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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]

Introduction: Data acquisition and image reconstruction protocols affect image quality and quantification accuracy in PET imaging. We aimed to standardize and optimize image acquisition, and reconstruction parameter sets using a simultaneous quantitative and qualitative assessment framework for a lutetium oxyorthosilicate (LSO)-based PET/CT scanner. Methods: The NEMA IEC Body Phantom acquisition was performed in list mode for 10 minutes with four spheres to background ratios (SBRs). Raw PET data were reconstructed using 60 different protocols. Image quality was evaluated for standardization using contrast, CNR, and noise. Recovery coefficient (RC) measurements were performed for different common VOI definitions. Results: No significant differences were observed between RCs for various acquisition durations. The contrast to noise ratio (CNR) increased at all SBRs by expanding the acquisition duration from 60 to 600 seconds. PET scan time was reduced to 90 seconds per bed position while preserving image quality. Up to 50% improvement in CNR for the highest sub-iteration with a high level of smoothing was observed. PSF-based reconstruction produced a positive bias of RCmax in high SBRs (8 and 10) using higher sub-iterations (30 to 60) with Gaussian filters less than 6 mm FWHM. Moreover, a Sub-iteration of more than 32 with a 4-6 mm FWHM Gaussian filter provides optimized reconstruction sets. Conclusion: Our study demonstrates it would be feasible for PET image acquisition and reconstruction settings to simultaneously allow optimal lesion detection with high image quality while providing accurate quantification. [ABSTRACT FROM AUTHOR]

Background: Practice effects on cognitive testing in mild cognitive impairment (MCI) and Alzheimer's disease (AD) remain understudied, especially with how they compare to biomarkers of AD. Objective: The current study sought to add to this growing literature. Methods: Cognitively intact older adults (n = 68), those with amnestic MCI (n = 52), and those with mild AD (n = 45) completed a brief battery of cognitive tests at baseline and again after one week, and they also completed a baseline amyloid PET scan, a baseline MRI, and a baseline blood draw to obtain APOE ɛ4 status. Results: The intact participants showed significantly larger baseline cognitive scores and practice effects than the other two groups on overall composite measures. Those with MCI showed significantly larger baseline scores and practice effects than AD participants on the composite. For amyloid deposition, the intact participants had significantly less tracer uptake, whereas MCI and AD participants were comparable. For total hippocampal volumes, all three groups were significantly different in the expected direction (intact > MCI > AD). For APOE ɛ4, the intact had significantly fewer copies of ɛ4 than MCI and AD. The effect sizes of the baseline cognitive scores and practice effects were comparable, and they were significantly larger than effect sizes of biomarkers in 7 of the 9 comparisons. Conclusion: Baseline cognition and short-term practice effects appear to be sensitive markers in late life cognitive disorders, as they separated groups better than commonly-used biomarkers in AD. Further development of baseline cognition and short-term practice effects as tools for clinical diagnosis, prognostic indication, and enrichment of clinical trials seems warranted. [ABSTRACT FROM AUTHOR]

INTRODUCTION: The standardized uptake value ratio (SUVR) is used to measure amyloid beta–positron emission tomography (Aβ‐PET) uptake in the brainDifferences in PET scanner technologies and image reconstruction techniques can lead to variability in PET images across scanners. This poses a challenge for Aβ‐PET studies conducted in multiple centers. The aim of harmonization is to achieve consistent Aβ‐PET measurements across different scanners. In this study, we propose an Aβ‐PET harmonization method of matching spatial resolution, as measured via a barrel phantom, across PET scanners. Our approach was validated using paired subject data, for which patients were imaged on multiple scanners. METHODS: In this study, three different PET scanners were evaluated: the Siemens Biograph Vision 600, Siemens Biograph molecular computed tomography (mCT), and Philips Gemini TF64. A total of five, eight, and five subjects were each scanned twice with [18F]‐NAV4694 across Vision‐mCT, mCT‐Philips, and Vision‐Philips scanner pairs. The Vision and mCT scans were reconstructed using various iterations, subsets, and post‐reconstruction Gaussian smoothing, whereas only one reconstruction configuration was used for the Philips scans. The full‐width at half‐maximum (FWHM) of each reconstruction configuration was calculated using [18F]‐filled barrel phantom scans with the Society of Nuclear Medicine and Molecular Imaging (SNMMI) phantom analysis toolkit. Regional SUVRs were calculated from 72 brain regions using the automated anatomical labelling atlas 3 (AAL3) atlas for each subject and reconstruction configuration. Statistical similarity between SUVRs was assessed using paired (within subject) t‐tests for each pair of reconstructions across scanners; the higher the p‐value, the greater the similarity between the SUVRs. RESULTS: Vision‐mCT harmonization: Vision reconstruction with FWHM = 4.10 mm and mCT reconstruction with FWHM = 4.30 mm gave the maximal statistical similarity (maximum p‐value) between regional SUVRs. Philips‐mCT harmonization: The FWHM of the Philips reconstruction was 8.2 mm and the mCT reconstruction with the FWHM of 9.35 mm, which gave the maximal statistical similarity between regional SUVRs. Philips–Vision harmonization: The Vision reconstruction with an FWHM of 9.1 mm gave the maximal statistical similarity between regional SUVRs when compared with the Philips reconstruction of 8.2 mm and were selected as the harmonized for each scanner pair. CONCLUSION: Based on data obtained from three sets of participants, each scanned on a pair of PET scanners, it has been verified that using reconstruction configurations that produce matched‐barrel, phantom spatial resolutions results in maximally harmonized Aβ‐PET quantitation between scanner pairs. This finding is encouraging for the use of PET scanners in multi‐center trials or updates during longitudinal studies. Highlights: Question: Does the process of matching the barrel phantom‐derived spatial resolution between scanners harmonize amyloid beta–standardized uptake value ratio (Aβ‐SUVR) quantitation?Pertinent findings: It has been validated that reconstruction pairs with matched barrel phantom‐derived spatial resolution maximize the similarity between subjects paired Aβ‐PET (positron emission tomography) SUVR values recorded on two scanners.Implications for patient care: Harmonization between scanners in multi‐center trials and PET camera updates in longitudinal studies can be achieved using a simple and efficient phantom measurement procedure, beneficial for the validity of Aβ‐PET quantitation measurements. [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]

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]

Background: The Quick Dementia Rating System (QDRS) is a brief, informant-reported dementia staging tool that approximates scores on the Clinical Dementia Rating Scale in patients with Alzheimer's disease (AD). Objective: The current study sought to examine change in the QDRS across time, which is necessary for clinical and research efforts. Methods: One-hundred ten older adults (intact, mild cognitive impairment [MCI], mild AD, classified with Alzheimer's Disease Neuroimaging Initiative criteria) were rated on the QDRS by an informant and had an amyloid positron emission tomography scan at baseline. The informant re-rated each participant on the QDRS after one year. Dependent t-tests compared the entire sample and various subgroups (e.g., cognitive status, amyloid status) on baseline and follow-up QDRS scores. Results: In the entire sample, the Total score on the QDRS significantly increased (i.e., worsened) on follow-up (p < 0.001). When subgroups were analyzed, the MCI and mild AD subjects showed increasing (i.e., worsening) QDRS Total scores (both p < 0.001), but the intact subjects remained stable over time (p = 0.28). Additionally, those classified as being amyloid positive at baseline showed significantly increased QDRS Total scores at follow-up (p < 0.001) compared to those who were amyloid negative at baseline, whose QDRS Total scores remained stable over time (p = 0.63). Conclusion: The QDRS can potentially demonstrate worsening functioning status across one year, especially in those who have MCI or mild AD and those who are amyloid positive. Therefore, the current results preliminarily suggest that the QDRS may provide an efficient tool for tracking progression in clinical trials in AD. [ABSTRACT FROM AUTHOR]

Purpose: The main goal of this work is to describe a phantom design, data acquisition and data analysis methodology enabling comparison of small lesion detectability between PET imaging systems and reconstruction algorithms. Several methods are currently available to characterize intrinsic and image quality performance, but none focus exclusively on small lesion detectability. Methods: We previously developed a small‐lesion detection phantom and described initial results using a head‐size phantom. Unlike most fillable nuclear medicine phantoms, this phantom offers a semi‐realistic heterogenous background and wall‐less contrast features. In this work, the methodology is extended to include (a) the use of both head‐ and body‐sized phantoms and (b) a multi‐scan data collection and analysis method. We present an example use case of the phantom and detection estimation methodology, comparing the small‐lesion detection performance across four commercial PET/CT systems. Results: Repeat acquisitions of the phantom enabled estimation of model observer performance and surrogates of detectability. As anticipated, estimated detectability increased with the square root of system sensitivity and TOF offered marked improvement in detectability, especially for the body sized object. The proposed approach characterizing detectability at different times during the decay of the phantom enabled comparison of small lesion detectability at matched activity concentrations (and scan durations) across different scanners. Conclusion: The proposed approach offers a reproducible tool for evaluating relative tradeoffs of system performance on small lesion detectability. [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]

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]

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]

Introduction: Recently, the American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) staging system was updated for its 8th edition. F-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) is a useful imaging tool to diagnose and predict prognoses for esophageal cancer. However, there was no previous study to explore the role of FDG PET/CT in the staging system based on the 8th edition. The prognostic value of FDG PET/CT was investigated in patients with esophageal squamous cell carcinoma (SqCC) considering the new 8th AJCC/UICC staging system. Methods: Subjects were 721 patients with esophageal SqCC undergoing pretherapeutic FDG PET/CT. Clinico-pathological variables and the maximum standardized uptake value (SUVmax) of the primary tumor were included in survival analysis. Subgroup analysis was performed to compare hazard ratios according to pathological stage and SUVmax. A new staging classification including FDG uptake was proposed. Results: In multivariate survival analysis, pathological stage and SUVmax of the primary tumor were selected as independent prognostic factors for overall survival in both the 7th and 8th editions. The proposed new staging system showed better discrimination for overall survival between stage I and II than did the conventional staging system (hazard ratios: 2.250 vs. 1.341). Conclusions: The FDG uptake of the primary tumor was found to be an independent prognostic factor along with pathological stage based on both 7th and 8th AJCC/UICC staging systems in patients with esophageal SqCC. The suggested new staging system including SUVmax was better for predicting prognoses than the conventional staging system. [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]

Introduction: The Quick Dementia Rating System (QDRS) is a brief, patient-reported dementia staging tool that has approximated scores on the Clinical Dementia Rating Scale in patients with Alzheimer's disease (AD). However, no studies have examined its relationship with AD-related biomarkers. Methods: One-hundred twenty-one older adults (intact, amnestic mild cognitive impairment, mild AD) completed the QDRS, and three biomarkers (amyloid deposition via positron emission tomography, hippocampal volume via magnetic resonance imaging, and apolipoprotein [APOE] ε4 status). Results: The Total score on the QDRS was statistically significantly related to all three biomarkers (after controlling for age, education, sex, and race), with greater levels of dementia severity being associated with greater amyloid deposition, smaller hippocampi, and having copies of APOE ε4 allele. Discussion: In participants across the cognitive spectrum, the QDRS showed modest relationships with amyloid deposition, hippocampal volumes, and APOE status. Therefore, the QDRS may offer a cost-effective screening method for clinical trials in AD. [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]

Cortical amyloid deposition is one of the hallmark biomarkers of Alzheimer's disease (AD). However, given how cost- and timeintensive amyloid imaging can be, there is a continued need for a low-cost, non-invasive, and accessible enrichment strategy to pre-screen individuals for their likelihood of amyloid prior to imaging. Previous work supports the use of coordinated limb movement as a potential screening tool, even after controlling for cognitive and daily function. Thirty-six patients diagnosed with amnestic mild cognitive impairment over the age of 65 underwent 18F-Flutemetamol amyloid-positron emission tomography (PET) imaging and then completed a timed motor task involving upper limb coordination. This task takes ∼5 minutes to administer and score. Multivariate linear regression and receiver operator characteristic analyses showed that including motor task performance improved model prediction of amyloid burden. Results support the rationale for including functional upper extremity motor assessment as a cost- and time-effective means to screen participants for amyloid deposition. [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]

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]

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]

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]

Quantitative imaging biomarkers (QIBs) provide medical image-derived intensity, texture, shape, and size features that may help characterize cancerous tumors and predict clinical outcomes. Successful clinical translation of QIBs depends on the robustness of their measurements. Biomarkers derived from positron emission tomography images are prone to measurement errors owing to differences in image processing factors such as the tumor segmentation method used to define volumes of interest over which to calculate QIBs. We illustrate a new Bayesian statistical approach to characterize the robustness of QIBs to different processing factors. Study data consist of 22 QIBs measured on 47 head and neck tumors in 10 positron emission tomography/computed tomography scans segmented manually and with semiautomated methods used by 7 institutional members of the NCI Quantitative Imaging Network. QIB performance is estimated and compared across institutions with respect to measurement errors and power to recover statistical associations with clinical outcomes. Analysis findings summarize the performance impact of different segmentation methods used by Quantitative Imaging Network members. Robustness of some advanced biomarkers was found to be similar to conventional markers, such as maximum standardized uptake value. Such similarities support current pursuits to better characterize disease and predict outcomes by developing QIBs that use more imaging information and are robust to different processing factors. Nevertheless, to ensure reproducibility of QIB measurements and measures of association with clinical outcomes, errors owing to segmentation methods need to be reduced. [ABSTRACT FROM AUTHOR]

The National Cancer Institute's Quantitative Imaging Network (QIN) has thrived over the past 12 years with an emphasis on the development of image-based decision support software tools for improving measurements of imaging metrics. An overarching goal has been to develop advanced tools that could be translated into clinical trials to provide for improved prediction of response to therapeutic interventions. This article provides an overview of the successes in development and translation of new algorithms into the clinical workflow by the many research teams of the Quantitative Imaging Network. [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]

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]

Objective: Clinical joint count assessment is important for detecting synovitis but its reliability is a subject of controversy. This study was undertaken to assess the correlation of positron emission tomography (PET)–derived parameters in 68 joints with disease activity and to compare the reliability of joint counts between PET with computed tomography (CT) and clinical assessment in patients with rheumatoid arthritis (RA). Methods: We enrolled 91 patients with active RA (69 in a development group and 22 in a validation group) who underwent concurrent 18F‐fluorodeoxyglucose (18F‐FDG)–PET‐CT and clinical disease activity evaluation. PET‐derived parameters were compared with disease activity assessed using clinical joint count parameters. A Disease Activity Score (DAS) using counts of PET‐positive joints was developed, and then validation studies were performed in an independent group. Results: The number of PET‐positive joints (of 28 and 68 joints) was significantly correlated with the swollen joint count (SJC) and tender joint count (TJC) and the DAS in 28 joints using the erythrocyte sedimentation rate (DAS28‐ESR). Intraobserver and interobserver reliability of PET for the affected joint counts were excellent. Interobserver reliability between nuclear medicine physicians and rheumatologists was good for the SJC and TJC in both 28 joints and 68 joints. After multivariate analyses, including ESR and patient's global assessment of disease activity (PtGA) in addition to PET‐derived parameters, the PET/DAS was derived as (0.063 × number of PET‐positive joints in 28 joints) + (0.011 × ESR) + (0.030 × PtGA). A significant correlation between the PET/DAS and the DAS28‐ESR was confirmed in the validation group (P < 0.001). Conclusion: PET‐CT could serve as a sensitive and reliable method in the evaluation of disease activity in RA patients, and may be applicable as a research tool, particularly in clinical trials. [ABSTRACT FROM AUTHOR]

Purpose: The concrete vault, cyclotron body, and peripheral equipment in a cyclotron room become radioactivated by neutrons generated by operating an unshielded cyclotron. Radionuclides and the amounts of radioactivated materials must be identified before discarding a cyclotron system. The present study aimed to reduce the amounts of concrete from cyclotron vaults, as well as cyclotron components and peripheral equipment, that will be disposed of as radioactivated waste by clarifying the nature and quantity of radioactivated materials remaining in facilities after cyclotron operations have ceased. Methods: Cylindrical concrete cores were bored into all four walls, ceiling, and floor of a room where a Cypris 370 cyclotron had been operated for 22.8 yr and then cooled for 40 months. The accelerated particles comprised protons and deuterons with constant energy of 18 and 10 MeV, respectively. The types and amounts of radionuclides in these cores, in 38 components of the cyclotron including the yoke, and in 13 pieces of equipment in the room, were determined by γ‐ray spectrometry. Concentrations of radioactivity were also calculated using an updated version of Particle and Heavy Ion Transport System and DCHAIN‐SP. Amounts of materials with both measured and calculated total radioactivity concentration (ΣD) of <0.1 Bq/g were identified as being nonradioactivated. Results: The major radionuclides in the concrete were 60Co and 152Eu. The radioactivated concrete was distributed to a depth of <38 cm. Most cyclotron components and equipment were radioactivated by neutrons. The major radionuclides in cyclotron components and equipment were 54Mn, 60Co, and 65Zn. A 33% volume of the yoke was regarded as nonradioactivated. Conclusions: The estimated amount of radioactivated waste in the concrete was about 70,000 kg (12.5% of the total concrete). Most components of the cyclotron except for the 33% volume of the yoke (20% of the cyclotron body), as well as most peripheral equipment in the room, were radioactivated. Part‐by‐part assessments of radioactive materials using measurements and calculations could distinguish nonradioactive from radioactive materials before they are discarded. [ABSTRACT FROM AUTHOR]

Purpose: Near-infrared spectroscopy (NIRS) has recently been proposed as an indirect technique to assess brown adipose tissue (BAT) in young men. NIRS arises as a novel technique to avoid the limitations of the "gold-standard" 2-deoxy-2-[18F]fluoro-D-glucose ([18F]DG) positron emission tomography combined with X-ray computed tomography (PET/CT). The aim of this study was to examine the association between near-infrared spatially resolved spectroscopy (NIRSRS) parameters and BAT volume and activity estimated by [18F]DG-PET/CT in 18 young healthy women.Procedures: NIRSRS parameters [tissue saturation index and concentrations of total haemoglobin, oxy-haemoglobin, and deoxy-haemoglobin] were continuously measured in the supraclavicular and forearm regions, in both warm and cold (2 h of personalised cold exposure) conditions. Then, the NIRSRS data were analysed as an average of 5 min in 4 different periods: (i) warm period as the baseline record, (ii) cold period I, (iii) cold period II, and (iv) cold period III. The data were then correlated with BAT volume and activity (SUVmean and SUVpeak) estimated by [18F]DG-PET/CT.Results: There was no association between the NIRSRS parameters in the supraclavicular region in warm conditions (no previous cold exposure) and BAT volume and activity (P > 0.05). Similarly, the cold-induced changes of the NIRSRS parameters in the supraclavicular region were not associated with BAT volume and activity (P > 0.05).Conclusions: NIRSRS does not seem to be a valid technique to indirectly assess BAT in young healthy women. Further research is needed to validate this technique against other methods such as PET/CT using different radiotracers or magnetic resonance imaging. [ABSTRACT FROM AUTHOR]

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Purpose: We evaluated the feasibility of dynamic stress 201Tl/rest 99mTc-tetrofosmin SPECT imaging using a cardiac camera equipped with cadmium-zinc-telluride detectors for the quantification of myocardial perfusion reserve (MPR).Methods: Subjects with stable known or suspected coronary artery disease (CAD) who had undergone or were scheduled to undergo fractional flow reserve (FFR) measurement were prospectively enrolled. Dynamic stress 201Tl/rest 99mTc-tetrofosmin SPECT imaging was performed using a dedicated multiple pinhole SPECT camera with cadmium-zinc-telluride detectors. MPR was derived using Corridor4DM software.Results: A total of 34 subjects were enrolled (25 men and 9 women; mean age 60.4 years). FFR was measured in 65 coronary arteries with intermediate lesions. The average global MPR was 2.58 ± 1.03. Global MPR was associated with the extent of CAD (P = 0.028) and global summed stress score (r = −0.60, P < 0.001). Regional MPR showed a significant correlation with diameter stenosis (r = −0.57, P < 0.001), minimum lumen diameter (r = 0.50, P < 0.001), summed stress score (r = −0.52, P < 0.001) and FFR (r = 0.52, P < 0.001). The area under the receiver operating characteristic curve of MPR for the diagnosis of functionally significant stenosis (FFR ≤0.8) was 0.79 (P < 0.001). The sensitivity and specificity of regional MPR were 67% and 83%, respectively, using a cut-off value of 2.0.Conclusion: Dynamic stress 201Tl/rest 99mTc-tetrofosmin SPECT imaging and quantification of MPR is feasible in patients with stable CAD. The preliminary results of this study in a small number of patients require confirmation in a larger cohort to determine their implications for bolstering the role of SPECT imaging in the diagnosis and risk prediction of CAD. [ABSTRACT FROM AUTHOR]

Purpose: Oncogenic osteomalacia is an endocrine disorder induced by small benign tumours (TIO) producing excessive fibroblast growth factor-23 (FGF23). The only way of curing oncogenic osteomalacia is surgical resection of the culprit TIO, which is extremely difficult to detect using conventional imaging modalities due to its small size and variable location in the body. Since TIO frequently overexpress somatostatin receptors, a clinical utility of SPECT or PET with radiolabelled somatostatin analogues has been reported. Among them, 68Ga-DOTA-TOC has recently been granted a marketing authorization, facilitating its routine application. We report here the results of the first series evaluating the diagnostic performance of 68Ga-DOTA-TOC PET/CT in detecting TIO and its impact on patient management.Methods: 68Ga-DOTA-TOC PET/CT and clinical and imaging data from 15 patients with clinical and biochemical signs of oncogenic osteomalacia were retrospectively reviewed. The 68Ga-DOTA-TOC PET/CT findings were compared with the results of post-surgical pathology and clinical and biochemical follow-up.Results: 68Ga-DOTA-TOC PET/CT resulted in the detection of one focus suspicious for TIO in nine of 15 patients (60%), and a tumour was surgically removed in eight. Post-operative pathology confirmed a TIO in those eight patients whose symptoms diminished promptly and biochemical anomalies resolved. 68Ga-DOTA-TOC PET/CT sensitivity, specificity and accuracy were 73%, 67% and 71%, respectively. 68Ga-DOTA-TOC PET/CT findings affected patient management in 67% of cases. In particular, 68Ga-DOTA-TOC PET/CT was able to detect the TIO with a negative or a false-positive result of a previous 111In-pentetreotide SPECT/CT in 5/8 patients (63%) or a previous FDG PET/CT in 7/11 patients (64%). No close relationship was found between the positivity of 68Ga-DOTA-TOC PET/CT and the serum level of a biochemical marker. However, a true-positive result of 68Ga-DOTA-TOC PET/CT was obtained in only one patient with a non-elevated serum level of FGF23.Conclusion: 68Ga-DOTA-TOC PET/CT is an accurate imaging modality in the detection of TIO; in particular, it is worthwhile after failure of somatostatin receptor SPECT(/CT) or FDG PET/CT. [ABSTRACT FROM AUTHOR]

Summary: Context: The 68Ga‐labelled somatostatin analogues (68Ga‐DOTA‐SSAs) is becoming popular as an important diagnostic tool in neuroendocrine tumours as evidenced by a growing number of reports detailing institutional experience with various DOTA peptides. However, only few prospective studies have compared 68Ga‐DOTA‐SSAs and somatostatin receptor scintigraphy (SRS) in gastroenteropancreatic neuroendocrine tumours (GEP‐NETs) and pulmonary neuroendocrine tumours. Objective: The aim of our prospective study was to perform head‐to‐head comparison between 68 Ga‐DOTATATE PET/CT and standard imaging work‐up (SI) that included multiphasic CT, liver MRI and SRS using single photon emission computed tomography. Design: In this prospective study, the patients were enrolled only if they met any of the following inclusion criteria: (i) initial staging of a NETs without distant metastases on SI or neuroendocrine tumour with unknown primary on SI; (ii) restaging of NETs that could be treated by focused therapeutic interventions; (iii) elevated serum neuroendocrine hormones or peptides. The exclusion criteria was grade 3 GEP‐NETs. Results: Thirty‐two patients were enrolled in the study. Eleven patients (6 pancreas, 4 ileum, 1 duodenal) were included for initial evaluation and staging of NETs, 8 patients (5 pancreas, 1 ileal, 1 lung, 1 duodenal gastrinoma) for restaging, and 13 patients for elevated serum neuroendocrine biomarkers (5 ectopic Cushing's syndrome, 5 organic hypoglycaemia, 1 patient each with elevated vasoactive inhibitory peptide, chromogranin A and neuron‐specific enolase). 68Ga‐DOTATATE PET/CT detected more primary tumours than SRS (15/18 vs 10/18: P = .074). The missed tumours on 68Ga‐DOTATATE PET/CT were located in the lung in two cases and duodenum in one case. For other anatomical regions (nodal and distant metastasis), no statistical difference was observed between imaging modalities using 68Ga‐DOTATATE PET/CT and SRS. Overall, 68Ga‐DOTATATE PET/CT+CT+MRI detected 31/33 of the involved regions (including primaries) (29 and 22 for 68Ga‐DOTATATE and SRS, respectively). Conclusion: Our study shows that 68Ga‐DOTATATE PET/CT detected similar number of sites than combination of SRS, liver MRI and thoraco‐abdominopelvic CT on region‐based analysis. 68Ga‐DOTATATE PET/CT missed half of primary lung carcinoids with ectopic Cushing's syndrome. [ABSTRACT FROM AUTHOR]

Purpose: The objective of this study was to explore the feasibility of harmonising performance for PET/CT systems equipped with time-of-flight (ToF) and resolution modelling/point spread function (PSF) technologies. A second aim was producing a working prototype of new harmonising criteria with higher contrast recoveries than current EARL standards using various SUV metrics.Methods: Four PET/CT systems with both ToF and PSF capabilities from three major vendors were used to acquire and reconstruct images of the NEMA NU2-2007 body phantom filled conforming EANM EARL guidelines. A total of 15 reconstruction parameter sets of varying pixel size, post filtering and reconstruction type, with three different acquisition durations were used to compare the quantitative performance of the systems. A target range for recovery curves was established such that it would accommodate the highest matching recoveries from all investigated systems. These updated criteria were validated on 18 additional scanners from 16 sites in order to demonstrate the scanners’ ability to meet the new target range.Results: Each of the four systems was found to be capable of producing harmonising reconstructions with similar recovery curves. The five reconstruction parameter sets producing harmonising results significantly increased SUVmean (25%) and SUVmax (26%) contrast recoveries compared with current EARL specifications. Additional prospective validation performed on 18 scanners from 16 EARL accredited sites demonstrated the feasibility of updated harmonising specifications. SUVpeak was found to significantly reduce the variability in quantitative results while producing lower recoveries in smaller (≤17 mm diameter) sphere sizes.Conclusions: Harmonising PET/CT systems with ToF and PSF technologies from different vendors was found to be feasible. The harmonisation of such systems would require an update to the current multicentre accreditation program EARL in order to accommodate higher recoveries. SUVpeak should be further investigated as a noise resistant alternative quantitative metric to SUVmax. [ABSTRACT FROM AUTHOR]

Purpose: From 2010 until July 2016, the EANM Research Ltd. (EARL) FDG-PET/CT accreditation program has collected over 2500 phantom datasets from approximately 200 systems and 150 imaging sites worldwide. The objective of this study is to report the findings and impact of the accreditation program on the participating PET/CT systems. Methods: To obtain and maintain EARL accredited status, sites were required to complete and submit two phantom scans - calibration quality control (CalQC), using a uniform cylindrical phantom and image quality control (IQQC), using a NEMA NU2-2007 body phantom. Average volumetric SUV bias and SUV recovery coefficients (RC) were calculated and the data evaluated on the basis of quality control (QC) type, approval status, PET/CT system manufacturer and submission order. Results: SUV bias in 5% ( n = 96) of all CalQC submissions ( n = 1816) exceeded 10%. After corrective actions following EARL feedback, sites achieved 100% compliance within EARL specifications. 30% ( n = 1381) of SUVmean and 23% ( n = 1095) of SUVmax sphere recoveries from IQQC submissions failed to meet EARL accreditation criteria while after accreditation, failure rate decreased to 12% ( n = 360) and 9% ( n = 254), respectively. Most systems demonstrated longitudinal SUV bias reproducibility within ±5%, while RC values remained stable and generally within ±10% for the four largest and ±20% for the two smallest spheres. Conclusions: Regardless of manufacturer or model, all investigated systems are able to comply with the EARL specifications. Within the EARL accreditation program, gross PET/CT calibration errors are successfully identified and longitudinal variability in PET/CT performances reduced. The program demonstrates that a harmonising accreditation procedure is feasible and achievable. [ABSTRACT FROM AUTHOR]

Standardized uptake values (SUVs) are the most widely used quantitative imaging biomarkers in PET. It is important to evaluate the variability and repeatability of measured SUVs. Phantom studies seem to be essential for this purpose; however, repetitive phantom scanning is not recommended due to the decay of radioactivity. In this study, we performed count-based image reconstruction to avoid the influence of decay using two different PET/CT scanners. By adjusting the ratio of 18F-fluorodeoxyglucose solution to tap water, a NEMA IEC body phantom was set for SUVs of 4.0 inside six hot spheres. The PET data were obtained using two scanners (Aquiduo and Celesteion; Toshiba Medical Systems, Tochigi, Japan). We set the start time for image reconstruction when the total radioactivity in the phantom was 2.53 kBq/cc, and employed the counts of the first 2-min acquisition as the standard. To maintain the number of counts for each image, we set the acquisition time for image reconstruction depending on the decay of radioactivity. We obtained 50 images, and calculated the SUVmax and SUVpeak of all six spheres in each image. The average values of the SUVmax were used to calculate the recovery coefficients to compare those measured by the two different scanners. Bland-Altman analyses of the SUVs measured by the two scanners were also performed. The measured SUVs using the two scanners exhibited a 10–30% difference, and the standard deviation (SD) of the measured SUVs was between 0.1–0.2. The Celesteion always exhibited higher values than the Aquiduo. The smaller sphere exhibited a larger SD, and the SUVpeak had a smaller SD than the SUVmax. The Bland-Altman analyses showed poor agreement between the SUVs measured by the two scanners. The recovery coefficient curves obtained from the two scanners were considerably different. The Celesteion exhibited higher recovery coefficients than the Aquiduo, especially at approximately 20-mm-diameter. Additionally, the curves were lower than those calculated from the standard 30-min acquisition images. We propound count-based image reconstruction to evaluate the variability and repeatability of measured SUVs. These results are also applicable for the standardization and harmonization of SUVs in multi-institutional studies. [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]

Disordered postprandial metabolism of energy substrates is one of the main defining features of prediabetes and contributes to the development of several chronic diseases associated with obesity, such as type 2 diabetes and cardiovascular diseases. Postprandial energy metabolism has been studied using classical isotopic tracer approaches that are limited by poor access to splanchnic metabolism and highly dynamic and complex exchanges of energy substrates involving multiple organs and systems. Advances in noninvasive molecular imaging modalities, such as PET and MRI/magnetic resonance spectroscopy (MRS), have recently allowed important advances in our understanding of postprandial energy metabolism in humans. The present review describes some of these recent advances, with particular focus on glucose and fatty acid metabolism in the postprandial state, and discusses current gaps in knowledge and new perspectives of application of PET and MRI/MRS for the investigation and treatment of human metabolic diseases. [ABSTRACT FROM AUTHOR]

Objective(s): The aim of this study is to examine the effect of different smoothing filters on the image quality and SUVmax to achieve the guideline recommended positron emission tomography (PET) image without harmonization. Methods: We used a Biograph mCT PET scanner. A National Electrical Manufacturers Association (NEMA) the International Electrotechnical Commission (IEC) body phantom was filled with 18F solution with a background activity of 2.65 kBq/mL and a sphere-to-background ratio of 4. PET images obtained with the Biograph mCT PET scanner were reconstructed using the ordered subsets-expectation maximization (OSEM) algorithm with time-of-flight (TOF) models (iteration, 2; subset, 21); smoothing filters including the Gaussian, Butterworth, Hamming, Hann, Parzen, and Shepp-Logan filters with various full width at half maximum (FWHM) values (1-15 mm) were applied. The image quality was physically assessed according to the percent contrast (QH,10), background variability (N10), standardized uptake value (SUV), and recovery coefficient (RC). The results were compared with the guideline recommended range proposed by the Japanese Society of Nuclear Medicine and the Japanese Society of Nuclear Medicine Technology. The PET digital phantom was developed from the digital reference object (DRO) of the NEMA IEC body phantom smoothed using a Gaussian filter with a 10-mm FWHM and defined as the reference image. The difference in the SUV between the PET image and the reference image was evaluated according to the root mean squared error (RMSE). Results: The FWHMs of the Gaussian, Butterworth, Hamming, Hann, Parzen, and Shepp-Logan filters that satisfied the image quality of the FDG-PET/CT standardization guideline criteria were 8-12 mm, 9-11 mm, 9-13 mm, 10-13 mm, 9-11 mm, and 12- 15 mm, respectively. The FWHMs of the Gaussian, Butterworth, Hamming, Hann, Parzen, and Shepp-Logan filters that provided the smallest RMSE between the PET images and the 3D digital phantom were 7 mm, 8 mm, 8 mm, 8 mm, 7 mm, and 11 mm, respectively. Conclusion: The suitable FWHM for image quality or SUVmax depends on the type of smoothing filter that is applied. [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]

To date, there is no published detailed checklist with parameters referencing the DICOM tag information with respect to the quality control (QC) of PET/CT scans. The aims of these guidelines are to provide the know-how for effectively controlling the quality of PET/CT scans in multicenter studies, to standardize the QC, to give sponsors and regulatory agencies a basis for justification of the data quality when using standardized uptake values as an imaging biomarker, to document the compliance with the imaging guidelines, to verify the per protocol population versus intent to treat population, and to safeguard the validity of multicenter study conclusions employing standardized uptake value (SUV) as an imaging biomarker which is paramount to the scientific community. Following the proposed guidelines will ensure standardized prospective imaging QC of scans applicable to most studies where SUVs are used as an imaging biomarker. The multitude of factors affecting SUV measurements when not controlled inflicts noise on the data. Decisions on patient management with substantial noise would be devastating to patients, ultimately undermine treatment outcome, and invalidate the utility of SUV as an imaging biomarker usefulness. Strict control of the data quality used for the validation of SUV as an imaging biomarker would ensure trust and reliability of the data. [ABSTRACT FROM AUTHOR]

Quantitative positron emission tomography/computed tomography (PET/CT) can be used as diagnostic or prognostic tools (i.e. single measurement) or for therapy monitoring (i.e. longitudinal studies) in multicentre studies. Use of quantitative parameters, such as standardized uptake values (SUVs), metabolic active tumor volumes (MATVs) or total lesion glycolysis (TLG), in a multicenter setting requires that these parameters be comparable among patients and sites, regardless of the PET/CT system used. This review describes the motivations and the methodologies for quantitative PET/CT performance harmonization with emphasis on the EANM Research Ltd. (EARL) Fluorodeoxyglucose (FDG) PET/CT accreditation program, one of the international harmonization programs aiming at using FDG PET as a quantitative imaging biomarker. In addition, future accreditation initiatives will be discussed. The validation of the EARL accreditation program to harmonize SUVs and MATVs is described in a wide range of tumor types, with focus on therapy assessment using either the European Organization for Research and Treatment of Cancer (EORTC) criteria or PET Evaluation Response Criteria in Solid Tumors (PERCIST), as well as liver-based scales such as the Deauville score. Finally, also presented in this paper are the results from a survey across 51 EARL-accredited centers reporting how the program was implemented and its impact on daily routine and in clinical trials, harmonization of new metrics such as MATV and heterogeneity features. [ABSTRACT FROM AUTHOR]

PET using F-FDG for treatment monitoring in patients with lymphoma is one of the most well-developed clinical applications. PET/CT is nowadays used during treatment to assess chemosensitivity, with response-adapted therapy given according to 'interim' PET in clinical practice to adults and children with Hodgkin lymphoma. PET is also used to assess remission from disease and to predict prognosis in the pretransplant setting. Mature data have been reported for the common subtypes of aggressive B-cell lymphomas, with more recent data also supporting the use of PET for response assessment in T-cell lymphomas. The Deauville five-point scale incorporating the Deauville criteria (DC) is recommended for response assessment in international guidelines. FDG uptake is graded in relation to the reference regions of normal mediastinum and liver. The DC have been validated in most lymphoma subtypes. The DC permit the threshold for adequate or inadequate response to be adapted according to the clinical context or research question. It is important for PET readers to understand how the DC have been applied in response-adapted trials for correct interpretation and discussion with the multidisciplinary team. Quantitative methods to perform PET in standardized ways have also been developed which may further improve response assessment including a quantitative extension to the DC (qPET). This may have advantages in providing a continuous scale to refine the threshold for adequate/inadequate response in specific clinical situations or treatment optimization in trials. qPET is also less observer-dependent and limits the problem of optical misinterpretation due to the influence of background activity. [ABSTRACT FROM AUTHOR]

Purpose To improve the precision of multicenter clinical trials, several efforts are underway to determine scanner-specific parameters for harmonization using standardized phantom measurements. The goal of this study was to test the correspondence between quantification in phantom and patient images and validate the use of phantoms for harmonization of patient images. Methods The National Electrical Manufacturers' Association image quality phantom with hot spheres was scanned on two time-of-flight PET scanners. Whole-body [18F]-fluorodeoxyglucose (FDG)-PET scans were acquired of subjects on the same systems. List-mode events from spheres (diam.: 10-28 mm) measured in air on each scanner were embedded into the phantom and subject list-mode data from each scanner to create lesions with known uptake with respect to the local background in the phantom and each subject's liver and lung regions, as a proxy to characterize true lesion quantification. Images were analyzed using the contrast recovery coefficient ( CRC) typically used in phantom studies and serving as a surrogate for the standardized uptake value used clinically. Postreconstruction filtering (resolution recovery and Gaussian smoothing) was applied to determine if the effect on the phantom images translates equivalently to subject images. Three postfiltering strategies were selected to harmonize the CRC mean or CRC max values between the two scanners based on the phantom measurements and then applied to the subject images. Results Both the average CRC mean and CRC max values for lesions embedded in the lung and liver in four subjects (BMI range 25-38) agreed to within 5% with the CRC values for lesions embedded in the phantom for all lesion sizes. In addition, the relative changes in CRC mean and CRC max resulting from the application of the postfilters on the subject and phantom images were consistent within measurement uncertainty. Further, the root mean squared percent difference ( RMS pd) between CRC values on the two scanners calculated over the three sphere sizes was significantly reduced in the subjects using postfiltering strategies chosen to harmonize CRC mean or CRC max based on phantom measurements: RMS pd of the CRC mean values in subjects was reduced from 36% to < 8% after harmonizing CRC mean, while RMS pd for CRC max was reduced from ~33% to < 6% after harmonizing CRC max with a different strategy. However, with this strategy designed to harmonize CRC max, the RMS pd for CRC mean only improved to ~14% in subjects. Conclusions The consistency of the CRC measurements between the phantom and subject data demonstrates that harmonization strategies defined with phantom studies track well to patient images. However, quantitative agreement between different scanners as represented by the RMS pd depends on the metric chosen for harmonization. [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]