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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]

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]

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]

Positron emission tomography with x‐ray computed tomography (PET/CT) is increasingly being utilized for radiation treatment planning (RTP). Accurate delivery of RT therefore depends on quality PET/CT data. This study covers quality control (QC) procedures required for PET/CT for diagnostic imaging and incremental QC required for RTP. Based on a review of the literature, it compiles a list of recommended tests, performance frequencies, and tolerances, as well as references to documents detailing how to perform each test. The report was commissioned by the Canadian Organization of Medical Physicists as part of the Canadian Partnership for Quality Radiotherapy initiative. [ABSTRACT FROM AUTHOR]

In 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) studies, maximum standardized uptake value (SUVmax) is the parameter commonly used to provide a measurement of the metabolic activity of a tumor. SUV normalized by body mass is affected by the proportions of body fat and lean tissue, which present high variability in patients with cancer. SUV corrected by lean body mass (LBM), denoted as SUL, is recommended to provide more accurate, consistent, and reproducible SUV results; however, LBM is frequently estimated rather than measured. Given the increasing importance of a quantitative PET parameter, especially when comparing PET studies over time to evaluate disease response clinically, and its use in oncological clinical trials, we set out to evaluate the commonly used equations originally derived by James (1976) and Janmahasatian et al. (2005) against computerized tomography (CT)-derived measures of LBM. Methods: Whole-body 18F-FDG PET images of 195 adult patients with cancer were analyzed retrospectively. Representative liver SUVmean was normalized by total body mass. SUL was calculated using a quantitative determination of LBM based on the CT component of the PET/CT study (LBMCT) and compared against the equation-estimated SUL. Bland and Altman plots were generated for SUV-SUL differences. Results: This consecutive sample of patients undergoing usual care (men, n = 96; women, n = 99) varied in body mass (38-127 kg) and in Body Mass Index (BMI) (14.7-47.2 kg/m2). LBMCT weakly correlated with body mass (men, r² = 0.32; women, r² = 0.22), and thus SUV and SULCT were also weakly correlated (men, r² = 0.24; women, r² = 0.11). Equations proved inadequate for the assessment of LBM. LBM estimated by James' equation showed a mean bias (overestimation of LBM compared with LBMCT) in men (+6.13 kg; 95% CI 4.61-7.65) and in women (+6.32 kg; 95% CI 5.26-7.39). Janmahasatian's equation provided similarly poor performance. Conclusions: CT-based LBM determinations incorporate the patient's current body composition at the time of a PET/CT study, and the information garnered can provide care teams with information with which to more accurately determine FDG uptake values, allowing comparability over multiple scans and treatment courses and will provide a robust basis for the use of PET Response Criteria in Solid Tumors (PERCIST) in clinical trials. [ABSTRACT FROM AUTHOR]

Background: MR‐based methods for attenuation correction (AC) in PET/MRI either neglect attenuation of bone, or use MR‐signal derived information about bone, which leads to a bias in quantification of tracer uptake in PET. In a previous study, we presented a PET/MRI specific MR coil with an integrated transmission source (TX) system allowing for direct measurement of attenuation. In phantom measurements, this system successfully reproduced the linear attenuation coefficient of water. Purpose: The purpose of this study is to validate the TX system in a clinical setting using animals and to show its applicability compared to standard clinical methods. Methods: As test subject, a 15‐kg piglet was injected with 53 MBq of 18F‐NaF. The μ‐map obtained with the TX system and the reconstructed activity distribution were compared to four established AC methods: a Dixon sequence, an ultra‐short echo time (UTE) sequence, a CT scan, and a 511 keV transmission scan using a Siemens ECAT EXACT HR+ as the reference. The PET/MRI measurements were performed on a Siemens Biograph mMR to obtain the μ‐map using the TX system as well as the Dixon and UTE sequence directly followed by the CT and ECAT measurements. Results: The reconstructed activity distribution using the TX system for AC showed similar results compared to the reference (<5% difference in hot regions) and outperformed the MR‐based methods as implemented in the PET/MRI system (<10% difference in hot regions). However, the additional hardware of the TX system adds complexity to the acquisition process. Conclusion: Our porcine study demonstrates the feasibility of post‐injection transmission scans using the developed TX system in a clinical setting. This makes it a useful tool for PET/MRI in cases where transmission information is needed for AC. Potential applications are studies using larger animals where state‐of‐the‐art atlas‐based or artificial intelligence AC methods are not available. [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]

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]

Purpose: Recently, updated EARL specifications (EARL2) have been developed and announced. This study aims at investigating the impact of the EARL2 specifications on the quantitative reads of clinical PET–CT studies and testing a method to enable the use of the EARL2 standards whilst still generating quantitative reads compliant with current EARL standards (EARL1). Methods: Thirteen non-small cell lung cancer (NSCLC) and seventeen lymphoma PET–CT studies were used to derive four image datasets—the first dataset complying with EARL1 specifications and the second reconstructed using parameters as described in EARL2. For the third (EARL2F6) and fourth (EARL2F7) dataset in EARL2, respectively, 6 mm and 7 mm Gaussian post-filtering was applied. We compared the results of quantitative metrics (MATV, SUVmax, SUVpeak, SUVmean, TLG, and tumor-to-liver and tumor-to-blood pool ratios) obtained with these 4 datasets in 55 suspected malignant lesions using three commonly used segmentation/volume of interest (VOI) methods (MAX41, A50P, SUV4). Results: We found that with EARL2 MAX41 VOI method, MATV decreases by 22%, TLG remains unchanged and SUV values increase by 23–30% depending on the specific metric used. The EARL2F7 dataset produced quantitative metrics best aligning with EARL1, with no significant differences between most of the datasets (p>0.05). Different VOI methods performed similarly with regard to SUV metrics but differences in MATV as well as TLG were observed. No significant difference between NSCLC and lymphoma cancer types was observed. Conclusions: Application of EARL2 standards can result in higher SUVs, reduced MATV and slightly changed TLG values relative to EARL1. Applying a Gaussian filter to PET images reconstructed using EARL2 parameters successfully yielded EARL1 compliant data. [ABSTRACT FROM AUTHOR]

Purpose: The α2-adrenoceptors mediate many effects of norepinephrine and epinephrine, and participate in the regulation of neuronal, endocrine, cardiovascular, vegetative, and metabolic functions. Of the three receptor subtypes, only α2A and α2C are found in the brain in significant amounts. Subtype-selective positron emission tomography (PET) imaging of α2-adrenoceptors has been limited to the α2C subtype. Here, we report the synthesis of 6-[18F]fluoro-marsanidine, a subtype-selective PET tracer candidate for α2A-adrenoceptors, and its preclinical evaluation in rats and mice. Procedures: 6-[18F]Fluoro-marsanidine was synthesized using electrophilic F-18 fluorination with [18F]Selectfluor bis(triflate). The tracer was evaluated in Sprague Dawley rats and in α2A-knockout (KO) and wild-type (WT) mice for subtype selectivity. In vivo PET imaging and ex vivo brain autoradiography were performed to determine the tracer distribution in the brain. The specificity of the tracer for the target was determined by pretreatment with the subtype-non-selective α2-agonist medetomidine. The peripheral biodistribution and extent of metabolism of 6-[18F]fluoro-marsanidine were also analyzed. Results: 6-[18F]Fluoro-marsanidine was synthesized with [18F]Selectfluor bis(triflate) in a radiochemical yield of 6.4 ± 1.7 %. The molar activity was 3.1 to 26.6 GBq/μmol, and the radiochemical purity was > 99 %. In vivo studies in mice revealed lower uptake in the brains of α2A-KO mice compared to WT mice. The results for selectivity were confirmed by ex vivo brain autoradiography. Blocking studies revealed reduced uptake in α2A-adrenoceptor-rich brain regions in pretreated animals, demonstrating the specificity of the tracer. Metabolite analyses revealed very rapid metabolism of 6-[18F]fluoro-marsanidine with blood-brain barrier-permeable metabolites in both rats and mice. Conclusion: 6-[18F]Fluoro-marsanidine was synthesized and evaluated as a PET tracer candidate for brain α2A-adrenoceptors. However, rapid metabolism, extensive presence of labeled metabolites in the brain, and high non-specific uptake in mouse and rat brain make 6-[18F]fluoro-marsanidine unsuitable for α2A-adrenoceptor targeting in rodents in vivo. [ABSTRACT FROM AUTHOR]

Objective: Early detection plays a role in the prognosis of melanoma, the most aggressive skin cancer. 64Cu- and 68Ga-labeled alpha-melanocyte-stimulating hormone (α-MSH) analogs targeting the melanocortin-1 receptor are promising positron emission tomography (PET) tracers for detecting melanoma, and the use of 18F-labeling will further contribute to the detectability and availability. However, the high radiochemistry demand related to the conventional 18F-labeling methods has restricted the development of 18F-labeled α-MSH analogs. A recently developed radiofluorination method using aluminum-fluoride (Al18F) offers a simple, efficient, and time-saving labeling procedure compared to the conventional 18F-labeling methods. Herein, we sought to establish a simple preparation method for an 18F-labeled α-MSH analog using Al18F, and we examined its potential for the early detection of melanoma.Methods: A 1,4,7-triazacyclononane-N,N',N″-triacetic acid (NOTA)-conjugated α-MSH analog (NOTA-GGNle-CycMSHhex) was prepared by the Fmoc solid-phase strategy. NOTA-GGNle-CycMSHhex was labeled with Al18F by heating at 105 °C using a microwave synthesizer for 15 min. Biodistribution study was conducted on B16/F10-luc melanoma-bearing mice at 30 min, 1 h and 3 h after injection of Al18F-NOTA-GGNle-CycMSHhex. PET imaging was conducted on melanoma-bearing mice at 1 h post-injection. One day prior to the PET imaging, bioluminescence imaging was also performed.Results: Al18F-NOTA-GGNle-CycMSHhex was readily prepared with a high radiochemical yield (94.0 ± 2.8%). The biodistribution study showed a high accumulation of Al18F-NOTA-GGNle-CycMSHhex in the tumor at 30 min and 1 h post-injection (6.69 ± 1.49 and 7.70 ± 1.71%ID/g, respectively). The tumor-to-blood ratio increased with time: 3.46 ± 0.89, 12.67 ± 1.29, and 35.27 ± 9.12 at 30 min, 1 h, and 3 h post-injection, respectively. In the PET imaging, Al18F-NOTA-GGNle-CycMSHhex clearly visualized the tumors and depicted very small tumors (< 3 mm).Conclusions: We successfully prepared Al18F-NOTA-GGNle-CycMSHhex in a simple and efficient manner. Al18F-NOTA-GGNle-CycMSHhex showed high tumor accumulation and clearly visualized very small tumors in melanoma-bearing mice. These findings suggest that Al18F-NOTA-GGNle-CycMSHhex will be a promising PET tracer for melanoma imaging at an earlier stage. [ABSTRACT FROM AUTHOR]

Evaluation of PET image quality is central to annual physics surveys, quality assurance, and laboratory accreditation. A common method is to image the American College of Radiology (ACR) PET phantom, which contains hot and cold structures of various sizes in a warm background. Performance evaluation involves qualitative assessment of hot and cold structure visibility and overall image quality. Some criteria are quantitative and rely on manually drawn regions of interest (ROIs) to measure SUV. Fully automated scoring of ACR PET phantom images would improve efficiency, avoid observer-related dependencies, and possibly provide more robust evaluation of image quality. Methods: Software was developed to coregister PET images to a phantom template and to compute ROI measurements of hot vial activity (SUVmax) and background activity (SUVmean) automatically. In addition, 3-dimensional volumes of interest (VOIs) were generated to measure hot vial activity (SUVvial), background activity, and cold rod contrast. Consistency of the ROI-based and VOI-based methods was evaluated using phantom data from a total of 17 annual physics surveys of 3 PET/CT scanners with the same PET detector design. Results: The automated software processed all PET phantom datasets successfully. SUV consistency for hot vials was improved through use of cylindric VOIs and through normalization with respect to assayed activities and dilution volumes used in phantom preparation. Average vial SUV SD improved from 8.0% for standard SUVmax to 3.2% for normalized SUVvial Similarly, the SD for the SUV ratio of 16- to 25-mm vials improved from 5.0% for SUVmax to 3.2% for SUVvial Background SUVmean had a similar consistency between the ROI and VOI methods. Cold rod contrast was highly consistent, offering a potential alternative to qualitative visual assessment of low-contrast performance. Conclusion: Automated quantitative scoring of the ACR PET phantom is feasible and offers the advantages of more efficient, consistent, and thorough performance characterization. Acceptance ranges for SUVs and ratios likely can be tightened if normalized VOI measurements are used. Further testing with phantom data from a variety of PET scanners is necessary to establish suitable quantitative thresholds for acceptable performance. [ABSTRACT FROM AUTHOR]

Purpose: Positron emission tomography (PET)/computed tomography (CT) with 68Ga-labelled 1,4,7,10-tetraazacyclododecane-N,N′,N″,N″'-tetraacetic acid-d-Phe1-Tyr3-octreotide (DOTATOC) has been accepted as a diagnostic imaging tool especially for patients with neuroendocrine tumours. However, its clinical usefulness for restaging of renal cell carcinoma (RCC) has not been fully investigated. This retrospective study was performed to elucidate the clinical value of PET/CT using 68Ga-DOTATOC in patients with known or suspected recurrent RCC. Methods: We analysed 25 consecutive patients who underwent DOTATOC-PET/CT scans after surgery for RCC (23 clear cell, 1 papillary, 1 unclassified). PET/CT findings were reviewed and the detection rate was calculated on a patient and lesion basis. The detectability was compared in patients who also underwent PET/CT scans with 18F-fluorodeoxyglucose (FDG). Histopathological findings or clinical follow-up were used as the reference standard. Results: Based on the final diagnosis, 76 recurrent or metastatic lesions were confirmed in this population. Of these lesions, 66 lesions in 22 patients were positive by DOTATOC-PET/CT. The patient-based and lesion-based sensitivity was 88% (22/25) and 87% (66/76), respectively. Twelve patients underwent both DOTATOC-PET/CT and FDG-PET/CT. The lesion-based sensitivity of DOTATOC was 74% (20/27), while that of FDG was 59% (16/27). Eight lesions were identified only by DOTATOC, but four lesions from papillary RCC were detected only by FDG. Conclusion: Our data indicate that DOTATOC-PET/CT would be useful for detecting recurrent foci in patients with clear cell RCC. DOTATOC-PET/CT and FDG-PET/CT are considered to have complementary roles. [ABSTRACT FROM AUTHOR]

Purpose: The high diagnostic performance of somatostatin receptor positron emission tomography with computed tomography (PET/CT) in neuroendocrine tumours (NETs) was demonstrated by several articles. However, only some studies evaluated the detection rate (DR) of this imaging method in patients with metastatic NETs and unknown primary tumours (CUP-NETs). Therefore, we aimed to perform a meta-analysis to add evidence-based data in this setting. Methods: A comprehensive computer literature search of studies listed in PubMed/MEDLINE, EMBASE, and Cochrane library databases through December 2018 and regarding the use of somatostatin receptor PET/CT in patients with CUP-NETs was carried out. Pooled DR of CUP-NETs by using somatostatin receptor PET/CT was calculated. A pooled analysis evaluating the percentage of change of management by using somatostatin receptor PET/CT in these patients was also performed. Results: Twelve studies on the use of somatostatin receptor PET/CT in detecting CUP-NETs in 383 metastatic patients were included. The meta-analysis of all these studies provided the following DR on a per patient-based analysis: 56% (95% confidence interval (95% CI): 48–63%). Moderate heterogeneity among the selected studies was found (I2 = 50%), whereas a significant publication bias was excluded by Egger's test (p = 0.45). The most common primary tumour sites were the bowel and the pancreas. A change of management by using somatostatin receptor PET/CT was demonstrated in 20% (95% CI: 10–33%) of patients with CUP-NET. Conclusions: Somatostatin receptor PET/CT is very useful in detecting CUP-NETs in patients with metastatic disease. More studies on the change of management by using this imaging method in this setting are needed. [ABSTRACT FROM AUTHOR]

Abstract: Brown adipose tissue (BAT) is a recently rediscovered tissue in people that has shown promise as a potential therapeutic target against obesity and its metabolic abnormalities. Reliable non‐invasive assessment of BAT volume and activity is critical to allow its importance in metabolic control to be evaluated. Positron emission tomography/computed tomography (PET/CT) in combination with 2‐deoxy‐2‐[18F]fluoroglucose administration is currently the most frequently used and most established method for the detection and quantification of activated BAT in humans. However, it involves radiation exposure and can detect activated (e.g. after cold exposure), but not quiescent, BAT. Several alternative methods that overcome some of these limitations have been developed including different PET approaches, single‐photon emission imaging, CT, magnetic resonance based approaches, contrast‐enhanced ultrasound, near infrared spectroscopy, and temperature assessment of fat depots containing brown adipocytes. The purpose of this review is to summarize and critically evaluate the currently available methods that non‐invasively probe various aspects of BAT biology in order to assess BAT volume and/or metabolism. Although several of these methods show promise for the non‐invasive assessment of BAT volume and function, further research is needed to optimize them to enable an accurate, reproducible and practical means for the assessment of human BAT content and its metabolic function. [ABSTRACT FROM AUTHOR]

Purpose: Quality control plays an increasingly important role in quantitative PET imaging and is typically performed using phantoms. The purpose of this work was to develop and validate a fully automated analysis method for two common PET/CT quality assurance phantoms: the NEMA NU‐2 IQ and SNMMI/CTN oncology phantom. The algorithm was designed to only utilize the PET scan to enable the analysis of phantoms with thin‐walled inserts. Methods: We introduce a model‐based method for automated analysis of phantoms with spherical inserts. Models are first constructed for each type of phantom to be analyzed. A robust insert detection algorithm uses the model to locate all inserts inside the phantom. First, candidates for inserts are detected using a scale‐space detection approach. Second, candidates are given an initial label using a score‐based optimization algorithm. Third, a robust model fitting step aligns the phantom model to the initial labeling and fixes incorrect labels. Finally, the detected insert locations are refined and measurements are taken for each insert and several background regions. In addition, an approach for automated selection of NEMA and CTN phantom models is presented. The method was evaluated on a diverse set of 15 NEMA and 20 CTN phantom PET/CT scans. NEMA phantoms were filled with radioactive tracer solution at 9.7:1 activity ratio over background, and CTN phantoms were filled with 4:1 and 2:1 activity ratio over background. For quantitative evaluation, an independent reference standard was generated by two experts using PET/CT scans of the phantoms. In addition, the automated approach was compared against manual analysis, which represents the current clinical standard approach, of the PET phantom scans by four experts. Results: The automated analysis method successfully detected and measured all inserts in all test phantom scans. It is a deterministic algorithm (zero variability), and the insert detection RMS error (i.e., bias) was 0.97, 1.12, and 1.48 mm for phantom activity ratios 9.7:1, 4:1, and 2:1, respectively. For all phantoms and at all contrast ratios, the average RMS error was found to be significantly lower for the proposed automated method compared to the manual analysis of the phantom scans. The uptake measurements produced by the automated method showed high correlation with the independent reference standard (R2 ≥ 0.9987). In addition, the average computing time for the automated method was 30.6 s and was found to be significantly lower (P ≪ 0.001) compared to manual analysis (mean: 247.8 s). Conclusions: The proposed automated approach was found to have less error when measured against the independent reference than the manual approach. It can be easily adapted to other phantoms with spherical inserts. In addition, it eliminates inter‐ and intraoperator variability in PET phantom analysis and is significantly more time efficient, and therefore, represents a promising approach to facilitate and simplify PET standardization and harmonization efforts. [ABSTRACT FROM AUTHOR]

Background: This study evaluates the consistency of PET evaluation response criteria in solid tumours (PERCIST) and European Organisation for Research and Treatment of Cancer (EORTC) classification across different reconstruction algorithms and whether aligning standardized uptake values (SUVs) to the European Association of Nuclear Medicine acquisition (EANM)/EARL standards provides more consistent response classification. Materials and methods: Baseline () and response assessment () scans in 61 patients with non-small cell lung cancer were acquired in protocols compliant with the EANM guidelines and were reconstructed with point-spread function (PSF) or PSF + time-of-flight (TOF) reconstruction for optimal tumour detection and with a standardized ordered subset expectation maximization (OSEM) reconstruction known to fulfil EANM harmonizing standards. Patients were recruited in three centres. Following reconstruction, EQ.PET, a proprietary software solution was applied to the PSF ± TOF data (PSF ± TOF.EQ) to harmonize SUVs to the EANM standards. The impact of differing reconstructions on PERCIST and EORTC classification was evaluated using standardized uptake values corrected for lean body mass (SUL). Results: Using OSEM/OSEM (standard scenario), responders displayed a reduction of −57.5% ± 23.4 and −63.9% ± 22.4 for SUL and SUL, respectively, while progressing tumours had an increase of +63.4% ± 26.5 and +60.7% ± 19.6 for SUL and SUL respectively. The use of PSF ± TOF reconstruction impacted the classification of tumour response. For example, taking the OSEM/PSF ± TOF scenario reduced the apparent reduction in SUL in responding tumours (−39.7% ± 31.3 and −55.5% ± 26.3 for SUL and SUL, respectively) but increased the apparent increase in SUL in progressing tumours (+130.0% ± 50.7 and +91.1% ± 39.6 for SUL and SUL, respectively). Consequently, variation in reconstruction methodology (PSF ± TOF/OSEM or OSEM /PSF ± TOF) led, respectively, to 11/61 (18.0%) and 10/61 (16.4%) PERCIST classification discordances and to 17/61 (28.9%) and 19/61 (31.1%) EORTC classification discordances. An agreement was better for these scenarios with application of the propriety filter, with kappa values of 1.00 and 0.95 compared to 0.75 and 0.77 for PERCIST and kappa values of 0.93 and 0.95 compared to 0.61 and 0.55 for EORTC, respectively. Conclusion: PERCIST classification is less sensitive to reconstruction algorithm-dependent variability than EORTC classification but harmonizing SULs within the EARL program is equally effective with either. [ABSTRACT FROM AUTHOR]

Pain is a complex sensory and emotional experience that is heavily influenced by prior experience and expectations of pain. Before the development of noninvasive human brain imaging, our grasp of the brain's role in pain processing was limited to data from postmortem studies, direct recording of brain activity, patient experience and stimulation during neurosurgical procedures, and animal models of pain. Advances made in neuroimaging have bridged the gap between brain activity and the subjective experience of pain and allowed us to better understand the changes in the brain that are associated with both acute and chronic pain. Additionally, cognitive influences on pain such as attention, anticipation, and fear can now be directly observed, allowing for the interpretation of the neural basis of the psychological modulation of pain. The use of functional brain imaging to measure changes in endogenous neurochemistry has increased our understanding of how states of increased resilience and vulnerability to pain are maintained. [ABSTRACT FROM AUTHOR]

Unlabelled: Algorithms are able to compute myocardial blood flow (MBF) from dynamic PET data for each of the 17 left ventricular segments, with global MBF obtained by averaging segmental values. This study was undertaken to compare MBFs with and without the basal-septal segments.Methods: Data were examined retrospectively for 196 patients who underwent rest and regadenoson-stress (82)Rb PET/CT scanning for evaluation of known or suspected coronary artery disease. MBF data were acquired in gated list mode and rebinned to isolate the first-pass dynamic portion. Coronary vascular resistance (CVR) was computed as mean arterial pressure divided by MBF. MBF inhomogeneity was computed as the ratio of SD to mean MBF. Relative perfusion scores were obtained using (82)Rb-specific normal limits applied to polar maps of myocardial perfusion generated from myocardial equilibrium portions of PET data. MBF and CVRs from 17 and 14 segments were compared.Results: Mean MBFs were lower for 17- than 14-segment means for rest (0.78 ± 0.50 vs. 0.85 ± 0.54 mL/g/min, paired t test P < 0.0001) and stress (1.50 ± 0.88 vs. 1.67 ± 0.96 mL/g/min, P < 0.0001). Bland-Altman plots of MBF differences versus means exhibited nonzero intercept (-0.04 ± 0.01, P = 0.0004) and significant correlation (r = -0.64, P < 0.0001), with slopes significantly different from 0.0 (-7.2% ± 0.6% and -8.3% ± 0.7% for rest and stress MBF; P < 0.0001). Seventeen-segment CVRs were higher than 14-segment CVRs for rest (159 ± 86 vs. 147 ± 81 mm Hg/mL/g/min, paired t test P < 0.0001) and stress CVR (85 ± 52 vs. 76 ± 48 mm Hg/mL/g/min, P < 0.0001). MBF inhomogeneity correlated significantly (P < 0.0001) with summed perfusion scores, but values correlated significantly more strongly for 14- than 17-segment values for rest (r = 0.67 vs. r = 0.52, P = 0.02) and stress (r = 0.69 vs. r = 0.47, P = 0.001). When basal segments were included in MBF determinations, perfusion inhomogeneity was greater both for rest (39% ± 10% vs. 31% ± 10%, P < 0.0001) and for stress (42% ± 12% vs. 32% ± 11%, P < 0.0001).Conclusion: Averaging 17 versus 14 segments leads to systematically 7%-8% lower MBF calculations, higher CVRs, and greater computed inhomogeneity. Consideration should be given to excluding basal-septal segments from standard global MBF determination. [ABSTRACT FROM AUTHOR]

The use of F-FDG PET/CT as a quantitative imaging biomarker requires standardization and harmonization of imaging procedures and PET/CT system performance to obtain repeatable and reproducible quantitative data. However, a PET/CT system optimized to meet international quantitative standards is not necessarily optimized for use as a diagnostic tool (i.e. for lesion detectability). Several solutions have been proposed and validated, but until recently none of them had been implemented commercially. Vendor-provided solutions allowing the use of PET/CT both as a diagnostic tool and as a quantitative imaging biomarker are therefore greatly needed and would be highly appreciated. In this invited perspective one such solution is highlighted. [ABSTRACT FROM AUTHOR]

ABSTRACT This study explored the use of the α2C-adrenoceptor PET tracer [11C]ORM-13070 to monitor α2C-AR occupancy in the human brain. The subtype-nonselective α2-AR antagonist atipamezole was administered to eight healthy volunteer subjects to determine its efficacy and potency ( Emax and EC50) at inhibiting tracer uptake. We also explored whether the tracer could reveal changes in the synaptic concentrations of endogenous noradrenaline in the brain, in response to several pharmacological and sensory challenge conditions. We assessed occupancy from the bound-to-free ratio measured during 5-30 min post injection. Based on extrapolation of one-site binding, the maximal extent of inhibition of striatal [11C]ORM-13070 uptake ( Emax) achievable by atipamezole was 78% (95% CI 69-87%) in the caudate nucleus and 65% (53-77%) in the putamen. The EC50 estimates of atipamezole (1.6 and 2.5 ng/ml, respectively) were in agreement with the drug's affinity to α2C-ARs. These findings represent clear support for the use of [11C]ORM-13070 for monitoring drug occupancy of α2C-ARs in the living human brain. Three of the employed noradrenaline challenges were associated with small, approximately 10-16% average reductions in tracer uptake in the dorsal striatum (atomoxetine, ketamine, and the cold pressor test; P < 0.05 for all), but insulin-induced hypoglycemia did not affect tracer uptake. The tracer is suitable for studying central nervous system receptor occupancy by α2C-AR ligands in human subjects. [11C]ORM-13070 also holds potential as a tool for in vivo monitoring of synaptic concentrations of noradrenaline, but this remains to be further evaluated in future studies. Synapse 69:172-181, 2015. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Purpose: The rapid growth and usage of small-animal positron emission tomography (PET) in molecular imaging research has led to increased demand on PET scanner's time. One potential solution to increase throughput is to scan multiple rodents simultaneously. However, this is achieved at the expense of deterioration of image quality and loss of quantitative accuracy owing to enhanced effects of photon attenuation and Compton scattering. The purpose of this work is, first, to characterize the magnitude and spatial distribution of the scatter component in small-animal PET imaging when scanning single and multiple rodents simultaneously and, second, to assess the relevance and evaluate the performance of scatter correction under similar conditions. Methods: The LabPET™-8 scanner was modelled as realistically as possible using Geant4 Application for Tomographic Emission Monte Carlo simulation platform. Monte Carlo simulations allow the separation of unscattered and scattered coincidences and as such enable detailed assessment of the scatter component and its origin. Simple shape-based and more realistic voxel-based phantoms were used to simulate single and multiple PET imaging studies. The modelled scatter component using the single-scatter simulation technique was compared to Monte Carlo simulation results. PET images were also corrected for attenuation and the combined effect of attenuation and scatter on single and multiple small-animal PET imaging evaluated in terms of image quality and quantitative accuracy. Results: A good agreement was observed between calculated and Monte Carlo simulated scatter profiles for single- and multiple-subject imaging. In the LabPET™-8 scanner, the detector covering material (kovar) contributed the maximum amount of scatter events while the scatter contribution due to lead shielding is negligible. The out-of field-of-view (FOV) scatter fraction (SF) is 1.70, 0.76, and 0.11 % for lower energy thresholds of 250, 350, and 400 keV, respectively. The increase in SF ranged between 25 and 64 % when imaging multiple subjects (three to five) of different size simultaneously in comparison to imaging a single subject. The spill-over ratio (SOR) increases with increasing the number of subjects in the FOV. Scatter correction improved the SOR for both water and air cold compartments of single and multiple imaging studies. The recovery coefficients for different body parts of the mouse whole-body and rat whole-body anatomical models were improved for multiple imaging studies following scatter correction. Conclusions: The magnitude and spatial distribution of the scatter component in small-animal PET imaging of single and multiple subjects simultaneously were characterized, and its impact was evaluated in different situations. Scatter correction improves PET image quality and quantitative accuracy for single rat and simultaneous multiple mice and rat imaging studies, whereas its impact is insignificant in single mouse imaging. [ABSTRACT FROM AUTHOR]

Positron emission tomography (PET) has become a standard in staging Head and Neck cancer. While F-fluoro-2-deoxy- d-glucose (FDG) is the most frequently used radiopharmaceutical, glycolysis is not the only metabolic process that can be visualized. Different PET tracers can also be used to visualize other metabolic processes and in this manner, the disadvantages of FDG PET can be avoided. In this review, we describe a comprehensive overview of alternatives to FDG that can be used in identifying head and neck cancer. The potential advantages and disadvantages of these radiopharmaceuticals are discussed. [ABSTRACT FROM AUTHOR]

Purpose: Positron emission tomography (PET) image quality deteriorates as the object size increases owing to increased detection of scattered and random events. The characterization of the scatter component in small animal PET imaging has received little attention owing to the small scatter fraction (SF) when imaging rodents. The purpose of this study is first to design and fabricate a cone-shaped phantom which can be used for measurement of object size-dependent SF and noise equivalent count rates (NECR), and second, to assess these parameters for two small animal PET scanners as function of radial offset, object size and lower energy threshold (LET). Methods: The X-PET™ and LabPET-8™ scanners were modeled as realistically as possible using GATE Monte Carlo simulation platform. The simulation models were validated against experimental measurements in terms of sensitivity, SF and NECR. The dedicated phantom was fabricated in-house using high-density polyethylene. The optimized dimensions of the cone-shaped phantom are 158 mm (length), 20 mm (minimum diameter), 70 mm (maximum diameter) and taper angle of 9°. Results: The relative difference between simulated and experimental results for the LabPET-8™ scanner varied between 0.7% and 10% except for a few results where it was below 16%. Depending on the radial offset from the center of the central axial field-of-view (3-6 cm diameter), the SF for the cone-shaped phantom varied from 26.3% to 18.2%, 18.6 to 13.1% and 10.1 to 7.6% for the X-PET™, whereas it varied from 34.4% to 26.9%, 19.1 to 17.0% and 9.1 to 7.3% for the LabPET-8™, for LETs of 250, 350 and 425 keV, respectively. The SF increases as the radial offset decreases, LET decreases and object size increases. The SF is higher for the LabPET-8™ compared with the X-PET™ scanner. The NECR increases as the radial offset increases and object size decreases. The maximum NECR was obtained at a LET of 350 keV for the LabPET-8™ and 250 keV for the X-PET™. High correlation coefficients for SF and NECR were observed between the cone-shaped phantom and an equivalent volume cylindrical phantom for the three considered axial fields of view. Conclusions: A single cone-shaped phantom enables the assessment of the impact of three factors, namely radial offset, LET and object size on PET SF and count rate estimates. This phantom is more realistic owing to the non-uniform shape of rodents' bodies compared to cylindrical uniform phantoms and seems to be well suited for evaluation of object size-dependent SF and NECR. [ABSTRACT FROM AUTHOR]

PET imaging studies with 4-[F]fluoro-L- m-tyrosine (FMT) in normal macaca monkeys showed selective accumulations of radioactivity in the striatum with time. In monkeys rendered hemiparkinsonian by intracarotid infusion of l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP), FMT uptake was eliminated in the lesioned striatum. FMT-PET studies were able to detect dopaminergic terminals in both normal and hemiparkinsonian monkeys, and clearly showed a reduction in aromatic L-amino acid decarboxylase (AAAD) activities in the MPTP-lesioned striatum. These results show that FMT is promising as a PET tracer for the evaluation of central dopaminergic systems in parkinsonism. [ABSTRACT FROM AUTHOR]