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BackgroundIntegrin alpha-V-beta-3 (αvβ3) pathway is involved in intraplaque angiogenesis and inflammation and represents a promising target for molecular imaging in cardiovascular diseases such as atherosclerosis. The aim of this study was to assess the clinical correlates of arterial wall accumulation of 68Ga-NODAGA-RGD, a specific αvβ3 integrin ligand for PET.Materials and methodsThe data of 44 patients who underwent 68Ga-NODAGA-RGD PET/CT scans were retrospectively analyzed. Tracer accumulation in the vessel wall of major arteries was analyzed semi-quantitatively by blood-pool-corrected target-to-background ratios. Tracer uptake was compared with clinically documented atherosclerotic cardiovascular disease, cardiovascular risk factors and calcified plaque burden. Data were compared using the Mann–Whitney U test, Pearson correlation and Spearman correlation.Results68Ga-NODAGA-RGD arterial uptake was significantly higher in patients with previous clinically documented atherosclerotic cardiovascular disease (mean TBR 2.44 [2.03–2.55] vs. 1.81 [1.56–1.96], p = 0.001) and showed a significant correlation with prior cardiovascular or cerebrovascular event (r = 0.33, p = 0.027), BMI (ρ = 0.38, p = 0.01), plaque burden (ρ = 0.31, p = 0.04) and hypercholesterolemia (r = 0.31, p = 0.04).Conclusions68Ga-NODAGA-RGD holds promise as a non-invasive marker of disease activity in atherosclerosis, providing information about intraplaque angiogenesis.

Assessing the individual risk of Major Adverse Cardiac Events (MACE) is of major importance as cardiovascular diseases remain the leading cause of death worldwide. Quantitative Myocardial Perfusion Imaging (MPI) parameters such as stress Myocardial Blood Flow (sMBF) or Myocardial Flow Reserve (MFR) constitutes the gold standard for prognosis assessment. We propose a systematic investigation of the value of Artificial Intelligence (AI) to leverage [ 82 Rb] Silicon PhotoMultiplier (SiPM) PET MPI for MACE prediction. We establish a general pipeline for AI model validation to assess and compare the performance of global (i.e. average of the entire MPI signal), regional (17 segments), radiomics and Convolutional Neural Network (CNN) models leveraging various MPI signals on a dataset of 234 patients. Results showed that all regional AI models significantly outperformed the global model ( p < 0.001 ), where the best AUC of 73.9% (CI 72.5–75.3) was obtained with a CNN model. A regional AI model based on MBF averages from 17 segments fed to a Logistic Regression (LR) constituted an excellent trade-off between model simplicity and performance, achieving an AUC of 73.4% (CI 72.3–74.7). A radiomics model based on intensity features revealed that the global average was the least important feature when compared to other aggregations of the MPI signal over the myocardium. We conclude that AI models can allow better personalized prognosis assessment for MACE.

Deletion of p53 and pRB leads to gene instability and replication errors that contribute to oncogenesis. [...]given the very unfavourable prognosis of these tumours, it seems legitimate to perform surgery and completely stop immunosuppression. Conflict of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Background We aimed to estimate 82 Rb paediatric dosimetry based on adult biokinetic and prospectively acquired paediatric biokinetic data. Organ absorbed doses (OAD) and effective doses (E) were estimated using ICRP-103 based OLINDA/EXM.2.1 software. We extrapolated paediatric OAD and E from existing adult biokinetic data (OAD p, Ab and E p, Ab respectively). 82 Rb EANM paediatric dosage card (PDC) cluster and the recommended administered activity were determined. Ten paediatric participants (M: F 7:3; mean age 8.8 ± 6.6y) underwent prospectively 3D-SiPM 82 Rb PET/CT. Using PMOD software, source organs volumes were delineated to obtain source organ time activity curves and participant specific organ masses based on PET/CT data. Subject specific OAD (OAD p and E p respectively) were derived from original paediatric data. Results 82 Rb was assigned to the EANM PDC B-Cluster. Estimated ranges for E p, Ab resp. E p were 2.19E-02 ̶ 1.15E-03 resp. 9.62E-03 ̶ 1.04E-03 mSv/MBq. E p, Ab resp. E p with 10 MBq/kg and 5MBq/kg after a single 82 Rb infusion was between 0.5 and 0.7 mSv resp. 0.4–0.8 mSv and 0.2–0.4 mSv. The most irradiated organs were the kidneys and the heart wall in infant and newborn group, followed by heart wall in the other age groups, hence, the small intestine, pancreas, lungs, adrenals, and rest of the gastrointestinal tract. 82 Rb PET/CT was safe and well-tolerated by all participants. Conclusions We firstly provide original dosimetry data for the use of 82 Rb PET/CT in the paediatric population, showing reasonably low radiation exposure, and confirming safety and tolerability of 82 Rb PET/CT in this population.

BackgroundSmall-vessel disease (SVD) plays a crucial role in cardiac and brain ischemia, but little is known about potential interrelation between both. We retrospectively evaluated 370 patients, aiming at assessing the interrelation between cardiac and brain SVD by using quantitative 82Rb cardiac PET/CT and brain MRI.ResultsIn our population of 370 patients, 176 had normal myocardial perfusion, 38 had pure cardiac SVD and 156 had obstructive coronary artery disease. All underwent both a cardiac 82Rb PET/CT and a brain 1.5T or 3T MRI. Left-ventricle myocardial blood flow (LV-MBF) and flow reserve (LV-MFR) were recorded from 82Rb PET/CT, while Fazekas score, white matter lesion (WMab) volume, deep gray matter lesion (GMab) volume, and brain morphometry (for z-score calculation) using the MorphoBox research application were derived from MRI. Groups were compared with Kruskal–Wallis test, and the potential interrelation between heart and brain SVD markers was assessed using Pearson’s correlation coefficient. Patients with cardiac SVD had lower stress LV-MBF and MFR (P < 0.001) than patients with normal myocardial perfusion; Fazekas scores and WMab volumes were similar in those two groups (P > 0.45). In patients with cardiac SVD only, higher rest LV-MBF was associated with a lower left-putamen (rho = − 0.62, P = 0.033), right-thalamus (rho = 0.64, P = 0.026), and right-pallidum (rho = 0.60, P = 0.039) z-scores and with a higher GMab volume. Lower stress LV-MBF was associated with lower left-caudate z-score (rho = 0.69, P = 0.014), while lower LV-MFR was associated with lower left (rho = 0.75, P = 0.005)- and right (rho = 0.59, P = 0.045)-putamen z-scores, as well as higher right-thalamus GMab volume (rho = − 0.72, P = 0.009).ConclusionSignificant interrelations between cardiac and cerebral SVD markers were found, especially regarding deep gray matter alterations, which supports the hypothesis of SVD as a systemic disease.

The development of immune checkpoint inhibitors (ICIs) has revolutionized cancer therapy but only a fraction of patients benefits from this therapy. Model‐informed drug development can be used to assess prognostic and predictive clinical factors or biomarkers associated with treatment response. Most pharmacometric models have thus far been developed using data from randomized clinical trials, and further studies are needed to translate their findings into the real‐world setting. We developed a tumor growth inhibition model based on real‐world clinical and imaging data in a population of 91 advanced melanoma patients receiving ICIs (i.e., ipilimumab, nivolumab, and pembrolizumab). Drug effect was modeled as an ON/OFF treatment effect, with a tumor killing rate constant identical for the three drugs. Significant and clinically relevant covariate effects of albumin, neutrophil to lymphocyte ratio, and Eastern Cooperative Oncology Group (ECOG) performance status were identified on the baseline tumor volume parameter, as well as NRAS mutation on tumor growth rate constant using standard pharmacometric approaches. In a population subgroup (n = 38), we had the opportunity to conduct an exploratory analysis of image‐based covariates (i.e., radiomics features), by combining machine learning and conventional pharmacometric covariate selection approaches. Overall, we demonstrated an innovative pipeline for longitudinal analyses of clinical and imaging RWD with a high‐dimensional covariate selection method that enabled the identification of factors associated with tumor dynamics. This study also provides a proof of concept for using radiomics features as model covariates.

PurposeThe main objective of this study was to evaluate the ability of a large field Cadmium Zinc Telluride (CZT) camera to estimate thyroid uptake (TU) on single photon emission computed tomography (SPECT) images with and without attenuation correction (Tomo-AC and Tomo-NoAC) compared with Planar acquisition in a series of 23 consecutive patients. The secondary objective was to determine radiation doses for the tracer administration and for the additional Computed Tomography (CT) scan.MethodsCross-calibration factors were determined using a thyroid phantom, for Planar, Tomo-AC and Tomo-NoAC images. Then Planar and SPECT/CT acquisitions centered on the thyroid were performed on 5 anthropomorphic phantoms with activity ranging from 0.4 to 10 MBq, and 23 patients after administration of 79.2 ± 3.7 MBq of [99mTc]-pertechnetate. We estimated the absolute thyroid activity (AThA) for the anthropomorphic phantoms and the TU for the patients. Radiation dose was also determined using International Commission on Radiological Protection (ICRP) reports and VirtualDoseTMCT software.ResultsCross-calibration factors were 66.2 ± 4.9, 60.7 ± 0.7 and 26.5 ± 0.3 counts/(MBq s), respectively, for Planar, Tomo-AC and Tomo-NoAC images. Theoretical and estimated AThA for Planar, Tomo-AC and Tomo-NoAC images were statistically highly correlated (r < 0.99; P < 10–4) and the average of the relative percentage difference between theoretical and estimated AThA were (8.6 ± 17.8), (− 1.3 ± 5.2) and (12.8 ± 5.7) %, respectively. Comparisons between TU based on different pairs of images (Planar vs Tomo-AC, Planar vs Tomo-NoAC and Tomo-AC vs Tomo-NoAC) showed statistically significant correlation (r = 0.972, 0.961 and 0.935, respectively; P < 10–3). Effective and thyroid absorbed doses were, respectively (0.34CT + 0.95NM) mSv, and (3.88CT + 1.74NM) mGy.ConclusionAThA estimation using Planar and SPECT/CT acquisitions on a new generation of CZT large-field cameras is feasible. In addition, TU on SPECT/CT was as accurate as conventional planar acquisition, but the CT induced additional thyroid exposure.Trial registration Name of the registry: Thyroid Uptake Quantification on a New Generation of Gamma Camera (QUANTHYC). Trial number: NCT05049551. Registered September 20, 2021—Retrospectively registered, https://clinicaltrials.gov/ct2/show/record/NCT05049551?cntry=MC&draw=2&rank=4.

Studies using arginine–glycine–aspartate (RGD)-PET agents in cardiovascular diseases have been recently published. The aim of this systematic review was to perform an updated, evidence-based summary about the role of RGD-based PET agents in patients with cardiovascular diseases to better address future research in this setting. Original articles within the field of interest reporting the role of RGD-based PET agents in patients with cardiovascular diseases were eligible for inclusion in this systematic review. A systematic literature search of PubMed/MEDLINE and Cochrane library databases was performed until October 26, 2021. Literature shows an increasing role of RGD-based PET agents in patients with cardiovascular diseases. Overall, two main topics emerged: the infarcted myocardium and atherosclerosis. The existing studies support that α v β 3 integrin expression in the infarcted myocardium is well evident in RGD PET/CT scans. RGD-based PET radiotracers accumulate at the site of infarction as early as 3 days and seem to be peaking at 1–3 weeks post myocardial infarction before decreasing, but only 1 study assessed serial changes of myocardial RGD-based PET uptake after ischemic events. RGD-based PET uptake in large vessels showed correlation with CT plaque burden, and increased signal was found in patients with prior cardiovascular events. In human atherosclerotic carotid plaques, increased PET signal was observed in stenotic compared with non-stenotic areas based on MR or CT angiography data. Histopathological analysis found a co-localization between tracer accumulation and areas of α v β 3 expression. Promising applications using RGD-based PET agents are emerging, such as prediction of remodeling processes in the infarcted myocardium or detection of active atherosclerosis, with potentially significant clinical impact.

A 54-year-old man, with previous history of neurogenic heterotopic ossification (HO) in muscles around the left hip following a spinal cord injury ten months earlier, was referred to our nuclear medicine center for an [.sup.18]fluorine-fluorodeoxyglucose ([.sup.18]F-FDG) positron emission tomography/computed tomography (PET/CT) to rule out a spondylodiscitis. No sign of spondylodiscitis was found on [.sup.18]F-FDG PET/CT, but images revealed an increased [.sup.18]F-FDG uptake in HO areas, matching with ongoing osteoblastic activity on a following bone scan.

A 54-year-old man, with previous history of neurogenic heterotopic ossification (HO) in muscles around the left hip following a spinal cord injury ten months earlier, was referred to our nuclear medicine center for an 18fluorine-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) to rule out a spondylodiscitis. No sign of spondylodiscitis was found on 18F-FDG PET/CT, but images revealed an increased 18F-FDG uptake in HO areas, matching with ongoing osteoblastic activity on a following bone scan.