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Objecive: To investigate temporal trends in the individual workload of nuclear medicine physicians at a large tertiary care academic center between 2008 and 2023., Methods: This study analyzed the reporting workload of nuclear medicine physicians in a large tertiary care academic center in The Netherlands on 36 unique (randomly sampled) calendar days, for each year between 2008 and 2023. The average daily departmental workload (measured with relative value units) was calculated for each year between 2008 and 2023. The individual workload was calculated by dividing the average daily departmental workload in each year by the available full-time equivalent nuclear medicine physicians in each year. Mann-Kendall tests were used to assess for any temporal monotonic trends in individual workload and types of nuclear medicine procedures performed., Results: Individual workload increased significantly between 2008 and 2023 (Mann-Kendall tau of 0.611, P = 0.001). Individual workload in 2023 was 86% higher than in 2008. The use of positron emission tomography (PET) increased significantly (Mann-Kendall tau of 0.912, P < 0.001) between 2008 and 2023. The use of diagnostic scintigraphy decreased significantly in the same period (Mann-Kendall tau of -0.817, P < 0.001). The use of DEXA also showed a significant decrease (Mann-Kendall tau of -0.467, P = 0.013), but this decrease was negligible on a relative scale. The number of therapeutic procedures (Mann-Kendall tau of -0.100, P = 0.626) remained statistically stable in this period., Conclusions: Our single-center study showed that the individual workload of nuclear medicine physicians has increased significantly between 2008 and 2023, driven by the rise in PET scans. The demand for both diagnostic and therapeutic nuclear medicine procedures and associated workload is expected to keep on increasing in the foreseeable future. This workload trend should be taken into account by policymakers involved in nuclear medicine staffing planning. A healthy balance between the nuclear medicine workforce and workload is necessary to maintain the quality of care, to be able to perform other important (academic) tasks such as research, educating and training medical students and residents, and management, and to prevent physician burnout and dropout., (© 2024. The Author(s) under exclusive licence to The Japanese Society of Nuclear Medicine.)

Most pharmacological treatments for depression target monoamine transporters and about 50 % of treated patients attain symptomatic remission. Once remission is attained, it is hard to distinguish the changes on brain monoaminergic transmission induced by the antidepressants, from those associated to remission per se. In this study, we aimed at studying the brain of spontaneously remitted rats from repeated social defeat (RSD)-induced depression in terms of dopamine D 2 /D 3 receptor and serotonin transporter (SERT) availability, showing absence of depressive symptoms 2 weeks after RSD. We combined behavioral tests and positron emission tomography (PET) with [ 11 C]raclopride and [ 11 C]DASB to explore the changes in dopamine D 2 /D 3 receptor and serotonin transporter (SERT) availability, respectively. Male rats submitted to RSD showed increased peripheral corticosterone levels, decreased body weight and anhedonia, as measured with the sucrose preference test, 1 day after RSD, confirming depressive-like symptoms. These depressive-like symptoms were no longer present 2 weeks after RSD. Rats that recovered from depressive-like symptoms showed decreased D 2 /D 3 receptor binding in the caudate putamen and increased SERT availability in the brainstem, insular cortex, midbrain and thalamus, compared to control non-stressed animals. Our study shows that remission of depressive-like symptoms does not just "normalize" monoaminergic transmission, as changes in dopaminergic and serotonergic neurotransmission linger in several brain regions even after depressive-like symptoms have already resolved. These results provide new insights into the brain changes associated to remission in the RSD-induced depression model in rats., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Funding for this study was provided by FONDECYT grant N° 1,240,804 (JS). The salary of RM was paid by Becas Chile Doctorado en el extranjero – ANID, Chile. Funding sources had no role in study design, collection and/or analysis and/or interpretation of data, in the writing of the publication, or in the decision to submit the paper for publication. If there are other authors, they 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 Inc. All rights reserved.)

[ 18 F]-dihydroxyphenylalanine ([ 18 F]FDOPA) is a radiopharmaceutical used in a broad spectrum of diseases, including neuroendocrine tumors (NETs), congenital hyperinsulinism, parkinsonian syndromes and neuro-oncology. Genetic analysis and disease specific biomarkers may guide the optimum selection of patients that may benefit most from [ 18 F]FDOPA PET in different stages of several neuroendocrine neoplasms and in congenital hyperinsulinism. For clinical routine in neuro-oncology, indications for [ 18 F]FDOPA PET include tumor delineation and distinguishing between treatment related changes and recurrent disease. New developments as the advent of large axial field of view PET/CT or integrated PET/MRI systems may provide more unique opportunities, such as those related to detection of smaller lesions in primary staging of NETs, dose reduction in children with congenital hyperinsulinism, or possibilities to obtain more extensive noninvasive quantification of cerebral uptake by using image derived input functions. Although the widespread use of [ 18 F]FDOPA has been hampered by complex synthesis methods and high production costs in the past, significant efforts have been undertaken to provide robust GMP compliant synthesis methods with high activity yield and molar activity., 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 Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Cardiac magnetic resonance elastography (MRE) shows promise in assessing the mechanofunctional properties of the heart but faces clinical challenges, mainly synchronization with cardiac cycle, breathing, and external harmonic stimulation., Purpose: To determine the reproducibility of in vivo cardiac multifrequency MRE (MMRE) for assessing diastolic left ventricular (LV) stiffness and viscosity., Study Type: Prospective., Subjects: This single-center study included a total of 28 participants (mean age, 56.6 ± 23.0 years; 16 male) consisting of randomly selected healthy participants (mean age, 44.6 ± 20.1 years; 9 male) and patients with aortic stenosis (mean age, 78.3 ± 3.8 years; 7 male)., Field Strength/sequence: 3 T, 3D multifrequency MRE with a single-shot spin-echo planar imaging sequence., Assessment: Each participant underwent two cardiac MMRE examinations on the same day. Full 3D wave fields were acquired in diastole at frequencies of 80, 90, and 100 Hz during a total of three breath-holds. Shear wave speed (SWS) and penetration rate (PR) were reconstructed as a surrogate for tissue stiffness and inverse viscous loss. Epicardial and endocardial ROIs were manually drawn by two independent readers to segment the LV myocardium., Statistical Tests: Shapiro-Wilk test, Bland-Altman analysis and intraclass correlation coefficient (ICC). P-value <0.05 were considered statistically significant., Results: Bland-Altman analyses and intraclass correlation coefficients (ICC = 0.96 for myocardial stiffness and ICC = 0.93 for viscosity) indicated near-perfect test-retest repeatability among examinations on the same day. The mean SWS for scan and re-scan diastolic LV myocardium were 2.42 ± 0.24 m/s and 2.39 ± 0.23 m/s; the mean PR were 1.24 ± 0.17 m/s and 1.22 ± 0.14 m/s. Inter-reader variability showed good to excellent agreement for myocardial stiffness (ICC = 0.92) and viscosity (ICC = 0.85)., Data Conclusion: Cardiac MMRE is a promising and reproducible method for noninvasive assessment of diastolic LV stiffness and viscosity., Level of Evidence: 2 TECHNICAL EFFICACY: 1., (© 2024 The Author(s). Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Methods to shorten [ 18 F]FDG Patlak PET imaging procedures ranging from 65-90 to 20-30 min after injection, using a population-averaged input function (PIF) scaled to patient-specific image-derived input function (IDIF) values, were recently evaluated. The aim of the present study was to explore the feasibility of ultrashort 10-min [ 18 F]FDG Patlak imaging at 55-65 min after injection using a PIF combined with direct Patlak reconstructions to provide reliable quantitative accuracy of lung tumor uptake, compared with a full-duration 65-min acquisition using an IDIF. Methods: Patients underwent a 65-min dynamic PET acquisition on a long-axial-field-of-view (LAFOV) Biograph Vision Quadra PET/CT scanner. Subsequently, direct Patlak reconstructions and image-based (with reconstructed dynamic images) Patlak analyses were performed using both the IDIF (time to relative kinetic equilibrium between blood and tissue concentration (t*) = 30 min) and a scaled PIF at 30-60 min after injection. Next, direct Patlak reconstructions were performed on the system console using only the last 10 min of the acquisition, that is, from 55 to 65 min after injection, and a scaled PIF using maximum crystal ring difference settings of both 85 and 322. Tumor lesion and healthy-tissue uptake was quantified and compared between the differently obtained parametric images to assess quantitative accuracy. Results: Good agreement was obtained between direct- and image-based Patlak analyses using the IDIF (t* = 30 min) and scaled PIF at 30-60 min after injection, performed using the different approaches, with no more than 8.8% deviation in tumor influx rate value ( K i ) (mean difference ranging from -0.0022 to 0.0018 mL/[min × g]). When direct Patlak reconstruction was performed on the system console, excellent agreement was found between the use of a scaled PIF at 30-60 min after injection versus 55-65 min after injection, with 2.4% deviation in tumor K i (median difference, -0.0018 mL/[min × g]; range, -0.0047 to 0.0036 mL/[min × g]). For different maximum crystal ring difference settings using the scan time interval of 55-65 min after injection, only a 0.5% difference (median difference, 0.0000 mL/[min × g]; range, -0.0004 to 0.0013 mL/[min × g]) in tumor K i was found. Conclusion: Ultrashort whole-body [ 18 F]FDG Patlak imaging is feasible on an LAFOV Biograph Vision Quadra PET/CT system without loss of quantitative accuracy to assess lung tumor uptake compared with a full-duration 65-min acquisition. The ultrashort 10-min direct Patlak reconstruction with PIF allows for its implementation in clinical practice., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Objectives: Significant variability exists in the contrast phases applied during computed tomography (CT) studies when assessing morphometric measurements of muscle area (CT-assessed sarcopenia) and density (CT-assessed myosteatosis) and visceral adipose tissue area (CT-assessed visceral obesity). This study explored the impact of contrast phase timing on changes in morphometric measurements of body composition., Methods: This single-center retrospective cohort study included 459 patients undergoing a multiphase CT scan. Morphometric measurements were obtained at the third lumbar vertebra level. Patients were classified as sarcopenic, myosteatotic, or visceral obese using predefined cutoff values. The intraclass correlation coefficient was used to assess correlations across different enhancement phases, and Cohen's κ measured the inter-enhancement agreement for sarcopenia, myosteatosis, and visceral obesity., Results: Significant differences were observed in mean visceral adipose tissue area, muscle density, and muscle area (P < 0.001). The intraclass correlation coefficient between unenhanced and arterial phases was 0.987 (95% confidence interval [CI], 0.759-0.996) for adipose tissue, 0.995 (95% CI, 0.989-0.997) for muscle area, and 0.850 (95% CI, 0.000-0.956) for muscle density. However, when morphometric measurements were categorized using predefined cutoffs, the κ agreement was considerably lower, particularly for CT-assessed myosteatosis, ranging from 0.635 (unenhanced to arterial) to 0.331 (unenhanced to late venous phase)., Conclusions: Different CT contrast phases induce small but clinically significant alterations in the measurements of muscle area and density and visceral fat. Such minor changes can result in misclassification issues when fixed cutoff values are used to diagnose myosteatosis with CT. This underscores the importance of reporting absolute values and the specific contrast phase used in future studies., 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 article., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background : Multiple sclerosis (MS) has two main phenotypes: relapse-remitting MS (RRMS) and progressive MS (PMS), distinguished by disability profiles and treatment response. Differentiating them using conventional MRI is challenging. Objective : This study explores the use of scaled subprofile modelling using principal component analysis (SSM/PCA) on MRI data to distinguish between MS phenotypes. Methods : MRI scans were performed on patients with RRMS (n = 30) and patients with PMS (n = 20), using the standard sequences T 1 w, T 2 w, T 2 w-FLAIR, and the myelin-sensitive sequences magnetisation transfer (MT) ratio (MTR), quantitative MT (qMT), inhomogeneous MT ratio (ihMTR), and quantitative inhomogeneous MT (qihMT). Results : SSM/PCA analysis of qihMT images best differentiated PMS from RRMS, with the highest specificity (87%) and positive predictive value (PPV) (83%), but a lower sensitivity (67%) and negative predictive value (NPV) (72%). Conversely, T 1 w data analysis showed the highest sensitivity (93%) and NPV (89%), with a lower PPV (67%) and specificity (53%). Phenotype classification agreement between T 1 w and qihMT was observed in 57% of patients. In the subset with concordant classifications, the sensitivity, specificity, PPV, and NPV were 100%, 88%, 90%, and 100%, respectively. Conclusions : SSM/PCA on MRI data revealed distinctive patterns for MS phenotypes. Optimal discrimination occurred with qihMT and T 1 w sequences, with qihMT identifying PMS and T 1 w identifying RRMS. When qihMT and T 1 w analyses align, MS phenotype prediction improves.

Imaging water pathways in the human body provides an excellent way of measuring accurately the blood flow directed to different organs. This makes it a powerful diagnostic tool for a wide range of diseases that are related to perfusion and oxygenation. Although water PET has a long history, its true potential has not made it into regular clinical practice. The article highlights the potential of water PET in molecular imaging and suggests its prospective role in becoming an essential tool for the 21st century precision medicine in different domains ranging from preclinical to clinical research and practice. The recent technical advances in high-sensitivity PET imaging can play a key accelerating role in empowering this technique, though there are still several challenges to overcome., 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 © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Hepatic artery complications (HACs), such as a thrombosis or stenosis, are serious causes of morbidity and mortality after paediatric liver transplantation (LT). This study will investigate the incidence, current management practices and outcomes in paediatric patients with HAC after LT, including early and late complications., Methods and Analysis: The HEPatic Artery stenosis and Thrombosis after liver transplantation In Children (HEPATIC) Registry is an international, retrospective, multicentre, observational study. Any paediatric patient diagnosed with HAC and treated for HAC (at age <18 years) after paediatric LT within a 20-year time period will be included. The primary outcomes are graft and patient survivals. The secondary outcomes are technical success of the intervention, primary and secondary patency after HAC intervention, intraprocedural and postprocedural complications, description of current management practices, and incidence of HAC., Ethics and Dissemination: All participating sites will obtain local ethical approval and (waiver of) informed consent following the regulations on the conduct of observational clinical studies. The results will be disseminated through scientific presentations at conferences and through publication in peer-reviewed journals., Trial Registration Number: The HEPATIC registry is registered at the ClinicalTrials.gov website; Registry Identifier: NCT05818644., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To determine how much timesaving and reduction of interruptions reading room assistants can provide by taking over non-image interpretation tasks (NITs) from radiology residents during on-call hours., Methods: Reading room assistants are medical students who were trained to take over NITs from radiology residents (e.g. answering telephone calls, administrative tasks and logistics) to reduce residents' workload during on-call hours. Reading room assistants' and residents' activities were tracked during 6 weekend dayshifts in a tertiary care academic center (with more than 2.5 million inhabitants in its catchment area) between 10 a.m. and 5p.m. (7-hour shift, 420 min), and time spent on each activity was recorded., Results: Reading room assistants spent the most time on the following timesaving activities for residents: answering incoming (41 min, 19%) and outgoing telephone calls (35 min, 16%), ultrasound machine related activities (19 min, 9%) and paramedical assistance such as supporting residents during ultrasound guided procedures and with patients (17 min, 8%). Reading room assistants saved 132 min of residents' time by taking over NITs while also spending circa 31 min consulting the resident, resulting in a net timesaving of 101 min (24%) during a 7-hour shift. The reading room assistants also prevented residents from being interrupted, at a mean of 18 times during the 7-hour shift., Conclusion: This study shows that the implementation of reading room assistants to radiology on-call hours could provide a timesaving for residents and also reduce the number of times residents are being interrupted during their work., 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: Estrogen receptors (ER) are implicated in psychiatric disorders. We assessed if ER availability in the human brain could be quantified using 16α-[ 18 F]-fluoro-17β-estradiol ([ 18 F]FES) positron emission tomography (PET)., Procedures: Seven post‑menopausal women underwent a dynamic [ 18 F]FES PET scan with arterial blood sampling. A T1-weighted MRI was acquired for anatomical information. After one week, four subjects received a selective ER degrader (SERD), four hours before the PET scan. Pharmacokinetic analysis was performed using a metabolite-corrected plasma curve as the input function. The optimal kinetic model was selected based on the Akaike information criterion and standard error of estimated parameters. Accuracy of Logan graphical analysis and standardized uptake value (SUV) was determined via correlational analyses., Results: The reversible two-tissue compartment model (2T4k) model with fixed K 1 /k 2 was preferred. The total volume of distribution (V T ) could be more reliably estimated than the binding potential (BP ND ). A high correlation of V T with Logan graphical analysis was observed, but only a moderate correlation with SUV. SERD administration resulted in a reduced V T in the pituitary gland, but not in other regions., Conclusions: The optimal quantification method for [ 18 F]FES was the 2T4k with fixed K 1 /k 2 or Logan graphical analysis, but specific binding was only observed in the pituitary gland., (© 2024. Crown.)

Adenosine A 2A -receptors (A 2A R) and dopamine D 2 -receptors (D 2 R) are known to work together in a synergistic manner. Inhibiting A 2A Rs by genetic or pharmacological means can relief symptoms and have neuroprotective effects in certain conditions. We applied PET imaging to evaluate the impact of the A 2A R antagonist KW6002 on D 2 R availability and neuroinflammation in an animal model of Parkinson's disease. Male Wistar rats with 6-hydroxydopamine-induced damage to the right striatum were given 3 mg/kg of KW6002 daily for 20 days. Motor function was assessed using the rotarod and cylinder tests, and neuroinflammation and dopamine receptor availability were measured using PET scans with the tracers [ 11 C]PBR28 and [ 11 C]raclopride, respectively. On day 7 and 22 following 6-OHDA injection, rats were sacrificed for postmortem analysis. PET scans revealed a peak in neuroinflammation on day 7. Chronic treatment with KW6002 significantly reduced [ 11 C]PBR28 uptake in the ipsilateral striatum [normalized to contralateral striatum] and [ 11 C]raclopride binding in both striata when compared to the vehicle group. These imaging findings were accompanied by an improvement in motor function. Postmortem analysis showed an 84% decrease in the number of Iba-1 + cells in the ipsilateral striatum [normalized to contralateral striatum] of KW6002-treated rats compared to vehicle rats on day 22 (p = 0.007), corroborating the PET findings. Analysis of tyrosine hydroxylase levels showed less dopaminergic neuron loss in the ipsilateral striatum of KW6002-treated rats compared to controls on day 7. These findings suggest that KW6002 reduces inflammation and dopaminergic neuron loss, leading to less motor symptoms in this animal model of Parkinson's disease., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Because of the limited axial field of view of conventional PET scanners, the internal carotid arteries are commonly used to obtain an image-derived input function (IDIF) in quantitative brain PET. However, time-activity curves extracted from the internal carotids are prone to partial-volume effects due to the limited PET resolution. This study aimed to assess the use of the internal carotids for quantifying brain glucose metabolism before and after partial-volume correction. Methods: Dynamic [ 18 F]FDG images were acquired on a 106-cm-long PET scanner, and quantification was performed with a 2-tissue-compartment model and Patlak analysis using an IDIF extracted from the internal carotids. An IDIF extracted from the ascending aorta was used as ground truth. Results: The internal carotid IDIF underestimated the area under the curve by 37% compared with the ascending aorta IDIF, leading to K i values approximately 17% higher. After partial-volume correction, the mean relative K i differences calculated with the ascending aorta and internal carotid IDIFs dropped to 7.5% and 0.05%, when using a 2-tissue-compartment model and Patlak analysis, respectively. However, microparameters ( K 1 , k 2 , k 3 ) derived from the corrected internal carotid curve differed significantly from those obtained using the ascending aorta. Conclusion: These results suggest that partial-volume-corrected internal carotids may be used to estimate K i but not kinetic microparameters. Further validation in a larger patient cohort with more variable kinetics is needed for more definitive conclusions., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Purpose: To determine the association between workload and diagnostic errors on 18 F-FDG-PET/CT., Materials and Methods: This study included 103 18 F-FDG-PET/CT scans with a diagnostic error that was corrected with an addendum between March 2018 and July 2023. All scans were performed at a tertiary care center. The workload of each nuclear medicine physician or radiologist who authorized the 18 F-FDG-PET/CT report was determined on the day the diagnostic error was made and normalized for his or her own average daily production (workload normalized ). A workload normalized of more than 100% indicates that the nuclear medicine physician or radiologist had a relative work overload, while a value of less than 100% indicates a relative work underload on the day the diagnostic error was made. The time of the day the diagnostic error was made was also recorded. Workload normalized was compared to 100% using a signed rank sum test, with the hypothesis that it would significantly exceed 100%. A Mann-Kendall test was performed to test the hypothesis that diagnostic errors would increase over the course of the day., Results: Workload normalized (median of 121%, interquartile range: 71 to 146%) on the days the diagnostic errors were made was significantly higher than 100% (P = 0.014). There was no significant upward trend in the frequency of diagnostic errors over the course of the day (Mann-Kendall tau = 0.05, P = 0.7294)., Conclusion: Work overload seems to be associated with diagnostic errors on 18 F-FDG-PET/CT. Diagnostic errors were encountered throughout the entire working day, without any upward trend towards the end of the day., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Reducing proteinuria is a crucial approach in preventing kidney function loss. Previous preclinical studies indicated that caloric restriction (CR) imposed at a young age protects against age-related proteinuria. However, these studies have not explored CR in established renal disease. Therefore, this study aimed to investigate the impact of CR on established proteinuria. Rats, aged 12 ± 2 weeks, were administered 2.1 mg/kg of Adriamycin. Six weeks after injection, protein excretion was measured, and a [ 13 N]ammonia positron emission tomography (PET) scan was conducted to assess kidney perfusion. After 7 weeks rats were divided into four groups: ad libitum (AL) and CR groups fed either a 12% or a 20% protein diet. All groups were treated for 12 weeks. Blood pressure was measured and a second PET scan was acquired at the end of the study. The animals subjected to CR exhibited a 20.3% decrease in protein excretion (p = 0.003) compared to those in the AL groups. Additionally, blood pressure in the CR group was 21.2% lower (p < 0.001) than in the AL groups. While kidney function declined over time in all groups, the 20% CR group demonstrated the smallest decline. Thus CR effectively reduces urinary protein excretion and lowers blood pressure in rats with established proteinuria., (© 2024 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Disruption of the immune system during embryonic brain development by environmental chemicals was proposed as a possible cause of neurodevelopmental disorders. We previously found adverse effects of di-n-octyltin dichloride (DOTC) on maternal and developing immune systems of rats in an extended one-generation reproductive toxicity study according to the OECD 443 test guideline. We hypothesize that the DOTC-induced changes in the immune system can affect neurodevelopment. Therefore, we used in-vivo MRI and PET imaging and genomics, in addition to behavioral testing and neuropathology as proposed in OECD test guideline 443, to investigate the effect of DOTC on structural and functional brain development. Male rats were exposed to DOTC (0, 3, 10, or 30 mg/kg of diet) from 2 weeks prior to mating of the F0-generation until sacrifice of F1-animals. The brains of rats, exposed to DOTC showed a transiently enlarged volume of specific brain regions (MRI), altered specific gravity, and transient hyper-metabolism ([ 18 F]FDG PET). The alterations in brain development concurred with hyper-responsiveness in auditory startle response and slight hyperactivity in young adult animals. Genomics identified altered transcription of key regulators involved in neurodevelopment and neural function (e.g. Nrgrn , Shank3 , Igf1r , Cck , Apba2 , Foxp2 ); and regulators involved in cell size, cell proliferation, and organ development, especially immune system development and functioning (e.g. LOC679869 , Itga11 , Arhgap5 , Cd47 , Dlg1 , Gas6 , Cml5 , Mef2c ). The results suggest the involvement of immunotoxicity in the impairment of the nervous system by DOTC and support the hypothesis of a close connection between the immune and nervous systems in brain development.

Purpose: Accurate preoperative localization is imperative to guide surgery in primary hyperparathyroidism (pHPT). It remains unclear which second-line imaging technique is most effective after negative first-line imaging. In this study, we compare the diagnostic effectiveness of [ 11 C]methionine PET/CT, [ 11 C]choline PET/CT, and four dimensional (4D)-CT head-to-head in patients with pHPT, to explore which of these imaging techniques to use as a second-line scan., Methods: We conducted a powered, prospective, blinded cohort study in patients with biochemically proven pHPT and prior negative or discordant first-line imaging consisting of ultrasonography and 99m Tc-sestamibi. All patients underwent [ 11 C]methionine PET/CT, [ 11 C]choline PET/CT, and 4D-CT. At first, all scans were interpreted by a nuclear medicine physician, and a radiologist who were blinded from patient data and all imaging results. Next, a non-blinded scan reading was performed. The scan results were correlated with surgical and histopathological findings. Serum calcium values at least 6 months after surgery were used as gold standard for curation of HPT., Results: A total of 32 patients were included in the study. With blinded evaluation, [ 11 C]choline PET/CT was positive in 28 patients (88%), [ 11 C]methionine PET/CT in 23 (72%), and 4D-CT in 15 patients (47%), respectively. In total, 30 patients have undergone surgery and 32 parathyroid lesions were histologically confirmed as parathyroid adenomas. Based on the blinded evaluation, lesion-based sensitivity of [ 11 C]choline PET/CT, [ 11 C]methionine PET/CT, and 4D-CT was respectively 85%, 67%, and 39%. The sensitivity of [ 11 C]choline PET/CT differed significantly from that of [ 11 C]methionine PET/CT and 4D-CT (p = 0.031 and p < 0.0005, respectively)., Conclusion: In the setting of pHPT with negative first-line imaging, [ 11 C]choline PET/CT is superior to [ 11 C]methionine PET/CT and 4D-CT in localizing parathyroid adenomas, allowing correct localization in 85% of adenomas. Further studies are needed to determine cost-benefit and efficacy of these scans, including the timing of these scans as first- or second-line imaging techniques., (© 2023. The Author(s).)

This study aimed to evaluate the effectiveness of different treatments for hepatic artery thrombosis (HAT) and hepatic artery stenosis (HAS) after pediatric liver transplantation. We systematically reviewed studies published since 2000 that investigated the management of HAT and/or HAS after pediatric liver transplantation. Studies with a minimum of 5 patients in one of the treatment methods were included. The primary outcomes were technical success rate and graft and patient survival. The secondary outcomes were hepatic artery patency, complications, and incidence of HAT and HAS. Of 3570 studies, we included 19 studies with 328 patients. The incidence was 6.2% for HAT and 4.1% for HAS. Patients with an early HAT treated with surgical revascularization had a median graft survival of 45.7% (interquartile range, 30.7%-60%) and a patient survival of 61.3% (interquartile range, 58.7%-66.9%) compared with the other treatments (conservative, endovascular revascularization, or retransplantation). As for HAS, endovascular and surgical revascularization groups had a patient survival of 85.7% and 100% (interquartile range, 85%-100%), respectively. Despite various treatment methods, HAT after pediatric liver transplantation remains a significant issue that has profound effects on the patient and graft survival. Current evidence is insufficient to determine the most effective treatment for preventing graft failure., (Copyright © 2023 American Association for the Study of Liver Diseases.)

Background: The use of computed tomography (CT) for attenuation correction (AC) in whole-body PET/CT can result in a significant contribution to radiation exposure. This can become a limiting factor for reducing considerably the overall radiation exposure of the patient when using the new long axial field of view (LAFOV) PET scanners. However, recent CT technology have introduced features such as the tin (Sn) filter, which can substantially reduce the CT radiation dose., Purpose: The purpose of this study was to investigate the ultra-low dose CT for attenuation correction using the Sn filter together with other dose reduction options such as tube current (mAs) reduction. We explore the impact of dose reduction in the context of AC-CT and how it affects PET image quality., Methods: The study evaluated a range of ultra-low dose CT protocols using five physical phantoms that represented a broad collection of tissue electron densities. A long axial field of view (LAFOV) PET/CT scanner was used to scan all phantoms, applying various CT dose reduction parameters such as reducing tube current (mAs), increasing the pitch value, and applying the Sn filter. The effective dose resulting from the CT scans was determined using the CTDI Vol reported by the scanner. Several voxel-based and volumes of interest (VOI)-based comparisons were performed to compare the ultra-low dose CT images, the generated attenuation maps, and corresponding PET images against those images acquired with the standard low dose CT protocol. Finally, two patient datasets were acquired using one of the suggested ultra-low dose CT settings., Results: By incorporating the Sn filter and adjusting mAs to the lowest available value, the radiation dose in CT images of PBU-60 phantom was significantly reduced; resulting in an effective dose of nearly 2% compared to the routine low dose CT protocols currently in clinical use. The assessment of PET images using VOI and voxel-based comparisons indicated relative differences (RD%) of under 6% for mean activity concentration (AC) in the torso phantom and patient dataset and under 8% for a source point in the CIRS phantom. The maximum RD% value of AC was 14% for the point source in the CIRS phantom. Increasing the tube current from 6 mAs to 30 mAs in patients with high BMI, or with arms down, can suppress the photon starvation artifact, whilst still preserving a dose reduction of 90%., Conclusions: Introducing a Sn filter in CT imaging lowers radiation dose by more than 90%. This reduction has minimal effect on PET image quantification at least for patients without Body Mass Index (BMI) higher than 30. Notably, this study results need validation using a larger clinical PET/CT dataset in the future, including patients with higher BMI., (© 2023 The Authors. Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Objectives: To evaluate the current job market for medical specialists in radiology and nuclear medicine (NM) in the Netherlands., Methods: Vacancies posted for radiologists and nuclear medicine physicians in the Netherlands between December 2020 and February 2022 were collected and analyzed., Results: A total of 157 vacancies (146 for radiologist and 11 for nuclear medicine physicians) were included. The most sought-after subspecialties were all-round (22%), abdominal (19%), and interventional radiology (14%), and 30% of vacancies preferred applicants with additional non-clinical skills (research, teaching, management, information and communications technology (ICT)/artificial intelligence (AI)). Non-academic hospitals significantly more frequently requested all-round radiologists (n = 31) than academic hospitals (n = 1) (p = 0.001), while the distribution of other requested subspecialties was not significantly different between non-academic and academic vacancies. Non-academic hospitals also significantly more frequently requested additional research tasks in their vacancies (n = 35) compared to academic hospitals (n = 4) (p = 0.011). There were non-significant trends for non-academic hospitals more frequently requesting teaching tasks in their vacancies (n =18) than academic hospitals (n = 1) (p = 0.051), and for non-academic hospitals more frequently asking for management skills (n = 11) than academic hospitals (n = 0) (p = 0.075)., Conclusion: All-round, abdominal, and interventional radiologists are most in demand on the job market in the Netherlands. All-round radiologists are particularly sought after by non-academic hospitals, whereas nuclear radiologists who completed the Dutch integrated NM and radiology residency seem to be welcomed by hospitals searching for a nuclear medicine specialist. Finally, non-clinical skills (research, teaching, management, ICT/AI) are commonly requested. These data can be useful for residents and developers of training curricula., Clinical Relevance Statement: An overview of the radiology job market and the requested skills is important for residents, for those who seek work as a radiologist, and for those who are involved in the design and revision of residency programs., Key Points: Review of job vacancies over an extended period of time provides valuable information to residents and feedback to potentially improve radiology and nuclear medicine (NM) residency programs. All-round radiologists are wanted in non-academic hospitals and nuclear radiologists (those who have completed an integrated NM-radiology curriculum) are welcomed by hospitals searching for nuclear medicine specialists in the Netherlands. There is a need to train residents in important non-clinical skills, such as research and teaching, but also management and communications technology/artificial intelligence., (© 2023. The Author(s).)

Background: The apolipoprotein E-deficient (apoE -/- ) mouse is a well-established model for studying atherosclerosis. However, its small size limits its use in longitudinal positron emission tomography (PET) imaging studies. Recently, the apoE -/- rat has emerged as an alternative. With this study, we investigate the feasibility of using apoE -/- rats as an in vivo model for longitudinal atherosclerotic PET/CT imaging., Results: ApoE -/- rats showed significantly higher [ 18 F]FDG uptake than controls in the aortic arch (+ 18.5%, p < 0.001) and abdominal aorta (+ 31.0%, p < 0.001) at weeks 12, 26, and 51. ApoE -/- rats exhibited hypercholesterolemia, as evidenced by plasma cholesterol levels that were up to tenfold higher, and total hepatic cholesterol levels that were up to threefold higher than the control rats at the end of the study. Fast protein liquid chromatography cholesterol profiling indicated very high levels of pro-atherogenic apoB-containing very low-density lipoprotein and low-density lipoprotein fractions in the apoE -/- rats. Atherosclerotic lesions cover 19.9% of the surface of the aortic arch (p = 0.0013), and there was a significantly higher subendothelial accumulation of ED1-positive macrophages in the abdominal aorta of the apoE -/- rats compared to control rats (Ctrl) (p = 0.01). No differences in neutral sterols were observed but higher levels of bile acids were found in the apoE -/- rats., Conclusion: These data demonstrate early signs of hypercholesterolemia, high levels of bile acids, the development of atherosclerotic lesions, and macrophage accumulation in apoE -/- rats. Therefore, this model shows promise for atherosclerosis imaging studies., (© 2023. The Author(s).)

Background: The role of small vessel disease in the development of dementia is not yet completely understood. Functional brain connectivity has been shown to differ between individuals with and without cerebral small vessel disease. However, a comprehensive measure of small vessel disease quantifying the overall damage on the brain is not consistently used and studies using such measure in mild cognitive impairment individuals are missing., Method: Functional brain connectivity differences were analyzed between mild cognitive impairment individuals with absent or low ( n  = 34) and high ( n  = 34) small vessel disease burden using data from the Parelsnoer Institute, a Dutch multicenter study. Small vessel disease was characterized using an ordinal scale considering: lacunes, microbleeds, perivascular spaces in the basal ganglia, and white matter hyperintensities. Resting state functional MRI data using 3 Tesla scanners was analyzed with group-independent component analysis using the CONN toolbox., Results: Functional connectivity between areas of the cerebellum and between the cerebellum and the thalamus and caudate nucleus was higher in the absent or low small vessel disease group compared to the high small vessel disease group., Conclusion: These findings might suggest that functional connectivity of mild cognitive impairment individuals with low or absent small vessel disease burden is more intact than in mild cognitive impairment individuals with high small vessel disease. These brain areas are mainly responsible for motor, attentional and executive functions, domains which in previous studies were found to be mostly associated with small vessel disease markers. Our results support findings on the involvement of the cerebellum in cognitive functioning., Competing Interests: None., (© 2023 The Author(s).)

Introduction: P-glycoprotein (P-gp) is one of the most studied efflux transporters at the blood-brain barrier. It plays an important role in brain homeostasis by protecting the brain from a variety of endogenous and exogeneous substances. Changes in P-gp function are associated both with the onset of neuropsychiatric diseases, including Alzheimer's disease and Parkinson's disease, and with drug-resistance, for example in treatment-resistant depression. The most widely used approach to measure P-gp function in vivo is (R)-[ 11 C]verapamil PET. (R)-[ 11 C]verapamil is, however, an avid P-gp substrate, which complicates the use of this tracer to measure an increase in P-gp function as its baseline uptake is already very low. [ 18 F]MC225 was developed to measure both increases and decreases in P-gp function., Aim: The aim of this study was (1) to identify the pharmacokinetic model that best describes [ 18 F]MC225 kinetics in the human brain and (2) to determine test-retest variability., Methods: Five (2 male, 3 female) of fourteen healthy subjects (8 male, 6 female, age 67 ± 5 years) were scanned twice (injected dose 201 ± 47 MBq) with a minimum interval of 2 weeks between scans. Each scanning session consisted of a 60-min dynamic [ 18 F]MC225 scan with continuous arterial sampling. Whole brain grey matter data were fitted to a single tissue compartment model, and to reversible and irreversible two tissue-compartment models to obtain various outcome parameters (in particular the volume of distribution (V T ), K i , and the rate constants K 1 and k 2 ). In addition, a reversible two-tissue compartment model with fixed k 3 /k 4 was included. The preferred model was selected based on the weighted Akaike Information Criterion (AIC) score. Test-retest variability (TRTV) was determined to assess reproducibility., Results: Sixty minutes post-injection, the parent fraction was 63.8 ± 4.0%. The reversible two tissue compartment model corrected for plasma metabolites with an estimated blood volume (V B ) showed the highest AIC weight score of 34.3 ± 17.6%. The TRVT of the V T for [ 18 F]MC225 PET scans was 28.3 ± 20.4% for the whole brain grey matter region using this preferred model., Conclusion: [ 18 F]MC225 V T , derived using a reversible two-tissue compartment model, is the preferred parameter to describe P-gp function in the human BBB. This outcome parameter has an average test-retest variability of 28%., Trial Registration: EudraCT 2020-001564-28 . Registered 25 May 2020., (© 2023. The Author(s).)

The latest technical development in the field of positron emission tomography/computed tomography (PET/CT) imaging has been the extension of the PET axial field-of-view. As a result of the increased number of detectors, the long axial field-of-view (LAFOV) PET systems are not only characterized by a larger anatomical coverage but also by a substantially improved sensitivity, compared with conventional short axial field-of-view PET systems. In clinical practice, this innovation has led to the following optimization: (1) improved overall image quality, (2) decreased duration of PET examinations, (3) decreased amount of radioactivity administered to the patient, or (4) a combination of any of the above. In this review, novel applications of LAFOV PET in oncology are highlighted and future directions are discussed.

MRI is the gold standard for treatment response assessments for glioblastoma. However, there is no consensus regarding the optimal interval for MRI follow-up during standard treatment. Moreover, a reliable assessment of treatment response is hindered by the occurrence of pseudoprogression. It is unknown if a radiological follow-up strategy at 2-3 month intervals actually benefits patients and how it influences clinical decision making about the continuation or discontinuation of treatment. This study assessed the consequences of scheduled follow-up scans post-chemoradiotherapy (post-CCRT), after three cycles of adjuvant chemotherapy [TMZ3/6], and after the completion of treatment [TMZ6/6]), and of unscheduled scans on treatment decisions during standard concomitant and adjuvant treatment in glioblastoma patients. Additionally, we evaluated how often follow-up scans resulted in diagnostic uncertainty (tumor progression versus pseudoprogression), and whether perfusion MRI improved clinical decision making. Scheduled follow-up scans during standard treatment in glioblastoma patients rarely resulted in an early termination of treatment (2.3% post-CCRT, 3.2% TMZ3/6, and 7.8% TMZ6/6), but introduced diagnostic uncertainty in 27.7% of cases. Unscheduled scans resulted in more major treatment consequences (30%; p < 0.001). Perfusion MRI caused less diagnostic uncertainty ( p = 0.021) but did not influence treatment consequences ( p = 0.871). This study does not support the current pragmatic follow-up strategy and suggests a more tailored follow-up approach.

The molecular imaging of biomarkers plays an increasing role in medical diagnostics. In particular, the imaging of enzyme activity is a promising approach, as it enables the use of its inherent catalytic activity for the amplification of an imaging signal. The increased activity of a sulfatase enzyme has been observed in several types of cancers. We describe the development and in vitro evaluation of molecular imaging agents that allow for the detection of sulfatase activity using the whole-body, non-invasive MRI and CEST imaging methods. This approach relies on a responsive ligand that features a sulfate ester moiety, which upon sulfatase-catalyzed hydrolysis undergoes an elimination process that changes the functional group, coordinating with the metal ion. When Gd 3+ is used as the metal, the complex can be used for MRI, showing a 25% decrease at 0.23T and a 42% decrease at 4.7T in magnetic relaxivity after enzymatic conversion, thus providing a "switch-off" contrast agent. Conversely, the use of Yb 3+ as the metal leads to a "switch-on" effect in the CEST imaging of sulfatase activity. Altogether, the results presented here provide a molecular basis and a proof-of-principle for the magnetic imaging of the activity of a key cancer biomarker.

Background: Early detection of recurrent or progressive HCC remains the strongest prognostic factor for survival. Dual tracer PET/CT imaging with [ 11 C]CH and [ 18 F]FDG can further increase detection rates as both tracers entail different metabolic pathways involved in HCC development. We investigated dual-tracer PET/CT in clinical decision making in patients suspected of recurrent or progressive HCC. All HCC patients who underwent both [ 11 C]CH and [ 18 F]FDG PET/CT in our institute from February 2018 to December 2021 were included. Both tracer PET/CT were within 4 weeks of each other with at least 6-month follow-up. Patients underwent dual tracer PET/CT because of unexplained and suspicious CT/MRI or sudden rise of serum tumour markers. A detected lesion was considered critical when the finding had prognostic consequences leading to treatment changes., Results: Nineteen patients who underwent [ 11 C]CH and [ 18 F]FDG PET/CT were included of which all but six patients were previously treated for HCC. Dual-tracer critical finding detection rate was 95%, with [ 18 F]FDG 68%, and [ 11 C]CH 84%. Intrahepatic HCC recurrence finding rate was 65% for both tracers. [ 18 F]FDG found more ablation site recurrences (4/5) compared to [ 11 C]CH (2/5). Only [ 11 C]CH found two needle tract metastases. Both tracers found 75% of the positive lymph nodes. Two new primary tumours were found, one by [ 18 F]FDG and both by [ 11 C]CH., Conclusions: Our study favours a dual-tracer approach in HCC staging in high-risk patients or when conventional imaging is non-conclusive., (© 2023. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background and Purpose: Cerebral microbleeds (CMBs) and fluid-attenuated-inversion recovery (FLAIR) hyperintensities on brain MRI scans after radiotherapy (RT) are considered markers for microvascular damage and related cognitive changes. However, the spatial distribution using existing scoring systems as well as colocation of these imaging biomarkers remain unclear, hampering clinical interpretation. This study aims to elucidate the distribution and colocation of these markers in patients with lower grade glioma (LGG)., Materials and Methods: CMBs were spatially classified on retrospective 1.5 T susceptibility weighted MRI scans according to the existing Microbleed Anatomical Rating Scale (MARS) and were additionally scored for being located in hippocampus, amygdala, cortex, white matter (WM), grey matter (GM), WM/GM junction and for their spatial relation to FLAIR hyperintensities. Scoring was performed for whole, ipsilateral and contralateral cerebrum (with respect to tumour bulk)., Results: Fifty-one scans were included of which 28 had at least one CMB. The majority of CMBs were localized in the lobar area and in deep and periventricular white matter (DPWM) - generally in WM. Only few CMBs were found in GM. In scans obtained up to 7 years after RT completion the majority of CMBs were not colocalized with FLAIR hyperintensities., Conclusion: CMBs and FLAIR hyperintensities appear to be separate imaging biomarkers for radiation therapy induced microvascular damage, as they are not colocalized in patients with LGG, especially not early on after completion of RT., Competing Interests: 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., (© 2023 The Author(s).)

Purpose: Monoclonal antibody (mAb)-based PET (immunoPET) imaging can characterise tumour lesions non-invasively. It may be a valuable tool to determine which patients may benefit from treatment with a specific monoclonal antibody (mAb) and evaluate treatment response. For 89 Zr immunoPET imaging, higher sensitivity of state-of-the art PET/CT systems equipped with silicon photomultiplier (SiPM)-based detector elements may be beneficial as the low positron abundance of 89 Zr causes a low signal-to-noise level. Moreover, the long physical half-life limits the amount of activity that can be administered to the patients leading to poor image quality even when using long scan durations. Here, we investigated the difference in semiquantitative performance between the PMT-based Biograph mCT, our clinical reference system, and the SiPM-based Biograph Vision PET/CT in 89 Zr immunoPET imaging. Furthermore, the effects of scan duration reduction using the Vision on semiquantitative imaging parameters and its influence on image quality assessment were evaluated., Methods: Data were acquired on day 4 post 37 MBq 89 Zr-labelled mAb injection. Five patients underwent a double scan protocol on both systems. Ten patients were scanned only on the Vision. For PET image reconstruction, three protocols were used, i.e. one camera-dependent protocol and European Association of Nuclear Medicine Research Limited (EARL) standards 1 and 2 compliant protocols. Vision data were acquired in listmode and were reprocessed to obtain images at shorter scan durations. Semiquantitative PET image parameters were derived from tumour lesions and healthy tissues to assess differences between systems and scan durations. Differently reconstructed images obtained using the Vision were visually scored regarding image quality by two nuclear medicine physicians., Results: When images were reconstructed using 100% acquisition time on both systems following EARL standard 1 compliant reconstruction protocols, results regarding semiquantification were comparable. For Vision data, reconstructed images that conform to EARL1 standards still resulted in comparable semiquantification at shorter scan durations (75% and 50%) regarding 100% acquisition time., Conclusion: Scan duration of 89 Zr immunoPET imaging using the Vision can be decreased up to 50% compared with using the mCT while maintaining image quality using the EARL1 compliant reconstruction protocol., (© 2023. The Author(s).)

Purpose: Patient-tailored management of thyroid nodules requires improved risk of malignancy stratification by accurate preoperative nodule assessment, aiming to personalize decisions concerning diagnostics and treatment. Here, we perform an exploratory pilot study to identify possible patterns on multispectral optoacoustic tomography (MSOT) for thyroid malignancy stratification. For the first time, we directly correlate MSOT images with histopathology data on a detailed level., Methods: We use recently enhanced data processing and image reconstruction methods for MSOT to provide next-level image quality by means of improved spatial resolution and spectral contrast. We examine optoacoustic features in thyroid nodules associated with vascular patterns and correlate these directly with reference histopathology., Results: Our methods show the ability to resolve blood vessels with diameters of 250 μm at depths of up to 2 cm. The vessel diameters derived on MSOT showed an excellent correlation (R 2 -score of 0.9426) with the vessel diameters on histopathology. Subsequently, we identify features of malignancy observable in MSOT, such as intranodular microvascularity and extrathyroidal extension verified by histopathology. Despite these promising features in selected patients, we could not determine statistically relevant differences between benign and malignant thyroid nodules based on mean oxygen saturation in thyroid nodules. Thus, we illustrate general imaging artifacts of the whole field of optoacoustic imaging that reduce image fidelity and distort spectral contrast, which impedes quantification of chromophore presence based on mean concentrations., Conclusion: We recommend examining optoacoustic features in addition to chromophore quantification to rank malignancy risk. We present optoacoustic images of thyroid nodules with the highest spatial resolution and spectral contrast to date, directly correlated to histopathology, pushing the clinical translation of MSOT., (© 2023. The Author(s).)

Background and Purpose: Previous pre-clinical research using [ 18 F]FDG-PET has shown that whole-brain photon-based radiotherapy can affect brain glucose metabolism. This study, aimed to investigate how these findings translate into regional changes in brain [ 18 F]FDG uptake in patients with head and neck cancer treated with intensity-modulated proton therapy (IMPT)., Materials and Methods: Twenty-three head and neck cancer patients treated with IMPT and available [ 18 F]FDG scans before and at 3 months follow-up were retrospectively evaluated. Regional assessment of the [ 18 F]FDG standardized uptake value (SUV) parameters and radiation dose in the left (L) and right (R) hippocampi, L and R occipital lobes, cerebellum, temporal lobe, L and R parietal lobes and frontal lobe were evaluated to understand the relationship between regional changes in SUV metrics and radiation dose., Results: Three months after IMPT, [ 18 F]FDG brain uptake calculated using SUVmean and SUVmax, was significantly higher than that before IMPT. The absolute SUVmean after IMPT was significantly higher than before IMPT in seven regions of the brain (p ≤ 0.01), except for the R (p = 0.11) and L (p = 0.15) hippocampi. Absolute and relative changes were variably correlated with the regional maximum and mean doses received in most of the brain regions., Conclusion: Our findings suggest that 3 months after completion of IMPT for head and neck cancer, significant increases in the uptake of [ 18 F]FDG (reflected by SUVmean and SUVmax) can be detected in several individual key brain regions, and when evaluated jointly, it shows a negative correlation with the mean dose. Future studies are needed to assess whether and how these results could be used for the early identification of patients at risk for adverse cognitive effects of radiation doses in non-tumor tissues., Competing Interests: 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., (© 2023 The Author(s).)

Purpose: To give a comprehensive literature overview of alterations in regional cerebral glucose metabolism, measured using [ 18 F]FDG PET, in conditions associated with hyperkinetic movement disorders and ataxia. In addition, correlations between glucose metabolism and clinical variables as well as the effect of treatment on glucose metabolism are discussed., Methods: A systematic literature search was performed according to PRISMA guidelines. Studies concerning tremors, tics, dystonia, ataxia, chorea, myoclonus, functional movement disorders, or mixed movement disorders due to autoimmune or metabolic aetiologies were eligible for inclusion. A PubMed search was performed up to November 2021., Results: Of 1240 studies retrieved in the original search, 104 articles were included. Most articles concerned patients with chorea (n = 27), followed by ataxia (n = 25), dystonia (n = 20), tremor (n = 8), metabolic disease (n = 7), myoclonus (n = 6), tics (n = 6), and autoimmune disorders (n = 5). No papers on functional movement disorders were included. Altered glucose metabolism was detected in various brain regions in all movement disorders, with dystonia-related hypermetabolism of the lentiform nuclei and both hyper- and hypometabolism of the cerebellum; pronounced cerebellar hypometabolism in ataxia; and striatal hypometabolism in chorea (dominated by Huntington disease). Correlations between clinical characteristics and glucose metabolism were often described. [ 18 F]FDG PET-showed normalization of metabolic alterations after treatment in tremors, ataxia, and chorea., Conclusion: In all conditions with hyperkinetic movement disorders, hypo- or hypermetabolism was found in multiple, partly overlapping brain regions, and clinical characteristics often correlated with glucose metabolism. For some movement disorders, [ 18 F]FDG PET metabolic changes reflected the effect of treatment., (© 2023. The Author(s).)

The aim of this study was to evaluate whether radiologically defined sarcopenia, or a low skeletal muscle index (SMI), could be used as a practical biomarker for frailty and postoperative complications (POC) in patients with head and neck skin cancer (HNSC). This was a retrospective study on prospectively collected data. The L3 SMI (cm 2 /m 2 ) was calculated with use of baseline CT or MRI neck scans and low SMIs were defined using sex-specific cut-off values. A geriatric assessment with a broad range of validated tools was performed at baseline. POC was graded with the Clavien-Dindo Classification (with a grade of > II as the cut-off). Univariate and multivariable regression analyses were performed with low SMIs and POC as the endpoints. The patients' (n = 57) mean age was 77.0 ± 9 years, 68.4% were male, and 50.9% had stage III-IV cancer. Frailty was determined according to Geriatric 8 (G8) score (OR 7.68, 95% CI 1.19-49.66, p = 0.032) and the risk of malnutrition was determined according to the Malnutrition Universal Screening Tool (OR 9.55, 95% CI 1.19-76.94, p = 0.034), and these were independently related to low SMIs. Frailty based on G8 score (OR 5.42, 95% CI 1.25-23.49, p = 0.024) was the only variable related to POC. However, POC was more prevalent in patients with low SMIs (∆ 19%, OR 1.8, 95% CI 0.5-6.0, p = 0.356).To conclude, a low SMI is a practical biomarker for frailty and malnutrition in HNSC. Future research should be focused on interventions based on low SMI scores and assess the effect of the intervention on SMI, frailty, malnutrition, and POC.

Major depressive disorder is a growing and poorly understood pathology. Due to technical and ethical limitations, a significant proportion of the research on depressive disorders cannot be performed on patients, but needs to be investigated in animal paradigms. Over the years, animal studies have provided new insight in the mechanisms underlying depression. Several of these studies have used PET imaging for the non-invasive and longitudinal investigation of the brain physiology. This review summarises the findings of preclinical PET imaging in different experimental paradigms of depression and compares these findings with observations from human studies. Preclinical PET studies in animal models of depression can be divided into three main different approaches: (a) investigation of glucose metabolism as a biomarker for regional and network involvement, (b) evaluation of the availability of different neuroreceptor populations associated with depressive phenotypes, and (c) monitoring of the inflammatory response in phenotypes of depression. This review also assesses the relevance of the use of PET imaging techniques in animal paradigms for the understanding of specific aspects of the depressive-like phenotypes, in particular whether it might contribute to achieve a more detailed characterisation of the clinical depressive phenotypes for the development of new therapies for depression., (© 2023. The Author(s).)

Purpose: Radiologically defined sarcopenia, or a low skeletal muscle index (SMI), is an emerging biomarker for adverse clinical outcomes in head and neck cancer (HNC) patients. Recently, SMI measurements have been validated at the level of the third cervical vertebra (C3) on diagnostic neck CT scans but are not yet validated on low-dose (LD) neck CT scans from the [ 18 F]-FDG PET-CT. This hampers SMI analysis in HNC patients without a diagnostic neck CT but with a [ 18 F]-FDG PET-CT scan. Therefore, the aim was to study whether (low) SMI based on LD CT scan from [ 18 F]-FDG PET-CT is comparable to those derived from diagnostic neck CT scans., Methods: HNC patients with both diagnostic CT and [ 18 F]-FDG PET-CT of the neck were prospectively included into the OncoLifeS data-biobank. Skeletal muscle was retrospectively delineated at the level of the third cervical vertebra (C3), and (low) SMI (cm 2 /m 2 ) was calculated for diagnostic and LD neck CTs. (Low) SMI from the diagnostic neck CT was considered the reference standard. Intra-class correlation coefficient (ICC), Bland-Altman plots, and Cohen's Kappa analysis were performed., Results: The cohort (n = 233) mean age was 66.2 ± 12.8 years, and 74.2% of patients were male. Inter-rater reliability was excellent (ICC > 0.990, 95% confidence interval 0.975-0.996, p < 0.001). The agreement of SMI between both modalities was high according to the Bland-Altman plot (mean ΔSMI =  - 0.19 cm 2 /m 2 ), and there was no substantial bias. Cohen's Kappa analysis showed an almost perfect agreement of low SMI between the two modalities (κ = 0.911, p < 0.001). The position of arms didn't affect the high agreement of (low) SMI., Conclusion: Skeletal muscle mass, as measured with (low) SMI, remains constant irrespective of CT acquisition parameters (diagnostic neck CT scans versus LD neck scans of the [18F]-FDG PET-CT scan), positioning of arms, and observers. These findings contribute to the construction of a clinically useful radiological biomarker for SMI and therefore identify patients at risk for adverse clinical outcomes., (© 2023. The Author(s).)

Pharmacokinetic modelling with arterial sampling is the gold standard for analysing dynamic PET data of the brain. However, the invasive character of arterial sampling prevents its widespread clinical application. Several methods have been developed to avoid arterial sampling, in particular reference region methods. Unfortunately, for some tracers or diseases, no suitable reference region can be defined. For these cases, other potentially non-invasive approaches have been proposed: (1) a population based input function (PBIF), (2) an image derived input function (IDIF), or (3) simultaneous estimation of the input function (SIME). This systematic review aims to assess the correspondence of these non-invasive methods with the gold standard. Studies comparing non-invasive pharmacokinetic modelling methods with the current gold standard methods using an input function derived from arterial blood samples were retrieved from PubMed/MEDLINE (until December 2021). Correlation measurements were extracted from the studies. The search yielded 30 studies that correlated outcome parameters (V T , DVR, or BP ND for reversible tracers; K i or CMR glu for irreversible tracers) from a potentially non-invasive method with those obtained from modelling using an arterial input function. Some studies provided similar results for PBIF, IDIF, and SIME-based methods as for modelling with an arterial input function (R 2  = 0.59-1.00, R 2  = 0.71-1.00, R 2  = 0.56-0.96, respectively), if the non-invasive input curve was calibrated with arterial blood samples. Even when the non-invasive input curve was calibrated with venous blood samples or when no calibration was applied, moderate to good correlations were reported, especially for the IDIF and SIME (R 2  = 0.71-1.00 and R 2  = 0.36-0.96, respectively). Overall, this systematic review illustrates that non-invasive methods to generate an input function are still in their infancy. Yet, IDIF and SIME performed well, not only with arterial blood calibration, but also with venous or no blood calibration, especially for some tracers without plasma metabolites, which would potentially make these methods better suited for clinical application. However, these methods should still be properly validated for each individual tracer and application before implementation., (© 2023. The Author(s).)

Myelin is the protective sheath wrapped around axons, consisting of a phospholipid bilayer with water between the wraps. The measurement of damage to the myelin sheaths, the evaluation of the efficacy of therapies aiming to promote remyelination and monitoring the degree of brain maturation in children all require non-invasive quantitative myelin imaging methods. To date, various myelin imaging techniques have been developed. Five different MRI approaches can be distinguished based on their biophysical principles: (i) imaging of the water between the lipid bilayers directly (e.g. myelin water imaging); (ii) imaging the non-aqueous protons of the phospholipid bilayer directly with ultra-short echo-time techniques; (iii) indirect imaging of the macromolecular content (e.g. magnetization transfer; inhomogeneous magnetization transfer); (iv) mapping of the effects of the myelin sheath's magnetic susceptibility on the MRI signal (e.g. quantitative susceptibility mapping); and (v) mapping of the effects of the myelin sheath on water diffusion. Myelin imaging with PET uses radioactive molecules with high affinity to specific myelin components, in particular myelin basic protein. This review aims to give an overview of the various myelin imaging techniques, their biophysical principles, image acquisition, data analysis and their validation status., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Over the last decades, the population at risk for invasive fungal disease (IFD) has increased because of medical therapy advances and diseases compromising patients' immune systems. The high morbidity and mortality associated with invasive fungal disease in the immunocompromised present the challenge of early diagnosis of the IFD and the need to closely monitor the infection during treatment. The definitive diagnosis of invasive fungal disease based on culture or histopathological methods often has reduced diagnostic accuracy in the immunocompromised and may be very invasive. Less invasive and indirect evidence of the fungal infection by serology and imaging has been used for the early diagnosis of fungal infection before definitive results are available or when the definitive methods of diagnosis are suboptimal. Imaging in invasive fungal disease is a non-invasive biomarker that helps in the early diagnosis of invasive fungal disease but helps follow-up the infection during treatment. Different imaging modalities are used in the workup to evaluate fungal disease. The different imaging modalities have advantages and disadvantages at different sites in the body and may complement each other in the management of IFD. Positron emission tomography integrated with computed tomography with [18F]Fluorodeoxyglucose (FDG PET/CT) has helped manage IFD. The combined functional data from PET and anatomical data from the CT from almost the whole body allows noninvasive evaluation of IFD and provides a semiquantitative means of assessing therapy. FDG PET/CT adds value to anatomic-based only imaging modalities. The nonspecificity of FDG uptake has led to the evaluation of other tracers in the assessment of IFD. However, these are mainly still at the preclinical level and are yet to be translated to humans. FDG PET/CT remains the most widely evaluated radionuclide-based imaging modality in IFD management. The limitations of FDG PET/CT must be well understood, and more extensive prospective studies in uniform populations are needed to validate its role in the management of IFD that can be international guidelines., (Copyright © 2022 Elsevier Inc. All rights reserved.)

This review describes the main benefits of using long axial field of view (LAFOV) PET in clinical applications. As LAFOV PET is the latest development in PET instrumentation, many studies are ongoing that explore the potentials of these systems, which are characterized by ultra-high sensitivity. This review not only provides an overview of the published clinical applications using LAFOV PET so far, but also provides insight in clinical applications that are currently under investigation. Apart from the straightforward reduction in acquisition times or administered amount of radiotracer, LAFOV PET also allows for other clinical applications that to date were mostly limited to research, e.g., dual tracer imaging, whole body dynamic PET imaging, omission of CT in serial PET acquisition for repeat imaging, and studying molecular interactions between organ systems. It is expected that this generation of PET systems will significantly advance the field of nuclear medicine and molecular imaging., (© 2022. The Author(s).)

Multiple sclerosis (MS) is an inflammatory demyelinating disease. Current treatments are focussed on immune suppression to modulate pathogenic activity that causes myelin damage. New treatment strategies are needed to prevent demyelination and promote remyelination. Development of such myelin repair therapies require a sensitive and specific biomarker for efficacy evaluation. Recently, it has been shown that quantification of myelin density is possible using [ 11 C]MeDAS PET. This method, however, requires arterial blood sampling to generate an arterial input function (AIF). As the invasive nature of arterial sampling will reduce clinical applicability, the purpose of this study was to assess whether an image-derived input function (IDIF) can be used as an alternative way to facilitate its routine clinical use. Six healthy controls and 11 MS patients underwent MRI and [ 11 C]MeDAS PET with arterial blood sampling. The application of both population-based whole blood-to-plasma conversion and metabolite corrections were assessed for the AIF. Next, summed images of the early time frames (0-70 s) and the frame with the highest blood-brain contrast were used to generate IDIFs. IDIFs were created using either the hottest 2, 4, 6 or 12 voxels, or an isocontour of the hottest 10% voxels of the carotid artery. This was followed by blood-to-plasma conversion and metabolite correction of the IDIF. The application of a population-based metabolite correction of the AIF resulted in high correlations of tracer binding (K i ) within subjects, but variable bias across subjects. All IDIFs had a sharper and higher peak in the blood curves than the AIF, most likely due to dispersion during blood sampling. All IDIF methods resulted in similar high correlations within subjects (r = 0.95-0.98), but highly variable bias across subjects (mean slope=0.90-1.09). Therefore, both the use of population based blood-plasma and metabolite corrections and the generation of the image-derived whole-blood curve resulted in substantial bias in [ 11 C]MeDAS PET quantification, due to high inter-subject variability. Consequently, when unbiased quantification of [ 11 C]MeDAS PET data is required, individual AIF needs to be used., (Copyright © 2022. Published by Elsevier Inc.)

In young adults, overweight and hypertension possibly already trigger cardiac remodeling as seen in mature adults, potentially overlapping non-ischemic cardiomyopathy findings. To this end, in young overweight and hypertensive adults, we aimed to investigate changes in left ventricular mass (LVM) and cardiac volumes, and the impact of different body scales for indexation. We also aimed to explore the presence of myocardial fibrosis, fat and edema, and changes in cellular mass with extracellular volume (ECV), T1 and T2 tissue characteristics. We prospectively recruited 126 asymptomatic subjects (51% male) aged 27-41 years for 3T cardiac magnetic resonance imaging: 40 controls, 40 overweight, 17 hypertensive and 29 hypertensive overweight. Myocyte mass was calculated as (100%-ECV) * height2.7-indexed LVM. Absolute LVM was significantly increased in overweight, hypertensive and hypertensive overweight groups (104 ± 23, 109 ± 27, 112 ± 26 g) versus controls (87 ± 21 g), with similar volumes. Body surface area (BSA) indexation resulted in LVM normalization in overweights (48 ± 8 g/m2) versus controls (47 ± 9 g/m2), but not in hypertensives (55 ± 9 g/m2) and hypertensive overweights (52 ± 9 g/m2). BSA-indexation overly decreased volumes in overweight versus normal-weight (LV end-diastolic volume; 80 ± 14 versus 92 ± 13 ml/m2), where height2.7-indexation did not. All risk groups had lower ECV (23 ± 2%, 23 ± 2%, 23 ± 3%) than controls (25 ± 2%) (P = 0.006, P = 0.113, P = 0.039), indicating increased myocyte mass (16.9 ± 2.7, 16.5 ± 2.3, 18.1 ± 3.5 versus 14.0 ± 2.9 g/m2.7). Native T1 values were similar. Lower T2 values in the hypertensive overweight group related to heart rate. In conclusion, BSA-indexation masks hypertrophy and causes volume overcorrection in overweight subjects compared to controls, height2.7-indexation therefore seems advisable., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Snel et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)