective study based on collected data, which has been approved by the Research Ethics Committee of Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine.

Deep learning image enhancement algorithms in PET/CT imaging: a phantom and sarcoma patient radiomic evaluation.

Bonney LM, Kalisvaart GM, van Velden FHP, Bradley KM, Hassan AB, Grootjans W, McGowan DR

pubmed logopapersJul 1 2025
PET/CT imaging data contains a wealth of quantitative information that can provide valuable contributions to characterising tumours. A growing body of work focuses on the use of deep-learning (DL) techniques for denoising PET data. These models are clinically evaluated prior to use, however, quantitative image assessment provides potential for further evaluation. This work uses radiomic features to compare two manufacturer deep-learning (DL) image enhancement algorithms, one of which has been commercialised, against 'gold-standard' image reconstruction techniques in phantom data and a sarcoma patient data set (N=20). All studies in the retrospective sarcoma clinical [ <math xmlns="http://www.w3.org/1998/Math/MathML"><mmultiscripts><mrow></mrow> <mrow></mrow> <mn>18</mn></mmultiscripts> </math> F]FDG dataset were acquired on either a GE Discovery 690 or 710 PET/CT scanner with volumes segmented by an experienced nuclear medicine radiologist. The modular heterogeneous imaging phantom used in this work was filled with [ <math xmlns="http://www.w3.org/1998/Math/MathML"><mmultiscripts><mrow></mrow> <mrow></mrow> <mn>18</mn></mmultiscripts> </math> F]FDG, and five repeat acquisitions of the phantom were acquired on a GE Discovery 710 PET/CT scanner. The DL-enhanced images were compared to 'gold-standard' images the algorithms were trained to emulate and input images. The difference between image sets was tested for significance in 93 international biomarker standardisation initiative (IBSI) standardised radiomic features. Comparing DL-enhanced images to the 'gold-standard', 4.0% and 9.7% radiomic features measured significantly different (p<sub>critical</sub> < 0.0005) in the phantom and patient data respectively (averaged over the two DL algorithms). Larger differences were observed comparing DL-enhanced images to algorithm input images with 29.8% and 43.0% of radiomic features measuring significantly different in the phantom and patient data respectively (averaged over the two DL algorithms). DL-enhanced images were found to be similar to images generated using the 'gold-standard' target image reconstruction method with more than 80% of radiomic features not significantly different in all comparisons across unseen phantom and sarcoma patient data. This result offers insight into the performance of the DL algorithms, and demonstrate potential applications for DL algorithms in harmonisation for radiomics and for radiomic features in quantitative evaluation of DL algorithms.

GAN-based Denoising for Scan Time Reduction and Motion Correction of 18F FP-CIT PET/CT: A Multicenter External Validation Study.

Han H, Choo K, Jeon TJ, Lee S, Seo S, Kim D, Kim SJ, Lee SH, Yun M

pubmed logopapersJul 1 2025
AI-driven scan time reduction is rapidly transforming medical imaging with benefits such as improved patient comfort and enhanced efficiency. A Dual Contrastive Learning Generative Adversarial Network (DCLGAN) was developed to predict full-time PET scans from shorter, noisier scans, improving challenges in imaging patients with movement disorders. 18F FP-CIT PET/CT data from 391 patients with suspected Parkinsonism were used [250 training/validation, 141 testing (hospital A)]. Ground truth (GT) images were reconstructed from 15-minute scans, while denoised images (DIs) were generated from 1-, 3-, 5-, and 10-minute scans. Image quality was assessed using normalized root mean square error (NRMSE), peak signal-to-noise ratio (PSNR), structural similarity index measure (SSIM), visual analysis, and clinical metrics like BPND and ISR for diagnosis of non-neurodegenerative Parkinson disease (NPD), idiopathic PD (IPD), and atypical PD (APD). External validation used data from 2 hospitals with different scanners (hospital B: 1-, 3-, 5-, and 10-min; hospital C: 1-, 3-, and 5-min). In addition, motion artifact reduction was evaluated using the Dice similarity coefficient (DSC). In hospital A, NRMSE, PSNR, and SSIM values improved with scan duration, with the 5-minute DIs achieving optimal quality (NRMSE 0.008, PSNR 42.13, SSIM 0.98). Visual analysis rated DIs from scans ≥3 minutes as adequate or higher. The mean BPND differences (95% CI) for each DIs were 0.19 (-0.01, 0.40), 0.11 (-0.02, 0.24), 0.08 (-0.03, 0.18), and 0.01 (-0.06, 0.07), with the CIs significantly decreasing. ISRs with the highest effect sizes for differentiating NPD, IPD, and APD (PP/AP, PP/VS, PC/VP) remained stable post-denoising. External validation showed 10-minute DIs (hospital B) and 1-minute DIs (hospital C) reached benchmarks of hospital A's image quality metrics, with similar trends in visual analysis and BPND CIs. Furthermore, motion artifact correction in 9 patients yielded DSC improvements from 0.89 to 0.95 in striatal regions. The DL-model is capable of generating high-quality 18F FP-CIT PET images from shorter scans to enhance patient comfort, minimize motion artifacts, and maintain diagnostic precision. Furthermore, our study plays an important role in providing insights into how imaging quality assessment metrics can be used to determine the appropriate scan duration for different scanners with varying sensitivities.

Data-efficient generalization of AI transformers for noise reduction in ultra-fast lung PET scans.

Wang J, Zhang X, Miao Y, Xue S, Zhang Y, Shi K, Guo R, Li B, Zheng G

pubmed logopapersJul 1 2025
Respiratory motion during PET acquisition may produce lesion blurring. Ultra-fast 20-second breath-hold (U2BH) PET reduces respiratory motion artifacts, but the shortened scanning time increases statistical noise and may affect diagnostic quality. This study aims to denoise the U2BH PET images using a deep learning (DL)-based method. The study was conducted on two datasets collected from five scanners where the first dataset included 1272 retrospectively collected full-time PET data while the second dataset contained 46 prospectively collected U2BH and the corresponding full-time PET/CT images. A robust and data-efficient DL method called mask vision transformer (Mask-ViT) was proposed which, after fine-tuned on a limited number of training data from a target scanner, was directly applied to unseen testing data from new scanners. The performance of Mask-ViT was compared with state-of-the-art DL methods including U-Net and C-Gan taking the full-time PET images as the reference. Statistical analysis on image quality metrics were carried out with Wilcoxon signed-rank test. For clinical evaluation, two readers scored image quality on a 5-point scale (5 = excellent) and provided a binary assessment for diagnostic quality evaluation. The U2BH PET images denoised by Mask-ViT showed statistically significant improvement over U-Net and C-Gan on image quality metrics (p < 0.05). For clinical evaluation, Mask-ViT exhibited a lesion detection accuracy of 91.3%, 90.4% and 91.7%, when it was evaluated on three different scanners. Mask-ViT can effectively enhance the quality of the U2BH PET images in a data-efficient generalization setup. The denoised images meet clinical diagnostic requirements of lesion detectability.

Deep learning-based time-of-flight (ToF) enhancement of non-ToF PET scans for different radiotracers.

Mehranian A, Wollenweber SD, Bradley KM, Fielding PA, Huellner M, Iagaru A, Dedja M, Colwell T, Kotasidis F, Johnsen R, Jansen FP, McGowan DR

pubmed logopapersJul 1 2025
To evaluate a deep learning-based time-of-flight (DLToF) model trained to enhance the image quality of non-ToF PET images for different tracers, reconstructed using BSREM algorithm, towards ToF images. A 3D residual U-NET model was trained using 8 different tracers (FDG: 75% and non-FDG: 25%) from 11 sites from US, Europe and Asia. A total of 309 training and 33 validation datasets scanned on GE Discovery MI (DMI) ToF scanners were used for development of DLToF models of three strengths: low (L), medium (M) and high (H). The training and validation pairs consisted of target ToF and input non-ToF BSREM reconstructions using site-preferred regularisation parameters (beta values). The contrast and noise properties of each model were defined by adjusting the beta value of target ToF images. A total of 60 DMI datasets, consisting of a set of 4 tracers (<sup>18</sup>F-FDG, <sup>18</sup>F-PSMA, <sup>68</sup>Ga-PSMA, <sup>68</sup>Ga-DOTATATE) and 15 exams each, were collected for testing and quantitative analysis of the models based on standardized uptake value (SUV) in regions of interest (ROI) placed in lesions, lungs and liver. Each dataset includes 5 image series: ToF and non-ToF BSREM and three DLToF images. The image series (300 in total) were blind scored on a 5-point Likert score by 4 readers based on lesion detectability, diagnostic confidence, and image noise/quality. In lesion SUV<sub>max</sub> quantification with respect to ToF BSREM, DLToF-H achieved the best results among the three models by reducing the non-ToF BSREM errors from -39% to -6% for <sup>18</sup>F-FDG (38 lesions); from -42% to -7% for <sup>18</sup>F-PSMA (35 lesions); from -34% to -4% for <sup>68</sup>Ga-PSMA (23 lesions) and from -34% to -12% for <sup>68</sup>Ga-DOTATATE (32 lesions). Quantification results in liver and lung also showed ToF-like performance of DLToF models. Clinical reader resulted showed that DLToF-H results in an improved lesion detectability on average for all four radiotracers whereas DLToF-L achieved the highest scores for image quality (noise level). The results of DLToF-M however showed that this model results in the best trade-off between lesion detection and noise level and hence achieved the highest score for diagnostic confidence on average for all radiotracers. This study demonstrated that the DLToF models are suitable for both FDG and non-FDG tracers and could be utilized for digital BGO PET/CT scanners to provide an image quality and lesion detectability comparable and close to ToF.

<sup>18</sup>F-FDG dose reduction using deep learning-based PET reconstruction.

Akita R, Takauchi K, Ishibashi M, Kondo S, Ono S, Yokomachi K, Ochi Y, Kiguchi M, Mitani H, Nakamura Y, Awai K

pubmed logopapersJul 1 2025
A deep learning-based image reconstruction (DLR) algorithm that can reduce the statistical noise has been developed for PET/CT imaging. It may reduce the administered dose of <sup>18</sup>F-FDG and minimize radiation exposure while maintaining diagnostic quality. This retrospective study evaluated whether the injected <sup>18</sup>F-FDG dose could be reduced by applying DLR to PET images. To this aim, we compared the quantitative image quality metrics and the false-positive rate between DLR with a reduced <sup>18</sup>F-FDG dose and Ordered Subsets Expectation Maximization (OSEM) with a standard dose. This study included 90 oncology patients who underwent <sup>18</sup>F-FDG PET/CT. They were divided into 3 groups (30 patients each): group A (<sup>18</sup>F-FDG dose per body weight [BW]: 2.00-2.99 MBq/kg; PET image reconstruction: DLR), group B (3.00-3.99 MBq/kg; DLR), and group C (standard dose group; 4.00-4.99 MBq/kg; OSEM). The evaluation was performed using the signal-to-noise ratio (SNR), target-to-background ratio (TBR), and false-positive rate. DLR yielded significantly higher SNRs in groups A and B than group C (p < 0.001). There was no significant difference in the TBR between groups A and C, and between groups B and C (p = 0.983 and 0.605, respectively). In group B, more than 80% of patients weighing less than 75 kg had at most one false positive result. In contrast, in group B patients weighing 75 kg or more, as well as in group A, less than 80% of patients had at most one false-positives. Our findings suggest that the injected <sup>18</sup>F-FDG dose can be reduced to 3.0 MBq/kg in patients weighing less than 75 kg by applying DLR. Compared to the recommended dose in the European Association of Nuclear Medicine (EANM) guidelines for 90 s per bed position (4.7 MBq/kg), this represents a dose reduction of 36%. Further optimization of DLR algorithms is required to maintain comparable diagnostic accuracy in patients weighing 75 kg or more.
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