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Purpose: The potential limitations of hepatic [ 18 F]FDG-PET imaging for individuals with obesity and excessive liver fat (NAFLD) are being investigated. In this study, we aim to determine the reliability of standardized uptake values (SUVs) focusing on adjustment for liver fat content (LFC) derived from DIXON images and the effects of whole-body normalizations., Methods: Lean and with obesity volunteers who underwent [ 18 F]FDG-PET/MRI were reviewed retrospectively. DIXON fat images were used to determine LFC and for adjustment of SUV mean . The hepatic SUVs (mean, fat adjusted mean and max) were normalized to body weight, lean body mass and body surface area. Blood samples were analysed for glucose, serological liver enzymes and lipoproteins for further correlation of [ 18 F]FDG uptake., Results: Out of 11 volunteers with obesity (M:8, F:3, BMI:30-39 kg/m 2 ), 9 confirmed the presence of NAFLD (>5.6 % fat). 22 age-matched lean volunteers (M:10, F:11, BMI:19-26 kg/m 2 ) were used as control group. Both SUV mean , before and after adjustment to LFC, did not provide any difference between lean and with obesity groups under BW, LBM and BSA. SUV max BW showed a difference between groups (p = 0.05). SUVs were independent of levels of GPT, GOT, gGT, insulin, HOMA-IR, triglycerides, cholesterol and LDL. Volunteers with low HDL were clustered with an increased hepatic [ 18 F]FDG uptake., Conclusion: Our method for adjustment of hepatic [ 18 F]FDG-PET with DIXON fat images allows to achieve accurate results for individuals with NAFLD and obesity. For homogenic results, raw SUV mean should be combined with adjustment for liver fat, appropriate normalization and consideration of HDL levels., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: Multidrug resistance-associated protein 1 (MRP1) is a transport protein with a widespread tissue distribution, which has been implicated in the pathophysiology of Alzheimer's and chronic respiratory disease. PET with 6-bromo-7-[ 11 C]methylpurine ([ 11 C]BMP) has been used to measure MRP1 function in rodents. In this study, [ 11 C]BMP was for the first time characterised in humans to assess the function of MRP1 and other MRP subtypes in different tissues., Methods: Thirteen healthy volunteers (7 men, 6 women) underwent dynamic whole-body PET scans on a long axial field-of-view (LAFOV) PET/CT system after intravenous injection of [ 11 C]BMP. Three subjects of each sex were scanned a second time to assess reproducibility. Volumes of interest were outlined for MRP-expressing tissues (cerebral cortex, cerebellum, choroid plexus, retina, lungs, myocardium, kidneys, and liver). From the time-activity curves, the elimination rate constant (k E , h - 1 ) was derived as a parameter for tissue MRP function and its test-retest variability (TRTV, %) was calculated. Radiation dosimetry was calculated using the Medical Internal Radiation Dose (MIRD) methodology., Results: Mean k E and corresponding TRTV values were: cerebral cortex: 0.055 ± 0.010 h - 1 (- 4 ± 24%), cerebellum: 0.033 ± 0.009 h - 1 (1 ± 39%), choroid plexus: 0.292 ± 0.059 h - 1 (0.1 ± 16%), retina: 0.234 ± 0.045 h - 1 (30 ± 38%), lungs: 0.875 ± 0.095 h - 1 (- 3 ± 11%), myocardium: 0.641 ± 0.105 h - 1 (11 ± 25%), kidneys: 1.378 ± 0.266 h - 1 (14 ± 16%), and liver: 0.685 ± 0.072 h - 1 (7 ± 9%). Significant sex differences were found for k E in the cerebellum, lungs and kidneys. Effective dose was 4.67 ± 0.18 µSv/MBq for men and 4.55 ± 0.18 µSv/MBq for women., Conclusion: LAFOV PET/CT with [ 11 C]BMP potentially allows for simultaneous assessment of MRP function in multiple human tissues. Mean TRTV of k E in different tissues was in an acceptable range, except for the retina. The radiation dosimetry of [ 11 C]BMP was in the typical range of 11 C-tracers. LAFOV PET/CT holds great potential to assess at a whole-body, multi-tissue level molecular targets relevant for drug disposition in humans., Trial Registration: EudraCT 2021-006348-29. Registered 15 December 2021., (© 2024. The Author(s).)

Background: Approaches targeting the sodium-glucose cotransporter (SGLT) could represent a promising future therapeutic strategy for numerous oncological and metabolic diseases. In this study, we evaluated the safety, biodistribution and radiation dosimetry of the glucose analogue positron emission tomography (PET) agent [ 18 F] labeled alpha-methyl-4-deoxy-4-[ 18 F]fluoro-D-glucopyranoside ([ 18 F]Me4FDG) with high sodium-glucose cotransporter and low glucose transporter (GLUT) affinity. For this purpose, five healthy volunteers (1 man, 4 women) underwent multiple whole-body PET/computed tomography (CT) examinations starting with injection and up to 4 h after injection of averaged (2.4 ± 0.1) MBq/kg (range: 2.3-2.5 MBq/kg) administered activity. The PET/CT scans were conducted in 5 separate sessions, blood pressure and temperature were measured, and blood and urine samples were collected before the scans and one hour after injection to assess toxicity. Measurements of [ 18 F]Me4FDG radioactivity in organs of interest were determined from the PET/CT scans at 5 time points. Internal dosimetry was performed on voxel level using a fast Monte Carlo approach., Results: All studied volunteers could well tolerate the [ 18 F]Me4FDG and no adverse event was reported. The calculated effective dose was (0.013 ± 0.003) mSv/MBq. The organs with the highest absorbed dose were the kidneys with 0.05 mSv/MBq per kidney. The brain showed almost no uptake. After 60 min, (12 ± 15) % of the administered dose was excreted into the bladder., Conclusion: Featuring an effective dose of only 0.013 ± 0.003 mSv/MBq and no occurrence of side effects, the glucose analogue [ 18 F]Me4FDG seems to be a safe radio-tracer with a favorable biodistribution for PET imaging and also within several consecutive scans., Trial Registration Number: NCT03557138, Registered 22 February 2017, https://ichgcp.net/clinical-trials-registry/NCT03557138 ., (© 2024. The Author(s).)

St. John's wort (SJW) extract, a herbal medicine with antidepressant effects, is a potent inducer of intestinal and/or hepatic cytochrome P450 (CYP) enzymes and P-glycoprotein (P-gp), which can cause clinically relevant drug interactions. It is currently not known whether SJW can also induce P-gp activity at the human blood-brain barrier (BBB), which may potentially lead to decreased brain exposure and efficacy of certain central nervous system (CNS)-targeted P-gp substrate drugs. In this study, we used a combination of positron emission tomography (PET) imaging and cocktail phenotyping to gain a comprehensive picture on the effect of SJW on central and peripheral P-gp and CYP activities. Before and after treatment of healthy volunteers (n = 10) with SJW extract with a high hyperforin content (3-6%) for 12-19 days (1800 mg/day), the activity of P-gp at the BBB was assessed by means of PET imaging with the P-gp substrate [ 11 C]metoclopramide and the activity of peripheral P-gp and CYPs was assessed by administering a low-dose phenotyping cocktail (caffeine, omeprazole, dextromethorphan, and midazolam or fexofenadine). SJW significantly increased peripheral P-gp, CYP3A, and CYP2C19 activity. Conversely, no significant changes in the peripheral metabolism, brain distribution, and P-gp-mediated efflux of [ 11 C]metoclopramide across the BBB were observed following the treatment with SJW extract. Our data suggest that SJW does not lead to significant P-gp induction at the human BBB despite its ability to induce peripheral P-gp and CYPs. Simultaneous intake of SJW with CNS-targeted P-gp substrate drugs is not expected to lead to P-gp-mediated drug interactions at the BBB., (© 2024 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

The sensitivity of a PET system highly depends on the axial acceptance angle or maximum ring difference (MRD), which can be particularly high for total-body scanners due to their larger axial field of views (aFOVs). This study aims to evaluate the impact on image quality (IQ) and noise performance when MRD85 (18°), the current standard for clinical use, is increased to MRD322 (52°) for the Biograph Vision Quadra (Siemens Healthineers)., Methods: Studies with a cylindrical phantom covering the 106 cm aFOV and an IEC phantom filled with 18 F, 68 Ga and 89 Zr were performed for acquisition times from 60 to 1800 s and activity concentrations from 0.4 to 3 kBq/ml to assess uniformity, contrast recovery coefficients (CRCs) and to characterize noise by coefficient of variation (CV). Spatial resolution was compared for both MRDs by sampling a quadrant of the FOV with a point source. Further IQ, CV, liver SUV mean and SUV max were compared for a cohort of 5 patients scanned with [ 18 F]FDG (3 MBq/kg, 1 h p.i.) from 30 to 300 s., Results: CV was improved by a factor of up to 1.49 and is highest for short acquisition times, peaks at the center field of view and mitigates parabolic in axial direction with no difference to MRD85 beyond the central 80 cm. No substantial differences between the two evaluated MRDs in regards to uniformity, SUV mean or CRC for the different isotopes were observed. A degradation of the average spatial resolution of 0.9 ± 0.2 mm in the central 40 cm FOV was determined with MRD322. Depending on the acquisition time MRD322 resulted in a decrease of SUV max between 23.8% (30 s) and 9.0% (300 s)., Conclusion: Patient and phantom studies revealed that scan time could be lowered by approximately a factor of two with MRD322 while maintaining similar noise performance. The moderate degradation in spatial resolution for MRD322 is worth to exploit the full potential of the Quadra by either shorten scan times or leverage noise performance in particular for low count scenarios such as ultra-late imaging or dynamic studies with high temporal resolution., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Fabian Schmidt and Christian la Fougère have received research support from Siemens. Maurizio Conti is a full-time employee of Siemens Healthineers. All other authors have no conflicts of interest regarding this study to report., (Copyright © 2023 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

To investigate the use of kinetic parameters derived from direct Patlak reconstructions of [ 68 Ga]Ga-PSMA-11 positron emission tomography/computed tomography (PET/CT) to predict the histological grade of malignancy of the primary tumor of patients with prostate cancer (PCa). Thirteen patients (mean age 66 ± 10 years) with a primary, therapy-naïve PCa (median PSA 9.3 [range: 6.3-130 µg/L]) prior radical prostatectomy, were recruited in this exploratory prospective study. A dynamic whole-body [ 68 Ga]Ga-PSMA-11 PET/CT scan was performed for all patients. Measured quantification parameters included Patlak slope (Ki: absolute rate of tracer consumption) and Patlak intercept (Vb: degree of tracer perfusion in the tumor). Additionally, the mean and maximum standardized uptake values (SUVmean and SUVmax) of the tumor were determined from a static PET 60 min post tracer injection. In every patient, initial PSA (iPSA) values that were also the PSA level at the time of the examination and final histology results with Gleason score (GS) grading were correlated with the quantitative readouts. Collectively, 20 individual malignant prostate lesions were ascertained and histologically graded for GS with ISUP classification. Six lesions were classified as ISUP 5, two as ISUP 4, eight as ISUP 3, and four as ISUP 2. In both static and dynamic PET/CT imaging, the prostate lesions could be visually distinguished from the background. The average values of the SUVmean, slope, and intercept of the background were 2.4 (±0.4), 0.015 1/min (±0.006), and 52% (±12), respectively. These were significantly lower than the corresponding parameters extracted from the prostate lesions (all p < 0.01). No significant differences were found between these values and the various GS and ISUP (all p > 0.05). Spearman correlation coefficient analysis demonstrated a strong correlation between static and dynamic PET/CT parameters (all r ≥ 0.70, p < 0.01). Both GS and ISUP grading revealed only weak correlations with the mean and maximum SUV and tumor-to-background ratio derived from static images and dynamic Patlak slope. The iPSA demonstrated no significant correlation with GS and ISUP grading or with dynamic and static PET parameter values. In this cohort of mainly high-risk PCa, no significant correlation between [ 68 Ga]Ga-PSMA-11 perfusion and consumption and the aggressiveness of the primary tumor was observed. This suggests that the association between SUV values and GS may be more distinctive when distinguishing clinically relevant from clinically non-relevant PCa.

The aim of the study was to evaluate the effect of reduced injected [18F]FDG activity levels on the quantitative and diagnostic accuracy of PET images of patients with non-lesional epilepsy (NLE).Nine healthy volunteers and nine patients with NLE underwent 60-min dynamic list-mode (LM) scans on a fully-integrated PET/MRI system. Injected FDG activity levels were reduced virtually by randomly removing counts from the last 10-min of the LM data, so as to simulate the following activity levels: 50 %, 35 %, 20 %, and 10 % of the original activity. Four image reconstructions were evaluated: standard OSEM, OSEM with resolution recovery (PSF), the A-MAP, and the Asymmetrical Bowsher (AsymBowsher) algorithms. For the A-MAP algorithms, two weights were selected (low and high). Image contrast and noise levels were evaluated for all subjects while the lesion-to-background ratio (L/B) was only evaluated for patients. Patient images were scored by a Nuclear Medicine physician on a 5-point scale to assess clinical impression associated with the various reconstruction algorithms.The image contrast and L/B ratio characterizing all four reconstruction algorithms were similar, except for reconstructions based on only 10 % of total counts. Based on clinical impression, images with diagnostic quality can be achieved with as low as 35 % of the standard injected activity. The selection of algorithms utilizing an anatomical prior did not provide a significant advantage for clinical readings, despite a small improvement in L/B (< 5 %) using the A-MAP and AsymBowsher reconstruction algorithms.In patients with NLE who are undergoing [18F]FDG-PET/MR imaging, the injected [18F]FDG activity can be reduced to 35 % of the original dose levels without compromising., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Background: Total-body PET scanners with axial field of views (FOVs) longer than 1 m enable new applications to study multiple organs (e.g., the brain-gut-axis) simultaneously. As the spatial resolution and the associated partial volume effect (PVE) can vary significantly along the FOV, detailed knowledge of the contrast recovery coefficients (CRCs) is a prerequisite for image analysis and interpretation of quantitative results. The aim of this study was to determine the CRCs, as well as voxel noise, for multiple isotopes throughout the 1.06 m axial FOV of the Biograph Vision Quadra PET/CT system (Siemens Healthineers)., Materials and Methods: Cylindrical phantoms equipped with three different sphere sizes (inner diameters 7.86 mm, 28 and 37 mm) were utilized for the PVE evaluation. The 7.86 mm sphere was filled with F-18 (8:1 and 4:1), Ga-68 (8:1) and Zr-89 (8:1). The 28 mm and 37 mm spheres were filled with F-18 (8:1). Background concentration in the respective phantoms was of ~ 3 kBq/ml. The phantoms were measured at multiple positions in the FOV (axial: 0, 10, 20, 30, 40 and 50 cm, transaxial: 0, 10, 20 cm). The data were reconstructed with the standard clinical protocol, including PSF correction and TOF information with up to 10 iterations for maximum ring differences (MRDs) of 85 and 322; CRCs, as well as voxel noise levels, were determined for each position., Results: F-18 CRCs (SBR 8:1 and 4:1) of the 7.86 mm sphere decreased up to 18% from the center FOV (cFOV) toward the transaxial edge and increased up to 17% toward the axial edge. Noise levels were below 15% for the default clinical reconstruction parameters. The larger spheres exhibited a similar pattern. Zr-89 revealed ~ 10% lower CRCs than F-18 but larger noise (9.1% (F-18), 19.1% (Zr-89); iteration 4, cFOV) for the default reconstruction. Zr-89 noise levels in the cFOV significantly decreased (~ 28%) when reconstructing the data with MRD322 compared with MRD85 along with a slight decrease in CRC values. Ga-68 exhibited the lowest CRCs for the three isotopes and noise characteristics comparable to those of F-18., Conclusions: Distinct differences in the PVE within the FOV were detected for clinically relevant isotopes F-18, Ga-68 and Zr-89, as well as for different sphere sizes. Depending on the positions inside the FOV, the sphere-to-background ratios, count statistics and isotope used, this can result in an up to 50% difference between CRCs. Hence, these changes in PVE can significantly affect the quantitative analysis of patient data. MRD322 resulted in slightly lower CRC values, especially in the center FOV, whereas the voxel noise significantly decreased compared with MRD85., (© 2023. The Author(s).)

Objectives: Advanced MR imaging of brain tumors is still mainly based on qualitative imaging. PET imaging offers additive metabolic information, and MR fingerprinting (MRF) offers a novel approach to quantitative data acquisition. The purpose of this study was to evaluate the ability of MRF to predict tumor regions and grading in combination with PET., Methods: Seventeen patients with histologically verified infiltrating gliomas and available amino-acid PET data were enrolled. ROIs for solid tumor parts (SPo), perifocal edema (ED1), and normal-appearing white matter (NAWM) were selected on conventional MRI sequences and aligned to the MRF and PET images. The predictability of gliomas by region and grading as well as intermodal correlations were assessed., Results: For MRF, we calculated an overall predictability by region (SPo, ED1, and NAWM) for all of the MRF parameters of 76.5%, 47.1%, and 94.1%, respectively. The overall ability to distinguish low- from high-grade gliomas using MRF was 88.9% for LGG and 75% for HGG, with an accuracy of 82.4%, a ppV of 85.71%, and an npV of 80%. PET positivity was found in 13/17 patients for solid tumor parts, and in 3/17 patients for the edema region. However, there was no significant difference in region-specific MRF values between PET positive and PET negative patients., Conclusions: MRF and PET provide quantitative measurements of the tumor tissue characteristics of gliomas, with good predictability. Nonetheless, the results are dissimilar, reflecting the different underlying mechanisms of each method.

The nervous and circulatory system interconnects the various organs of the human body, building hierarchically organized subsystems, enabling fine-tuned, metabolically expensive brain-body and inter-organ crosstalk to appropriately adapt to internal and external demands. A deviation or failure in the function of a single organ or subsystem could trigger unforeseen biases or dysfunctions of the entire network, leading to maladaptive physiological or psychological responses. Therefore, quantifying these networks in healthy individuals and patients may help further our understanding of complex disorders involving body-brain crosstalk. Here we present a generalized framework to automatically estimate metabolic inter-organ connectivity utilizing whole-body functional positron emission tomography (fPET). The developed framework was applied to 16 healthy subjects (mean age ± SD, 25 ± 6 years; 13 female) that underwent one dynamic 18 F-FDG PET/CT scan. Multiple procedures of organ segmentation (manual, automatic, circular volumes) and connectivity estimation (polynomial fitting, spatiotemporal filtering, covariance matrices) were compared to provide an optimized thorough overview of the workflow. The proposed approach was able to estimate the metabolic connectivity patterns within brain regions and organs as well as their interactions. Automated organ delineation, but not simplified circular volumes, showed high agreement with manual delineation. Polynomial fitting yielded similar connectivity as spatiotemporal filtering at the individual subject level. Furthermore, connectivity measures and group-level covariance matrices did not match. The strongest brain-body connectivity was observed for the liver and kidneys. The proposed framework offers novel opportunities towards analyzing metabolic function from a systemic, hierarchical perspective in a multitude of physiological pathological states., Competing Interests: Declaration of Competing Interest M. Hacker received consulting fees and/or honoraria from Bayer Healthcare BMS, Eli Lilly, EZAG, GE Healthcare, Ipsen, ITM, Janssen, Roche, and Siemens Healthineers. R. Lanzenberger received travel grants and/or conference speaker honoraria from Bruker BioSpin within the last three years and investigator-initiated research funding from Siemens Healthcare regarding clinical research using PET/MR. He is a shareholder of the start-up company BM Health GmbH since 2019. Ivo Rausch received a research grant from Siemens Healthineers not related to this study. All other authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2023. Published by Elsevier Inc.)

Introduction: Dynamic positron emission tomography (PET) and the application of kinetic models can provide important quantitative information based on its temporal information. This however requires arterial blood sampling, which can be challenging to acquire. Nowadays, state-of-the-art PET/CT systems offer fully automated, whole-body (WB) kinetic modelling protocols using image-derived input functions (IDIF) to replace arterial blood sampling. Here, we compared the validity of an automatic WB kinetic model protocol to the reference standard arterial input function (AIF) for both clinical and research settings. Methods: Sixteen healthy participants underwent dynamic WB [ 18 F]FDG scans using a continuous bed motion PET/CT system with simultaneous arterial blood sampling. Multiple processing pipelines that included automatic and manually generated IDIFs derived from the aorta and left ventricle, with and without motion correction were compared to the AIF. Subsequently generated quantitative images of glucose metabolism were compared to evaluate performance of the different input functions. Results: We observed moderate to high correlations between IDIFs and the AIF regarding area under the curve (r = 0.49-0.89) as well as for the cerebral metabolic rate of glucose (CMRGlu) (r = 0.68-0.95). Manual placing of IDIFs and motion correction further improved their similarity to the AIF. Discussion: In general, the automatic vendor protocol is a feasible approach for the quantification of CMRGlu for both, clinical and research settings where expertise or time is not available. However, we advise on a rigorous inspection of the placement of the volume of interest, the resulting IDIF, and the quantitative values to ensure valid interpretations. In protocols requiring longer scan times or where cohorts are prone to involuntary movement, manual IDIF definition with additional motion correction is recommended, as this has greater accuracy and reliability., Competing Interests: RL received investigator-initiated research funding from Siemens Healthcare regarding clinical research using PET/MR. He is a shareholder of the start-up company BM Health GmbH since 2019. MH received consulting fees and/or honoraria from Bayer Healthcare BMS, Eli Lilly, EZAG, GE Healthcare, Ipsen, ITM, Janssen, Roche, and Siemens Healthineers. IR received a research grant from Siemens Healthineers not related to this study. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor CC declared a past co-authorship with the authors TB and IR., (Copyright © 2023 Reed, Godbersen, Vraka, Rausch, Ponce de León, Popper, Geist, Nics, Komorowski, Karanikas, Beyer, Traub-Weidinger, Hahn, Langsteger, Hacker and Lanzenberger.)

Introduction: Amino-acid positron emission tomography (PET) is a validated metabolic imaging approach for the diagnostic work-up of gliomas. This study aimed to evaluate sex-specific radiomic characteristics of L-[S-methyl- 11 Cmethionine (MET)-PET images of glioma patients in consideration of the prognostically relevant biomarker isocitrate dehydrogenase (IDH) mutation status., Methods: MET-PET of 35 astrocytic gliomas (13 females, mean age 41 ± 13 yrs. and 22 males, mean age 46 ± 17 yrs.) and known IDH mutation status were included. All patients underwent radiomic analysis following imaging biomarker standardization initiative (IBSI)-conform guidelines both from standardized uptake value (SUV) and tumor-to-background ratio (TBR) PET values. Aligned Monte Carlo (MC) 100-fold split was utilized for SUV and TBR dataset pairs for both sex and IDH-specific analysis. Borderline and outlier scores were calculated for both sex and IDH-specific MC folds. Feature ranking was performed by R-squared ranking and Mann-Whitney U-test together with Bonferroni correction. Correlation of SUV and TBR radiomics in relation to IDH mutational status in male and female patients were also investigated., Results: There were no significant features in either SUV or TBR radiomics to distinguish female and male patients. In contrast, intensity histogram coefficient of variation (ih.cov) and intensity skewness (stat.skew) were identified as significant to predict IDH +/-. In addition, IDH+ females had significant ih.cov deviation (0.031) and mean stat.skew (-0.327) differences compared to IDH+ male patients (0.068 and -0.123, respectively) with two-times higher standard deviations of the normal brain background MET uptake as well., Discussion: We demonstrated that female and male glioma patients have significantly different radiomic profiles in MET PET imaging data. Future IDH prediction models shall not be built on mixed female-male cohorts, but shall rely on sex-specific cohorts and radiomic imaging biomarkers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Papp, Rasul, Spielvogel, Krajnc, Poetsch, Woehrer, Patronas, Ecsedi, Furtner, Mitterhauser, Rausch, Widhalm, Beyer, Hacker and Traub-Weidinger.)

This article presents the protocol on Quality Controls in PET/CT and PET/MRI published online in May 2022 by the European Federation of Organisations for Medical Physics (EFOMP), which was developed by the Working group for PET/CT and PET/MRI Quality Control (QC) protocol. The main objective of this protocol was to comprehensively provide simple and practical procedures that may be integrated into clinical practice to identify changes in the PET/CT/MRI system's performance and avoid short- and long-term quality deterioration. The protocol describes the quality control procedures on radionuclide calibrators, weighing scales, PET, CT and MRI systems using selected and measurable parameters that are directly linked to clinical images quality. It helps to detect problems before they can impact clinical studies in terms of safety, image quality, quantification accuracy and patient radiation dose. CT and MRI QCs are described only in the context of their use for PET (attenuation correction and anatomical localization) imaging. Detailed step-by-step instructions have been provided, limiting any misinterpretations or interpersonal variations as much as possible. This paper presents the main characteristics of the protocol illustrated together with a brief summary of the content of each chapter. A regular QC based on the proposed protocol would guarantee that PET/CT and PET/MRI systems operate under optimal conditions, resulting in the best performance for routine clinical tasks., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

Aim: Recently, total-body PET/CT systems with an extended axial field-of-view (aFOV) became commercially available which allow acquiring physiologic information of multiple organs simultaneously. However, the nominal aFOV may clinically not be used effectively due to the inherently reduced sensitivity at the distal ends of the aFOV. The aim of this study was to assess the extent of the useful aFOV of the Biograph Vision Quadra PET/CT system., Methods: A NEMA image quality (IQ) phantom mimicking a standard [ 18 F]FDG examination was used. Image contrast and noise were assessed across the 106 cm aFOV of the Biograph Vision Quadra PET/CT system (Siemens Healthineers). Phantom acquisitions were performed at different axial positions. PET data were rebinned to simulate different acquisition times for a standard injected activity and reconstructed using different filter settings to evaluate the noise and images along the axial direction., Results: Image noise and contrast were stable within the central 80 cm of the aFOV. Outside this central area, image contrast variability as well as image noise increased. This degradation of IQ was in particular evident for short acquisition times of less than 30 s. At 10 min acquisition time and in the absence of post-reconstruction filtering, the useful aFOV was 100 cm. For a 2 min acquisition time, a useful aFOV with image noise below 15% was only achievable using Gaussian filtering with axial extents of between 83 and 103 cm when going from 2 to 6 mm full-width-half-maximum, respectively., Conclusion: Image noise increases substantially towards the ends of the aFOV. However, good IQ in compliance with generally accepted benchmarks is achievable for an aFOV of > 90 cm. When accepting higher image noise or using dedicated protocol settings such as stronger filtering a useful aFOV of around 1 m can be achieved for a 2 min acquisition time., (© 2022. The Author(s).)

The choice of materials challenges the development of Magnetic Resonance Imaging (MRI) phantoms and, to date, is mainly limited to water-filled compartments or gel-based components. Recently, solid materials have been introduced through additive manufacturing (AM) to mimic complex geometrical structures. Nonetheless, no such manufactured solid materials are available with controllable MRI contrast to mimic organ substructures or lesion heterogeneities. Here, we present a novel AM design that allows MRI contrast manipulation by varying the partial volume contribution to a ROI/voxel of MRI-visible material within an imaging object. Two sets of 11 cubes and three replicates of a spherical tumour model were designed and printed using AM. Most samples presented varying MRI-contrast in standard MRI sequences, based mainly on spin density and partial volume signal variation. A smooth and continuous MRI-contrast gradient could be generated in a single-compartment tumour model. This concept supports the development of more complex MRI phantoms that mimic the appearance of heterogeneous tumour tissues., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [The Medical University of Vienna has applied for a patent concerning the building technique of solid objects with variable MRI contrast. Ewald Unger and Ivo Rausch are quoted as inventors. The authors declare that the research was conducted without any further commercial or financial relationships that could be construed as a potential conflict of interest.], (Copyright © 2022. Published by Elsevier GmbH.)

Our purpose was to determine whether ComBat harmonization improves 18 F-FDG PET radiomics-based tissue classification in pooled PET/MRI and PET/CT datasets. Methods: Two hundred patients who had undergone 18 F-FDG PET/MRI (2 scanners and vendors; 50 patients each) or PET/CT (2 scanners and vendors; 50 patients each) were retrospectively included. Gray-level histogram, gray-level cooccurrence matrix, gray-level run-length matrix, gray-level size-zone matrix, and neighborhood gray-tone difference matrix radiomic features were calculated for volumes of interest in the disease-free liver, spleen, and bone marrow. For individual feature classes and a multiclass radiomic signature, tissue was classified on ComBat-harmonized and unharmonized pooled data, using a multilayer perceptron neural network. Results: Median accuracies in training and validation datasets were 69.5% and 68.3% (harmonized), respectively, versus 59.5% and 58.9% (unharmonized), respectively, for gray-level histogram; 92.1% and 86.1% (harmonized), respectively, versus 53.6% and 50.0% (unharmonized), respectively, for gray-level cooccurrence matrix; 84.8% and 82.8% (harmonized), respectively, versus 62.4% and 58.3% (unharmonized), respectively, for gray-level run-length matrix; 87.6% and 85.6% (harmonized), respectively, versus 56.2% and 52.8% (unharmonized), respectively, for gray-level size-zone matrix; 79.5% and 77.2% (harmonized), respectively, versus 54.8% and 53.9% (unharmonized), respectively, for neighborhood gray-tone difference matrix; and 86.9% and 84.4% (harmonized), respectively, versus 62.9% and 58.3% (unharmonized), respectively, for radiomic signature. Conclusion: ComBat harmonization may be useful for multicenter 18 F-FDG PET radiomics studies using pooled PET/MRI and PET/CT data., (© 2022 by the Society of Nuclear Medicine and Molecular Imaging.)

Aim: The aim of this study was to assess the effects of including somatostatin receptor agonist (SSTR) PET imaging in meningioma radiotherapy planning by means of changes in inter-observer variability (IOV). Further, the possibility of using threshold-based delineation approaches for semiautomatic tumor volume definition was assessed. Patients and Methods: Sixteen patients with meningioma undergoing fractionated radiotherapy were delineated by five radiation oncologists. IOV was calculated by comparing each delineation to a consensus delineation, based on the simultaneous truth and performance level estimation (STAPLE) algorithm. The consensus delineation was used to adapt a threshold-based delineation, based on a maximization of the mean Dice coefficient. To test the threshold-based approach, seven patients with SSTR-positive meningioma were additionally evaluated as a validation group. Results: The average Dice coefficients for delineations based on MRI alone was 0.84 ± 0.12. For delineation based on MRI + PET, a significantly higher dice coefficient of 0.87 ± 0.08 was found (p < 0.001). The Hausdorff distance decreased from 10.96 ± 11.98 mm to 8.83 ± 12.21 mm (p < 0.001) when adding PET for the lesion delineation. The best threshold value for a threshold-based delineation was found to be 14.0% of the SUVmax, with an average Dice coefficient of 0.50 ± 0.19 compared to the consensus delineation. In the validation cohort, a Dice coefficient of 0.56 ± 0.29 and a Hausdorff coefficient of 27.15 ± 21.54 mm were found for the threshold-based approach. Conclusions: SSTR-PET added to standard imaging with CT and MRI reduces the IOV in radiotherapy planning for patients with meningioma. When using a threshold-based approach for PET-based delineation of meningioma, a relatively low threshold of 14.0% of the SUVmax was found to provide the best agreement with a consensus delineation.

Background: Hybrid imaging (e.g., positron emission tomography [PET]/computed tomography [CT], PET/magnetic resonance imaging [MRI]) helps one to visualize and quantify morphological and physiological tumor characteristics in a single study. The noninvasive characterization of tumor heterogeneity is essential for grading, treatment planning, and following-up oncological patients. However, conventional (CONV) image-based parameters, such as tumor diameter, tumor volume, and radiotracer activity uptake, are insufficient to describe tumor heterogeneities. Here, radiomics shows promise for a better characterization of tumors. Nevertheless, the validation of such methods demands imaging objects capable of reflecting heterogeneities in multi-modality imaging. We propose a phantom to simulate tumor heterogeneity repeatably in PET, CT, and MRI., Methods: The phantom consists of three 50-ml plastic tubes filled partially with acrylic spheres of S1: 1.6 mm, S2: 50%(1.6 mm)/50%(6.3 mm), or S3: 6.3-mm diameter. The spheres were fixed to the bottom of each tube by a plastic grid, yielding one sphere free homogeneous region and one heterogeneous (S1, S2, or S3) region per tube. A 3-tube phantom and its replica were filled with a fluorodeoxyglucose (18F) solution for test-retest measurements in a PET/CT Siemens TPTV and a PET/MR Siemens Biograph mMR system. A number of 42 radiomic features (10 first order and 32 texture features) were calculated for each phantom region and imaging modality. Radiomic features stability was evaluated through coefficients of variation (COV) across phantoms and scans for PET, CT, and MRI. Further, the Wilcoxon test was used to assess the capability of stable features to discriminate the simulated phantom regions., Results: The different patterns (S1-S3) did present visible heterogeneity in all imaging modalities. However, only for CT and MRI, a clear visual difference was present between the different patterns. Across all phantom regions in PET, CT, and MR images, 10, 16, and 21 features out of 42 evaluated features in total had a COV of 10% or less. In particular, CONV, histogram, and gray-level run length matrix features showed high repeatability for all the phantom regions and imaging modalities. Several of repeatable texture features allowed the image-based discrimination of the different phantom regions (p < 0.05). However, depending on the feature, different pattern discrimination capabilities were found for the different imaging modalities., Conclusion: The proposed phantom appears suitable for simulating heterogeneities in PET, CT, and MRI. We demonstrate that it is possible to select radiomic features for the readout of the phantom. Most of these features had been shown to be relevant in previous clinical studies., (© 2022 The Authors. Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Background: The NMDA receptor (NMDAR) plays a key role in the central nervous system, e.g., for synaptic transmission. While synaptic NMDARs are thought to have protective characteristics, activation of extrasynaptic NMDARs might trigger excitotoxic processes linked to neuropsychiatric disorders. Since extrasynaptic NMDARs are typically GluN2B-enriched, the subunit is an interesting target for drug development and treatment monitoring. Recently, the novel GluN2B-specific PET radioligand (R)-[ 11 C]Me-NB1 was investigated in rodents and for the first time successfully translated to humans. To assess whether (R)-[ 11 C]Me-NB1 is a valuable radioligand for (repeated) clinical applications, we evaluated its safety, biodistribution and dosimetry., Methods: Four healthy subjects (two females, two males) underwent one whole-body PET/MR measurement lasting for more than 120 min. The GluN2B-specific radioligand (R)-[ 11 C]Me-NB1 was administered simultaneously with the PET start. Subjects were measured in nine passes and six bed positions from head to mid-thigh. Regions of interest was anatomically defined for the brain, thyroid, lungs, heart wall, spleen, stomach contents, pancreas, liver, kidneys, bone marrow and urinary bladder contents, using both PET and MR images. Time-integrated activity coefficients were estimated to calculate organ equivalent dose coefficients and the effective dose coefficient. Additionally, standardized uptake values (SUV) were computed to visualize the biodistribution., Results: Administration of the radioligand was safe without adverse events. The organs with the highest uptake were the urinary bladder, spleen and pancreas. Organ equivalent dose coefficients were higher in female in almost all organs, except for the urinary bladder of male. The effective dose coefficient was 6.0 µSv/MBq., Conclusion: The GluN2B-specific radioligand (R)-[ 11 C]Me-NB1 was well-tolerated without reported side effects. Effective dose was estimated to 1.8 mSv when using 300 MBq of presented radioligand. The critical organ was the urinary bladder. Due to the low effective dose coefficient of this radioligand, longitudinal studies for drug development and treatment monitoring of neuropsychiatric disorders including neurodegenerative diseases are possible. Trial registration Registered on 11th of June 2019 at https://www.basg.gv.at (EudraCT: 2018-002933-39)., (© 2022. The Author(s).)

Aim: To evaluate the effect of combining positron range correction (PRC) with point-spread-function (PSF) correction and to compare different methods of implementation into iterative image reconstruction for 124 I-PET imaging., Materials and Methods: Uniform PR blurring kernels of 124 I were generated using the GATE (GEANT4) framework in various material environments (lung, water, and bone) and matched to a 3D matrix. The kernels size was set to 11 × 11 × 11 based on the maximum PR in water and the voxel size of the PET system. PET image reconstruction was performed using the standard OSEM algorithm, OSEM with PRC implemented before the forward projection (OSEM+PRC simplified) and OSEM with PRC implemented in both forward- and back-projection steps (full implementation) (OSEM+PRC). Reconstructions were repeated with resolution recovery, point-spread function (PSF) included. The methods and kernel variation were validated using different phantoms filled with 124 I acquired on a Siemens mCT PET/CT system. The data was evaluated for contrast recovery and image noise., Results: Contrast recovery improved by 2-10% and 4-37% with OSEM+PRC simplified and OSEM+PRC, respectively, depending on the sphere size of the NEMA IQ phantom. Including PSF in the reconstructions further improved contrast by 4-19% and 3-16% with the PSF+PRC simplified and PSF+PRC, respectively. The benefit of PRC was more pronounced within low-density material. OSEM-PRC and OSEM-PSF as well as OSEM-PSF+PRC in its full- and simplified implementation showed comparable noise and convergence. OSEM-PRC simplified showed comparably faster convergence but at the cost of increased image noise., Conclusions: The combination of the PSF and PRC leads to increased contrast recovery with reduced image noise compared to stand-alone PSF or PRC reconstruction. For OSEM-PRC reconstructions, a full implementation in the reconstruction is necessary to handle image noise. For the combination of PRC with PSF, a simplified PRC implementation can be used to reduce reconstruction times., (© 2022. The Author(s).)

Purpose: To assess dose levels in routine nuclear medicine (NUC) procedures in Austria as a prior to a legislative update of the National Diagnostic Reference Levels (NDRL)., Method: As part of a nationwide survey of common NUC-examinations between June 2019 and November 2019, data sets were collected from 33 Austrian hospitals with NUC equipment. All hospitals were asked to report the NUC imaging devices in use (model, type, year of manufacture, detector material, collimators), the standard protocol parameters for selected examinations (standard activity, collimator, average acquisition time, reconstruction type, use of time-of-flight) and to report data from 10 representative examinations (e.g. injected activity, weight), incl. the most common NUC-examinations for planar imaging/SPECT and PET. Median/mean values for injected activity were calculated and compared to current Austrian and international NDRL. A Pearson correlation coefficient was computed comparing different variables., Results: In total, all 33 hospitals (100% response rate) reported data for this study for 60 SPECT devices, 21 PET/CT devices and 23 scintigraphy devices. Fixed activity values for scintigraphy/SPECT and PET were employed by about 90% and 56% of the hospitals, respectively. The most widely performed examinations for scintigraphy/SPECT are bone imaging, thyroid imaging, renal imaging (with MAG3/EC) and lung perfusion imaging (in 88% of the hospitals) and F-18 FDG-PET studies for oncology indications (in 100% of the hospitals). Significant correlations were found for patient weight and injected activity (scintigraphy/SPECT), use of iterative reconstruction and injected activity (PET) as well as size of field-of-view and injected activity (PET)., Conclusions: The reported injected activity levels were comparable to those in other countries. However, for procedures for which NDRL exist, deviations in injected activities of >20% compared to the NDRL were found. These deviations are assumed to result mainly from advances in technology but also from deviations between NDRL and prescribed activities as given in the information leaflets of the radiopharmaceuticals., (Copyright © 2021. Published by Elsevier GmbH.)

Background: Cardiac positron emission tomography/magnetic resonance imaging (PET/MRI) can assess various cardiovascular diseases. In this study, we intra-individually compared right (RV) and left ventricular (LV) parameters obtained from dual-tracer PET/MRI scan., Methods: In 22 patients with coronary heart disease (69 ± 9 years) dynamic [ 13 N]NH 3 (NH 3 ) and [ 18 F]FDG (FDG) PET scans were acquired. The first 2 minutes were used to calculate LV and RV first-pass ejection fraction (FPEF). Additionally, LV end-systolic (LVESV) and end-diastolic (LVEDV) volume and ejection fraction (LVEF) were calculated from the early (EP) and late-myocardial phases (LP). MRI served as a reference., Results: RVFPEF and LVFPEF from FDG and NH 3 as well as RVEF and LVEF from MRI were (28 ± 11%, 32 ± 15%), (32 ± 11%, 41 ± 14%) and (42 ± 16%, 45 ± 19%), respectively. LVESV, LVEDV and LVEF from EP FDG and NH 3 in 8 and 16 gates were [71 (15 to 213 mL), 98 (16 to 241 mL), 32 ± 17%] and [50 (17 to 206 mL), 93 (13 to 219 mL), 36 ± 17%] as well as [60 (19 to 360 mL), 109 (56 to 384 mL), 41 ± 22%] and [54 (16 to 371 mL), 116 (57 to 431 mL), 46 ± 24%], respectively. Moreover, LVESV, LVEDV and LVEF acquired from LP FDG and NH 3 were (85 ± 63 mL, 138 ± 63 mL, 47 ± 19%) and (79 ± 56 mL, 137 ± 63 mL, 47 ± 20%), respectively. The LVESV, LVEDV from MRI were 93 ± 66 mL and 153 ± 71 mL, respectively. Significant correlations were observed for RVFPEF and LVFPEF between FDG and MRI (R = .51, P = .01; R = .64, P = .001), respectively. LVESV, LVEDV, and LVEF revealed moderate to strong correlations to MRI when they acquired from EP FDG and NH 3 in 16 gates (all R > .7, P = .000). Similarly, all LV parameters from LP FDG and NH 3 correlated good to strongly positive with MRI (all R > .7, and P < .001), except EDV from NH3 weakly correlated to EDV of MRI (R = .54, P < .05). Generally, Bland-Altman plots showed good agreements between PET and MRI., Conclusions: Deriving LV and RV functional values from various phases of dynamic NH 3 and FDG PET is feasible. These results could open a new perspective for further clinical applications of the PET examinations., (© 2020. The Author(s).)

(1) Background: Recent developments in 7T magnetic resonance spectroscopic imaging (MRSI) made the acquisition of high-resolution metabolic images in clinically feasible measurement times possible. The amino acids glutamine (Gln) and glycine (Gly) were identified as potential neuro-oncological markers of importance. For the first time, we compared 7T MRSI to amino acid PET in a cohort of glioma patients. (2) Methods: In 24 patients, we co-registered 7T MRSI and routine PET and compared hotspot volumes of interest (VOI). We evaluated dice similarity coefficients (DSC), volume, center of intensity distance (CoI), median and threshold values for VOIs of PET and ratios of total choline (tCho), Gln, Gly, myo-inositol (Ins) to total N-acetylaspartate (tNAA) or total creatine (tCr). (3) Results: We found that Gln and Gly ratios generally resulted in a higher correspondence to PET than tCho. Using cutoffs of 1.6-times median values of a control region, DSCs to PET were 0.53 ± 0.36 for tCho/tNAA, 0.66 ± 0.40 for Gln/tNAA, 0.57 ± 0.36 for Gly/tNAA, and 0.38 ± 0.31 for Ins/tNAA. (4) Conclusions: Our 7T MRSI data corresponded better to PET than previous studies at lower fields. Our results for Gln and Gly highlight the importance of future research (e.g., using Gln PET tracers) into the role of both amino acids.

Aim: The aim of this study was to evaluate and correct for partial-volume-effects (PVE) on [ 68 Ga]Ga-Pentixafor uptake in atherosclerotic plaques of the carotid arteries, and the impact of ignoring bone in MR-based attenuation correction (MR-AC)., Methods: Twenty [ 68 Ga]Ga-pentixafor PET/MR examinations including a high-resolution T2-TSE MR of the neck were included in this study. Carotid plaques located at the carotid bifurcation were delineated and the anatomical information was used for partial-volume-correction (PVC). Mean and max tissue-to-background ratios (TBR) of the [ 68 Ga]Ga-Pentixafor uptake were compared for standard and PVC-PET images. A potential influence of ignoring bone in MR-AC was assessed in a subset of the data reconstructed after incorporating bone into MR-AC and a subsequent comparison of standardized-uptake values (SUV)., Results: In total, 34 atherosclerotic plaques were identified. Following PVC, mean and max TBR increased by 77 and 95%, respectively, when averaged across lesions. When accounting for bone in the MR-AC, SUV of plaque changed by 0.5%., Conclusion: Quantitative readings of [ 68 Ga]Ga-pentixafor uptake in plaques are strongly affected by PVE, which can be reduced by PVC. Including bone information into the MR-AC yielded no clinically relevant effect on tracer quantification., (© 2020. The Author(s).)

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., (© 2022 The Authors. Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Aim: To develop and evaluate a new approach for spatially variant and tissue-dependent positron range (PR) correction (PRC) during the iterative PET image reconstruction., Materials and Methods: The PR distributions of three radionuclides ( 18 F, 68 Ga, and 124 I) were simulated using the GATE (GEANT4) framework in different material compositions (lung, water, and bone). For every radionuclide, the uniform PR kernel was created by mapping the simulated 3D PR point cloud to a 3D matrix with its size defined by the maximum PR in lung ( 18 F) or water ( 68 Ga and 124 I) and the PET voxel size. The spatially variant kernels were composed from the uniform PR kernels by analyzing the material composition of the surrounding medium for each voxel before implementation as tissue-dependent, point-spread functions into the iterative image reconstruction. The proposed PRC method was evaluated using the NEMA image quality phantom ( 18 F, 68 Ga, and 124 I); two unique PR phantoms were scanned and evaluated following OSEM reconstruction with and without PRC using different metrics, such as contrast recovery, contrast-to-noise ratio, image noise and the resolution evaluated in terms of full width at half maximum (FWHM)., Results: The effect of PRC on 18 F-imaging was negligible. In contrast, PRC improved image contrast for the 10-mm sphere of the NEMA image quality phantom filled with 68 Ga and 124 I by 33 and 24%, respectively. While the effect of PRC was less noticeable for the larger spheres, contrast recovery still improved by 5%. The spatial resolution was improved by 26% for 124 I (FWHM of 4.9 vs. 3.7 mm)., Conclusion: For high energy positron-emitting radionuclides, the proposed PRC method helped recover image contrast with reduced noise levels and with improved spatial resolution. As such, the PRC approach proposed here can help improve the quality of PET data in clinical practice and research., Competing Interests: VP, DB, JC, and MC are employees of Siemens Medical Solutions USA, Inc. (Knoxville, TN, United States) and report no conflict of interest with this study. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kertész, Beyer, Panin, Jentzen, Cal-Gonzalez, Berger, Papp, Kench, Bharkhada, Cabello, Conti and Rausch.)

Purpose: To investigate the possibility of reducing the injected activity for whole-body [18F]FDG-PET/CT studies of paediatric oncology patients and to assess the usefulness of time-of-flight (TOF) acquisition on PET image quality at reduced count levels., Procedures: Twenty-nine paediatric oncology patients (12F/17M, 3-18 years old (median age 13y), weight 45±20 kg, BMI 19±4 kg/m 2 ), who underwent routine whole-body PET/CT examinations on a Siemens Biograph mCT TrueV system with TOF capability (555ps) were included in this study. The mean injected activity was 156 ± 45 MBq (3.8 ± 0.8 kg/MBq) and scaled to patient weight. The raw data was collected in listmode (LM) format and pre-processed to simulate reduced levels of [18F]FDG activity (75, 50, 35, 20 and 10% of the original counts) by randomly removing events from the original LM data. All data were reconstructed using the vendor-specific e7-tools with standard OSEM only, with OSEM plus resolution recovery (PSF). The reconstructions were repeated with added TOF (TOF) and PSF+TOF. The benefit of TOF together with the reduced count levels was evaluated by calculating the gains in signal-to-noise ratio (SNR) in the liver and contrast-to-noise ratio (CNR) in all PET-positive lesions before and after TOF employed at every simulated reduced count level. Finally, the PSF+TOF images at 50, 75 and 100% of counts were evaluated clinically on a 5-point scale by three nuclear medicine physicians., Results: The visual inspection of the reconstructed images did not reveal significant differences in image quality between 75 and 100% count levels for PSF+TOF. The improvements in SNR and CNR were the greatest for TOF reconstruction and PSF combined. Both SNR and CNR gains did increase linearly with the patients BMI for both OSEM only and PSF reconstruction. These benefits were observed until reducing the counts to 50 and 35% for SNR and CNR, respectively., Conclusions: The benefit of using TOF was noticeable when using 50% or greater of the counts when evaluating the CNR and SNR. For [18F]FDG-PET/CT, whole-body paediatric imaging the injected activity can be reduced to 75% of the original dose without compromising PET image quality., (© 2021. The Author(s).)

Purpose: Risk classification of primary prostate cancer in clinical routine is mainly based on prostate-specific antigen (PSA) levels, Gleason scores from biopsy samples, and tumor-nodes-metastasis (TNM) staging. This study aimed to investigate the diagnostic performance of positron emission tomography/magnetic resonance imaging (PET/MRI) in vivo models for predicting low-vs-high lesion risk (LH) as well as biochemical recurrence (BCR) and overall patient risk (OPR) with machine learning., Methods: Fifty-two patients who underwent multi-parametric dual-tracer [ 18 F]FMC and [ 68 Ga]Ga-PSMA-11 PET/MRI as well as radical prostatectomy between 2014 and 2015 were included as part of a single-center pilot to a randomized prospective trial (NCT02659527). Radiomics in combination with ensemble machine learning was applied including the [ 68 Ga]Ga-PSMA-11 PET, the apparent diffusion coefficient, and the transverse relaxation time-weighted MRI scans of each patient to establish a low-vs-high risk lesion prediction model (M LH ). Furthermore, M BCR and M OPR predictive model schemes were built by combining M LH , PSA, and clinical stage values of patients. Performance evaluation of the established models was performed with 1000-fold Monte Carlo (MC) cross-validation. Results were additionally compared to conventional [ 68 Ga]Ga-PSMA-11 standardized uptake value (SUV) analyses., Results: The area under the receiver operator characteristic curve (AUC) of the M LH model (0.86) was higher than the AUC of the [ 68 Ga]Ga-PSMA-11 SUV max analysis (0.80). MC cross-validation revealed 89% and 91% accuracies with 0.90 and 0.94 AUCs for the M BCR and M OPR models respectively, while standard routine analysis based on PSA, biopsy Gleason score, and TNM staging resulted in 69% and 70% accuracies to predict BCR and OPR respectively., Conclusion: Our results demonstrate the potential to enhance risk classification in primary prostate cancer patients built on PET/MRI radiomics and machine learning without biopsy sampling.

Background: PET/MRI phantom studies are challenged by the need of phantom-specific attenuation templates to account for attenuation properties of the phantom material. We present a PET/MRI phantom built from MRI-visible material for which attenuation correction (AC) can be performed using the standard MRI-based AC., Methods: A water-fillable phantom was 3D-printed with a commercially available MRI-visible polymer. The phantom had a cylindrical shape and the fillable compartment consisted of a homogeneous region and a region containing solid rods of different diameters. The phantom was filled with a solution of water and [18F]FDG. A 30 min PET/MRI acquisition including the standard Dixon-based MR-AC method was performed. In addition, a CT scan of the phantom was acquired on a PET/CT system. From the Dixon in-phase, opposed-phase and fat images, a phantom-specific AC map (Phantom MR-AC) was produced by separating the phantom material from the water compartment using a thresholding-based method and assigning fixed attenuation coefficients to the individual compartments. The PET data was reconstructed using the Phantom MR-AC, the original Dixon MR-AC, and an MR-AC just containing the water compartment (NoWall-AC) to estimate the error of ignoring the phantom walls. CT-based AC was employed as the reference standard. Average %-differences in measured activity between the CT corrected PET and the PET corrected with the other AC methods were calculated., Results: The phantom housing and the liquid compartment were both visible and distinguishable from each other in the Dixon images and allowed the segmentation of a phantom-specific MR-based AC. Compared to the CT-AC PET, average differences in measured activity in the whole water compartment in the phantom of -0.3%, 9.4%, and -24.1% were found for Dixon phantom MR-AC, MR-AC, and NoWall-AC based PET, respectively. Average differences near the phantom wall in the homogeneous region were -0.3%, 6.6%, and -34.3%, respectively. Around the rods, activity differed from the CT-AC PET by 0.7%, 8.9%, and -45.5%, respectively., Conclusion: The presented phantom material is visible using standard MR sequences, and thus, supports the use of standard, phantom-independent MR measurements for MR-AC in PET/MRI phantom studies.

Purpose of the Report: F-FDG PET is limited for assessment of central nervous system lymphoma (CNSL) due to physiologic tracer accumulation in the brain. We prospectively evaluated the novel PET tracer Ga-pentixafor, which targets the C-X-C chemokine receptor 4 (CXCR4), for lesion visualization and response assessment of CNSL., Materials and Methods: Seven CNSL patients underwent Ga-pentixafor PET/MRI with contrast enhancement (CE-MRI) and diffusion-weighted sequences. The accuracy of Ga-pentixafor PET for CNSL lesion detection relative to the CE-MRI reference standard was determined. Standardized uptake values (SUVmean and SUVmax), PET-based (PTV) and MRI-based (VOLMRI) tumor volumes, and apparent diffusion coefficients (ADCs) were assessed, and correlation coefficients were calculated. Three SUVmax thresholds (41%, 50%, and 70%) were evaluated for PTV definitions (PTV41%, PTV50%, and PTV70%) and tested against VOLMRI using paired sample t tests., Results: Twelve Ga-pentixafor PET/MRI examinations (including 5 follow-up scans) of 7 patients were evaluated. Ga-pentixafor PET demonstrated 18 lesions, all of which were confirmed by CE-MRI; there were no false-positive lesions on PET (accuracy, 100%). PTV41% showed the highest concordance with lesion morphology, with no significant difference compared with VOLMRI (mean difference, -0.24 cm; P = 0.45). The correlation between ADCmean and SUVmean41% (r = 0.68) was moderate. Changes in PTV41% on follow-up PET/MRI showed the same trend as VOLMRI changes, including progression of 1 lesion each in patient 1 (+456.0% PTV41% and +350.8% VOLMRI) and patient 3 (+110.4% PTV41% and +85.1% VOLMRI)., Conclusions: Ga-pentixafor PET may be feasible for assessment and follow-up of CNSL. Future studies need to focus on testing its clinical value to distinguish between glioma and CNSL, and between radiation-induced inflammation and viable residual tumor.

Group interactions are widely observed in nature to optimize a set of critical collective behaviors, most notably sensing and decision making in uncertain environments. Nevertheless, these interactions are commonly modeled using local (proximity) networks, in which individuals interact within a certain spatial range. Recently, other interaction topologies have been revealed to support the emergence of higher levels of scalability and rapid information exchange. One prominent example is scale-free networks. In this study, we aim to examine the impact of scale-free communication when implemented for a swarm foraging task in dynamic environments. We model dynamic (uncertain) environments in terms of changes in food density and analyze the collective response of a simulated swarm with communication topology given by either proximity or scale-free networks. Our results suggest that scale-free networks accelerate the process of building up a rapid collective response to cope with the environment changes. However, this comes at the cost of lower coherence of the collective decision. Moreover, our findings suggest that the use of scale-free networks can improve swarm performance due to two side-effects introduced by using long-range interactions and frequent network regeneration. The former is a topological consequence, while the latter is a necessity due to robot motion. These two effects lead to reduced spatial correlations of a robot's behavior with its neighborhood and to an enhanced opinion mixing, i.e., more diversified information sampling. These insights were obtained by comparing the swarm performance in presence of scale-free networks to scenarios with alternative network topologies, and proximity networks with and without packet loss., (Copyright © 2020 Rausch, Simoens and Khaluf.)

Background: In oncology, lesion characterization is essential for tumor grading, treatment planning, and follow-up of cancer patients. Hybrid imaging systems, such as Single Photon Emission Computed Tomography (SPECT)/CT, Positron Emission Tomography (PET)/CT, or PET/magnetic resonance imaging (MRI), play an essential role for the noninvasive quantification of tumor characteristics. However, most of the existing approaches are challenged by intra- and intertumor heterogeneity. Novel quantitative imaging parameters that can be derived from textural feature analysis (as part of radiomics) are promising complements for improved characterization of tumor heterogeneity, thus, supporting clinically relevant implementations of personalized medicine concepts. Nevertheless, establishing new quantitative parameters for tumor characterization requires the use of standardized imaging objects to test the reliability of results prior to their implementation in patient studies., Methods: In this review, we summarize existing reports on heterogeneous phantoms with a focus on simulating tumor heterogeneity. We discuss the techniques, materials, advantages, and limitations of the existing phantoms for PET, CT, and MR imaging modalities., Conclusions: Finally, we outline the future directions and requirements for the design of cross modality imaging phantoms., (© 2020 The Authors. Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)

In the past, determination of absolute values of cerebral metabolic rate of glucose (CMRGlc) in clinical routine was rarely carried out due to the invasive nature of arterial sampling. With the advent of combined PET/MR imaging technology, CMRGlc values can be obtained non-invasively, thereby providing the opportunity to take advantage of fully quantitative data in clinical routine. However, CMRGlc values display high physiological variability, presumably due to fluctuations in the intrinsic activity of the brain at rest. To reduce CMRGlc variability associated with these fluctuations, the objective of this study was to determine whether functional connectivity measures derived from resting-state fMRI (rs-fMRI) could be used to correct for these fluctuations in intrinsic brain activity., Methods: We studied 10 healthy volunteers who underwent a test-retest dynamic [18F]FDG-PET study using a fully integrated PET/MR system (Siemens Biograph mMR). To validate the non-invasive derivation of an image-derived input function based on combined analysis of PET and MR data, arterial blood samples were obtained. Using the arterial input function (AIF), parametric images representing CMRGlc were determined using the Patlak graphical approach. Both directed functional connectivity (dFC) and undirected functional connectivity (uFC) were determined between nodes in six major networks (Default mode network, Salience, L/R Executive, Attention, and Sensory-motor network) using either a bivariate-correlation (R coefficient) or a Multi-Variate AutoRegressive (MVAR) model. In addition, the performance of a regional connectivity measure, the fractional amplitude of low frequency fluctuations (fALFF), was also investigated., Results: The average intrasubject variability for CMRGlc values between test and retest was determined as (14 ±8%) with an average inter-subject variability of 25% at test and 15% at retest. The average CMRGlc value (umol/100 g/min) across all networks was 39 ±10 at test and increased slightly to 43 ±6 at retest. The R, MVAR and fALFF coefficients showed relatively large test-retest variability in comparison to the inter-subjects variability, resulting in poor reliability (intraclass correlation in the range of 0.11-0.65). More importantly, no significant relationship was found between the R coefficients (for uFC), MVAR coefficients (for dFC) or fALFF and corresponding CMRGlc values for any of the six major networks., Discussion: Measurement of functional connectivity within established brain networks did not provide a means to decrease the inter- or intrasubject variability of CMRGlc values. As such, our results indicate that connectivity measured derived from rs-fMRI acquired contemporaneously with PET imaging are not suited for correction of CMRGlc variability associated with intrinsic fluctuations of resting-state brain activity. Thus, given the observed substantial inter- and intrasubject variability of CMRGlc values, the relevance of absolute quantification for clinical routine is presently uncertain., (Copyright © 2020 Shiyam Sundar, Baajour, Beyer, Lanzenberger, Traub-Weidinger, Rausch, Pataraia, Hahn, Rischka, Hienert, Klebermass and Muzik.)

We describe a fully automated processing pipeline to support the noninvasive absolute quantification of the cerebral metabolic rate for glucose (CMRGlc) in a clinical setting. This pipeline takes advantage of "anatometabolic" information associated with fully integrated PET/MRI. Methods: Ten healthy volunteers (5 men and /5 women; 27 ± 7 y old; 70 ± 10 kg) underwent a test-retest 18 F-FDG PET/MRI examination of the brain. The imaging protocol consisted of a 60-min PET list-mode acquisition with parallel MRI acquisitions, including 3-dimensional time-of-flight MR angiography, MRI navigators, and a T1-weighted MRI scan. State-of-the-art MRI-based attenuation correction was derived from T1-weighted MRI (pseudo-CT [pCT]). For validation purposes, a low-dose CT scan was also performed. Arterial blood samples were collected as the reference standard (arterial input function [AIF]). The developed pipeline allows the derivation of an image-derived input function (IDIF), which is subsequently used to create CMRGlc maps by means of a Patlak analysis. The pipeline also includes motion correction using the MRI navigator sequence as well as a novel partial-volume correction that accounts for background heterogeneity. Finally, CMRGlc maps are used to generate a normative database to facilitate the detection of metabolic abnormalities in future patient scans. To assess the performance of the developed pipeline, IDIFs extracted by both CT-based attenuation correction (CT-IDIF) and MRI-based attenuation correction (pCT-IDIF) were compared with the reference standard (AIF) using the absolute percentage difference between the areas under the curves as well as the absolute percentage difference in regional CMRGlc values. Results: The absolute percentage differences between the areas under the curves for CT-IDIF and pCT-IDIF were determined to be 1.4% ± 1.0% and 3.4% ± 2.6%, respectively. The absolute percentage difference in regional CMRGlc values based on CT-IDIF and pCT-IDIF differed by less than 6% from the reference values obtained from the AIF. Conclusion: By taking advantage of the capabilities of fully integrated PET/MRI, we developed a fully automated computational pipeline that allows the noninvasive determination of regional CMRGlc values in a clinical setting. This methodology might facilitate the proliferation of fully quantitative imaging into the clinical arena and, as a result, might contribute to improved diagnostic efficacy., (© 2020 by the Society of Nuclear Medicine and Molecular Imaging.)

The purpose of this study was to establish a non-invasive clinical PET/MR protocol using [ 18 F]-labeled deoxyglucose (FDG) that provides physicians with regional metabolic rate of glucose (MRGlc) values and to clarify the contribution of absolute quantification to clinical management of patients with non-lesional extratemporal lobe epilepsy (ETLE). The study included a group of 15 patients with non-lesional ETLE who underwent a dynamic FDG PET study using a fully-integrated PET/MRI system (Siemens Biograph). FDG tracer uptake images were converted to MRGlc (μmol/100 g/min) maps using an image derived input function that was extracted based on the combined analysis of PET and MRI data. In addition, the same protocol was applied to a group of healthy controls, yielding a normative database. Abnormality maps for ETLE patients were created with respect to the normative database, defining significant hypo- or hyper-metabolic regions that exceeded ±2 SD of normal regional mean MRGlc values. Abnormality maps derived from MRGlc images of ETLE patients contributed to the localization of hypo-metabolic areas against visual readings in 53% and increased the confidence in the original clinical readings in 33% of all cases. Moreover, quantification allowed identification of hyper-metabolic areas that are associated with frequently spiking cortex, rarely acknowledged in clinical readings. Overall, besides providing some confirmatory information to visual readings, quantitative PET imaging demonstrated only a moderate impact on clinical management of patients with complex pathology that leads to epileptic seizures, failing to provide new decisive information that would have changed classification of patients from being rejected to being considered for surgical intervention., (Copyright © 2020 Traub-Weidinger, Muzik, Sundar, Aull-Watschinger, Beyer, Hacker, Hahn, Kasprian, Klebermass, Lanzenberger, Mitterhauser, Pilz, Rausch, Rischka, Wadsak and Pataraia.)

Purpose: PET/MRI has recently been introduced into clinical practice. We prospectively investigated the clinical impact of PET/MRI compared with PET/CT, in a mixed population of cancer patients, and performed an economic evaluation of PET/MRI., Methods: Cancer patients referred for routine staging or follow-up by PET/CT underwent consecutive PET/CT and PET/MRI, using single applications of [ 18 F]FDG, [ 68 Ga]Ga-DOTANOC, or [ 18 F]FDOPA, depending on tumor histology. PET/MRI and PET/CT were rated separately, and lesions were assessed per anatomic region; based on regions, per-examination and per-patient accuracies were determined. A simulated, multidisciplinary team meeting served as reference standard and determined whether differences between PET/CT and PET/MRI affected patient management. The McNemar tests were used to compare accuracies, and incremental cost-effectiveness ratios (ICERs) for PET/MRI were calculated., Results: Two hundred sixty-three patients (330 same-day PET/CT and PET/MRI examinations) were included. PET/MRI was accurate in 319/330 examinations and PET/CT in 277/330 examinations; the respective accuracies of 97.3% and 83.9% differed significantly (P < 0.001). The additional findings on PET/MRI-mainly liver and brain metastases-had implications for patient management in 21/263 patients (8.0%). The per-examination cost was 596.97 EUR for PET/MRI and 405.95 EUR for PET/CT. ICERs for PET/MRI were 14.26 EUR per percent of diagnostic accuracy and 23.88 EUR per percent of correctly managed patients., Conclusions: PET/MRI enables more appropriate management than PET/CT in a nonnegligible fraction of cancer patients. Since the per-examination cost is about 50% higher for PET/MRI than for PET/CT, a histology-based triage of patients to either PET/MRI or PET/CT may be meaningful.

Background: Several MR-based attenuation correction (AC) approaches were developed to conquer the challenging AC in hybrid PET/MR imaging. These AC methods are commonly evaluated on standardized uptake values or tissue concentration. However, in neurotransmitter system studies absolute quantification is more favorable due to its accuracy. Therefore, our aim was to investigate the accuracy of segmentation- and atlas-based MR AC approaches on serotonin transporter (SERT) distribution volumes and occupancy after a drug challenge., Methods: 18 healthy subjects (7 male) underwent two [ 11 C]DASB PET/MRI measurements in a double-blinded, placebo controlled, cross-over design. After 70 min the selective serotonin reuptake inhibitor (SSRI) citalopram or a placebo was infused. The parameters total and specific volume of distribution (V T , V S = BP P ) and occupancy were quantified. All subjects underwent a low-dose CT scan as reference AC method. Besides the standard AC approaches DIXON and UTE, a T1-weighted structural image was recorded to estimate a pseudo-CT based on an MR/CT database (pseudoCT). Another evaluated AC approach superimposed a bone model on AC DIXON. Lastly, an approach optimizing the segmentation of UTE images was analyzed (RESOLUTE). PET emission data were reconstructed with all 6 AC methods. The accuracy of the AC approaches was evaluated on a region of interest-basis for the parameters V T , BP P , and occupancy with respect to the results of AC CT., Results: Variations for V T and BP P were found with all AC methods with bias ranging from -15 to 17%. The smallest relative errors for all regions were found with AC pseudoCT (<|5%|). Although the bias between BP P SSRI and BP P placebo varied markedly with AC DIXON (<|12%|) and AC UTE (<|9%|), a high correlation to AC CT was obtained ( r 2 ∼1). The relative difference of the occupancy for all tested AC methods was small for SERT high binding regions (<|4%|)., Conclusion: The high correlation might offer a rescaling from the biased parameters V T and BP P to the true values. Overall, the pseudoCT approach yielded smallest errors and the best agreement with AC CT. For SERT occupancy, all AC methods showed little bias in high binding regions, indicating that errors may cancel out in longitudinal assessments., (Copyright © 2019 Rischka, Gryglewski, Berroterán-Infante, Rausch, James, Klöbl, Sigurdardottir, Hartenbach, Hahn, Wadsak, Mitterhauser, Beyer, Kasper, Prayer, Hacker and Lanzenberger.)

Hybrid PET/MR offers new opportunities in radiation oncology for tissue/tumour characterisation and response assessment. Attenuation correction (AC) is an important issue especially in the presence of immobilization devices and flat table tops (FTT). The goal of this study was to compare two methods of AC using CT- and 68 Ge/ 68 Ga transmission scan-based attenuation maps (μ-maps) for a custom-designed FTT. Measurements were performed in the mMR PET/MR and TrueV PET/CT Biograph Siemens scanners with three different phantoms, namely the Siemens MR-QA, a cubic canister and the NEMA IEC body phantom. The study revealed that the MR image quality is not hampered by the presence of the FTT. For cubic canister applying the scanner's inherent AC alone resulted in inaccuracies in PET images, with up to -4.0% underestimation of the activity. The mean NEMA sphere activity measurements without FTT, agreed within 3.5% with the respective inserted activity. Placing the FTT in the PET/MR scanner resulted in a difference to the injected activity of 4.5% when the table was not corrected for. By introducing the μ-maps the discrepancy between the used activity and the measurements decreased down to 2.6%. To improve the AC of the FTT the creation of a dedicated μ-map was necessary while the CT-based μ-map performed equally good as the source transmission scan-based one., (Copyright © 2019 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

Aim: To assess if tumour grading based on dynamic [18F]FET positron emission tomography/magnetic resonance imaging (PET/MRI) studies is affected by different MRI-based attenuation correction (AC) methods., Methods: Twenty-four patients with suspected brain tumours underwent dynamic [18F]FET-PET/MRI examinations and subsequent low-dose computed tomography (CT) scans of the head. The dynamic PET data was reconstructed using the following AC methods: standard Dixon-based AC and ultra-short echo time MRI-based AC (MR-AC) and a model-based AC approach. All data were reconstructed also using CT-based AC (reference). For all lesions and reconstructions, time-activity curves (TACs) and time to peak (TTP) were extracted using different region-of-interest (ROI) and volume-of-interest (VOI) definitions. According to the most common evaluation approaches, TACs were categorised into two or three distinct curve patterns. Changes in TTP and TAC patterns compared to PET using CT-based AC were reported., Results: In the majority of cases, TAC patterns did not change. However, TAC pattern changes as well as changes in TTP were observed in up to 8% and 17% of the cases when using different MR-AC methods and ROI/VOI definitions, respectively. However, these changes in TTP and TAC pattern were attributed to different delineations of the ROIs/VOIs in PET corrected with different AC methods., Conclusion: PET/MRI using different MR-AC methods can be used for the assessment of TAC patterns in dynamic [18F]FET studies, as long as a meaningful delineation of the area of interest within the tumour is ensured., Key Points: • PET/MRI using different MR-AC methods can be used for dynamic [18F]FET studies. • A meaningful segmentation of the area of interest needs to be ensured, mandating a visual validation of the delineation by an experienced reader.

Absolute quantification of PET brain imaging requires the measurement of an arterial input function (AIF), typically obtained invasively via an arterial cannulation. We present an approach to automatically calculate an image-derived input function (IDIF) and cerebral metabolic rates of glucose (CMRGlc) from the [18F]FDG PET data using an integrated PET/MRI system. Ten healthy controls underwent test-retest dynamic [18F]FDG-PET/MRI examinations. The imaging protocol consisted of a 60-min PET list-mode acquisition together with a time-of-flight MR angiography scan for segmenting the carotid arteries and intermittent MR navigators to monitor subject movement. AIFs were collected as the reference standard. Attenuation correction was performed using a separate low-dose CT scan. Assessment of the percentage difference between area-under-the-curve of IDIF and AIF yielded values within ±5%. Similar test-retest variability was seen between AIFs (9 ± 8) % and the IDIFs (9 ± 7) %. Absolute percentage difference between CMRGlc values obtained from AIF and IDIF across all examinations and selected brain regions was 3.2% (interquartile range: (2.4-4.3) %, maximum < 10%). High test-retest intravariability was observed between CMRGlc values obtained from AIF (14%) and IDIF (17%). The proposed approach provides an IDIF, which can be effectively used in lieu of AIF.