Dual time-point [18F]FDG PET imaging for quantification of metabolic uptake rate: Evaluation of a simple, clinically feasible method.

PURPOSE: We aimed to investigate whether a clinically feasible dual time-point (DTP) approach can accurately estimate the metabolic uptake rate constant (Ki) and to explore reliable acquisition times through simulations and clinical assessment considering patient comfort and quantification accuracy. METHODS: We simulated uptake kinetics in different tumors for four sets of DTP PET images within the routine clinical static acquisition at 60-min post-injection (p.i.). We determined Ki for a total of 81 lesions. Ki quantification from full dynamic PET data (Patlak-Ki) and Ki from DTP (DTP-Ki) were compared. In addition, we scaled a population-based input function (PBIFscl) with the image-derived blood pool activity sampled at different time points to assess the best scaling time-point for Ki quantifications in the simulation data. RESULTS: In the simulation study, Ki estimated using DTP via (30,60-min), (30,90-min), (60,90-min), and (60,120-min) samples showed strong correlations (r ≥ 0.944, P < 0.0001) with the true value of Ki. The DTP results with the PBIFscl at 60-min time-point in (30,60-min), (60,90-min), and (60,120-min) were linearly related to the true Ki with a slope of 1.037, 1.008, 1.013 and intercept of -6 × 10-4, 2 × 10-5, 5 × 10-5, respectively. In a clinical study, strong correlations (r ≥ 0.833, P < 0.0001) were observed between Patlak-Ki and DTP-Ki. The Patlak-derived mean values of Ki, tumor-to-background-ratio, signal-to-noise-ratio, and contrast-to-noise-ratio were linearly correlated with the DTP method. CONCLUSIONS: Besides calculating the retention index as a commonly used quantification parameter inDTP imaging,our DTP method can accurately estimate Ki.

An Update on the Role of mpMRI and 68Ga-PSMA PET Imaging in Primary and Recurrent Prostate Cancer.

The objective of this work was to review comparisons of the efficacy of 68Ga-PSMA-11 (prostate-specific membrane antigen) PET/CT and multiparametric magnetic resonance imaging (mpMRI) in the detection of prostate cancer among patients undergoing initial staging prior to radical prostatectomy or experiencing recurrent prostate cancer, based on histopathological data. A comprehensive search was conducted in PubMed and Web of Science, and relevant articles were analyzed with various parameters, including year of publication, study design, patient count, age, PSA (prostate-specific antigen) value, Gleason score, standardized uptake value (SUVmax), detection rate, treatment history, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and PI-RADS (prostate imaging reporting and data system) scores. Only studies directly comparing PSMA-PET and mpMRI were considered, while those examining combined accuracy or focusing on either modality alone were excluded. In total, 24 studies comprising 1717 patients were analyzed, with the most common indication for screening being staging, followed by relapse. The findings indicated that 68Ga-PSMA-PET/CT effectively diagnosed prostate cancer in patients with suspected or confirmed disease, and both methods exhibited comparable efficacy in identifying lesion-specific information. However, notable heterogeneity was observed, highlighting the necessity for standardization of imaging and histopathology systems to mitigate inter-study variability. Future research should prioritize evaluating the combined diagnostic performance of both modalities to enhance sensitivity and reduce unnecessary biopsies. Overall, the utilization of PSMA-PET and mpMRI in combination holds substantial potential for significantly advancing the diagnosis and management of prostate cancer.

Machine learning-based analysis of 68Ga-PSMA-11 PET/CT images for estimation of prostate tumor grade.

Early diagnosis of prostate cancer, the most common malignancy in men, can improve patient outcomes. Since the tissue sampling procedures are invasive and sometimes inconclusive, an alternative image-based method can prevent possible complications and facilitate treatment management. We aim to propose a machine-learning model for tumor grade estimation based on 68 Ga-PSMA-11 PET/CT images in prostate cancer patients. This study included 90 eligible participants out of 244 biopsy-proven prostate cancer patients who underwent staging 68Ga-PSMA-11 PET/CT imaging. The patients were divided into high and low-intermediate groups based on their Gleason scores. The PET-only images were manually segmented, both lesion-based and whole prostate, by two experienced nuclear medicine physicians. Four feature selection algorithms and five classifiers were applied to Combat-harmonized and non-harmonized datasets. To evaluate the model's generalizability across different institutions, we performed leave-one-center-out cross-validation (LOOCV). The metrics derived from the receiver operating characteristic curve were used to assess model performance. In the whole prostate segmentation, combining the ANOVA algorithm as the feature selector with Random Forest (RF) and Extra Trees (ET) classifiers resulted in the highest performance among the models, with an AUC of 0.78 and 083, respectively. In the lesion-based segmentation, the highest AUC was achieved by MRMR feature selector + Linear Discriminant Analysis (LDA) and Logistic Regression (LR) classifiers (0.76 and 0.79, respectively). The LOOCV results revealed that both the RF_ANOVA and ET_ANOVA models showed high levels of accuracy and generalizability across different centers, with an average AUC value of 0.87 for the ET_ANOVA combination. Machine learning-based analysis of radiomics features extracted from 68Ga-PSMA-11 PET/CT scans can accurately classify prostate tumors into low-risk and intermediate- to high-risk groups.

Quantifying partial volume effect in SPECT and planar imaging: optimizing region of interest for activity concentration estimation in different sphere sizes.

INTRODUCTION: To quantify the partial volume effect in single photon emission tomography (SPECT) and planar images of Carlson phantom as well as providing an optimum region of interest (ROI) required to more accurately estimate the activity concentration for different sphere sizes. METHODS: 131 I solution with the 161.16 kBq/ml concentration was uniformly filled into the different spheres of Carlson phantom (cold background condition) with the diameters of 7.3, 9.2, 11.4, 14.3, 17.9, 22.4 and 29.9 mm, and there was no background activity. In the hot background condition, the spheres were filled with the solution of 131 I with the 1276.5 kBq/ml addition to the background activity concentration of 161.16 kBq/ml in all the phantoms. The spheres were mounted inside the phantom and underwent SPECT and planar images. ROI was drawn closely on the boundary of each sphere image and it was extended to extract the true count. RESULTS: In the cold background condition, the recovery coefficient (RC) value for SPECT images ranged between 0.8 and 1.03. However, in planar imaging, the RC value was 0.72 for the smallest sphere size and it increased for larger spheres until 0.98 for 29.9 mm. In the hot background condition, the RC value for sphere diameters larger than 20 mm was overestimated more than in the cold background condition. The ROI/size required to more accurately determine activity concentration for the cold background ranged from 1.18 to 2.7. However, in the hot background condition, this ratio varied from 1.34 to 4.05. CONCLUSION: In the quantification of partial volume effects, the spill-out effect seems to play a crucial role in the distribution of the image counts beyond the boundaries of the image pixels. However, more investigations are needed to accurately characterize limitations regarding the object size, background levels, and other factors.

Automated segmentation of lesions and organs at risk on [68Ga]Ga-PSMA-11 PET/CT images using self-supervised learning with Swin UNETR.

BACKGROUND: Prostate-specific membrane antigen (PSMA) PET/CT imaging is widely used for quantitative image analysis, especially in radioligand therapy (RLT) for metastatic castration-resistant prostate cancer (mCRPC). Unknown features influencing PSMA biodistribution can be explored by analyzing segmented organs at risk (OAR) and lesions. Manual segmentation is time-consuming and labor-intensive, so automated segmentation methods are desirable. Training deep-learning segmentation models is challenging due to the scarcity of high-quality annotated images. Addressing this, we developed shifted windows UNEt TRansformers (Swin UNETR) for fully automated segmentation. Within a self-supervised framework, the model's encoder was pre-trained on unlabeled data. The entire model was fine-tuned, including its decoder, using labeled data. METHODS: In this work, 752 whole-body [68Ga]Ga-PSMA-11 PET/CT images were collected from two centers. For self-supervised model pre-training, 652 unlabeled images were employed. The remaining 100 images were manually labeled for supervised training. In the supervised training phase, 5-fold cross-validation was used with 64 images for model training and 16 for validation, from one center. For testing, 20 hold-out images, evenly distributed between two centers, were used. Image segmentation and quantification metrics were evaluated on the test set compared to the ground-truth segmentation conducted by a nuclear medicine physician. RESULTS: The model generates high-quality OARs and lesion segmentation in lesion-positive cases, including mCRPC. The results show that self-supervised pre-training significantly improved the average dice similarity coefficient (DSC) for all classes by about 3%. Compared to nnU-Net, a well-established model in medical image segmentation, our approach outperformed with a 5% higher DSC. This improvement was attributed to our model's combined use of self-supervised pre-training and supervised fine-tuning, specifically when applied to PET/CT input. Our best model had the lowest DSC for lesions at 0.68 and the highest for liver at 0.95. CONCLUSIONS: We developed a state-of-the-art neural network using self-supervised pre-training on whole-body [68Ga]Ga-PSMA-11 PET/CT images, followed by fine-tuning on a limited set of annotated images. The model generates high-quality OARs and lesion segmentation for PSMA image analysis. The generalizable model holds potential for various clinical applications, including enhanced RLT and patient-specific internal dosimetry.

Enhanced direct joint attenuation and scatter correction of whole-body PET images via context-aware deep networks.

In positron emission tomography (PET), attenuation and scatter corrections are necessary steps toward accurate quantitative reconstruction of the radiopharmaceutical distribution. Inspired by recent advances in deep learning, many algorithms based on convolutional neural networks have been proposed for automatic attenuation and scatter correction, enabling applications to CT-less or MR-less PET scanners to improve performance in the presence of CT-related artifacts. A known characteristic of PET imaging is to have varying tracer uptakes for various patients and/or anatomical regions. However, existing deep learning-based algorithms utilize a fixed model across different subjects and/or anatomical regions during inference, which could result in spurious outputs. In this work, we present a novel deep learning-based framework for the direct reconstruction of attenuation and scatter-corrected PET from non-attenuation-corrected images in the absence of structural information in the inference. To deal with inter-subject and intra-subject uptake variations in PET imaging, we propose a novel model to perform subject- and region-specific filtering through modulating the convolution kernels in accordance to the contextual coherency within the neighboring slices. This way, the context-aware convolution can guide the composition of intermediate features in favor of regressing input-conditioned and/or region-specific tracer uptakes. We also utilized a large cohort of 910 whole-body studies for training and evaluation purposes, which is more than one order of magnitude larger than previous works. In our experimental studies, qualitative assessments showed that our proposed CT-free method is capable of producing corrected PET images that accurately resemble ground truth images corrected with the aid of CT scans. For quantitative assessments, we evaluated our proposed method over 112 held-out subjects and achieved an absolute relative error of 14.30±3.88% and a relative error of -2.11%±2.73% in whole-body.

Radiomics and Artificial Intelligence in Radiotheranostics: A Review of Applications for Radioligands Targeting Somatostatin Receptors and Prostate-Specific Membrane Antigens.

Radiotheranostics refers to the pairing of radioactive imaging biomarkers with radioactive therapeutic compounds that deliver ionizing radiation. Given the introduction of very promising radiopharmaceuticals, the radiotheranostics approach is creating a novel paradigm in personalized, targeted radionuclide therapies (TRTs), also known as radiopharmaceuticals (RPTs). Radiotherapeutic pairs targeting somatostatin receptors (SSTR) and prostate-specific membrane antigens (PSMA) are increasingly being used to diagnose and treat patients with metastatic neuroendocrine tumors (NETs) and prostate cancer. In parallel, radiomics and artificial intelligence (AI), as important areas in quantitative image analysis, are paving the way for significantly enhanced workflows in diagnostic and theranostic fields, from data and image processing to clinical decision support, improving patient selection, personalized treatment strategies, response prediction, and prognostication. Furthermore, AI has the potential for tremendous effectiveness in patient dosimetry which copes with complex and time-consuming tasks in the RPT workflow. The present work provides a comprehensive overview of radiomics and AI application in radiotheranostics, focusing on pairs of SSTR- or PSMA-targeting radioligands, describing the fundamental concepts and specific imaging/treatment features. Our review includes ligands radiolabeled by 68Ga, 18F, 177Lu, 64Cu, 90Y, and 225Ac. Specifically, contributions via radiomics and AI towards improved image acquisition, reconstruction, treatment response, segmentation, restaging, lesion classification, dose prediction, and estimation as well as ongoing developments and future directions are discussed.

Comparable assessment of adolescent repeated physical or psychological stress effects on adult cardiac performance in female rats.

Extensive evidence highlights a robust connection between various forms of chronic stress and cardiovascular disease (CVD). In today's fast-paced world, with chronic stressors abound, CVD has emerged as a leading global cause of mortality. The intricate interplay of physical and psychological stressors triggers distinct neural networks within the brain, culminating in diverse health challenges. This study aims to discern the unique impacts of chronic physical and psychological stress on the cardiovascular system, unveiling their varying potencies in precipitating CVD. Twenty-one adolescent female rats were methodically assigned to three groups: (1) control (n = 7), (2) physical stress (n = 7), and (3) psychological stress (n = 7). Employing a two-compartment enclosure, stressors were administered to the experimental rats over five consecutive days, each session lasting 10 min. After a 1.5-month recovery period post-stress exposure, a trio of complementary techniques characterized by high specificity or high sensitivity were employed to meticulously evaluate CVD. Echocardiography and single-photon emission computed tomography (SPECT) were harnessed to scrutinize left ventricular architecture and myocardial viability, respectively. Subsequently, the rats were ethically sacrificed to facilitate heart removal, followed by immunohistochemistry staining targeting glial fibrillary acidic protein (GFAP). Rats subjected to psychological stress showed a wider range of significant cardiac issues compared to control rats. This included left ventricular hypertrophy [IVSd: 0.1968 ± 0.0163 vs. 0.1520 ± 0.0076, P < 0.05; LVPWd: 0.2877 ± 0.0333 vs. 0.1689 ± 0.0057, P < 0.01; LVPWs: 0.3180 ± 0.0382 vs. 0.2226 ± 0.0121, P < 0.05; LV-mass: 1.283 ± 0.0836 vs. 1.000 ± 0.0241, P < 0.01], myocardial ischemia [21.30% vs. 32.97%, P < 0.001], and neuroinflammation. This outcome underscores the imperative of prioritizing psychological well-being during adolescence, presenting a compelling avenue to curtail the prevalence of CVD in adulthood. Furthermore, extending such considerations to individuals grappling with CVD might prospectively enhance their overall quality of life.

Differential privacy preserved federated transfer learning for multi-institutional 68Ga-PET image artefact detection and disentanglement.

PURPOSE: Image artefacts continue to pose challenges in clinical molecular imaging, resulting in misdiagnoses, additional radiation doses to patients and financial costs. Mismatch and halo artefacts occur frequently in gallium-68 (68Ga)-labelled compounds whole-body PET/CT imaging. Correcting for these artefacts is not straightforward and requires algorithmic developments, given that conventional techniques have failed to address them adequately. In the current study, we employed differential privacy-preserving federated transfer learning (FTL) to manage clinical data sharing and tackle privacy issues for building centre-specific models that detect and correct artefacts present in PET images. METHODS: Altogether, 1413 patients with 68Ga prostate-specific membrane antigen (PSMA)/DOTA-TATE (TOC) PET/CT scans from 3 countries, including 8 different centres, were enrolled in this study. CT-based attenuation and scatter correction (CT-ASC) was used in all centres for quantitative PET reconstruction. Prior to model training, an experienced nuclear medicine physician reviewed all images to ensure the use of high-quality, artefact-free PET images (421 patients' images). A deep neural network (modified U2Net) was trained on 80% of the artefact-free PET images to utilize centre-based (CeBa), centralized (CeZe) and the proposed differential privacy FTL frameworks. Quantitative analysis was performed in 20% of the clean data (with no artefacts) in each centre. A panel of two nuclear medicine physicians conducted qualitative assessment of image quality, diagnostic confidence and image artefacts in 128 patients with artefacts (256 images for CT-ASC and FTL-ASC). RESULTS: The three approaches investigated in this study for 68Ga-PET imaging (CeBa, CeZe and FTL) resulted in a mean absolute error (MAE) of 0.42 ± 0.21 (CI 95%: 0.38 to 0.47), 0.32 ± 0.23 (CI 95%: 0.27 to 0.37) and 0.28 ± 0.15 (CI 95%: 0.25 to 0.31), respectively. Statistical analysis using the Wilcoxon test revealed significant differences between the three approaches, with FTL outperforming CeBa and CeZe (p-value < 0.05) in the clean test set. The qualitative assessment demonstrated that FTL-ASC significantly improved image quality and diagnostic confidence and decreased image artefacts, compared to CT-ASC in 68Ga-PET imaging. In addition, mismatch and halo artefacts were successfully detected and disentangled in the chest, abdomen and pelvic regions in 68Ga-PET imaging. CONCLUSION: The proposed approach benefits from using large datasets from multiple centres while preserving patient privacy. Qualitative assessment by nuclear medicine physicians showed that the proposed model correctly addressed two main challenging artefacts in 68Ga-PET imaging. This technique could be integrated in the clinic for 68Ga-PET imaging artefact detection and disentanglement using multicentric heterogeneous datasets.

Vimentin-targeted radiopeptide 99m Tc-HYNIC-(tricine/EDDA)-VNTANST: a promising drug for pulmonary fibrosis imaging.

OBJECTIVE: Idiopathic pulmonary fibrosis (IPF) is a fatal disease characterized by the accumulation of extracellular matrix. Because there is no effective treatment for advanced IPF to date, its early diagnosis can be critical. Vimentin is a cytoplasmic intermediate filament that is significantly up-regulated at the surface of fibrotic foci with a crucial role in fibrotic morphological changes. METHODS: In the present study, VNTANST sequence as a known vimentin-targeting peptide was conjugated to hydrazinonicotinic acid (HYNIC) and labeled with 99m Tc. The stability test in saline and human plasma and log P determination were performed. Next, the biodistribution study and single photon emission computed tomography (SPECT) integrated with computed tomography (CT) scanning were performed in healthy and bleomycin-induced fibrosis mice models. RESULTS: The 99m Tc-HYNIC-(tricine/EDDA)-VNTANST showed a hydrophilic nature (log P  = -2.20 ±â€…0.38) and high radiochemical purity > 97% and specific activity (336 Ci/mmol). The radiopeptide was approximately 93% and 86% intact in saline and human plasma within 6 h, respectively. The radiopeptide was substantially accumulated in the pulmonary fibrotic lesions (test vs. control = 4.08 ±â€…0.08% injected dose per gram (ID/g) vs. 0.36 ±â€…0.01% ID/g at 90 min postinjection). SPECT-CT images in fibrosis-bearing mice also indicated the fibrotic foci and kidneys. CONCLUSION: Because there is no available drug for the treatment of advanced pulmonary fibrosis, early diagnosis is the only chance. The 99m Tc-HYNIC-(tricine/EDDA)-VNTANST could be a potential tracer for SPECT imaging of pulmonary fibrosis.

Radiomics predictive modeling from dual-time-point FDG PET Ki parametric maps: application to chemotherapy response in lymphoma.

BACKGROUND: To investigate the use of dynamic radiomics features derived from dual-time-point (DTP-feature) [18F]FDG PET metabolic uptake rate Ki parametric maps to develop a predictive model for response to chemotherapy in lymphoma patients. METHODS: We analyzed 126 lesions from 45 lymphoma patients (responding n = 75 and non-responding n = 51) treated with chemotherapy from two different centers. Static and DTP radiomics features were extracted from baseline static PET images and DTP Ki parametric maps. Spearman's rank correlations were calculated between static and DTP features to identify features with potential additional information. We first employed univariate analysis to determine correlations between individual features, and subsequently utilized multivariate analysis to derive predictive models utilizing DTP and static radiomics features before and after ComBat harmonization. For multivariate modeling, we utilized both the minimum redundancy maximum relevance feature selection technique and the XGBoost classifier. To evaluate our model, we partitioned the patient datasets into training/validation and testing sets using an 80/20% split. Different metrics for classification including area under the curve (AUC), sensitivity (SEN), specificity (SPE), and accuracy (ACC) were reported in test sets. RESULTS: Via Spearman's rank correlations, there was negligible to moderate correlation between 32 out of 65 DTP features and some static features (ρ < 0.7); all the other 33 features showed high correlations (ρ ≥ 0.7). In univariate modeling, no significant difference between AUC of DTP and static features was observed. GLRLM_RLNU from static features demonstrated a strong correlation (AUC = 0.75, p value = 0.0001, q value = 0.0007) with therapy response. The most predictive DTP features were GLCM_Energy, GLCM_Entropy, and Uniformity, each with AUC = 0.73, p value = 0.0001, and q value < 0.0005. In multivariate analysis, the mean ranges of AUCs increased following harmonization. Use of harmonization plus combining DTP and static features was shown to provide significantly improved predictions (AUC = 0.97 ± 0.02, accuracy = 0.89 ± 0.05, sensitivity = 0.92 ± 0.09, and specificity = 0.88 ± 0.05). All models depicted significant performance in terms of AUC, ACC, SEN, and SPE (p < 0.05, Mann-Whitney test). CONCLUSIONS: Our results demonstrate significant value in harmonization of radiomics features as well as combining DTP and static radiomics models for predicting response to chemotherapy in lymphoma patients.

Diagnostic value of [ 68 Ga]Ga-Pentixafor versus [ 18 F]FDG PET/CTs in non-small cell lung cancer: a head-to-head comparative study.

OBJECTIVE: In this study, we aimed to compare the diagnostic value of [ 68 Ga]Ga-Pentixafor and [ 18 F]FDG PET/CT in the evaluation of non-small cell lung cancer (NSCLC) patients. METHODS: Patients with pathology-proven NSCLC were prospectively included. Patients underwent [ 18 F]FDG and [ 68 Ga]Ga-Pentixafor PET/CT within 1 week. All suspicious lesions were interpreted as benign or malignant, and the corresponding PET/CT semi-quantitative parameters were recorded. A two-sided P -value <0.05 was considered significant. RESULTS: Twelve consecutive NSCLC patients (mean age: 60 ±â€…7) were included. All patients underwent both [ 18 F]FDG and [ 68 Ga]Ga-Pentixafor PET/CT scans with a median interval of 2 days. Overall, 73 abnormal lesions were detected, from which 58 (79%) were concordant between [ 18 F]FDG and [ 68 Ga]Ga-Pentixafor PET/CT. All primary tumors were clearly detectable in both scans visually. Also, [ 68 Ga]Ga-Pentixafor PET/CT demonstrated rather comparable results with [ 18 F]FDG PET/CT scan in detecting metastatic lesions. However, malignant lesions demonstrated significantly higher SUVmax and SUVmean in [ 18 F]FDG PET/CT ( P -values <0.05). Regarding the advantages, [ 68 Ga]Ga-Pentixafor depicted two brain metastases that were missed by [ 18 F]FDG PET/CT. Also, a highly suspicious lesion for recurrence on [ 18 F]FDG PET/CT scan was correctly classified as benign by subsequent [ 68 Ga]Ga-Pentixafor PET/CT. CONCLUSION: [ 68 Ga]Ga-Pentixafor PET/CT was concordant with [ 18 F]FDG PET/CT in detecting primary NSCLC tumors and could visualize the majority of metastatic lesions. Moreover, this modality was found to be potentially helpful in excluding tumoural lesions when the [ 18 F]FDG PET/CT was equivocal, as well as in detecting brain metastasis where [ 18 F]FDG PET/CT suffers from poor sensitivity. However, the count statistics were significantly lower.

Multicenter quantitative 18F-fluorodeoxyglucose positron emission tomography performance harmonization: use of hottest voxels towards more robust quantification.

Background: Harmonization methods reduce variability between different make and models of positron emission tomography (PET) scanners. The study aims to explore harmonization strategies that lead to comparable and robust quantitative metrics in a multicenter setting. Methods: NEMA IEC Phantom data acquisition was performed for low and high spheres-to-background ratios (SBR4:1 and 10:1) on six PET/CT (computed tomography) scanners. Different reconstruction sets, including the number of sub-iterations, number of subsets, and full width at half maximum (FWHM) for each scanner, were evaluated towards optimized and harmonized reconstruction settings. Recovery coefficients (RCs) of four quantitative metrics, including standardized uptake value (SUV)max, SUVISO-50 (SUVmean in 50% isocontour), SUVpeak, and mean uptake of 10 highest concentration voxels were evaluated as RCmax, RCISO-50, RCpeak, and RC10V, representing percent difference relative to the static ground truth case as functions of sphere sizes. A set of image reconstruction parameters was proposed for harmonized reconstruction to minimize variability between scanners. The root mean square error (RMSE), curvature, and reproducibility were examined. The proposed reconstruction protocols for harmonization and standard clinical reconstruction settings were compared to each other across all scanners. Results: A significant difference (P value <0.0001) was observed in the aforementioned quantitative metrics between SBR10 and SBR4. Reconstruction parameter sets with the smallest RMSE and RC values within 10% bias were identified as the best candidate for harmonization. The coefficient of variation of the mean value of RCs (CVMRC) shows a remarkable reduction of about 28%, 26%, 32%, and 19% in harmonized reconstruction settings for MRCmax, MRCISO-50, MRCpeak, and MRC10V, respectively. CVMRC for MRC10V in the harmonized reconstruction setting was 5.9% in SBR4, while the smallest value in SBR10 belongs to MRCpeak, with a value of 5.8%. The reproducibility of RC is improved by deriving the value from ten hottest voxels and is equally reproducible with RCpeak. Compared to RCmax and RCISO-50, the variability is reduced by 18% and 22% if ten voxels are pooled. Conclusions: Harmonizing PET/CT systems with and without point spread function/time of flight (PSF/TOF) using various vendor-developed image reconstruction algorithms improves the quantification reproducibility. RC10V, likewise RCpeak, is superior to the rest of the quantitative indices in terms of accuracy and reproducibility and helpful in quantifying lesion volume below 1 mL.

QCard-NM: Developing a semiautomatic segmentation method for quantitative analysis of the right ventricle in non-gated myocardial perfusion SPECT imaging.

BACKGROUND: Recent studies have shown that the right ventricular (RV) quantitative analysis in myocardial perfusion imaging (MPI) SPECT can be beneficial in the diagnosis of many cardiopulmonary diseases. This study proposes a new algorithm for right ventricular 3D segmentation and quantification. METHODS: The proposed Quantitative Cardiac analysis in Nuclear Medicine imaging (QCard-NM) algorithm provides RV myocardial surface estimation and creates myocardial contour using an iterative 3D model fitting method. The founded contour is then used for quantitative RV analysis. The proposed method was assessed using various patient datasets and digital phantoms. First, the physician's manually drawn contours were compared to the QCard-NM RV segmentation using the Dice similarity coefficient (DSC). Second, using repeated MPI scans, the QCard-NM's repeatability was evaluated and compared with the QPS (quantitative perfusion SPECT) algorithm. Third, the bias of the calculated RV cavity volume was analyzed using 31 digital phantoms using the QCard-NM and QPS algorithms. Fourth, the ability of QCard-NM analysis to diagnose coronary artery diseases was assessed in 60 patients referred for both MPI and coronary angiography. RESULTS: The average DSC value was 0.83 in the first dataset. In the second dataset, the coefficient of repeatability of the calculated RV volume between two repeated scans was 13.57 and 43.41 ml for the QCard-NM and QPS, respectively. In the phantom study, the mean absolute percentage errors for the calculated cavity volume were 22.6% and 42.2% for the QCard-NM and QPS, respectively. RV quantitative analysis using QCard-NM in detecting patients with severe left coronary system stenosis and/or three-vessel diseases achieved a fair performance with the area under the ROC curve of 0.77. CONCLUSION: A novel model-based iterative method for RV segmentation task in non-gated MPI SPECT is proposed. The precision, accuracy, and consistency of the proposed method are demonstrated by various validation techniques. We believe this preliminary study could lead to developing a framework for improving the diagnosis of cardiopulmonary diseases using RV quantitative analysis in MPI SPECT.

Attenuation Correction for Dedicated Cardiac SPECT Imaging Without Using Transmission Data.

Objectives: Attenuation correction (AC) using transmission scanning-like computed tomography (CT) is the standard method to increase the accuracy of cardiac single-photon emission computed tomography (SPECT) images. Recently developed dedicated cardiac SPECT do not support CT, and thus, scans on these systems are vulnerable to attenuation artifacts. This study presented a new method for generating an attenuation map directly from emission data by segmentation of precisely non-rigid registration extended cardiac-torso (XCAT)-digital phantom with cardiac SPECT images. Methods: In-house developed non-rigid registration algorithm automatically aligns the XCAT- phantom with cardiac SPECT image to precisely segment the contour of organs. Pre-defined attenuation coefficients for given photon energies were assigned to generate attenuation maps. The CT-based attenuation maps were used for validation with which cardiac SPECT/CT data of 38 patients were included. Segmental myocardial counts of a 17-segment model from these databases were compared based on the basis of the paired t-test. Results: The mean, and standard deviation of the mean square error and structural similarity index measure of the female stress phase between the proposed attenuation maps and the CT attenuation maps were 6.99±1.23% and 92±2.0%, of the male stress were 6.87±3.8% and 96±1.0%. Proposed attenuation correction and computed tomography based attenuation correction average myocardial perfusion count was significantly higher than that in non-AC in the mid-inferior, mid-lateral, basal-inferior, and lateral regions (p<0.001). Conclusion: The proposed attenuation maps showed good agreement with the CT-based attenuation map. Therefore, it is feasible to enable AC for a dedicated cardiac SPECT or SPECT standalone scanners.

Breathing-induced Errors in Quantification and Description of Dominant Intra-Prostatic Lesions (Dils) in PET Images: A Simulation Study by Means of The 4D NCAT Phantom.

Background: Respiratory movement and the motion range of the diaphragm can affect the quality and quantity of prostate images. Objective: This study aimed to investigate the magnitude of respiratory-induced errors to determine Dominant Intra- prostatic Lesions (DILs) in positron emission tomography (PET) images. Material and Methods: In this simulation study, we employed the 4D NURBS-based cardiac-torso (4D-NCAT) phantom with a realistic breathing model to simulate the respiratory cycles of a patient to assess the displacement, volume, maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), signal to noise ratio (SNR), and the contrast of DILs in frames within the respiratory cycle. Results: Respiration in a diaphragm motion resulted in the maximum superior-inferior displacement of 3.9 and 6.1 mm, and the diaphragm motion amplitudes of 20 and 35 mm. In a no-motion image, the volume measurement of DILs had the smallest percentage of errors. Compared with the no-motion method, the percentages of errors in the average method in 20 and 35 mm- diaphragm motion were 25% and 105%, respectively. The motion effect was significantly reduced in terms of the values of SUVmax and SUVmean in comparison with the values of SUVmax and SUVmean in no- motion images. The contrast values in respiratory cycle frames were at a range of 3.3-19.2 mm and 6.5-46 for diaphragm movements' amplitudes of 20 and 35 mm. Conclusion: The respiratory movement errors in quantification and delineation of DILs were highly dependent on the range of motion, while the average method was not suitable to precisely delineate DILs in PET/CT in the dose-painting technique.

Evaluation of Dose-Painting in the Dominant Intraprostatic Lesions by Radiobiological Parameters using 68Ga- PSMA PET/CT.

Background: Patients diagnosed with dominant intraprostatic lesions (DIL) may need radiation doses over than 80 Gy. Dose-painting by contours (DPC) is a useful technique which helps the patients. Dose-painting approach need to be evaluated. Objective: To evaluate the DCP technique in the case of boosting the DILs by radiobiological parameters, tumor control probability (TCP), and normal tissue complication probability (NTCP) via PET/CT images traced by 68Ga-PSMA. Material and Methods: In this analytical study, 68Ga-PSMA PET/CT images were obtained from patients with DILs that were delineated using the Fuzzy c-mean (FCM) algorithm and thresholding methods. The protocol of therapy included two phases; at the first phase (ph1), a total dose of 72 Gy in 36 fractions were delivered to the planning target volume (PTV1); the seconds phase consisted of the application of variable doses to the PTV2. Moreover, two concepts were also considered to calculate the TCP using the Zaider-Minerbo model. Results: The lowest volume in DILs belonged to the DIL1 extracted by the FCM method. According to dose-volume parameters of the rectum and bladder, by the increase in the PTV dose higher than 92 Gy, the amounts of rectum and bladder doses are increased. There was no difference between the TCPs of DILs at doses higher than 86 Gy and 100 Gy for ordinary and high clone density, respectively. Conclusion: Consequently, our dose-painting approach for DILs, extracted by the FCM method via PET/CT images, can reduce the total dose for prostate radiation with 100% tumor control and less normal tissue complications.

Harmonization based on quantitative analysis of standardized uptake value variations across PET/CT scanners: a multicenter phantom study.

OBJECTIVES: This study aimed to measure standardized uptake value (SUV) variations across different PET/computed tomography (CT) scanners to harmonize quantification across systems. METHODS: We acquired images using the National Electrical Manufacturers Association International Electrotechnical Commission phantom from three PET/CT scanners operated using routine imaging protocols at each site. The SUVs of lesions were assessed in the presence of reference values by a digital reference object (DRO) and recommendations by the European Association of Nuclear Medicine (EANM/EARL) to measure inter-site variations. For harmonization, Gaussian filters with tuned full width at half maximum (FWHM) values were applied to images to minimize differences in SUVs between reference and images. Inter-site variation of SUVs was evaluated in both pre- and postharmonization situations. Test-retest analysis was also carried out to evaluate repeatability. RESULTS: SUVs from different scanners became significantly more consistent, and inter-site differences decreased for SUV mean , SUV max and SUV peak from 17.3, 20.7, and 15.5% to 4.8, 4.7, and 2.7%, respectively, by harmonization ( P values <0.05 for all). The values for contrast-to-noise ratio in the smallest lesion of the phantom verified preservation of image quality following harmonization (>2.8%). CONCLUSIONS: Harmonization significantly lowered variations in SUV measurements across different PET/CT scanners, improving reproducibility while preserving image quality.

Potential advantages of FDG-PET radiomic feature map for target volume delineation in lung cancer radiotherapy.

PURPOSE: To investigate the potential benefits of FDG PET radiomic feature maps (RFMs) for target delineation in non-small cell lung cancer (NSCLC) radiotherapy. METHODS: Thirty-two NSCLC patients undergoing FDG PET/CT imaging were included. For each patient, nine grey-level co-occurrence matrix (GLCM) RFMs were generated. gross target volume (GTV) and clinical target volume (CTV) were contoured on CT (GTVCT , CTVCT ), PET (GTVPET40 , CTVPET40 ), and RFMs (GTVRFM , CTVRFM ,). Intratumoral heterogeneity areas were segmented as GTVPET50-Boost and radiomic boost target volume (RTVBoost ) on PET and RFMs, respectively. GTVCT in homogenous tumors and GTVPET40 in heterogeneous tumors were considered as GTVgold standard (GTVGS ). One-way analysis of variance was conducted to determine the threshold that finds the best conformity for GTVRFM with GTVGS . Dice similarity coefficient (DSC) and mean absolute percent error (MAPE) were calculated. Linear regression analysis was employed to report the correlations between the gold standard and RFM-derived target volumes. RESULTS: Entropy, contrast, and Haralick correlation (H-correlation) were selected for tumor segmentation. The threshold values of 80%, 50%, and 10% have the best conformity of GTVRFM-entropy , GTVRFM-contrast , and GTVRFM-H-correlation with GTVGS , respectively. The linear regression results showed a positive correlation between GTVGS and GTVRFM-entropy (r = 0.98, p < 0.001), between GTVGS and GTVRFM-contrast (r = 0.93, p < 0.001), and between GTVGS and GTVRFM-H-correlation (r = 0.91, p < 0.001). The average threshold values of 45% and 15% were resulted in the best segmentation matching between CTVRFM-entropy and CTVRFM-contrast with CTVGS , respectively. Moreover, we used RFM to determine RTVBoost in the heterogeneous tumors. Comparison of RTVBoost with GTVPET50-Boost MAPE showed the volume error differences of 31.7%, 36%, and 34.7% in RTVBoost-entropy , RTVBoost-contrast , and RTVBoost-H-correlation , respectively. CONCLUSIONS: FDG PET-based radiomics features in NSCLC demonstrated a promising potential for decision support in radiotherapy, helping radiation oncologists delineate tumors and generate accurate segmentation for heterogeneous region of tumors.

COVID-19 prognostic modeling using CT radiomic features and machine learning algorithms: Analysis of a multi-institutional dataset of 14,339 patients.

BACKGROUND: We aimed to analyze the prognostic power of CT-based radiomics models using data of 14,339 COVID-19 patients. METHODS: Whole lung segmentations were performed automatically using a deep learning-based model to extract 107 intensity and texture radiomics features. We used four feature selection algorithms and seven classifiers. We evaluated the models using ten different splitting and cross-validation strategies, including non-harmonized and ComBat-harmonized datasets. The sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were reported. RESULTS: In the test dataset (4,301) consisting of CT and/or RT-PCR positive cases, AUC, sensitivity, and specificity of 0.83 ± 0.01 (CI95%: 0.81-0.85), 0.81, and 0.72, respectively, were obtained by ANOVA feature selector + Random Forest (RF) classifier. Similar results were achieved in RT-PCR-only positive test sets (3,644). In ComBat harmonized dataset, Relief feature selector + RF classifier resulted in the highest performance of AUC, reaching 0.83 ± 0.01 (CI95%: 0.81-0.85), with a sensitivity and specificity of 0.77 and 0.74, respectively. ComBat harmonization did not depict statistically significant improvement compared to a non-harmonized dataset. In leave-one-center-out, the combination of ANOVA feature selector and RF classifier resulted in the highest performance. CONCLUSION: Lung CT radiomics features can be used for robust prognostic modeling of COVID-19. The predictive power of the proposed CT radiomics model is more reliable when using a large multicentric heterogeneous dataset, and may be used prospectively in clinical setting to manage COVID-19 patients.