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Copper (Cu) is used as a cofactor in all organisms, and yet it can be toxic at high intracellular concentrations, causing cell death. Diethyldithiocarbamate (DDC) is a Cu ionophore that can transport Cu effectively into the cell. Copper-diethyldithiocarbamate (Cu-DDC) can treat prostate cancer (PCa) and may correlate with the cell death process. However, the specific Cu-DDC-related cell death genes in PCa are still unknown. Information about the Cu-DDC-related cell death genes was obtained from a previous study. Concurrently, the RNA expression profiles and clinical data were downloaded from public databases such as GEO, TCGA, and CPGEA. Using data from TCGA database, the logistic and lasso regression models were generated using R software. The influence of these genes in affecting PCa progression and prognosis was analyzed. Finally, the expression of these genes was verified in clinical samples. We found five Cu-DDC-related cell death genes associated with the occurrence of PCa from GSE35988, a gene dataset, namely, CDKN2A, PRC1, CDK1, SOX2, and ZNF365. CDKN2A, PRC1, and CDK1 are known to influence PCa patients' disease-free survival (DFS) status and were overexpressed, whereas SOX2 and ZNF365 were under-expressed in PCa in the different databases. Some of these genes can affect PCa progression. Consistent with the database results, the mRNA and protein expression of CDKN2A, PRC1, and CDK1 was also higher in clinical samples. In conclusion, we identified five hub genes which are important for Cu-DDC-related cell death process that can predict the development of PCa. [ABSTRACT FROM AUTHOR]

Background: [18F]FDG PET denoising by SubtlePET™ using deep learning artificial intelligence (AI) was previously found to induce slight modifications in lesion and reference organs' quantification and in lesion detection. As a next step, we aimed to evaluate its clinical impact on [18F]FDG PET solid tumour treatment response assessments, while comparing "standard PET" to "AI denoised half-duration PET" ("AI PET") during follow-up. Results: 110 patients referred for baseline and follow-up standard digital [18F]FDG PET/CT were prospectively included. "Standard" EORTC and, if applicable, PERCIST response classifications by 2 readers between baseline standard PET1 and follow-up standard PET2 as a "gold standard" were compared to "mixed" classifications between standard PET1 and AI PET2 (group 1; n = 64), or between AI PET1 and standard PET2 (group 2; n = 46). Separate classifications were established using either standardized uptake values from ultra-high definition PET with or without AI denoising (simplified to "UHD") or EANM research limited v2 (EARL2)-compliant values (by Gaussian filtering in standard PET and using the same filter in AI PET). Overall, pooling both study groups, in 11/110 (10%) patients at least one EORTCUHD or EARL2 or PERCISTUHD or EARL2 mixed vs. standard classification was discordant, with 369/397 (93%) concordant classifications, unweighted Cohen's kappa = 0.86 (95% CI: 0.78–0.94). These modified mixed vs. standard classifications could have impacted management in 2% of patients. Conclusions: Although comparing similar PET images is preferable for therapy response assessment, the comparison between a standard [18F]FDG PET and an AI denoised half-duration PET is feasible and seems clinically satisfactory. [ABSTRACT FROM AUTHOR]

Background: Standard measures of response such as Response Evaluation Criteria in Solid Tumors are ineffective for bone lesions, often making breast cancer patients that have bone-dominant metastases ineligible for clinical trials with potentially helpful therapies. In this study we prospectively evaluated the test-retest uptake variability of 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG) in a cohort of breast cancer patients with bone-dominant metastases to determine response criteria. The thresholds for 95% specificity of change versus no-change were then applied to a second cohort of breast cancer patients with bone-dominant metastases. Methods: For this study, nine patients with 38 bone lesions were imaged with 18F-FDG in the same calibrated scanner twice within 14 days. Tumor uptake was quantified by the most commonly used PET parameter, the maximum tumor voxel normalized by dose and body weight (SUVmax) and also by the mean of a 1-cc maximal uptake volume normalized by dose and lean-body-mass (SULpeak). The asymmetric repeatability coefficients with confidence intervals for SUVmax and SULpeak were used to determine the limits of 18F-FDG uptake variability. A second cohort of 28 breast cancer patients with bone-dominant metastases that had 146 metastatic bone lesions was imaged with 18F-FDG before and after standard-of-care therapy for response assessment. Results: The mean relative difference of SUVmax and SULpeak in 38 bone tumors of the first cohort were 4.3% and 6.7%. The upper and lower asymmetric limits of the repeatability coefficient were 19.4% and − 16.3% for SUVmax, and 21.2% and − 17.5% for SULpeak. 18F-FDG repeatability coefficient confidence intervals resulted in the following patient stratification using SULpeak for the second patient cohort: 11-progressive disease, 5-stable disease, 7-partial response, and 1-complete response with three inevaluable patients. The asymmetric repeatability coefficients response criteria for SULpeak changed the status of 3 patients compared to the standard Positron Emission Tomography Response Criteria in Solid Tumors of ± 30% SULpeak. Conclusion: In evaluating bone tumor response for breast cancer patients with bone-dominant metastases using 18F-FDG SUVmax, the repeatability coefficients from test-retest studies show that reductions of more than 17% and increases of more than 20% are unlikely to be due to measurement variability. Serial 18F-FDG imaging in clinical trials investigating bone lesions in these patients, such as the ECOG-ACRIN EA1183 trial, benefit from confidence limits that allow interpretation of response. [ABSTRACT FROM AUTHOR]

Circulating tumor DNA (ctDNA), which circulates in the blood after being shed from cancer cells in the body, has recently gained attention as an excellent tumor marker. The purpose of this study was to evaluate whether ct human papillomavirus (HPV) 16 DNA (ctHPV16DNA) levels were associated with quantitative PET parameters in patients with HPV-positive head and neck (HN) squamous cell carcinoma (SCC). Fifty patients with oropharyngeal SCC (OPSCC) and 5 with SCC of unknown primary (SCCUP) before treatment were included. They all underwent blood sampling to test ctHPV16DNA levels and FDG PET-CT examinations. Quantitative PET parameters included SUVmax, metabolic tumor volume (MTV), MTV of whole-body lesions (wbMTV), and 56 texture features. ctHPV16DNA levels were compared to texture features of primary tumors in OPSCC patients (Group A) or the largest primary or metastatic lymph node lesions in OPSCC and SCCUP patients (Group B) and to other PET parameters. Spearman rank correlation test and multiple regression analysis were used to confirm the associations between ctHPV16DNA levels and PET parameters. ctHPV16DNA levels moderately correlated with wbMTV, but not with SUVmax or MTV in Groups A and B. ctHPV16DNA levels exhibited a weak negative correlation with low gray-level zone emphasis in Groups A and B. Multiple regression analysis revealed that wbMTV and high gray-level zone emphasis were the significant factors for ctHPV16DNA levels in Group B. These results were not observed in Group A. This study demonstrated that ctHPV16DNA levels correlated with the whole-body tumor burden and tumor heterogeneity visualized on FDG PET-CT in patients with HPV-positive HNSCC. [ABSTRACT FROM AUTHOR]

Attenuation correction (AC) is essential for quantitative positron emission tomography (PET) images. Attenuation coefficient maps (μ-maps) are usually generated from computed tomography (CT) images when PET-CT combined systems are used. If CT has been performed prior to PET imaging, pre-acquired CT can be used for brain PET AC, because the human head is almost rigid. This pre-acquired CT-based AC approach is suitable for stand-alone brain-dedicated PET, such as VRAIN (ATOX Co. Ltd., Tokyo, Japan). However, the headrest of PET is different from the headrest in pre-acquired CT images, which may degrade the PET image quality. In this study, we prepared three different types of μ-maps: (1) based on the pre-acquired CT, where namely the headrest is different from the PET system (μ-map-diffHr); (2) manually removing the headrest from the pre-acquired CT (μ-map-noHr); and (3) artificially replacing the headrest region with the headrest of the PET system (μ-map-sameHr). Phantom images by VRAIN using each μ-map were investigated for uniformity, noise, and quantitative accuracy. Consequently, only the uniformity of the images using μ-map-diffHr was out of the acceptance criteria. We then proposed an automated method for removing the headrest from pre-acquired CT images. In comparisons of standardized uptake values in nine major brain regions from the 18F-fluoro-2-deoxy-D-glucose-PET of 10 healthy volunteers, no significant differences were found between the μ-map-noHr and the μ-map-sameHr. In conclusion, pre-acquired CT-based AC with automated headrest removal is useful for brain-dedicated PET such as VRAIN. [ABSTRACT FROM AUTHOR]

Objective: Non-blinded image deblurring with deep learning was performed on blurred numerical brain images without point spread function (PSF) reconstruction to obtain edge artifacts (EA)-free images. This study uses numerical simulation to investigate the mechanism of EA in PSF reconstruction based on the spatial frequency characteristics of EA-free images. Methods: In 256 × 256 matrix brain images, the signal values of gray matter (GM), white matter, and cerebrospinal fluid were set to 1, 0.25, and 0.05, respectively. We assumed ideal projection data of a two-dimensional (2D) parallel beam with no degradation factors other than detector response blur to precisely grasp EA using the PSF reconstruction algorithm from blurred projection data. The detector response was assumed to be a shift-invariant and one-dimensional (1D) Gaussian function with 2–5 mm full width at half maximum (FWHM). Images without PSF reconstruction (non-PSF), PSF reconstruction without regularization (PSF) and with regularization of relative difference function (PSF-RD) were generated by ordered subset expectation maximization (OSEM). For non-PSF, the image deblurring with a deep image prior (DIP) was applied using a 2D Gaussian function with 2–5 mm FWHM. The 1D object-specific modulation transfer function (1D-OMTF), which is the ratio of 1D amplitude spectrum of the original and reconstructed images, was used as the index of spatial frequency characteristics. Results: When the detector response was greater than 3 mm FWHM, EA in PSF was observed in GM borders and narrow GM. No remarkable EA was observed in the DIP, and the FWHM estimated from the recovery coefficient for the deblurred image of non-PSF at 5 mm FWHM was reduced to 3 mm or less. PSF of 5 mm FWHM showed higher spatial frequency characteristics than that of DIP up to around 2.2 cycles/cm but was lower than the latter after 3 cycles/cm. PSF-RD showed almost the same spatial frequency characteristics as that of DIP above 3 cycles/cm but was inferior below 3 cycles/cm. PSF-RD has a lower spatial resolution than DIP. Conclusions: Unlike DIP, PSF lacks high-frequency components around the Nyquist frequency, generating EA. PSF-RD mitigates EA while simultaneously suppressing the signal, diminishing spatial resolution. [ABSTRACT FROM AUTHOR]

In radiomics research, the issue of different instruments being used is significant. In this study, we compared three correction methods to reduce the batch effects in radiogenomic data from fluorodeoxyglucose (FDG) PET/CT images of lung cancer patients. Texture features of the FDG PET/CT images and genomic data were retrospectively obtained. The features were corrected with different methods: phantom correction, ComBat method, and Limma method. Batch effects were estimated using three analytic tools: principal component analysis (PCA), the k-nearest neighbor batch effect test (kBET), and the silhouette score. Finally, the associations of features and gene mutations were compared between each correction method. Although the kBET rejection rate and silhouette score were lower in the phantom-corrected data than in the uncorrected data, a PCA plot showed a similar variance. ComBat and Limma methods provided correction with low batch effects, and there was no significant difference in the results of the two methods. In ComBat- and Limma-corrected data, more texture features exhibited a significant association with the TP53 mutation than in those in the phantom-corrected data. This study suggests that correction with ComBat or Limma methods can be more effective or equally as effective as the phantom method in reducing batch effects. [ABSTRACT FROM AUTHOR]

Background: In order to support the ongoing research across Europe to facilitate access to novel radionuclides, the PRISMAP consortium (European medical radionuclides programme) was established to offer the broadest catalog of non-conventional radionuclides for medical and translational research. The aim of this article is to introduce readers with current status of novel radionuclides in Europe. Main body: A consortium questionnaire was disseminated through the PRISMAP consortium and user community, professional associations and preclinical/clinical end users in Europe and the current status of clinical end-users in nuclear medicine were identified. A total of 40 preclinical/clinical users institutions took part in the survey. Clinical end users currently use the following radionuclides in their studies: 177Lu, 68 Ga, 111In, 90Y, other alpha emitters, 225Ac, 64Cu and Terbium isotopes. Radionuclides that would be of interest for users within the next 2–5 years are 64Cu, Terbium radionuclide "family" and alpha emitters, such as 225Ac. Conclusions: Thanks to a questionnaire distributed by the PRISMAP consortium, the current status and needs of clinical end-users in nuclear medicine were identified. [ABSTRACT FROM AUTHOR]

Despite being thirteen years since the installation of the first PET-MR system, the scanners constitute a very small proportion of the total hybrid PET systems installed. This is in stark contrast to the rapid expansion of the PET-CT scanner, which quickly established its importance in patient diagnosis within a similar timeframe. One of the main hurdles is the development of an accurate, reproducible and easy-to-use method for attenuation correction. Quantitative discrepancies in PET images between the manufacturer-provided MR methods and the more established CT- or transmission-based attenuation correction methods have led the scientific community in a continuous effort to develop a robust and accurate alternative. These can be divided into four broad categories: (i) MR-based, (ii) emission-based, (iii) atlas-based and the (iv) machine learning-based attenuation correction, which is rapidly gaining momentum. The first is based on segmenting the MR images in various tissues and allocating a predefined attenuation coefficient for each tissue. Emission-based attenuation correction methods aim in utilising the PET emission data by simultaneously reconstructing the radioactivity distribution and the attenuation image. Atlas-based attenuation correction methods aim to predict a CT or transmission image given an MR image of a new patient, by using databases containing CT or transmission images from the general population. Finally, in machine learning methods, a model that could predict the required image given the acquired MR or non-attenuation-corrected PET image is developed by exploiting the underlying features of the images. Deep learning methods are the dominant approach in this category. Compared to the more traditional machine learning, which uses structured data for building a model, deep learning makes direct use of the acquired images to identify underlying features. This up-to-date review goes through the literature of attenuation correction approaches in PET-MR after categorising them. The various approaches in each category are described and discussed. After exploring each category separately, a general overview is given of the current status and potential future approaches along with a comparison of the four outlined categories. [ABSTRACT FROM AUTHOR]

Background: Several software tools have been developed for gated PET imaging that use distinct algorithms to analyze tracer uptake, myocardial perfusion, and left ventricle volumes and function. Studies suggest that different software tools cannot be used interchangeably in humans. In this study, we sought to compare the left ventricular parameters in gated 18F-FDG PET/CT imaging in mice by three commercially available software tools: PMOD, MIM, and QGS. Methods and results: Healthy mice underwent ECG-gated 18F-FDG imaging using a small-animal nanoPET/CT (Mediso) under isoflurane narcosis. Reconstructed gates PET images were subsequently analyzed in three different software tools, and cardiac volume and function (end-diastolic (EDV), end-systolic volumes (ESV), stroke volume (SV), and ejection fraction (EF)) were evaluated. While cardiac volumes correlated well between PMOD, MIM, and QGS, the left ventricular parameters and cardiac function differed in agreement using Bland–Altman analysis. EDV in PMOD vs. QGS: r = 0.85; p < 0.001, MIM vs. QGS: r = 0.92; p < 0.001, and MIM vs. PMOD: r = 0.88; p < 0.001, showed good correlations. Correlation was also found in ESV: PMOD vs. QGS: r = 0.48; p = 0.07, MIM vs QGS: r = 0.79; p < 0.001, and MIM vs. PMOD: r = 0.69; p < 0.01. SV showed good correlations in: PMOD vs. QGS: r = 0.73; p < 0.01, MIM vs. QGS: r = 0.86; p < 0.001, and MIM vs. PMOD: r = 0.92; p < 0.001. However, EF among correlated poorly: PMOD vs. QGS: r = −0.31; p = 0.26, MIM vs. QGS: r = 0.48; p = 0.07, and MIM vs. PMOD: r = 0.23; p = 0.41. Inter-class and intra-class correlation coefficient were > 0.9 underlining repeatability in using PMOD, MIM, and QGS for cardiac volume and function assessment. Conclusions: All three commercially available software tools are feasible in small animal cardiac volume assessment in gated 18F-FDG PET/CT imaging. However, due to software-related differences in agreement analysis for cardiac volumes and function, PMOD, MIM, and QGS cannot be used interchangeably in murine research. [ABSTRACT FROM AUTHOR]

Judicious selection of constituents for concrete composite can minimize the concentration of induced radio-isotopes in the shielding components around the beam loss points of an accelerator. In the present work, 18 concrete composites were prepared using different rock aggregates and cements. Samples were irradiated in the fast neutron environment to estimate the induced short-lived isotopes. Study identified least production of 24Na, 56Mn isotopes in the composite prepared using calcitic marble and white Portland cement. Utilization of this concrete composite mixture can minimize the induced isotope production, specifically at high neutron fluence regions to reduce the occupational exposures during maintenance operations. Article highlights: • Selection of potentially low induced activity generating raw materials are recommended. • Rock aggregates and cements depending on radiation type and energy can generate 24Na and 56Mn. • Composites with calcitic marble and white Portland cement can be used as strippable shielding layer. [ABSTRACT FROM AUTHOR]

The ability to adaptively guide behaviour requires the integration of external information with internal motivational factors. Decision-making capabilities can be impaired by acute stress and is often exacerbated by chronic pain. Chronic neuropathic pain patients often present with cognitive dysfunction, including impaired decision-making. The mechanisms underlying these changes are not well understood but may include altered monoaminergic transmission in the brain. In this study we investigated the relationships between dopamine, serotonin, and their metabolites in key brain regions that regulate motivated behaviour and decision-making. The neurochemical profiles of the medial prefrontal cortex, orbital prefrontal cortex, and nucleus accumbens were analysed using HPLC in rats that received a chronic constriction injury (CCI) of the right sciatic nerve and an acute stress (15-min restraint), prior to an outcome devaluation task. CCI alone significantly decreased dopamine but not serotonin concentrations in the medial prefrontal cortex. By contrast, restraint stress acutely increased dopamine in the medial prefrontal cortex, and the nucleus accumbens; and increased serotonin in the medial prefrontal cortex 2 h later. The sustained dopaminergic and serotonergic responses to acute stress highlight the importance of an animal's ability to mount an effective coping response. In addition, these data suggest that the impact of nerve injury and acute stress on outcome-devaluation occurs independently of dopaminergic and serotonergic transmission in the medial prefrontal cortex, orbital prefrontal cortex and nucleus accumbens of rats. [ABSTRACT FROM AUTHOR]

Purpose: This review aims to provide a comprehensive overview of the latest literature on personalized lung cancer management using different ligands and radionuclide-based tumor-targeting agents. Background: Lung cancer is the leading cause of cancer-related deaths worldwide. Due to the heterogeneity of lung cancer, advances in precision medicine may enhance the disease management landscape. More recently, theranostics using the same molecule labeled with two different radionuclides for imaging and treatment has emerged as a promising strategy for systemic cancer management. In radionuclide-based theranostics, the target, ligand, and radionuclide should all be carefully considered to achieve an accurate diagnosis and optimal therapeutic effects for lung cancer. Methods: We summarize the latest radiotracers and radioligand therapeutic agents used in diagnosing and treating lung cancer. In addition, we discuss the potential clinical applications and limitations associated with target-dependent radiotracers as well as therapeutic radionuclides. Finally, we provide our views on the perspectives for future development in this field. Conclusions: Radionuclide-based theranostics show great potential in tailored medical care. We expect that this review can provide an understanding of the latest advances in radionuclide therapy for lung cancer and promote the application of radioligand theranostics in personalized medicine. [ABSTRACT FROM AUTHOR]

Background: Differentiating atypical lipomatous tumors (ALTs) and well-differentiated liposarcomas (WDLs) from benign lipomatous lesions is important for guiding clinical management, though conventional visual analysis of these lesions is challenging due to overlap of imaging features. Radiomics-based approaches may serve as a promising alternative and/or supplementary diagnostic approach to conventional imaging. Purpose: The purpose of this study is to review the practice of radiomics-based imaging and systematically evaluate the literature available for studies evaluating radiomics applied to differentiating ALTs/WDLs from benign lipomas. Review: A background review of the radiomic workflow is provided, outlining the steps of image acquisition, segmentation, feature extraction, and model development. Subsequently, a systematic review of MEDLINE, EMBASE, Scopus, the Cochrane Library, and the grey literature was performed from inception to June 2022 to identify size studies using radiomics for differentiating ALTs/WDLs from benign lipomas. Radiomic models were shown to outperform conventional analysis in all but one model with a sensitivity ranging from 68 to 100% and a specificity ranging from 84 to 100%. However, current approaches rely on user input and no studies used a fully automated method for segmentation, contributing to interobserver variability and decreasing time efficiency. Conclusion: Radiomic models may show improved performance for differentiating ALTs/WDLs from benign lipomas compared to conventional analysis. However, considerable variability between radiomic approaches exists and future studies evaluating a standardized radiomic model with a multi-institutional study design and preferably fully automated segmentation software are needed before clinical application can be more broadly considered. [ABSTRACT FROM AUTHOR]

Here we aim to provide updated guidance and standards for the indication, acquisition, and interpretation of PSMA PET/CT for prostate cancer imaging. Procedures and characteristics are reported for a variety of available PSMA small radioligands. Different scenarios for the clinical use of PSMA-ligand PET/CT are discussed. This document provides clinicians and technicians with the best available evidence, to support the implementation of PSMA PET/CT imaging in research and routine practice. [ABSTRACT FROM AUTHOR]

PET can reveal in vivo biological processes at the molecular level. PET-derived quantitative values have been used as a surrogate marker for clinical decision-making in numerous clinical studies and trials. However, quantitative values in PET are variable depending on technical, biological, and physical factors. The variability may have a significant impact on a study outcome. Appropriate scanner calibration and quality control, standardization of imaging protocols, and any necessary harmonization strategies are essential to make use of PET as a biomarker with low bias and variability. This review summarizes benefits, limitations, and remaining challenges for harmonization of quantitative PET, including whole-body PET in oncology, brain PET in neurology, PET/MR, and non-18F PET imaging. This review is expected to facilitate harmonization of quantitative PET and to promote the contribution of PET-derived biomarkers to research and development in medicine. [ABSTRACT FROM AUTHOR]

Background: Patient's breathing affects the quality of chest images acquired with positron emission tomography/computed tomography (PET/CT) studies. Movement correction is required to optimize PET quantification in clinical settings. We present a reproducible methodology to compare the impact of different movement compensation protocols on PET image quality. Static phantom images were set as reference values, and recovery coefficients (RCs) were calculated from motion compensated images for the phantoms in respiratory movement. Image quality was evaluated in terms of: (1) volume accuracy (VA) with the NEMA phantom; (2) concentration accuracy (CA) by six refillable inserts within the electron density CIRS phantom; and (3) spatial resolution (R) with the Jaszczak phantom. Three different respiratory patterns were applied to the phantoms. We developed an open-source package to automatically analyze VA, CA and R. We compared 10 different movement compensation protocols available in the Philips Gemini TF-64 PET/CT (4-, 6-, 8- and 10-time bins, 20%-, 30%-, 40%-window width in Inhale and Exhale). Results: The homemade package provided RC values for VA, CA and R of 102 PET images in less than 5 min. Results of the comparison of the 10 different protocols demonstrated the feasibility of the proposed method for quantifying the variations observed qualitatively. Overall, prospective protocols showed better motion compensation than retrospective. The best performance was obtained for the protocol Exhale 30% (0.3 s after maximum Exhale position and window width of 30%) with RC VA = 1.6 ± 1.3 , RC CA = 0.90 ± 0.09 and RC R = 0.6 ± 0.4 . Among retrospective protocols, 8 Phase protocol showed the best performance. Conclusion: We provided an open-source package able to automatically evaluate the impact of motion compensation methods on PET image quality. A setup based on commonly available experimental phantoms is recommended. Its application for the comparison of 10 time-based approaches showed that Exhale 30% protocol had the best performance. The proposed framework is not specific to the phantoms and protocols presented on this study. [ABSTRACT FROM AUTHOR]

Purpose: Although treatment planning and individualized dose application for emerging prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) are generally recommended, it is still difficult to implement in practice at the moment. In this study, we aimed to prove the concept of pretherapeutic prediction of dosimetry based on imaging and laboratory measurements before the RLT treatment. Methods: Twenty-three patients with metastatic castration-resistant prostate cancer (mCRPC) treated with 177Lu-PSMA I&T RLT were included retrospectively. They had available pre-therapy 68 Ga-PSMA-HEBD-CC PET/CT and at least 3 planar and 1 SPECT/CT imaging for dosimetry. Overall, 43 cycles of 177Lu-PSMA I&T RLT were applied. Organ-based standard uptake values (SUVs) were obtained from pre-therapy PET/CT scans. Patient dosimetry was calculated for the kidney, liver, spleen, and salivary glands using Hermes Hybrid Dosimetry 4.0 from the planar and SPECT/CT images. Machine learning methods were explored for dose prediction from organ SUVs and laboratory measurements. The uncertainty of these dose predictions was compared with the population-based dosimetry estimates. Mean absolute percentage error (MAPE) was used to assess the prediction uncertainty of estimated dosimetry. Results: An optimal machine learning method achieved a dosimetry prediction MAPE of 15.8 ± 13.2% for the kidney, 29.6% ± 13.7% for the liver, 23.8% ± 13.1% for the salivary glands, and 32.1 ± 31.4% for the spleen. In contrast, the prediction based on literature population mean has significantly larger MAPE (p < 0.01), 25.5 ± 17.3% for the kidney, 139.1% ± 111.5% for the liver, 67.0 ± 58.3% for the salivary glands, and 54.1 ± 215.3% for the spleen. Conclusion: The preliminary results confirmed the feasibility of pretherapeutic estimation of treatment dosimetry and its added value to empirical population-based estimation. The exploration of dose prediction may support the implementation of treatment planning for RLT. [ABSTRACT FROM AUTHOR]

Purpose of Review: The regulatory steps necessary to bring new PET radiopharmaceuticals to the clinic will be reviewed. The US Food and Drug Administration (FDA) provides approval to manufacture and use diagnostic radiopharmaceuticals, including those for cardiovascular PET/CT. Medicare not only provides insurance reimbursement for imaging procedures for its beneficiaries but also sets an example for third-party insurers to cover these procedures. Recent Findings: FDA provides extensive guidance for performing studies to obtain the safety and efficacy data needed to approve PET radiopharmaceuticals, and the pace of approval has recently increased. There also has been considerable progress in insurance coverage for PET by Medicare. Several promising agents for cardiovascular PET imaging are in the development pipeline. Challenges remain, however, including low levels of reimbursement and the application of appropriate use criteria for imaging procedures. Summary: It is important for cardiologists to understand the regulatory steps involved in translating PET radiopharmaceuticals to the clinic. Recent progress in both FDA approvals and Medicare coverage should facilitate the clinical use of new PET agents for molecular imaging of the heart. [ABSTRACT FROM AUTHOR]

Background: PET nuclides can have a considerable influence on the spatial resolution and image quality of PET/CT scans, which can influence diagnostics in oncology, for example. The individual impact of the positron energy of 18F, 68Ga, and 64Cu on spatial resolution and image quality was compared for PET/CT scans acquired using a clinical, digital scanner. Methods: A Jaszczak phantom and a NEMA PET body phantom were filled with 18F-FDG, 68Ga-HCl, or 64Cu-HCl, and PET/CT scans were performed on a Siemens Biograph Vision. Acquired images were analyzed regarding spatial resolution and image quality (recovery coefficients (RC), coefficient of variation within the background, contrast recovery coefficient (CRC), contrast–noise ratio (CNR), and relative count error in the lung insert). Data were compared between scans with different nuclides. Results: We found that image quality was comparable between 18F-FDG and 64Cu-HCl PET/CT measurements featuring similar maximal endpoint energies of the positrons. In comparison, RC, CRC, and CNR were degraded in 68Ga-HCl data despite similar count rates. In particular, the two smallest spheres of 10 mm and 13 mm diameter revealed lower RC, CRC, and CNR values. The spatial resolution was similar between 18F-FDG and 64Cu-HCl but up to 18% and 23% worse compared with PET/CT images of the NEMA PET body phantom filled with 68Ga-HCl. Conclusions: The positron energy of the PET nuclide influences the spatial resolution and image quality of a digital PET/CT scan. The image quality and spatial resolution of 68Ga-HCl PET/CT images were worse than those of 18F-FDG or 64Cu-HCl despite similar count rates. [ABSTRACT FROM AUTHOR]

Chronic pain, such as neuropathic pain, causes anxiety and other negative emotions, which aggravates the pain sensation and increases the risk of chronic pain over time. Dopamine receptor D1 (DRD1) and dopamine receptor D2 (DRD2) in the basolateral amygdala (BLA) have been implicated in mediating anxiety-related behaviors, but their potential roles in the BLA in neuropathic pain-induced anxiety have not been examined. Electroacupuncture (EA) is commonly used to treat chronic pain and emotional disorders, but it is still unclear whether EA plays a role in analgesia and anxiety relief through DRD1 and DRD2 in the BLA. Here, we used western blotting to examine the expression of DRD1 and DRD2 and pharmacological regulation combined with behavioral testing to detect anxiety-like behaviors. We observed that injection of the DRD1 antagonist SCH23390 or the DRD2 agonist quinpirole into the BLA contributed to anxiety-like behaviors in naive mice. EA also activated DRD1 or inhibited DRD2 in the BLA to alleviate anxiety-like behaviors. To further demonstrate the role of DRD1 and DRD2 in the BLA in spared nerve injury (SNI) model-induced anxiety-like behaviors, we injected the DRD1 agonist SKF38393 or the DRD2 antagonist sulpiride into the BLA. We found that both activation of DRD1 and inhibition of DRD2 could alleviate SNI-induced anxiety-like behaviors, and EA had a similar effect of alleviating anxiety. Additionally, neither DRD1 nor DRD2 in the BLA affected SNI-induced mechanical allodynia, but EA did. Overall, our work provides new insights into the mechanisms of neuropathic pain-induced anxiety and a possible explanation for the effect of EA treatment on anxiety caused by chronic pain. [ABSTRACT FROM AUTHOR]

Purpose: The goal of this guideline/procedure standard is to assist nuclear medicine physicians, other nuclear medicine professionals, oncologists or other medical specialists for recommended use of [18F]FDG PET/CT in oncological patients undergoing immunotherapy, with special focus on response assessment in solid tumors. Methods: In a cooperative effort between the EANM, the SNMMI and the ANZSNM, clinical indications, recommended imaging procedures and reporting standards have been agreed upon and summarized in this joint guideline/procedure standard. Conclusions: The field of immuno-oncology is rapidly evolving, and this guideline/procedure standard should not be seen as definitive, but rather as a guidance document standardizing the use and interpretation of [18F]FDG PET/CT during immunotherapy. Local variations to this guideline should be taken into consideration. Preamble: The European Association of Nuclear Medicine (EANM) is a professional non-profit medical association founded in 1985 to facilitate worldwide communication among individuals pursuing clinical and academic excellence in nuclear medicine. The Society of Nuclear Medicine and Molecular Imaging (SNMMI) is an international scientific and professional organization founded in 1954 to promote science, technology and practical application of nuclear medicine. The Australian and New Zealand Society of Nuclear Medicine (ANZSNM), founded in 1969, represents the major professional society fostering the technical and professional development of nuclear medicine practice across Australia and New Zealand. It promotes excellence in the nuclear medicine profession through education, research and a commitment to the highest professional standards. EANM, SNMMI and ANZSNM members are physicians, technologists, physicists and scientists specialized in the research and clinical practice of nuclear medicine. All three societies will periodically put forth new standards/guidelines for nuclear medicine practice to help advance the science of nuclear medicine and improve service to patients. Existing standards/guidelines will be reviewed for revision or renewal, as appropriate, on their fifth anniversary or sooner, if indicated. Each standard/guideline, representing a policy statement by the EANM/SNMMI/ANZSNM, has undergone a thorough consensus process, entailing extensive review. These societies recognize that the safe and effective use of diagnostic nuclear medicine imaging requires particular training and skills, as described in each document. These standards/guidelines are educational tools designed to assist practitioners in providing appropriate and effective nuclear medicine care for patients. These guidelines are consensus documents based on current knowledge. They are not intended to be inflexible rules or requirements of practice, nor should they be used to establish a legal standard of care. For these reasons and those set forth below, the EANM, SNMMI and ANZSNM caution against the use of these standards/guidelines in litigation in which the clinical decisions of a practitioner are called into question. The ultimate judgment regarding the propriety of any specific procedure or course of action must be made by medical professionals considering the unique circumstances of each case. Thus, there is no implication that an action differing from what is laid out in the guidelines/procedure standards, standing alone, is below standard of care. To the contrary, a conscientious practitioner may responsibly adopt a course of action different from that set forth in the standards/guidelines when, in the reasonable judgment of the practitioner, such course of action is indicated by the condition of the patient, limitations of available resources or advances in knowledge or technology subsequent to publication of the guidelines/procedure standards. The practice of medicine involves not only the science, but also the art of dealing with the prevention, diagnosis, alleviation and treatment of disease. The variety and complexity of human conditions make it impossible for general guidelines to consistently allow for an accurate diagnosis to be reached or a particular treatment response to be predicted. Therefore, it should be recognized that adherence to these standards/ guidelines will not ensure a successful outcome. All that should be expected is that practitioners follow a reasonable course of action, based on their level of training, current knowledge, clinical practice guidelines, available resources and the needs/context of the patient being treated. The sole purpose of these guidelines is to assist practitioners in achieving this objective. The present guideline/procedure standard was developed collaboratively by the EANM, the SNMMI and the ANZSNM, with the support of international experts in the field. They summarize also the views of the Oncology and Theranostics and the Inflammation and Infection Committees of the EANM, as well as the procedure standards committee of the SNMMI, and reflect recommendations for which the EANM and SNMMI cannot be held responsible. The recommendations should be taken into the context of good practice of nuclear medicine and do not substitute for national and international legal or regulatory provisions. [ABSTRACT FROM AUTHOR]

Purpose: Accurate prognostic markers are urgently needed to identify diffuse large B-Cell lymphoma (DLBCL) patients at high risk of progression or relapse. Our purpose was to investigate the potential added value of baseline radiomics features to the international prognostic index (IPI) in predicting outcome after first-line treatment. Methods: Three hundred seventeen newly diagnosed DLBCL patients were included. Lesions were delineated using a semi-automated segmentation method (standardized uptake value ≥ 4.0), and 490 radiomics features were extracted. We used logistic regression with backward feature selection to predict 2-year time to progression (TTP). The area under the curve (AUC) of the receiver operator characteristic curve was calculated to assess model performance. High-risk groups were defined based on prevalence of events; diagnostic performance was assessed using positive and negative predictive values. Results: The IPI model yielded an AUC of 0.68. The optimal radiomics model comprised the natural logarithms of metabolic tumor volume (MTV) and of SUVpeak and the maximal distance between the largest lesion and any other lesion (Dmaxbulk, AUC 0.76). Combining radiomics and clinical features showed that a combination of tumor- (MTV, SUVpeak and Dmaxbulk) and patient-related parameters (WHO performance status and age > 60 years) performed best (AUC 0.79). Adding radiomics features to clinical predictors increased PPV with 15%, with more accurate selection of high-risk patients compared to the IPI model (progression at 2-year TTP, 44% vs 28%, respectively). Conclusion: Prediction models using baseline radiomics combined with currently used clinical predictors identify patients at risk of relapse at baseline and significantly improved model performance. Trial registration number and date: EudraCT: 2006–005,174-42, 01–08-2008. [ABSTRACT FROM AUTHOR]

Not only visual interpretation for lesion detection, staging, and characterization, but also quantitative treatment response assessment are key roles for 18F-FDG PET in oncology. In multicenter oncology PET studies, image quality standardization and SUV harmonization are essential to obtain reliable study outcomes. Standards for image quality and SUV harmonization range should be regularly updated according to progress in scanner performance. Accordingly, the first aim of this study was to propose new image quality reference levels to ensure small lesion detectability. The second aim was to propose a new SUV harmonization range and an image noise criterion to minimize the inter-scanner and intra-scanner SUV variabilities. We collected a total of 37 patterns of images from 23 recent PET/CT scanner models using the NEMA NU2 image quality phantom. PET images with various acquisition durations of 30–300 s and 1800 s were analyzed visually and quantitatively to derive visual detectability scores of the 10-mm-diameter hot sphere, noise-equivalent count (NECphantom), 10-mm sphere contrast (QH,10 mm), background variability (N10 mm), contrast-to-noise ratio (QH,10 mm/N10 mm), image noise level (CVBG), and SUVmax and SUVpeak for hot spheres (10–37 mm diameters). We calculated a reference level for each image quality metric, so that the 10-mm sphere can be visually detected. The SUV harmonization range and the image noise criterion were proposed with consideration of overshoot due to point-spread function (PSF) reconstruction. We proposed image quality reference levels as follows: QH,10 mm/N10 mm ≥ 2.5 and CVBG ≤ 14.1%. The 10th–90th percentiles in the SUV distributions were defined as the new SUV harmonization range. CVBG ≤ 10% was proposed as the image noise criterion, because the intra-scanner SUV variability significantly depended on CVBG. We proposed new image quality reference levels to ensure small lesion detectability. A new SUV harmonization range (in which PSF reconstruction is applicable) and the image noise criterion were also proposed for minimizing the SUV variabilities. Our proposed new standards will facilitate image quality standardization and SUV harmonization of multicenter oncology PET studies. The reliability of multicenter oncology PET studies will be improved by satisfying the new standards. [ABSTRACT FROM AUTHOR]

Objective: In malignant melanoma patients treated with immune checkpoint inhibitor (ICI) therapy, three different FDG-PET criteria, European Organization for Research and Treatment of Cancer (EORTC), PET Response Criteria in Solid Tumors (PERCIST), immunotherapy-modified PERCIST (imPERCIST), were compared regarding response evaluation and prognosis prediction using standardized uptake value (SUV) harmonization of results obtained with various PET/CT scanners installed at different centers. Materials and methods: Malignant melanoma patients (n = 27) underwent FDG-PET/CT examinations before and again 3 to 9 months after therapy initiation (nivolumab, n = 21; pembrolizumab, n = 6) with different PET scanners at five hospitals. EORTC, PERCIST, and imPERCIST criteria were used to evaluate therapeutic response, then concordance of the results was assessed using Cohen's κ coefficient. Log-rank and Cox methods were employed to determine progression-free (PFS) and overall (OS) survival. Results: Complete metabolic response (CMR)/partial metabolic response (PMR)/stable metabolic disease (SMD)/progressive metabolic disease (PMD) with harmonized EORTC, PERCIST, and imPERCIST was seen in 3/5/4/15, 4/5/3/15, and 4/5/5/13 patients, respectively. Nearly perfect concordance between each pair of criteria was noted (κ = 0.939–0.972). Twenty patients showed progression and 14 died from malignant melanoma after a median 19.2 months. Responders (CMR/PMR) showed significantly longer PFS and OS than non-responders (SMD/PMD) (harmonized EORTC: p < 0.0001 and p = 0.011; harmonized PERCIST: p < 0.0001 and p = 0.0012; harmonized imPERCIST: p < 0.0001 and p = 0.0012, respectively). Conclusions: All harmonized FDG-PET criteria (EORTC, PERCIST, imPERCIST) showed accuracy for response evaluation of ICI therapy and prediction of malignant melanoma patient prognosis. Additional studies to determine their value in larger study populations will be necessary. [ABSTRACT FROM AUTHOR]

68 Ga-DOTA-peptide PET/CT is a valuable tool for diagnosing neuroendocrine tumors (NET). Various tumors and normal human tissue express the somatostatin receptor (SSTR), warranting attention to positive findings on 68 Ga-DOTA-peptide PET/CT. However, overexpression of SSTR in glomus tumors has not yet been reported. Gastric glomus tumors show many similar features of NET and are often misdiagnosed. We present the case of a 61-year-old male with a glomus tumor who underwent distal gastrectomy under the pretense of an NET grade 1 because the nodule showed focal intense uptake on preoperative 68 Ga-DOTATOC PET/CT. [ABSTRACT FROM AUTHOR]

Background: This study was conducted to clarify how patient body mass affects the image quality and quantification accuracy of images obtained using 89Zr PET/CT. 89Zr PET/CT images from time-of-flight (TOF) PET/CT and semiconductor (SC) PET/CT were obtained using three types (M, L, LL; corresponding to increasing patient body weight) of custom-made body phantoms designed similarly to the National Electrical Manufacturers Association (NEMA) IEC body phantom. The phantom data were analyzed visually and quantitatively to derive image quality metrics, namely detectability of the 10-mm-diameter hot sphere, percent contrast for the 10-mm-diameter hot sphere (QH,10 mm), percent background variability (N10mm), contrast-to-noise ratio (QH,10 mm/N10mm), and coefficient of variation of the background area (CVBG). Results: Visual assessment revealed that all the 10-mm-diameter hot spheres of the three types of phantoms were identifiable on both SC and TOF PET/CT images. The N10mm and CVBG values were within the proposed reference levels, and decreased with acquisition duration for both PET/CT types. At 10-min acquisition, the QH,10 mm/N10mm of SC PET/CT was greater than the proposed reference level in all phantoms. However, the QH,10 mm/N10mm of TOF PET/CT was greater than the proposed reference level in M-type phantom alone. All the SUVBG values were within 1.00 ± 0.05 for both PET/CT types. Conclusions: This study showed that the image quality and quantification accuracy depend on the patient's body mass, suggesting that acquisition time on 89Zr PET/CT should be changed according to the patient's body mass. [ABSTRACT FROM AUTHOR]

Purpose: Gastroenteropancreatic neuroendocrine tumors (GEP NETs) are often associated with high expression of somatostatin receptors (SSTRs) which allows for PET/CT imaging with radiolabeled somatostatin analogs such as 68Ga-DOTATOC. The interplay between 68Ga-DOTATOC and the synthetic somatostatin analogs commonly used to manage patient symptoms may lead to competition between the labelled and unlabeled peptides for receptor binding sites and current product labelling recommends patients be taken off somatostatin analogs before imaging. In this study, we prospectively investigated in human patients the effect of a pre-dose of octreotide, a short-acting somatostatin analog, on the distribution of 68Ga-DOTATOC in GEP NETs and normal organs. Procedure: Research participants with GEP NETs were studied on two occasions using dynamic whole-body 68Ga-DOTATOC PET/CT. The two imaging studies were performed within 21 days of each other, using an identical acquisition protocol except for the administration of 50 μg of short-acting octreotide (pre-dose) immediately before the second PET/CT. Paired t-tests were used to compare tracer uptake with and without octreotide, for tumor and various normal organs. Results: Seven participants with a mean age of 53 ± 10 years were studied. Octreotide pre-dosing decreased radiotracer uptake in the normal liver and spleen by 25 % (p = 0.04) and 47 % (p = 0.05) respectively but did not significantly change uptake in tumor (p = 0.53), red marrow (p = 0.12), kidneys (p =0.57), or pituitary gland (p = 0.27). Conclusions: Our data indicate SSTR imaging can be improved with a pre-dose of unlabeled octreotide given just prior to injection of the radiotracer. These data suggest there may be no need to discontinue somatostatin analog therapy prior to PET/CT with 68Ga-DOTATOC, allowing for a simpler, less disruptive patient protocol. This approach warrants further study in a variety of settings. [ABSTRACT FROM AUTHOR]

Phantoms are commonly used throughout medical imaging and medical physics for a multitude of applications, the designs of which vary between modalities and clinical or research requirements. Within positron emission tomography (PET) and nuclear medicine, phantoms have a well-established role in the validation of imaging protocols so as to reduce the administration of radioisotope to volunteers. Similarly, phantoms are used within magnetic resonance imaging (MRI) to perform quality assurance on clinical scanners, and gel-based phantoms have a longstanding use within the MRI research community as tissue equivalent phantoms. In recent years, combined PET/MRI scanners for simultaneous acquisition have entered both research and clinical use. This review explores the designs and applications of phantom work within the field of simultaneous acquisition PET/MRI as published over the period of a decade. Common themes in the design, manufacture and materials used within phantoms are identified and the solutions they provided to research in PET/MRI are summarised. Finally, the challenges remaining in creating multimodal phantoms for use with simultaneous acquisition PET/MRI are discussed. No phantoms currently exist commercially that have been designed and optimised for simultaneous PET/MRI acquisition. Subsequently, commercially available PET and nuclear medicine phantoms are often utilised, with CT-based attenuation maps substituted for MR-based attenuation maps due to the lack of MR visibility in phantom housing. Tissue equivalent and anthropomorphic phantoms are often developed by research groups in-house and provide customisable alternatives to overcome barriers such as MR-based attenuation correction, or to address specific areas of study such as motion correction. Further work to characterise materials and manufacture methods used in phantom design would facilitate the ability to reproduce phantoms across sites. [ABSTRACT FROM AUTHOR]

It is therefore conceivable to hypothesize that 18FDG uptake is different within these inflammatory processes and that TB-PET, beyond its usefulness for inflammation/tumor differentiation, could become a real phenotypic imaging capable of characterizing different inflammatory phenomena. Head-to-head comparison of 18F-DOPA PET/CT and 68Ga-DOTANOC PET/CT in patients with midgut neuroendocrine tumors. Nevertheless, PET imaging after SIRT is possible, 90Y being a positron emitter with a very low-emission abundance (0.0032%) limiting its use in clinical practice with actual PET systems. Imaging of tracer with low abundance emission and/or long half-life One of the particularly promising aspects of TB-PET imaging is the possibility of imaging under conditions of very low statistics, by the use of isotopes with low branching ratio and long half-time (89Zr, 64Cu, 90Y). [Extracted from the article]

Fibromyalgia is a common, chronic, and generalized pain syndrome that is often associated with comorbid depression. The etiology of fibromyalgia is complex; most researchers have documented that the hallmark symptoms are due to the central nervous system's abnormal functioning. Neurotransmitters such as serotonin, norepinephrine, and glutamate, have been reported to be key regulators of fibromyalgia syndrome. Daphnetin is a 7, 8 dihydroxy coumarin widely distributed in Thymelaeaceae family plants, possessing various activities such as anti-arthritic, anti-tumor, anti-malarial, and anti-parasitic. The present study was designed to explore the potential of daphnetin against reserpine-induced fibromyalgia in mice. In mice, a fibromyalgia-like state was achieved by injecting reserpine (0.5 mg/kg, s.c) continuously for 3 days. All behavioral tests were conducted on the 4th and 6th day of experimentation. Reserpine administration significantly increased the mechanical hypersensitivity in electronic von Frey (eVF) and pressure application measurement (PAM) tests. It also increased the immobility period and time to reach the platform in force swim test (FST) and Morris water maze (MWM) test, respectively. In the biochemical analysis, reserpine treatment upregulated the monoamine oxidase-A (MAO-A) activity and level of glutamate, tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), and thiobarbituric acid reactive substances (TBARS). Whereas, it decreased the level of glutathione (GSH), dopamine, serotonin, and norepinephrine. Daphnetin pretreatment attenuated the behavioral and biochemical changes induced by reserpine. Thus, the current investigation results delineate that daphnetin might exert its protective effect by inhibiting inflammatory stress and MAO-A-mediated neurotransmitter depletion and oxidative stress. [ABSTRACT FROM AUTHOR]

Purpose: Phantoms are routinely used in molecular imaging to assess scanner performance. However, traditional phantoms with fillable shapes do not replicate human anatomy. 3D-printed phantoms have overcome this by creating phantoms which replicate human anatomy which can be filled with radioactive material. The problem with these is that small objects suffer to a greater extent than larger objects from the effects of inactive walls, and therefore, phantoms without these are desirable. The purpose of this study was to explore the feasibility of creating resin-based 3D-printed phantoms using 18F. Methods: Radioactive resin was created using an emulsion of printer resin and 18F-FDG. A series of test objects were printed including twenty identical cylinders, ten spheres with increasing diameters (2 to 20 mm), and a double helix. Radioactive concentration uniformity, printing accuracy and the amount of leaching were assessed. Results: Creating radioactive resin was simple and effective. The radioactive concentration was uniform among identical objects; the CoV of the signal was 0.7% using a gamma counter. The printed cylinders and spheres were found to be within 4% of the model dimensions. A double helix was successfully printed as a test for the printer and appeared as expected on the PET scanner. The amount of radioactivity leached into the water was measurable (0.72%) but not visible above background on the imaging. Conclusions: Creating an 18F radioactive resin emulsion is a simple and effective way to create accurate and complex phantoms without inactive walls. This technique could be used to print clinically realistic phantoms. However, they are single use and cannot be made hollow without an exit hole. Also, there is a small amount of leaching of the radioactivity to take into consideration. [ABSTRACT FROM AUTHOR]

The use of cardiac PET, and in particular of quantitative myocardial perfusion PET, has been growing during the last years, because scanners are becoming widely available and because several studies have convincingly demonstrated the advantages of this imaging approach. Therefore, there is a need of determining the procedural modalities for performing high-quality studies and obtaining from this demanding technique the most in terms of both measurement reliability and clinical data. Although the field is rapidly evolving, with progresses in hardware and software, and the near perspective of new tracers, the EANM Cardiovascular Committee found it reasonable and useful to expose in an updated text the state of the art of quantitative myocardial perfusion PET, in order to establish an effective use of this modality and to help implementing it on a wider basis. Together with the many steps necessary for the correct execution of quantitative measurements, the importance of a multiparametric approach and of a comprehensive and clinically useful report have been stressed. [ABSTRACT FROM AUTHOR]

Aim: The aim of this prospective study was to evaluate a data-driven gating software's performance, in terms of identifying the respiratory signal, comparing [68Ga]Ga-DOTATOC and [18F]FDG examinations. In addition, for the [68Ga]Ga-DOTATOC examinations, tracer uptake quantitation and liver lesion detectability were assessed. Methods: Twenty-four patients with confirmed or suspected neuroendocrine tumours underwent whole-body [68Ga]Ga-DOTATOC PET/CT examinations. Prospective DDG was applied on all bed positions and respiratory motion correction was triggered automatically when the detected respiratory signal exceeded a certain threshold (R value ≥ 15), at which point the scan time for that bed position was doubled. These bed positions were reconstructed with quiescent period gating (QPG), retaining 50% of the total coincidences. A respiratory signal evaluation regarding the software's efficacy in detecting respiratory motion for [68Ga]Ga-DOTATOC was conducted and compared to [18F]FDG data. Measurements of SUVmax, SUVmean, and tumour volume were performed on [68Ga]Ga-DOTATOC PET and compared between gated and non-gated images. Results: The threshold of R ≥ 15 was exceeded and gating triggered on mean 2.1 bed positions per examination for [68Ga]Ga-DOTATOC as compared to 1.4 for [18F]FDG. In total, 34 tumours were evaluated in a quantitative analysis. An increase of 25.3% and 28.1%, respectively, for SUVmax (P < 0.0001) and SUVmean (P < 0.0001), and decrease of 21.1% in tumour volume (P < 0.0001) was found when DDG was applied. Conclusions: High respiratory signal was exclusively detected in bed positions where respiratory motion was expected, indicating reliable performance of the DDG software on [68Ga]Ga-DOTATOC PET/CT. DDG yielded significantly higher SUVmax and SUVmean values and smaller tumour volumes, as compared to non-gated images. [ABSTRACT FROM AUTHOR]

To present the feasibility of a dynamic whole-body (DWB) 68Ga-DOTATOC-PET/CT acquisition in patients with well-differentiated neuroendocrine tumors (WD-NETs). Sixty-one patients who underwent a DWB 68Ga-DOTATOC-PET/CT for a histologically proven/highly suspected WD-NET were prospectively included. The acquisition consisted in single-bed dynamic acquisition centered on the heart, followed by the DWB and static acquisitions. For liver, spleen and tumor (1–5/patient), Ki values (in ml/min/100 ml) were calculated according to Patlak's analysis and tumor-to-liver (TLR-Ki) and tumor-to-spleen ratios (TSR-Ki) were recorded. Ki-based parameters were compared to static parameters (SUVmax/SUVmean, TLR/TSRmean, according to liver/spleen SUVmean), in the whole-cohort and according to the PET system (analog/digital). A correlation analysis between SUVmean/Ki was performed using linear and non-linear regressions. Ki-liver was not influenced by the PET system used, unlike SUVmax/SUVmean. The regression analysis showed a non-linear relation between Ki/SUVmean (R2 = 0.55,0.68 and 0.71 for liver, spleen and tumor uptake, respectively) and a linear relation between TLRmean/TLR-Ki (R2 = 0.75). These results were not affected by the PET system, on the contrary of the relation between TSRmean/TSR-Ki (R2 = 0.94 and 0.73 using linear and non-linear regressions in digital and analog systems, respectively). Our study is the first showing the feasibility of a DWB 68Ga-DOTATOC-PET/CT acquisition in WD-NETs. [ABSTRACT FROM AUTHOR]

Purpose: In recurrent prostate carcinoma, determination of the site of recurrence is crucial to guide personalized therapy. In contrast to prostate-specific membrane antigen (PSMA)–positron emission tomography (PET) imaging, computed tomography (CT) has only limited capacity to detect lymph node metastases (LNM). We sought to develop a CT-based radiomic model to predict LNM status using a PSMA radioguided surgery (RGS) cohort with histological confirmation of all suspected lymph nodes (LNs). Methods: Eighty patients that received RGS for resection of PSMA PET/CT-positive LNMs were analyzed. Forty-seven patients (87 LNs) that received inhouse imaging were used as training cohort. Thirty-three patients (62 LNs) that received external imaging were used as testing cohort. As gold standard, histological confirmation was available for all LNs. After preprocessing, 156 radiomic features analyzing texture, shape, intensity, and local binary patterns (LBP) were extracted. The least absolute shrinkage and selection operator (radiomic models) and logistic regression (conventional parameters) were used for modeling. Results: Texture and shape features were largely correlated to LN volume. A combined radiomic model achieved the best predictive performance with a testing-AUC of 0.95. LBP features showed the highest contribution to model performance. This model significantly outperformed all conventional CT parameters including LN short diameter (AUC 0.84), LN volume (AUC 0.80), and an expert rating (AUC 0.67). In lymph node–specific decision curve analysis, there was a clinical net benefit above LN short diameter. Conclusion: The best radiomic model outperformed conventional measures for detection of LNM demonstrating an incremental value of radiomic features. [ABSTRACT FROM AUTHOR]

Tumor heterogeneity is a well-known prognostic factor in head and neck squamous cell carcinoma (HNSCC). A major limitation of tissue- and blood-derived tumor markers is the lack of spatial resolution to image tumor heterogeneity. Tissue markers derived from tumor biopsies usually represent only a small tumor subregion at a single timepoint and are therefore often not representative of the tumors' biology or the biological alterations during and after treatment. Similarly, liquid biopsies give an overall picture of the tumors' secreted factors but completely lack any spatial resolution. Radiomics has the potential to give complete three-dimensional information about the tumor. We conducted a comprehensive literature search to assess the correlation of radiomics to tumor biology and treatment outcome in HNSCC and to assess current limitations of the radiomic biomarkers. In total, 25 studies that explored the ability of radiomics to predict tumor biology and phenotype in HNSCC and 28 studies that explored radiomics to predict post-treatment events were identified. Out of these 53 studies, only three failed to show a significant correlation. The major technical challenges are currently artifacts due to metal implants, non-standardized contrast injection, and delineation uncertainties. All studies to date were retrospective and none of the above-mentioned radiomics signatures have been validated in an independent cohort using an independent software implementation, which shows that transferability due to the numerous technical challenges is currently a major limitation. However, radiomics is a very young field and these studies hopefully pave the way for clinical implementation of radiomics for HNSCC in the future. [ABSTRACT FROM AUTHOR]

Background: The combination of positron emission tomography (PET) and magnetic resonance imaging (MRI) (PET-MRI) is a unique hybrid imaging modality mainly used in oncology and neurology. The MRI-based attenuation correction (MRAC) is crucial for correct quantification of PET data. A suitable phantom to validate quantitative results in PET-MRI is currently missing. In particular, the correction of attenuation due to bone is usually not verified by commonly available phantoms. The aim of this work was, thus, the development of such a phantom and to explore whether such a phantom might be used to validate MRACs. Method: Various materials were investigated for their attenuation and MR properties. For the substitution of bone, water-saturated gypsum plaster was used. The attenuation of 511 keV annihilation photons was regulated by addition of iodine. Adipose tissue was imitated by silicone and brain tissue by agarose gel, respectively. The practicability with respect to the comparison of MRACs was checked as follows: A small flask inserted into the phantom and a large spherical phantom (serving as a reference with negligible error in MRAC) were filled with the very same activity concentration. The activity concentration was measured and compared using clinical protocols on PET-MRI and different built-in and offline MRACs. The same measurements were carried out using PET-CT for comparison. Results: The phantom imitates the human head in sufficient detail. All tissue types including bone were detected as such so that the phantom-based comparison of the quantification accuracy of PET-MRI was possible. Quantitatively, the activity concentration in the brain, which was determined using different MRACs, showed a deviation of about 5% on average and a maximum deviation of 11% compared to the spherical phantom. For PET-CT, the deviation was 5%. Conclusions: The comparatively small error in quantification indicates that it is possible to construct a brain PET-MRI phantom that leads to MR-based attenuation-corrected images with reasonable accuracy. [ABSTRACT FROM AUTHOR]

Knowledge on sex differences in myocardial perfusion, blood volume (MBV), and extracellular volume (ECV) in healthy individuals is scarce and conflicting. Therefore, this was investigated quantitatively by cardiovascular magnetic resonance (CMR). Healthy volunteers (n = 41, 51% female) underwent CMR at 1.5 T. Quantitative MBV [%] and perfusion [ml/min/g] maps were acquired during adenosine stress and at rest following an intravenous contrast bolus (0.05 mmol/kg, gadobutrol). Native T1 maps were acquired before and during adenosine stress, and after contrast (0.2 mmol/kg) at rest and during adenosine stress, rendering rest and stress ECV maps. Compared to males, females had higher perfusion, ECV, and MBV at stress, and perfusion and ECV at rest (p < 0.01 for all). Multivariate linear regression revealed that sex and MBV were associated with perfusion (sex beta −0.31, p = 0.03; MBV beta −0.37, p = 0.01, model R2 = 0.29, p < 0.01) while sex and hematocrit were associated with ECV (sex beta −0.33, p = 0.03; hematocrit beta −0.48, p < 0.01, model R2 = 0.54, p < 0.001). Myocardial perfusion, MBV, and ECV are higher in female healthy volunteers compared to males. Sex is an independent contributor to perfusion and ECV, beyond other physiological factors that differ between the sexes. These findings provide mechanistic insight into sex differences in myocardial physiology. [ABSTRACT FROM AUTHOR]

Background: In contrast to the energy-storing role of white adipose tissue (WAT), brown adipose tissue (BAT) acts as the main site of non-shivering thermogenesis in mammals and has been reported to play a role in protection against obesity and associated metabolic alterations in rodents. Infrared thermography (IRT) has been proposed as a novel non-invasive, safe, and quick method to estimate BAT thermogenic activation in humans. The aim of this study is to determine whether the IRT could be a potential new tool to estimate BAT thermogenic activation in patients with severe obesity in response to bariatric surgery. Methods: Supraclavicular BAT thermogenic activation was evaluated using IRT in a cohort of 31 patients (50 ± 10 years old, BMI = 44.5 ± 7.8; 15 undergoing laparoscopy sleeve gastrectomy and 16 Roux-en-Y gastric bypass) at baseline and 6 months after a bariatric surgery. Clinical parameters were determined at these same time points. Results: Supraclavicular BAT-related activity was detected in our patients by IRT after a cooling stimulus. The BAT thermogenic activation was higher at 6 months after laparoscopy sleeve gastrectomy (0.06 ± 0.1 vs 0.32 ± 0.1), while patients undergoing to a roux-en-Y gastric bypass did not change their thermogenic response using the same cooling stimulus (0.09 ± 0.1 vs 0.08 ± 0.1). Conclusions: Our study postulates the IRT as a potential tool to evaluate BAT thermogenic activation in patients with obesity before and after a bariatric surgery. Further studies are needed to evaluate differences between LSG technique and RYGB on BAT activation. [ABSTRACT FROM AUTHOR]

Introduction: Quantitative imaging biomarkers are becoming usual in oncology for assessing therapy response. The harmonization of image quantitation reporting has become of utmost importance due to the multi-center trials increase. The NEMA image quality test is often considered for the evaluation of quantitation and is more accurate with a radioactive solid phantom that reduces variability. The goal of this project is to determine the level of variability among imaging centers if acquisition and imaging protocol parameters are left to the center's preference while all other parameters are fixed including the scanner type. Methods: A NEMA-IQ phantom filled with radioactive 68Ge solid resin was imaged in five clinical sites throughout Europe. Sites reconstructed data with OSEM and BSREM algorithms applying the sites' clinical parameters. Images were analyzed according with the NEMA-NU2-2012 standard using the manufacturer-provided NEMA tools to calculate contrast recovery (CR) and background variability (BV) for each sphere and the lung error (LE) estimation. In addition, a 18F-filled NEMA-IQ phantom was also evaluated to obtain a gauge for variability among centers when the sites were provided with identical specific instructions for acquisition and reconstruction protocol (the aggregate of data from 12 additional sites is presented). Results: The data using the 68Ge solid phantom showed no statistical differences among different sites, proving a very good reproducibility among the PET center models even if dispersion of data is higher with OSEM compared to BSREM. Furthermore, BSREM shows better CR and comparable BV, while LE is slightly reduced. Two centers exhibit significant differences in CR and BV values for the 18F NEMA NU2-2012 experiments; these outlier results are explained. Conclusion: The same PET system type from the various sites produced similar quantitative results, despite allowing each site to choose their clinical protocols with no restriction on data acquisition and reconstruction parameters. BSREM leads to lower dispersion of quantitative data among different sites. A solid radioactive phantom may be recommended to qualify the sites to perform quantitative imaging. [ABSTRACT FROM AUTHOR]

Purpose: Nowadays, 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography (PET)/X-ray computed tomography (CT) is considered the best available technique to in vivo determination of human BAT volume. The most used Hounsfield unit (HU) threshold for BAT quantification is from - 250 to - 50 HU. Therefore, the main objective of the present study is (i) to examine the influence of SUV and HU thresholds on BAT quantification by [18F]FDG-PET/CT scan, (ii) to identify the proportion of BAT which is not detected by [18F]FDG-PET/CT scan when limiting the range between - 10 and - 50 HU, and (iii) to describe the distribution of BAT radiodensity by weight status and sex in young healthy individuals.Procedures: We measured 125 individuals after a personalized cooling protocol with a static [18F]FDG-PET/CT scan. We quantified BAT using different combination of threshold in every single HU for all participants.Results: We observed that the SUV threshold influences BAT quantification by [18F]FDG-PET/CT scans more than the HU range. We found that the range from - 50 to - 10 HU had the highest proportion of total BAT volume (43.2 %), which represents 41.4 % of the total BAT metabolic activity in our cohort. We also observed that BAT volume was not different between categories of body mass index, as well as BAT activity (SUVmean). In addition, BAT was less dense in women than in men, although the BAT activity (SUVmean) was higher in all ranges of HU. We also observed that the radiodensity of BAT located in the cervical area was mainly in the range from - 50 to - 10 HU.Conclusion: Therefore, all future human studies using static [18F]FDG-PET/CT scans should include BAT in the radiodensity range from - 50 to - 10 HU. [ABSTRACT FROM AUTHOR]

Sleep disturbances and chronic pain are considered public health concerns. They are frequently associated, and the direction of its relationship and possible mechanisms underlying it are frequently debated. The exploration of the sleep–pain association is of great clinical interest to explore in order to steer potential therapeutic avenues, accommodate the patient's experience, and adapt the common practice of health professionals. In this review, the direction between sleep–pain in adult and pediatric populations will be discussed. Moreover, the possible mechanisms contributing to this relationship as endogenous pain modulation, inflammation, affect, mood and other states, the role of different endogenous substances (dopamine, orexin, melatonin, vitamin D) as well as other lesser known such as cyclic alternating pattern among others, will be explored. Finally, directions for future studies on this area will be discussed, opening up to the addition of tools such as brain imaging (e.g., fMRI), electrophysiology and non-invasive brain stimulation techniques. Such resources paired with artificial intelligence are key to personalized medicine management for patients facing pain and sleep interacting conditions. [ABSTRACT FROM AUTHOR]

Background: 44Sc has been increasingly investigated as a potential alternative to 68Ga in the development of tracers for positron emission tomography (PET). The lower mean positron energy of 44Sc (0.63 MeV) compared to 68Ga (0.83 MeV) can result in better spatial image resolutions. However, high-energy γ-rays (1157 keV) are emitted at high rates (99.9%) during 44Sc decay, which can reduce image quality. Therefore, we investigated the impact of these physical properties and performed an unbiased performance evaluation of 44Sc and 68Ga with different imaging phantoms (image quality phantom, Derenzo phantom, and three-rod phantom) on two preclinical PET scanners (Mediso nanoScan PET/MRI, Siemens microPET Focus 120). Results: Despite the presence of high-energy γ-rays in 44Sc decay, a higher image resolution of small structures was observed with 44Sc when compared to 68Ga. Structures as small as 1.3 mm using the Mediso system, and as small as 1.0 mm using the Siemens system, could be visualized and analyzed by calculating full width at half maximum. Full widths at half maxima were similar for both isotopes. For image quality comparison, we calculated recovery coefficients in 1–5 mm rods and spillover ratios in either air, water, or bone-equivalent material (Teflon). Recovery coefficients for 44Sc were significantly higher than those for 68Ga. Despite the lower positron energy, 44Sc-derived spillover ratio (SOR) values were similar or slightly higher to 68Ga-derived SOR values. This may be attributed to the higher background caused by the additional γ-rays. On the Siemens system, an overestimation of scatter correction in the central part of the phantom was observed causing a virtual disappearance of spillover inside the three-rod phantom. Conclusion: Based on these findings, 44Sc appears to be a suitable alternative to 68Ga. The superior image resolution makes it an especially strong competitor in preclinical settings. The additional γ-emissions have a small impact on the imaging resolution but cause higher background noises and can effect an overestimation of scatter correction, depending on the PET system and phantom. [ABSTRACT FROM AUTHOR]

Objectives: The present study aims to assess the impact of acquisition time, different iterative reconstruction protocols as well as image context (including contrast levels and background activities) on the measured spatial resolution in PET images.Methods: Discovery 690 PET/CT scanner was used to quantify spatial resolutions in terms of full width half maximum (FWHM) as derived (i) directly from capillary tubes embedded in air and (ii) indirectly from 10 mm-diameter sphere of the NEMA phantom. Different signal-to-background ratios (SBRs), background activity levels and acquisition times were applied. The emission data were reconstructed using iterative reconstruction protocols. Various combinations of iterations and subsets (it × sub) were evaluated.Results: For capillary tubes, improved FWHM values were obtained for higher it × sub, with improved performance for PSF algorithms relative to non-PSF algorithms. For the NEMA phantom, by increasing acquisition times from 1 to 5 min, intrinsic FWHM for reconstructions with it × sub 32 (54) was improved by 15.3% (13.2%), 15.1% (13.8%), 14.5% (12.8%) and 13.7% (12.7%) for OSEM, OSEM + PSF, OSEM + TOF and OSEM + PSF + TOF, respectively. Furthermore, for all reconstruction protocols, the FWHM improved with more impact for higher it × sub.Conclusion: Our results indicate that PET spatial resolution is greatly affected by SBR, background activity and the choice of the reconstruction protocols. [ABSTRACT FROM AUTHOR]

The National Electrical Manufacturers Association's (NEMA) NU 4-2008 standard specifies methodology for evaluating the performance of small-animal PET scanners. The standard's goal is to enable comparison of different PET scanners over a wide range of technologies and geometries used. In this work, we discuss if the NEMA standard meets these goals and we point out potential flaws and improvements to the standard.For the evaluation of spatial resolution, the NEMA standard mandates the use of filtered backprojection reconstruction. This reconstruction method can introduce star-like artifacts for detectors with an anisotropic spatial resolution, usually caused by parallax error. These artifacts can then cause a strong dependence of the resulting spatial resolution on the size of the projection window in image space, whose size is not fully specified in the NEMA standard. If the PET ring has detectors which are perpendicular to a Cartesian axis, then the resolution along this axis will typically improve with larger projection windows.We show that the standard's equations for the estimation of the random rate for PET systems with intrinsic radioactivity are circular and not satisfiable. However, a modified version can still be used to determine an approximation of the random rates under the assumption of negligible random rates for small activities and a constant scatter fraction. We compare the resulting estimated random rates to random rates obtained using a delayed coincidence window and two methods based on the singles rates. While these methods give similar estimates, the estimation method based on the NEMA equations overestimates the random rates.In the NEMA standard's protocol for the evaluation of the sensitivity, the standard specifies to axially step a point source through the scanner and to take a different scan for each source position. Later, in the data analysis section, the standard does not specify clearly how the different scans have to be incorporated into the analysis, which can lead to unclear interpretations of publicized results.The standard's definition of the recovery coefficients in the image quality phantom includes the maximum activity in a region of interest, which causes a positive correlation of noise and recovery coefficients. This leads to an unintended trade-off between desired uniformity, which is negatively correlated with variance (i.e., noise), and recovery.With this work, we want to start a discussion on possible improvements in a next version of the NEMA NU-4 standard. [ABSTRACT FROM AUTHOR]

Background: We assessed and compared image quality obtained with clinical 18F-FDG whole-body oncologic PET protocols used in three different, state-of-the-art digital PET/CT and two conventional PMT-based PET/CT devices. Our goal was to evaluate an improved trade-off between administered activity (patient dose exposure/signal-to-noise ratio) and acquisition time (patient comfort) while preserving diagnostic information achievable with the recently introduced digital detector technology compared to previous analogue PET technology. Methods: We performed list-mode (LM) PET acquisitions using a NEMA/IEC NU2 phantom, with activity concentrations of 5 kBq/mL and 25 kBq/mL for the background (9.5 L) and sphere inserts, respectively. For each device, reconstructions were obtained varying the image statistics (10, 30, 60, 90, 120, 180, and 300 s from LM data) and the number of iterations (range 1 to 10) in addition to the employed local clinical protocol setup. We measured for each reconstructed dataset: the quantitative cross-calibration, the image noise on the uniform background assessed by the coefficient of variation (COV), and the recovery coefficients (RCs) evaluated in the hot spheres. Additionally, we compared the characteristic time-activity-product (TAP) that is the product of scan time per bed position × mass-activity administered (in min·MBq/kg) across datasets. Results: Good system cross-calibration was obtained for all tested datasets with < 6% deviation from the expected value was observed. For all clinical protocol settings, image noise was compatible with clinical interpretation (COV < 15%). Digital PET showed an improved background signal-to-noise ratio as compared to conventional PMT-based PET. RCs were comparable between digital and PMT-based PET datasets. Compared to PMT-based PET, digital systems provided comparable image quality with lower TAP (from ~ 40% less and up to 70% less). Conclusions: This study compared the achievable clinical image quality in three state-of-the-art digital PET/CT devices (from different vendors) as well as in two conventional PMT-based PET. Reported results show that a comparable image quality is achievable with a TAP reduction of ~ 40% in digital PET. This could lead to a significant reduction of the administered mass-activity and/or scan time with direct benefits in terms of dose exposure and patient comfort. [ABSTRACT FROM AUTHOR]

Introduction: miRNAs are small non-coding RNAs, some of which are expressed in adipose tissues, are present in the circulation, and are regulated in obesity. Bariatric surgery (BS) has been proposed to lead to activation of brown adipose tissue, an effect that may be related to beneficial effects of BS on systemic metabolism. Here, we evaluated circulating levels of miR-92a and miR-99b, two miRNAs proposed as biomarkers of brown fat activity, in a cohort of patients with severe obesity before and after BS, and studied their potential relationship with BS-associated improvements in metabolic parameters. Methods: Circulating levels of miR-92a and miR-99b were quantified in a cohort of 26 patients (age, 48 ± 10 years; BMI, 45 ± 7 kg/m2) before and 6 months after BS. Clinical parameters were determined at different time points and correlations among them were studied. Results: Basal levels of miR-92a were significantly increased in patients with obesity relative to lean controls. Serum miR-92a levels were strongly reduced at 6 months after BS, reaching levels similar to those in controls. Serum miR-99b levels were unchanged in relation to both the obese condition and BS. Elevated levels of miR-92a were directly correlated with worsened glucose homeostasis parameters and poor BS outcome. Conclusions: Our findings show that miR-92a is elevated in conditions of obesity, and its reduction after BS correlates with metabolic improvement. Further studies would be necessary to establish miR-92a as serum biomarker and potential predictor of the BS success in improving the metabolic status of patients with obesity. [ABSTRACT FROM AUTHOR]