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It is a growing concern that outcomes of neuroimaging studies often cannot be replicated. To counteract this, the magnetic resonance (MR) neuroimaging community has promoted acquisition standards and created data sharing platforms, based on a consensus on how to organize and share MR neuroimaging data. Here, we take a similar approach to positron emission tomography (PET) data. To facilitate comparison of findings across studies, we first recommend publication standards for tracer characteristics, image acquisition, image preprocessing, and outcome estimation for PET neuroimaging data. The co-authors of this paper, representing more than 25 PET centers worldwide, voted to classify information as mandatory, recommended, or optional. Second, we describe a framework to facilitate data archiving and data sharing within and across centers. Because of the high cost of PET neuroimaging studies, sample sizes tend to be small and relatively few sites worldwide have the required multidisciplinary expertise to properly conduct and analyze PET studies. Data sharing will make it easier to combine datasets from different centers to achieve larger sample sizes and stronger statistical power to test hypotheses. The combining of datasets from different centers may be enhanced by adoption of a common set of best practices in data acquisition and analysis.

Purpose: The performance of detectors is key for a PET scanner to achieve high spatial resolution and high sensitivity. This work aims to develop flood histogram generating algorithms to reduce the edge effect and improve the crystal identification of a PET detector consisting of two optically coupled pixelated scintillator detectors., Methods: The PET detector consists of two optically coupled detectors, each consisting of a 23×23 LYSO crystal array with a crystal size of 1.0×1.0×20 mm 3 read out by an 8×8 SiPM array with a pixel size of 3.0×3.0 mm 2 . The SiPM array is read out with a resistor network circuit to obtain four position encoding energy signals. A novel center of gravity (COG) positioning algorithm using six signals from the two detectors was proposed and compared to the traditional COG algorithms using either four or eight signals from the detectors. The raised-to-the-power (RTP) method was applied to the three COG algorithms for the PET detector. Different powers of the RTP from 1.0 to 2.5 were evaluated., Results: The proposed COG algorithm significantly improves the crystal identification at the junction of the two detectors as compared to the COG algorithm using four signals of each detector, and improves the crystal identification at the center of the two detectors as compared to the COG algorithm using eight signals from both detectors. The RTP method significantly improves the overall flood histogram qualities of the two COG algorithms using either eight or six signals from the two detectors, and the two COG algorithm provide similar flood histogram quality when a power of 1.5 is used., Conclusion: The novel positioning algorithms reduce the edge effect and improve the flood histogram quality for a PET detector consisting of two optically coupled detectors, each consisting of a pixelated scintillator crystal array and a SiPM array with highly multiplexed four signal readout. The positioning algorithms can be used in a PET scanner to improve the spatial resolution and sensitivity., (© 2024 American Association of Physicists in Medicine.)

Objective: Pathological amyloid-β (Aβ) accumulation and hyperphosphorylated tau proteins have been described in resected temporal lobe specimens of epilepsy patients. We aimed to determine cerebrospinal fluid (CSF) Aβ1-42 and p181-tau levels and cerebral Aβ deposits on positron emission tomography (Aβ PET) and correlate these findings with cognitive performance in adults with drug-resistant temporal lobe epilepsy (TLE)., Methods: In this cross-sectional study, we enrolled individuals with drug-resistant TLE who were 25-55 years old. Each participant underwent 18 F-flutemetamol PET, determination of CSF Aβ1-42, p181-tau, and total tau, and a comprehensive neuropsychological assessment. We evaluated normalized standard uptake value ratios (SUVRs) for different brain regions on Aβ PET., Results: Thirty patients (mean age = 41.9 ± SD 8.1 years, 57% men) were included. The median disease duration was 9.5 (interquartile range = 4-24) years. Twenty-six patients (87%) had a clinically significant cognitive impairment on neuropsychological evaluation, 18 (69%) of the amnesic type. On Aβ PET, high uptake was observed in both mesial temporal regions (ipsilateral: SUVR z-score = .90, 95% confidence interval [CI] = .60-1.20; contralateral: SUVR z-score = .92, 95% CI = .57-1.27; p < .001), which was higher when compared to SUVR z-scores in all the remaining regions (p < .001) and in the ipsilateral anterior cingulate (SUVR z-score = .27, 95% CI = .04-.49, p = .020). No significant deposition was observed in other regions. Seven patients (23%) had low Aβ1-42 levels, and two (7%) had elevated p181-tau levels in CSF. Higher p181-tau levels correlated with poorer verbal fluency (R = -.427, p = .044)., Significance: Our findings reveal a considerable Aβ deposition in mesial temporal regions and ipsilateral anterior cingulate among adults with drug-resistant TLE. Additionally, abnormal CSF Aβ1-42 levels were observed in a significant proportion of patients, and p181-tau levels were associated with verbal fluency. These results suggest that markers of neuronal damage can be observed in adults with TLE, warranting further investigation., (© 2024 International League Against Epilepsy.)

Cardiovascular diseases are the leading cause of death not only in Europe but also in the rest of the World. Preventive measures, however, often fail and cardiovascular disease may manifest as an acute coronary syndrome, stroke or even sudden death after years of silent progression. Thus, there is a considerable need for innovative diagnostic and therapeutic approaches to improve the quality of care and limit the burden of cardiovascular diseases. During the past 10 years, several retrospective and prospective clinical studies have been published using (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) to quantify inflammation in atherosclerotic plaques. However, the current variety of imaging protocols used for vascular (arterial) imaging with FDG PET considerably limits the ability to compare results between studies and to build large multicentre imaging registries. Based on the existing literature and the experience of the Members of the European Association of Nuclear Medicine (EANM) Cardiovascular Committee, the objective of this position paper was to propose optimized and standardized protocols for imaging and interpretation of PET scans in atherosclerosis. These recommendations do not, however, replace the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual study protocols used and the individual patient, in consultation with the patient and, where appropriate and necessary, the patient's guardian or carer. These recommendations suffer from the absence of conclusive evidence on many of the recommendations. Therefore, they are not intended and should not be used as "strict guidelines" but should, as already mentioned, provide a basis for standardized clinical atherosclerosis PET imaging protocols, which are subject to further and continuing evaluation and improvement. However, this EANM position paper might indeed be a first step towards "official" guidelines on atherosclerosis imaging with PET.

Until recently, PET was regarded as a luxurious way of performing myocardial perfusion scintigraphy, with excellent image quality and diagnostic capabilities that hardly justified the additional cost and procedural effort. Quantitative perfusion PET was considered a major improvement over standard qualitative imaging, because it allows the measurement of parameters not otherwise available, but for many years its use was confined to academic and research settings. In recent years, however, several factors have contributed to the renewal of interest in quantitative perfusion PET, which has become a much more readily accessible technique due to progress in hardware and the availability of dedicated and user-friendly platforms and programs. In spite of this evolution and of the growing evidence that quantitative perfusion PET can play a role in the clinical setting, there are not yet clear indications for its clinical use. Therefore, the Cardiovascular Committee of the European Association of Nuclear Medicine, starting from the experience of its members, decided to examine the current literature on quantitative perfusion PET to (1) evaluate the rationale for its clinical use, (2) identify the main methodological requirements, (3) identify the remaining technical difficulties, (4) define the most reliable interpretation criteria, and finally (5) tentatively delineate currently acceptable and possibly appropriate clinical indications. The present position paper must be considered as a starting point aiming to promote a wider use of quantitative perfusion PET and to encourage the conception and execution of the studies needed to definitely establish its role in clinical practice.

The history, present status, and possible future of nuclear medicine are presented. Beginning with development of the rectilinear scanner and gamma camera, evolution to the present forms of hybrid technology such as single photon emission computed tomography/computed tomography (CT) and positron emission tomography/CT is described. Both imaging and therapy are considered and the recent improvements in dose estimation using hybrid technologies are discussed. Future developments listed include novel radiopharmaceuticals created using short chains of nucleic acids and varieties of nanostructures. Patient-specific radiotherapy is an eventual outcome of this work. Possible application to proving the targeting of potential chemotherapeutics is also indicated.

Introduction: Occult nodal disease (OND) during clinically-N0 salvage total laryngectomy (TL) can be detected with the Neck-Imaging-Reporting-and-Data-Systems (NI-RADS). However, some patients will still have OND revealed on final pathology., Methods: A retrospective study on all patients who had OND during salvage TL with elective neck dissection (END) between 2009 and 2021 was performed. Repeat CT and PET scan interpretation was performed to evaluate their preoperative imaging for suspicious features., Results: Among 81 salvage TL patients undergoing END, 12 (16%) had OND and a total of 26 occult nodes were identified. On pathology, the average node length [SD] was 0.6 cm [0.3]. On CT, 31% (8 of 26) had rounded morphology. On PET, most had SUV max below blood pool. One patient scored NI-RADS 2; the rest scored 1., Conclusions: On re-review of preoperative imaging, occult nodes were subtle and challenging to identify. Despite no clear impact on survival, performing an END may provide prognostic information., (© 2024 Wiley Periodicals LLC.)

The dopamine hypothesis of schizophrenia posits that elevated striatal dopamine functioning underlies the development of psychotic symptoms. Chronic exposure to social stressors increases psychosis risk, possibly by upregulating striatal dopamine functioning. Here we systematically review single photon emission computed tomography (SPECT) and positron emission tomography (PET) studies that examined the relationship between chronic social stress exposure and in vivo striatal dopamine functioning in humans. We searched the scientific databases PubMed and PsycINFO from inception to August 2023. The quality of the included studies was evaluated with the ten-item Observational Study Quality Evaluation (PROSPERO: CRD42022308883). Twenty-eight studies were included, which measured different aspects of striatal dopamine functioning including dopamine synthesis capacity (DSC), vesicular monoamine transporter type 2 binding, dopamine release following a pharmacological or behavioral challenge, D 2/3 receptor binding, and dopamine transporter binding. We observed preliminary evidence of an association between childhood trauma and increased striatal DSC and dopamine release. However, exposure to low socioeconomic status, stressful life events, or other social stressors was not consistently associated with altered striatal dopamine functioning. The quality of available studies was generally low. In conclusion, there is insufficient evidence that chronic social stressors upregulate striatal dopamine functioning in humans. We propose avenues for future research, in particular to improve the measurement of chronic social stressors and the methodological quality of study designs., Competing Interests: Competing interests: Jan Booij is a consultant at GE Healthcare and received research grants from GE Healthcare (all payments to the institution). The other authors report no potential conflict of interest., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Objectives: The present study investigated various image reconstruction protocols for amyloid PET using phantom test criteria published by the Japanese Society of Nuclear Medicine (JSNM) and compared them with the composite standardized uptake value ratio (cSUVR) in clinical imaging., Methods: Hoffman 3D phantoms and cylindrical phantoms were collected for 30 min according to the JSNM guidelines. Images were created under various reconstruction protocols by three physical evaluation items in the guidelines and were assessed: gray matter/white matter contrast (%contrast), uniformity (SDuROImean), and image noise [coefficient of variation (CV)]. We compared the cSUVR of images reconstructed under 15 protocols using 18F-flutemetamol and 18F-florbetapir in 15 cases each and the guidelines for physical evaluation of reconstruction parameters., Results: No significant differences were observed in cSUVR between reconstruction protocols that satisfied the guidelines' criteria for %contrast and CV and those that did not; however, the visual impression of images differed. SDuROImean, which evaluated uniformity, met the criteria in all data., Conclusion: Reconstruction protocols should be selected appropriately using guidelines and other information, as cSUVR remains largely the same even if the visual impression of the images differs between different reconstruction protocols. When the relationship between %contrast and CV is expressed in terms of several reconstruction protocols, the graph shows a curved shape, and the optimal protocols for both %contrast and CV are near its center. Since cSUVR is similar to optimal parameters, even under parameters outside this range, multiple parameters need to be considered when selecting image reconstruction protocols for amyloid PET., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: To assess artificial intelligence (AI) ability to evaluate intraprostatic prostate cancer (PCa) on prostate-specific membrane antigen positron emission tomography (PSMA PET) scans prior to active treatment (radiotherapy or prostatectomy)., Materials and Methods: This systematic review was registered on the International Prospective Register of Systematic Reviews (PROSPERO identifier: CRD42023438706). A search was performed on Medline, Embase, Web of Science, and Engineering Village with the following terms: 'artificial intelligence', 'prostate cancer', and 'PSMA PET'. All articles published up to February 2024 were considered. Studies were included if patients underwent PSMA PET scan to evaluate intraprostatic lesions prior to active treatment. The two authors independently evaluated titles, abstracts, and full text. The Prediction model Risk Of Bias Assessment Tool (PROBAST) was used., Results: Our search yield 948 articles, of which 14 were eligible for inclusion. Eight studies met the primary endpoint of differentiating high-grade PCa. Differentiating between International Society of Urological Pathology (ISUP) Grade Group (GG) ≥3 PCa had an accuracy between 0.671 to 0.992, sensitivity of 0.91, specificity of 0.35. Differentiating ISUP GG ≥4 PCa had an accuracy between 0.83 and 0.88, sensitivity was 0.89, specificity was 0.87. AI could identify non-PSMA-avid lesions with an accuracy of 0.87, specificity of 0.85, and specificity of 0.89. Three studies demonstrated ability of AI to detect extraprostatic extensions with an area under curve between 0.70 and 0.77. Lastly, AI can automate segmentation of intraprostatic lesion and measurement of gross tumour volume., Conclusion: Although the current state of AI differentiating high-grade PCa is promising, it remains experimental and not ready for routine clinical application. Benefits of using AI to assess intraprostatic lesions on PSMA PET scans include: local staging, identifying otherwise radiologically occult lesions, standardisation and expedite reporting of PSMA PET scans. Larger, prospective, multicentre studies are needed., (© 2024 The Author(s). BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Background: Cardiac positron emission tomography (PET) can visualize and quantify the molecular and physiological pathways of cardiac function. However, cardiac and respiratory motion can introduce blurring that reduces PET image quality and quantitative accuracy. Dual cardiac- and respiratory-gated PET reconstruction can mitigate motion artifacts but increases noise as only a subset of data are used for each time frame of the cardiac cycle., Aim: The objective of this study is to create a zero-shot image denoising framework using a conditional generative adversarial networks (cGANs) for improving image quality and quantitative accuracy in non-gated and dual-gated cardiac PET images., Methods: Our study included retrospective list-mode data from 40 patients who underwent an 18 F-fluorodeoxyglucose ( 18 F-FDG) cardiac PET study. We initially trained and evaluated a 3D cGAN-known as Pix2Pix-on simulated non-gated low-count PET data paired with corresponding full-count target data, and then deployed the model on an unseen test set acquired on the same PET/CT system including both non-gated and dual-gated PET data., Results: Quantitative analysis demonstrated that the 3D Pix2Pix network architecture achieved significantly (p value<0.05) enhanced image quality and accuracy in both non-gated and gated cardiac PET images. At 5%, 10%, and 15% preserved count statistics, the model increased peak signal-to-noise ratio (PSNR) by 33.7%, 21.2%, and 15.5%, structural similarity index (SSIM) by 7.1%, 3.3%, and 2.2%, and reduced mean absolute error (MAE) by 61.4%, 54.3%, and 49.7%, respectively. When tested on dual-gated PET data, the model consistently reduced noise, irrespective of cardiac/respiratory motion phases, while maintaining image resolution and accuracy. Significant improvements were observed across all gates, including a 34.7% increase in PSNR, a 7.8% improvement in SSIM, and a 60.3% reduction in MAE., Conclusion: The findings of this study indicate that dual-gated cardiac PET images, which often have post-reconstruction artifacts potentially affecting diagnostic performance, can be effectively improved using a generative pre-trained denoising network., (© 2024. The Author(s), under exclusive licence to The Author(s) under exclusive licence to The Japanese Society of Nuclear Medicine.)

This research presents the development of positron emission tomography (PET) radiotracers for detecting Mycobacterium tuberculosis (MTB) for the diagnosis and monitoring of tuberculosis. Two phage display-derived peptides with proven selective binding to MTB were identified for development into PET radiopharmaceuticals: H8 (linear peptide) and PH1 (cyclic peptide). We sought to functionalize H8/PH1 with NODASA, a bifunctional chelator that allows complexation of PET-compatible radiometals such as gallium-68. Herein, we report on the chelator functionalization, optimized radiosynthesis, and assessment of the radiopharmaceutical properties of [ 68 Ga]Ga-NODASA-H8 and [ 68 Ga]Ga-NODASA-PH1. Robust radiolabeling was achieved using the established routine method, indicating consistent production of a radiochemically pure product (RCP ≥ 99.6%). For respective [ 68 Ga]Ga-NODASA-H8 and [ 68 Ga]Ga-NODASA-PH1, relatively high levels of decay-corrected radiochemical yield (91.2% ± 2.3%, 86.7% ± 4.0%) and apparent molar activity (A m , 3.9 ± 0.8 and 34.0 ± 5.3 GBq/μmol) were reliably achieved within 42 min, suitable for imaging purposes. Notably, [ 68 Ga]Ga-NODASA-PH1 remained stable in blood plasma for up to 2 h, while [ 68 Ga]Ga-NODASA-H8 degraded within 30 min. For both 68 Ga peptides, minimal whole-blood cell binding and plasma protein binding were observed, indicating a favorable pharmaceutical behavior. [ 68 Ga]Ga-NODASA-PH1 is a promising candidate for further in vitro/in vivo evaluation as a tuberculosis-specific infection imaging agent., (© 2024 The Author(s). Journal of Labelled Compounds and Radiopharmaceuticals published by John Wiley & Sons Ltd.)

In patients with drug-resistant epilepsy, difficulties in identifying the epileptogenic zone are well known to correlate with poorer clinical outcomes post-surgery. The integration of PET and MRI in the presurgical assessment of pediatric patients likely improves diagnostic precision by confirming or widening treatment targets. PET and MRI together offer superior insights compared to either modality alone. For instance, PET highlights abnormal glucose metabolism, while MRI precisely localizes structural anomalies, providing a comprehensive understanding of the epileptogenic zone. Furthermore, both methodologies, whether utilized through simultaneous PET/MRI scanning or the co-registration of separately acquired PET and MRI data, present unique advantages, having complementary roles in lesional and non-lesional cases. Simultaneous FDG-PET/MRI provides precise co-registration of functional (PET) and structural (MR) imaging in a convenient one-stop-shop approach, which minimizes sedation time and reduces radiation exposure in children. Commercially available fusion software that allows retrospective co-registration of separately acquired PET and MRI images is a commonly used alternative. This review provides an overview and illustrative cases that highlight the role of combining 18F-FDG-PET and MRI imaging and shares the authors' decade-long experience utilizing simultaneous PET/MRI in the presurgical evaluation of pediatric epilepsy., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: The development of a new tracer based on the cyclic sulfonamides (sultams) was investigated., Methods: 3-(Methoxy-phenyl-methyl)-1,6-dimethyl-1H benzo[c][1,2] thiazine 2,2-dioxide (benzo-δ-sultam) was synthesized and characterized by elemental analysis, FT-IR spectroscopy and single crystal X-ray structure determination. The prepared cyclic sulfonamide was labeled with non-commercial (62)Zn radioisotope for fast in vivo targeting and Coincidence imaging purposes (radiochemical purity 97 % ITLC, 96 % HPLC, specific activity 20-23 GBq/mmol). In vivo biodistribution of the final complex was investigated in Sprague Dawley(®) rats bearing fibro sarcoma tumor after 2, 4 and 8 h post injection and compared with free Zn(+2) cation., Results: Using instant paper chromatography method, the physicochemical properties of labeled compounds were found sufficiently stable in organic phases, e.g. a human serum, to be reliably used in bioapplications., Conclusions: The complex exhibited a rapid as well as high tumor uptake (tumor to blood ratio 4.38 and tumor to muscle ratio 9.63) resulting in an efficient tumor targeting agent.

Objective: The aims of this study were (1) to evaluate the effect of surrounding materials on the iterative reconstruction-based line-source response function (IR-RF) of (18)F, (11)C, (13)N, and (15)O using a preclinical PET system, and (2) to determine whether and how annihilation outside the source can be visualized experimentally., Methods: We performed all the measurements using the LabPET-8 PET/CT subsystem built-in the Triumph II platform (TriFoil Imaging, Inc., Northridge, CA, USA). IR-RF was measured for (18)F, (11)C, (13)N, and (15)O, and was expressed as full-width at half-maximum (FWHM) and full-width at tenth maximum (FWTM) using a glass capillary phantom mounted in materials of various densities, which were chosen to cover the wide range of real tissues. To determine whether and how annihilation outside the source can be visualized, we designed a concentric ring paper phantom, which consisted of a source at the center with 4 ring-like paper layers., Results: When the radionuclides were placed in air (material density 0 g/cm(3)), IR-RFs were similar among the radionuclides tested. As the surrounding material density increased, IR-RFs for higher energy-emitting radionuclides ((11)C, (13)N, and (15)O) became worse, whereas those of (18)F remained relatively constant over the range of surrounding material densities (0-2.17 g/cm(3)). Both FWHM and FWTM values were closely correlated with mean energy of radionuclides at middle to high material densities (material density 0.94-2.17 g/cm(3)). The FWTM/FWHM ratio of high energy-emitting radionuclides such as (15)O increased as a function of material density, which was followed by subsequent decrease at high material densities (1.2-2.17 g/cm(3)). Using a concentric ring paper phantom, annihilations outside the source were visible and measurable. The innermost layer was visible with all radionuclides, whereas the outer layers only with high energy positron emitters., Conclusions: The results indicate that surrounding material affects IR-RF particularly for high energy positron emitters. Furthermore, annihilation outside the radio-active source can be visualized with some circumstances such as those seen with a concentric ring paper phantom.

Background: Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET) stand as pivotal diagnostic tools for brain disorders, offering the potential for mutually enriching disease diagnostic perspectives. However, the costs associated with PET scans and the inherent radioactivity have limited the widespread application of PET. Furthermore, it is noteworthy to highlight the promising potential of high-field and ultra-high-field neuroimaging in cognitive neuroscience research and clinical practice. With the enhancement of MRI resolution, a related question arises: can high-resolution MRI improve the quality of PET images?, Purpose: This study aims to enhance the quality of synthesized PET images by leveraging the superior resolution capabilities provided by high-field and ultra-high-field MRI., Methods: From a statistical perspective, the joint probability distribution is considered the most direct and fundamental approach for representing the correlation between PET and MRI. In this study, we proposed a novel model, the joint diffusion attention model, namely, the joint diffusion attention model (JDAM), which primarily focuses on learning information about the joint probability distribution. JDAM consists of two primary processes: the diffusion process and the sampling process. During the diffusion process, PET gradually transforms into a Gaussian noise distribution by adding Gaussian noise, while MRI remains fixed. The central objective of the diffusion process is to learn the gradient of the logarithm of the joint probability distribution between MRI and noise PET. The sampling process operates as a predictor-corrector. The predictor initiates a reverse diffusion process, and the corrector applies Langevin dynamics., Results: Experimental results from the publicly available Alzheimer's Disease Neuroimaging Initiative dataset highlight the effectiveness of the proposed model compared to state-of-the-art (SOTA) models such as Pix2pix and CycleGAN. Significantly, synthetic PET images guided by ultra-high-field MRI exhibit marked improvements in signal-to-noise characteristics when contrasted with those generated from high-field MRI data. These results have been endorsed by medical experts, who consider the PET images synthesized through JDAM to possess scientific merit. This endorsement is based on their symmetrical features and precise representation of regions displaying hypometabolism, a hallmark of Alzheimer's disease., Conclusions: This study establishes the feasibility of generating PET images from MRI. Synthesis of PET by JDAM significantly enhances image quality compared to SOTA models., (© 2024 American Association of Physicists in Medicine.)

Objective: This study utilized a data-driven Bayesian model to automatically identify distinct latent disease factors represented by overlapping glucose metabolism patterns from 18 F-Fluorodeoxyglucose PET ( 18 F-FDG PET) to analyze heterogeneity among patients with TLE., Methods: We employed unsupervised machine learning to estimate latent disease factors from 18 F-FDG PET scans, representing whole-brain glucose metabolism patterns in seventy patients with TLE. We estimated the extent to which multiple distinct factors were expressed within each participant and analyzed their relevance to epilepsy burden, including seizure onset, duration, and frequency. Additionally, we established a predictive model for clinical prognosis and decision-making., Results: We identified three latent disease factors: hypometabolism in the unilateral temporal lobe and hippocampus (factor 1), hypometabolism in bilateral prefrontal lobes (factor 2), and hypometabolism in bilateral temporal lobes (factor 3), variably co-expressed within each patient. Factor 3 demonstrated the strongest negative correlation with the age of onset and duration (r =  - 0.33, - 0.38 respectively, P < 0.05). The supervised classifier, trained on latent disease factors for predicting patient-specific antiepileptic drug (AED) responses, achieved an area under the curve (AUC) of 0.655. For post-surgical seizure outcomes, the AUC was 0.857, and for clinical decision-making, it was 0.965., Conclusions: Decomposing 18 F-FDG PET-based phenotypic heterogeneity facilitates individual-level predictions relevant to disease monitoring and personalized therapeutic strategies., (© 2024. Fondazione Società Italiana di Neurologia.)

Purpose: Histone deacetylase 6 (HDAC6) has emerged as a therapeutic target for neurodegenerative diseases such as Alzheimer's disease. Noninvasive imaging of HDAC6 in the brain by positron emission tomography (PET) would accelerate research into its roles in these diseases. We recently discovered an 18 F-labeled derivative of the selective HDAC6 inhibitor SW-100 ([ 18 F]FSW-100) as a potential candidate for brain HDAC6 radioligand. As a mandatory step prior to clinical translation, we performed preclinical validation of [ 18 F]FSW-100., Methods: Process validation of [ 18 F]FSW-100 radiosynthesis for clinical use and assessment of preclinical toxicity and radiation dosimetry estimated from mouse distribution data were performed. In vitro selectivity of FSW-100 for 28 common receptors in the brain and HDAC isoforms was characterized. [ 18 F]FSW-100 PET imaging was performed in non-human primates in a conscious state to estimate the feasibility of HDAC6 imaging in humans., Results: Three consecutive validation runs of the automated radiosynthesis gave [ 18 F]FSW-100 injections with radiochemical yields of 12%, and the injections conformed to specified quality control criteria for batch release. No acute toxicity was observed for non-radiolabeled FSW-100 or radioactivity decayed [ 18 F]FSW-100 injection, and the former was negative in the Ames test. The whole-body effective dose estimated from biodistribution in mice was within the range of that of previously reported 18 F-radioligands in humans. In vitro selectivity against common receptors and other HDAC isoforms was confirmed. [ 18 F]FSW-100 demonstrated good penetration in monkey brain, and in vivo blocking studies suggested that the uptake was specific., Conclusion: These results support the clinical utility of [ 18 F]FSW-100 for in vivo imaging of HDAC6 in the brain., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Primary pediatric lung tumors are uncommon and have many overlapping clinical and imaging features. In contrast to adult lung tumors, these rare pediatric neoplasms have a relatively broad histologic spectrum. Informed by a single-institution 13-year retrospective record review, we present an overview of the most common primary pediatric lung neoplasms, with a focus on the role of positron emission tomography (PET), specifically 18 F-fluorodeoxyglucose (FDG) PET and 68 Ga-DOTATATE PET, in the management of primary pediatric lung tumors. In addition to characteristic conventional radiographic and cross-sectional imaging findings, knowledge of patient age, underlying cancer predisposition syndromes, and PET imaging features may help narrow the differential. While metastases from other primary malignancies remain the most commonly encountered pediatric lung malignancy, the examples presented in this pictorial essay highlight many of the important conventional radiologic and PET imaging features of primary pediatric lung malignancies., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: A solid-state PET/CT system uses bismuth germanium oxide (BGO) scintillating crystals coupled to silicon photomultipliers over an extended 32 cm axial field-of-view (FOV) to provide high spatial resolution and very high sensitivity. Performance characteristics were determined for this digital-BGO system, including NEMA and EARL standards., Methods: Spatial resolution, scatter fraction (SF), noise equivalent count rate (NECR), sensitivity, count rate accuracy, and image quality (IQ) were evaluated for the digital-BGO system as per NEMA NU 2-2018, at 2 sites of first clinical install. System energy resolution was measured. Bayesian penalized-likelihood reconstruction (BPL) was used for IQ. EARL Standards 2 studies were reconstructed by BPL combined with a contrast-enhancing deep learning algorithm. An Esser PET phantom was evaluated. Three patient examples were obtained with low-dose radiotracer activity: 2 MBq/kg of [ 18 F]FDG ([ 18 F]-2-fluoro-2-deoxy-D-glucose), 2.3 MBq/kg [ 68 Ga]Ga-DOTA-TATE ([dodecane tetra-acetic acid,Tyr 3 ]-octreotate), and 14.5 MBq/kg [ 82 Rb]RbCl ([ 82 Rb]-rubidium-chloride). Total scan times were ≤ 8 min., Results: NEMA sensitivity was 47.6 cps/kBq at the axial center. Spatial resolution at 1 cm from the center axis was ≤4.5 mm (filtered back projection) and ≤3.8 mm (ordered subset expectation maximization). SF was 35.6%, count rate accuracy was 2.16%, and peak NECR was 485.2 kcps at 16.9 kBq/mL. Contrast for IQ was 61.1 to 90.7% (smallest to largest sphere) with background variations from 7.6 to 2.1%, and a "lung" error of 4.7%. The average detector energy resolution was 9.67%. Image quality for patient scans was good. EARL Standards 2 criteria were robustly met and Esser phantom features ≥4.8 mm were resolved at 2 min per bed position., Conclusion: A solid-state 32 cm axial FOV digital-BGO PET/CT system provides good spatial and energy resolution, high count rates, and superior NEMA sensitivity in its class, enabling fast clinical acquisitions with low-dose radiotracer activity., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: This study explored the feasibility of reducing the scan time of Patlak parametric imaging on the uEXPLORER., Methods: A total of 65 patients (27 females and 38 males, age 56.1 ± 10.4) were recruited in this study. 18F fluorodeoxyglucose was injected, and its dose was adjusted by body weight (4.07 MBq/kg). Total-body dynamic scanning was performed on the uEXPLORER total-body Positron emission tomography/computed tomography (CT) scanner with a total scan time of 60 min from the injection. The image derived input function (IDIF) was obtained from the aortic arch. The voxelwise Patlak analysis was applied to generate the K i images designated as G IDIF with different acquisition times (20-60, 30-60, 40-60, and 44-60 min). The population-based input function (PBIF) was constructed from the mean value of the IDIF from the population, and K i images designated as G PBIF were generated using the PBIF. Nonlocalmeans (NLM) denoising was applied to the generated images to get two extra groups of (NLM-designated) images: G IDIF+NLM and G PBIF+NLM . Two radiologists evaluated the overall image quality, noise, and lesion detectability of the K i images from different groups. The 20-60 min scans in G IDIF were selected as the gold standard for each patient. We determined that image quality is at sufficient level if all the lesions can be recognized and meet the clinical criteria. K i values in muscle and lesion were compared across different groups to evaluate the quantitative accuracy., Results: The overall image quality, image noise, and lesion conspicuity were significantly better in long time series than short time series in all four groups (all p < 0.001). The K i images in the G IDIF and G PBIF groups generated from 30-min scans showed diagnostic value equivalent to the 40-min scans of G IDIF . While the image quality of the 16-min scans was poor, all lesions could still be detected. No significant difference was found between K i values estimated with G IDIF and G PBIF in muscle and lesion regions (all p > 0.5). After applying the NLM filter, the coefficient of variation could be reduced on the order of (1%, 15%, 19%, and 37%) and (110%, 125%, 94%, and 69%) with four acquisition time schemes for lesion and muscle. The reduction percentage did not have a substantial difference in IDIF and PBIF group. The K i images in the G IDIF+NLM and G PBIF+NLM groups generated from the 20-min acquisitions showed acceptable quality. All lesions could be found on the NLM processed images of the 16-min scans. No significant difference was found between K i values produced with G IDIF+NLM and G PBIF+NLM in muscle and lesion regions(all p > 0.7)., Conclusions: The K i images generated by the PBIF-based Patlak model using a 20-min dynamic scan with the NLM filter achieved a similar diagnostic efficiency to images with G IDIF from 40-min dynamic data, and there is no significant difference between K i images generated using IDIF or PBIF (p > 0.5)., (© 2022 American Association of Physicists in Medicine.)

Purpose: Detectors for positron emission tomography (PET) typically use two types of scintillation crystals, pixelated or monolithic. A variant of these types of scintillators are the so-called semi-monolithic crystals. They consist of a monolithic crystal segmented in one direction in pieces called slabs. These scintillators have the potential to successfully combine the benefits of pixelated and monolithic configurations, providing good timing and spatial resolutions as well as the capacity to decode the depth of interaction (DOI) information. In this work, the timing performance of a detector based on semi-monolithic crystals was studied in depth. The energy response was also evaluated., Methods: The semi-monolithic detector consists of 1 × 24 LYSO slabs of 25.4 × 12 × 0.95 mm 3 each. The bottom surface of the slabs is coupled to an array of 8 × 8 silicon photomultipliers (SiPMs) of 3 × 3 mm 2 active area, 50 μm cell size and 3.2 mm pitch. The 64 output signals were independently readout by the TOFPET2 ASIC. In order to achieve the best coincidence time resolution (CTR), four different time walk corrections were tested. Additional work investigated the best method of combining the timestamps belonging to the same event., Results: The resolvability of the slabs in the measured flood maps improves with the thickness of a light guide placed in between the scintillators and photosensors. The energy resolution does not change significantly with values as good as 13.7%. Regarding the CTR, values of 335.8, 363, 369.8, and 402.5 ps have been obtained for the whole detector for no light guide, 0.5, 1.0, and 1.5 mm thickness light guide cases, respectively. These values further improve to 276.1, 302.6, 305.6 and 336.2 ps, respectively, when energy-weighted averaging of timestamps is applied., Conclusions: We have shown both an excellent timing resolution and good energy resolution for a PET detector based on semi-monolithic crystals. The use of light guides of different thicknesses does not significantly affect the energy resolution of the whole detector, but the timing capabilities slightly worsen with the increasing thickness of the light guide., (© 2021 The Authors. Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Purpose: The net uptake rate constant (K i ) derived from dynamic imaging is considered the gold standard quantification index for FDG PET. In this study, we investigated the feasibility and assessed the clinical usefulness of generating K i images for FDG PET using only two 5-min scans with population-based input function (PBIF)., Methods: Using a Siemens Biograph mCT, 10 subjects with solid lung nodules underwent a single-bed dynamic FDG PET scan and 13 subjects (five healthy and eight cancer patients) underwent a whole-body dynamic FDG PET scan in continuous-bed-motion mode. For each subject, a standard K i image was generated using the complete 0-90 min dynamic data with Patlak analysis (t* = 20 min) and individual patient's input function, while a dual-time-point K i image was generated from two 5-min scans based on the Patlak equations at early and late scans with the PBIF. Different start times for the early (ranging from 20 to 55 min with an increment of 5 min) and late (ranging from 50 to 85 min with an increment of 5 min) scans were investigated with the interval between scans being at least 30 min (36 protocols in total). The optimal dual-time-point protocols were then identified. Regions of interest (ROI) were drawn on nodules for the lung nodule subjects, and on tumors, cerebellum, and bone marrow for the whole-body-imaging subjects. Quantification accuracy was compared using the mean value of each ROI between standard K i (gold standard) and dual-time-point K i , as well as between standard K i and relative standardized uptake value (SUV) change that is currently used in clinical practice. Correlation coefficients and least squares fits were calculated for each dual-time-point protocol and for each ROI. Then, the predefined criteria for identifying a reliable dual-time-point K i estimation for each ROI were empirically determined as: (1) the squared correlation coefficient (R 2 ) between standard K i and dual-time-point K i is larger than 0.9; (2) the absolute difference between the slope of the equality line (1.0) and that of the fitted line when plotting standard K i versus dual-time-point K i is smaller than 0.1; (3) the absolute value of the intercept of the fitted line when plotting standard K i versus dual-time-point K i normalized by the mean of the standard K i across all subjects for each ROI is smaller than 10%. Using Williams' one-tailed t test, the correlation coefficient (R) between standard K i and dual-time-point K i was further compared with that between standard K i and relative SUV change, for each dual-time-point protocol and for each ROI., Results: Reliable dual-time-point K i images were obtained for all the subjects using our proposed method. The percentage error introduced by the PBIF on the dual-time-point K i estimation was smaller than 1% for all 36 protocols. Using the predefined criteria, reliable dual-time-point K i estimation could be obtained in 25 of 36 protocols for nodules and in 34 of 36 protocols for tumors. A longer time interval between scans provided a more accurate K i estimation in general. Using the protocol of 20-25 min plus 80-85 or 85-90 min, very high correlations were obtained between standard K i and dual-time-point K i (R 2  = 0.994, 0.980, 0.971 and 0.925 for nodule, tumor, cerebellum, and bone marrow), with all the slope values with differences ≤0.033 from 1 and all the intercept values with differences ≤0.0006 mL/min/cm 3 from 0. The corresponding correlations were much lower between standard K i and relative SUV change (R 2  = 0.673, 0.684, 0.065, 0.246). Dual-time-point K i showed a significantly higher quantification accuracy with respect to standard K i than relative SUV change for all the 36 protocols (p < 0.05 using Williams' one-tailed t test)., Conclusions: Our proposed approach can obtain reliable K i images and accurate K i quantification from dual-time-point scans (5-min per scan), and provide significantly higher quantification accuracy than relative SUV change that is currently used in clinical practice., (© 2021 American Association of Physicists in Medicine.)

Background: Clinical practice shows degrading image quality in heavier patients who undergo myocardial perfusion imaging (MPI) with Rubidium-82 (Rb-82) PET when using a fixed tracer activity. Our aim was to derive and validate a patient-specific activity protocol resulting in a constant image quality in PET MPI., Methods: We included 251 patients who underwent rest MPI with Rb-82 PET (Discovery 670, GE Healthcare). 132 patients were included retrospectively and were scanned using a fixed activity of 740 MBq. The total number of measured prompts was normalized to activity and correlated to body weight, mass per body length and body mass index to find the best predicting parameter. Next, a patient-specific activity was derived and subsequently validated in 119 additional patients. Image quality was scored by three experts on a four-point scale., Results: Both image quality and prompts decreased in heavier patients when using a fixed activity (p < .005). Body weight was used to derive a new activity formula: Activity = 8.3 MBq/kg. When applying this formula, both measured prompts and scored image quality became independent of body weight (p > .60)., Conclusion: Administrating a Rb-82 activity that linearly depends on body weight resulted in a constant image quality across all patients and is recommended., (© 2019. American Society of Nuclear Cardiology.)

Positron emission tomography (PET) is a powerful tool in medicine and drug development, allowing for non-invasive imaging and quantitation of biological processes in live organisms. Targets are often probed with small molecules, but antibody-based PET is expanding because of many benefits, including ease of design of new antibodies toward targets, as well as the very strong affinities that can be expected. Application of antibodies to PET imaging of targets in the central nervous system (CNS) is a particularly nascent field, but one with tremendous potential. In this review, we discuss the growth of PET in imaging of CNS targets, present the promises and progress in antibody-based CNS PET, explore challenges faced by the field, and discuss questions that this promising approach will need to answer moving forward for imaging and perhaps even radiotherapy., (© 2023 The Authors. Journal of Labelled Compounds and Radiopharmaceuticals published by John Wiley & Sons Ltd.)

Functional imaging is playing an increasingly important role in pediatric radiology. Hybrid imaging techniques utilizing PET/CT (positron emission tomography/computed tomography), PET/MRI (positron emission tomography/magnetic resonance imaging), or SPECT/CT (single photon emission computed tomography/computed tomography) are now available in nearly every clinical practice. There are an increasing number of indications for the use of functional imaging, including oncologic and infectious indications, and it is essential to select and design the hybrid imaging protocol in order to optimize both the functional and anatomic components of the examination. Optimizing the protocol includes strategies for dose reduction, judicious use of contrast media and diagnostic quality imaging as appropriate, and for the greatest reduction in exposure to ionizing radiation, utilizing PET/MRI, whenever available. This review will provide an overview of hybrid imaging protocol considerations with a focus on oncologic and infectious indications., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Positron emission tomography (PET) is an essential technique in many clinical applications that allows for quantitative imaging at the molecular level. This study aims to develop a denoising method using a novel dilated convolutional neural network (CNN) to recover full-count images from low-count images., Methods: We adopted similar hierarchical structures as the conventional U-Net and incorporated dilated kernels in each convolution to allow the network to observe larger, more robust features within the image without the requirement of downsampling and upsampling internal representations. Our dNet was trained alongside a U-Net for comparison. Both models were evaluated using a leave-one-out cross-validation procedure on a dataset of 35 subjects (~3500 slabs), which were obtained from an ongoing 18 F-Fluorodeoxyglucose (FDG) study. Low-count PET data (10% count) were generated by randomly selecting one-tenth of all events in the associated listmode file. Analysis was done on the static image from the last 10 minutes of emission data. Both low-count PET and full-count PET were reconstructed using ordered subset expectation maximization (OSEM). Objective image quality metrics, including mean absolute percent error (MAPE), peak signal-to-noise ratio (PSNR), and structural similarity index metric (SSIM), were used to analyze the deep learning methods. Both deep learning methods were further compared to a traditional Gaussian filtering method. Further, region of interest (ROI) quantitative analysis was also used to compare U-Net and dNet architectures., Results: Both the U-Net and our proposed network were successfully trained to synthesize full-count PET images from the generated low-count PET images. Compared to low-count PET and Gaussian filtering, both deep learning methods improved MAPE, PSNR, and SSIM. Our dNet also systematically outperformed U-Net on all three metrics (MAPE: 4.99 ± 0.68 vs 5.31 ± 0.76, P < 0.01; PSNR: 31.55 ± 1.31 dB vs 31.05 ± 1.39, P < 0.01; SSIM: 0.9513 ± 0.0154 vs 0.9447 ± 0.0178, P < 0.01). ROI quantification showed greater quantitative improvements using dNet over U-Net., Conclusion: This study proposed a novel approach of using dilated convolutions for recovering full-count PET images from low-count PET images., (© 2020 American Association of Physicists in Medicine.)

Purpose: The LabPET II detection module is a potential candidate to create an magnetic resonance imaging (MRI) compatible positron emission tomography (PET)-insert with submillimeter spatial resolution for small animal applications. However, the feasibility of such an insert is hampered by the large radial size of the LabPET II front-end electronics and by components containing ferromagnetic materials. In this paper, a new low-profile front-end design based on the LabPET II architecture, called "low-profile detection module," is investigated., Materials and Methods: The performance of the low-profile detection module in the presence of MRI-like RF signals and gradient coil pulses was independently examined. The baseline of the analog signal, its RMS noise level, and the energy resolution, determined by a dual time-over-threshold (dTOT) method for each pixel of the new low-profile detection module, was measured in the presence of RF signals at different frequencies equivalent to the Larmor frequency of 3, 7, and 9.4 T MRI. The same parameters were investigated in the presence of a gradient coil switching at frequencies from 10 to 100 kHz. The performance of the low-profile detection module inside a 7 T MRI and its effects on an MR image have also been studied using gradient echo sequences. The same measurements were repeated for the shielded low-profile detection module, inside and outside the MRI., Results: Our results show that pulses in both the kilohertz and megahertz ranges cause up to 50% increase in the noise level of the baseline (DC analog signal at the output of the shaper filter) and up to 17% degradation in TOT energy resolution. By inserting a conducting composite layer as shielding around the low-profile detection module, these degrading effects were avoided. The performance measurement of the low-profile PET detection module inside a 7 T small animal MRI scanner confirmed that the shielded low-profile detection module behavior was similar inside and outside the MRI bore. In addition, gradient echo images of a water-filled phantom without and with the shielded and unshielded low-profile detection modules were acquired. The results demonstrated no evidence of artifacts in the MR image, either due to eddy currents or ferromagnetic materials with the shielded modules., Conclusion: A low-profile detection module based on the LabPET II technology was shown to be a viable candidate as a PET-insert for simultaneous PET/MRI applications considering its thin radial size and its EMI immunity due to placing it between two electronic boards. In comparison to the standard LabPET II detection module, it provides better performance in the presence of electromagnetic interferences, but a shielding layer is still required. When properly shielded, the proposed low-profile detection module can be operated inside an MRI without degrading the PET count rate or the MRI performance., (© 2020 American Association of Physicists in Medicine.)

Purpose: We present a new method for joint reconstruction of activity and attenuation images using both emission and transmission data and demonstrate its advantage over the standard maximum likelihood activity and attenuation (MLAA) reconstruction using emission data alone., Methods: We define a joint likelihood function including both time-of-flight (TOF) emission data and transmission data. The latter can be obtained from an external source or from Lu-176 background radiation. Activity and attenuation images are estimated jointly by maximizing the likelihood function. The proposed method solves the undetermined scale problem in the conventional MLAA. A monotonically convergent algorithm was derived to optimize the objective function. Furthermore, we present a theoretical analysis of the noise propagation in the joint reconstruction. Simulations and phantom experiments were conducted to validate the feasibility of the proposed method., Results: Quantitatively correct and less noisy images were reconstructed with the proposed method. Artifacts in the attenuation map reconstructed from the standard MLAA were removed by incorporating transmission data. Noise analysis was validated with different transmission sources and transmission count levels. The theoretical prediction indicated that noise of activity map would not change in a large range of transmission count level and a very low transmission count level could result in good estimation., Conclusions: The results demonstrate the feasibility of obtaining quantitatively correct images in TOF PET by using both emission and (weak) transmission data. The noise analysis also provides guidance for choosing a proper transmission source configuration to reduce noise propagation., (© 2019 American Association of Physicists in Medicine.)

Purpose: In this work, we proposed a triple-factor non-negative matrix factorization (TNMF) method to semiautomatically segment the regions of interest (ROIs) of the left ventricular (LV) cavity and myocardium to improve the reproducibility of myocardial blood flow (MBF) quantification from dynamic 82 Rb positron emission tomography (PET)., Methods: The proposed TNMF method was evaluated using NCAT phantom simulation with three noise levels. The segmented ROIs, time-activity curves (TACs), and K 1 derived from the TNMF method were compared with the ground truth simulated. The TNMF method was further evaluated in two patients each undergone both rest and stress 82 Rb PET studies. The TNMF and manual segmentations were implemented by two different observers, and the interoperator variations of MBF and myocardial flow reserve (MFR) were compared between the two methods., Results: Our simulation results showed that the TNMF method for dynamic PET image segmentation was robust as evidenced by the high Dice similarity coefficient, regardless of high or low count level. The relative bias in K 1 estimation was less than 1%. Our patient results also showed that reasonable ROIs for the LV cavity and myocardium could be obtained precisely for patients with and without myocardial perfusion defects. The TACs derived from the TNMF method were highly correlated with those obtained with the manual method (R 2  ≥ 0.964). The interoperator variations of MBF and MFR were markedly reduced using the TNMF method., Conclusions: In conclusion, the TNMF method is highly feasible for semiautomatic segmentation of the LV cavity and myocardium, with the potential to improve the precision of MBF quantification by improving segmentation., (© 2019 American Association of Physicists in Medicine.)

Background: We wished to document the prevalence and quantitative effects of compromised 82 Rb PET data acquisitions on myocardial flow reserve (MFR)., Methods and Results: Data were analyzed retrospectively for 246 rest and regadenoson-stress studies of 123 patients evaluated for known or suspected CAD. An automated injector delivered pre-determined activities of 82 Rb. Automated quality assurance algorithms identified technical problems for 7% (9/123) of patients. Stress data exhibited 2 instances of scanner saturation, 1 blood peak detection, 1 blood peak width, 1 gradual patient motion, and 2 abrupt patient motion problems. Rest data showed 1 instance of blood peak width and 2 abrupt patient motion problems. MFR was lower for patients with technical problems flagged by the quality assurance algorithms than those without technical problems (1.5 ± 0.5 versus 2.1 ± 0.7, P = 0.01), even though rest and stress ejection fraction, asynchrony and relative myocardial perfusion measures were similar for these two groups (P > 0.05), suggesting that MFR accuracy was adversely affected by technical errors., Conclusion: It is important to verify integrity of 82 Rb data to ensure MFR computation quality., (© 2021. American Society of Nuclear Cardiology.)

Background: As clinical use of myocardial blood flow (MBF) increases, dynamic series are becoming part of the typical workflow. The methods and parameters used to reconstruct these series require investigation to ensure accurate quantification., Methods: Fifty-nine rest/stress dynamic 82 Rb PET studies, acquired on a Biograph mCT, from a combination of normal volunteers and low-likelihood patients were reconstructed with and without time of flight (TOF) for varying iterations and processed to obtain relative perfusion and MBF polar maps. Regional values from mean polar maps were fit to a linear mixed-effect model to quantify convergence and select the optimal number of iterations., Results: TOF reconstructions converged faster and yielded more uniform relative perfusion polar maps. However, the stress MBF distribution for TOF reconstructions was more heterogeneous, with a higher-intensity septal wall. This phenomenon requires further investigation, with right ventricle blood pool spillover possibly having an effect. Optimal reconstructions were defined as 5-iteration non-TOF (24-subset) reconstructions and 3-iteration TOF (21-subset) reconstructions., Conclusion: Optimal cardiac reconstructions were identified for non-TOF and TOF reconstructions of dynamic series. TOF reconstruction presents as the more accurate method, given the more uniform relative perfusion distribution., (© 2021. American Society of Nuclear Cardiology.)