Background: Cell culture can be categorized into two major types: adherent and suspension. Both are used in a range of diverse research applications, exhibiting Pros and Cons, depending on what is being studied. In the field of Internal Emitters (IE), different morphological features such as nuclei size, cytoplasm ratio, and shape could influence its non-uniformity deposition and thus impact on the biological outcome. In this work we tested the hypothesis that cellular morphology differences, offered by adherent and suspension cultures, influence the radiosensitizing effect of gold nanoparticles (AuNPs).
Methods: Using two PC3 cellular models, taken using confocal microscopy, we conducted Monte Carlo simulations to investigate the effects of different irradiation conditions on cellular Survival Fractions (SF). Our simulations focused on cells exposed to two distinct irradiation sources: 60Co and 14 MeV protons, along both the longer and shorter axes of the cells to assess directional influences on cell survival. Additionally, we compared the SF of cells adherent to the culture flask with those in suspension, reflecting different experimental and potentially clinical scenarios.
Results: In the absence of AuNPs, neither cell type nor irradiation direction significantly affected SF for the radiation types tested. However, with AuNPs present, SF demonstrated a strong dependence on irradiation direction and cell morphology.
Conclusions: Our results indicate that the direction of irradiation plays a crucial role in determining the effectiveness of AuNPs in reducing SF. Furthermore, the results suggest that using cells in suspension will reduce the dependence of cell survival on the beam direction during irradiation, regardless of the radiation quality used.
Background: Textural Analysis features in molecular imaging require to be robust under repeat measurement and to be independent of volume for optimum use in clinical studies. Recent EANM and SNMMI guidelines for radiomics provide advice on the potential use of phantoms to identify robust features (Hatt in EJNMMI, 2022). This study applies the suggested phantoms to use in SPECT quantification for two radionuclides, 99 mTc and 177Lu.
Methods: Acquisitions were made with a uniform phantom to test volume dependency and with a customised 'Revolver' phantom, based on the PET phantom described in Hatt (EJNMMI, 2022) but with local adaptations for SPECT. Each phantom was filled separately with 99 mTc and 177Lu. Sixty-seven Textural Analysis features were extracted and tested for robustness and volume dependency.
Results: Features showing high volume dependency or high Coefficient of Variation (indicating poor repeatability) were removed from the list of features that may be suitable for use in clinical studies. After feature reduction, there were 39 features for 99 mTc and 33 features for 177Lu remaining.
Conclusion: The use of a uniform phantom to test volume dependency and a Revolver phantom to identify repeatable Textural Analysis features is possible for quantitative SPECT using 99 mTc or 177Lu. Selection of such features is likely to be centre-dependent due to differences in camera performance as well as acquisition and reconstruction protocols.
Objectives: The present study aimed to investigate the influence of the deep progressive learning reconstruction (DPR) algorithm on the 18F-FDG PET image quality and quantitative parameters.
Methods: In this retrospective study, data were collected from 55 healthy individuals and 184 patients with primary malignant pulmonary tumors who underwent 18F-FDG PET/CT examinations. PET data were reconstructed using the ordered subset expectation maximization (OSEM) and DPR algorithms. The influence of DPR algorithm on quantitative parameters was explored, including the SUVmax, SUVmean, standard deviation of SUV (SUVSD), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and tumor-to-background uptake ratio (TBR). Finally, the differences in image quality parameters, including signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR), between the two reconstruction algorithms were evaluated.
Results: DPR algorithm significantly reduced the SUVmax and SUVSD of background tissues (all, P < 0.001) compared to OSEM algorithm, while no statistical difference was observed in SUVmean between the two algorithms (all, P > 0.05). DPR algorithm notably increased the SUVmax, SUVmean, and TBR of lesions (all, P < 0.001) and reduced MTV (P = 0.005), with minimal differences in TLG noted between the reconstruction algorithms (P < 0.001). The percentage differences in SUVmax (P = 0.001), SUVmean (P = 0.005), and TBR (P = 0.001) between the two algorithms were significantly higher in solid nodules than in pure ground glass nodules (pGGNs). The ΔCNR between solid nodules (P = 0.031) and mixed ground glass nodules (P = 0.020) was greater than that between pGGNs. SNR and CNR obtained using the DPR algorithm were markedly improved compared to those determined using the OSEM algorithm (all, P < 0.001).
Conclusion: Under identical acquisition conditions, the DPR algorithm enhanced the accuracy of quantitative parameters in pulmonary lesions and potentially improved lesion detectability. The DPR algorithm increased image SNR and CNR compared to those obtained using the OSEM algorithm, significantly optimizing overall image quality. This advancement facilitated precise clinical diagnosis, underpinning its potential to significantly contribute to the field of medical imaging.
Purpose: This study aimed to determine a mathematical model for accurately calculating time-integrated activities (TIAs) of target tissue in 131I therapy for benign thyroid disease using the population-based model selection and non-linear mixed-effects (PBMS-NLME) method.
Methods: Biokinetic data of 131I in target tissue were collected from seventy-three patients at 2, 6, 24, 48, and 96 (N = 53) or 120 (N = 20) h after oral capsule administration with 1 MBq 131I. Based on the Akaike weight, the best sum-of-exponential function (SOEF) describing the biokinetic data was selected using PBMS-NLME modelling. Nine SOEF with three to six parameters (including the function from the European Association of Nuclear Medicine Standard Operational Procedure (EANM SOP)) were used. The fittings were repeated 1000 times with different starting values of the SOE parameters to find the optimal fit. Akaike weight was used to identify the performance of the best model from PBMS-NLME and the EANM SOP SOE function with individual fitting.
Results: Based on the PBMS-NLME analysis, the SOEF was selected as the function most supported by the data. The Akaike weight of the best function was approximately 100%. The best SOEF from the PBMS-NLME approach shows a better performance in describing the biokinetic data of 131I in the thyroid gland than the function from the EANM SOP with individual fitting, based on the Akaike weight.
Conclusions: The best mathematical model from the PBMS-NLME approach has one more free parameter than the EANM SOP function, which could lead to more accurate TIAs.
Background: Patients' diagnosis, treatment and follow-up increasingly rely on multimodality imaging. One of the main limitations for the optimal implementation of hybrid systems in clinical practice is the time and expertise required for applying standardized protocols for equipment quality assurance (QA). Experimental phantoms are commonly used for this purpose, but they are often limited to a single modality and single quality parameter, lacking automated analysis capabilities. In this study, we developed a multimodal 3D-printed phantom and software for QA in positron emission tomography (PET) hybrid systems, with computed tomography (CT) or magnetic resonance (MR), by assessing signal, spatial resolution, radiomic features, co-registration and geometric distortions.
Results: Phantom models and Python software for the proposed QA are available to download, and a user-friendly plugin compatible with the open-source 3D-Slicer software has been developed. The QA viability was proved by characterizing a Philips-Gemini-TF64-PET/CT in terms of signal response (mean, µ), intrinsic variability for three consecutive measurements (daily variation coefficient, CoVd) and reproducibility over time (variation coefficient across 5 months, CoVm). For this system, averaged recovery coefficient for activity concentration was µ = 0.90 ± 0.08 (CoVd = 0.6%, CoVm = 9%) in volumes ranging from 7 to 42 ml. CT calibration-curve averaged over time was with variability of slope and y-intercept of (CoVd = 0.4%, CoVm = 1.2%) and (CoVd = 0.4%, CoVm = 1.6%), respectively. Radiomics reproducibility resulted in (CoVd = 18%, CoVm = 30%) for PET and (CoVd = 15%, CoVm = 22%) for CT. Co-registration was assessed by Dice-Similarity-Coefficient (DSC) along 37.8 cm in superior-inferior (z) direction (well registered if DSC ≥ 0.91 and Δz ≤ 2 mm), resulting in 3/7 days well co-registered. Applicability to other scanners was additionally proved with Philips-Vereos-PET/CT (V), Siemens-Biograph-Vison-600-PET/CT (S) and GE-SIGNA-PET/MR (G). PET concentration accuracy was (µ = 0.86, CoVd = 0.3%) for V, (µ = 0.87, CoVd = 0.8%) for S, and (µ = 1.10, CoVd = 0.34%) for G. MR(T2) was well co-registered with PET in 3/4 cases, did not show significant distortion within a transaxial diameter of 27.8 cm and along 37 cm in z, and its radiomic variability was CoVd = 13%.
Conclusions: Open-source QA protocol for PET hybrid systems has been presented and its general applicability has been proved. This package facilitates simultaneously simple and semi-a
Background: Medical imaging data frequently encounter image-generation heterogeneity and class imbalance properties, challenging strong generalized predictive performances with data-driven machine-learning methods. The purpose of this study was to investigate the impact of harmonization and oversampling methods on multi-center imbalanced datasets, with specific application to PET-based radiomics modeling for histologic subtype prediction in non-small cell lung cancer (NSCLC).
Methods: The retrospective study included 245 patients with adenocarcinoma (ADC) and 78 patients with squamous cell carcinoma (SCC) from 4 centers. Utilizing 1502 radiomics features per patient, we trained, validated, and tested 4 machine-learning classifiers, to investigate the effect of no harmonization (NoH) or 4 feature harmonization methods, paired with no oversampling (NoO) or 5 oversampling methods on subtype prediction. Model performance was evaluated using the average area under the ROC curve (AUROC) and G-mean via 5 times 5-fold cross-validations. Statistical comparisons of the combined models against baseline (NoH + NoO) were performed for each fold of cross-validation using the DeLong test.
Results: The number of cross-combinations with both AUROC and G-mean outperforming baseline in validation and testing was 15, 4, 2, and 7 (out of 29) for random forest (RF), linear discriminant analysis (LDA), logistic regression (LR), and support vector machine (SVM), respectively. ComBat harmonization combined with oversampling (SMOTE) via RF yielded better performance than baseline (AUROC and G-mean of validation: 0.725 vs. 0.608 and 0.625 vs. 0.398; testing: 0.637 vs. 0.567 and 0.506 vs. 0.287), though statistical significances were not observed.
Conclusions: Applying harmonization and oversampling methods in multi-center imbalanced datasets can improve NSCLC-subtype prediction, but the effect varies widely across classifiers. We have created open-source comparisons of harmonization and oversampling on different classifiers for comprehensive evaluations in different studies.
Background: Magnetic resonance (MR) images have been applied in diagnostic and therapeutic nuclear medicine to improve the visualization and characterization of soft tissues and tumors. However, the physical density (ρ) and elemental composition of human tissues required for dosimetric calculation cannot be directly converted from MR images, obstructing MR-based personalized internal dosimetry. In this study, we proposed a method to derive physical densities from Dixon MR images for voxel-based internal dose calculation.
Methods: The proposed method defined human tissues as composed of four basic tissues. The physical densities of the human tissues were calculated using the standard tissue composition of the basic tissues and the volume fraction maps calculated from Dixon images. The derived ρ map was applied to calculate the whole-body internal dosimetry using a multiple voxel S-value (MSV) approach. The accuracy of the proposed method in deriving ρ and calculating the internal dose of 18F-FDG PET imaging was evaluated by comparing with those obtained from computed tomography (CT) images of the same patient and was compared with those obtained using generative adversarial networks (GANs).
Results: The proposed method was superior to the GANs in deriving ρ from Dixon MR images and the following internal dose calculation. On average of a validation set, the mean absolute percent errors (MAPEs) of the whole-body ρ derivation and internal dose calculation using the proposed method were 14.28 ± 11.11% and 3.31 ± 0.69%, respectively. The MAPEs were respectively reduced to 5.97 ± 2.51 and 2.75 ± 0.69% after excluding the intestinal gas with different locations in the Dixon MR and CT images.
Conclusions: The proposed method could be applied for accurate and efficient personalized internal dosimetry evaluation in MR-integrated nuclear medicine clinical applications.
Background: A deep progressive learning method for PET image reconstruction named deep progressive reconstruction (DPR) method was developed and presented in previous works. It has been shown in previous study that the DPR with one-third duration can maintain the image quality as OSEM with standard dose (3.7 MBq/kg). Subsequent studies have shown we can reduce the administered activity of 18F-FDG by up to 2/3 in a real-world deployment with DPR. The aim of this study is to assess the impact of the use of DPR on Deauville score (DS) and clinical interpretation of PET/CT in patients with lymphoma.
Methods: A total of 87 lymphoma patients (age, 45.1 ± 14.9 years) who underwent 18F-FDG PET imaging for during or post-treatment follow-up from November 2020 to February 2024 were prospectively enrolled. The patients were randomly assigned to two groups, including the 1/3 standard dose group and the standard dose group. Forty-four patients were injected with 1/3 standard dose (1.23 MBq/kg) and scanned for 6 min per bed and were reconstructed: ordered-subsets expectation maximization (OSEM) with 6 min per bed (OSEM_6 min_1/3), OSEM_2 min_1/3 and DPR_2 min_1/3. Forty-three patients were scanned according to the standard protocol (3.7 MBq/kg) and were reconstructed: OSEM with 2 min per bed (OSEM_2 min_full), OSEM_40 s_full and DPR_40 s_full. Additionally, the conventional 5-point scale measurement analysis was performed and DS for lymphoma were determined in different groups. Wilcoxon signed-rank test was used to compare the mean values of liver SUVmax and mediastinal blood pool (MBP) SUVmax in each group. Likert scale and DS were evaluated using Wilcoxon signed rank test.
Results: The patients with OSEM_6 min_1/3 and DPR_2 min_1/3 showed good image quality with 5(5,5) and 5(4,5) of Likert scoring, as well as the patients with OSEM_2 min_full and DPR_40 s_full. No significant difference was found between the OSEM_6 min_1/3 and DPR_2 min_1/3 groups in terms of liver SUVmax and MBP SUVmax (P = 0.452 and 0.430), as well as the patients with OSEM_2 min_full and DPR_40 s_full (P = 0.105 and 0.638). No significant difference was found between the OSEM_6 min_1/3 and DPR_2 min_1/3 groups in terms of lesion SUVmax (P = 0.080). There was a significant differences in lesion SUVmax between OSEM-2 min_full with DPR-40 s_full (P = 0.027). The DS results were consistent (100%) between OSEM-6 min_1/3 with DPR_2 min_1/3, and between OSEM-2 min_full with DPR-40 s_full, respectively.
Conclusions: DPR reconstruction demonstrated feasibility in reducing PET injection dose or scanning time, while ensuring the preservation of image quality and DS for during or post-treatment follow-up patients with lymphoma.

