Treatment strategies for hepatic artery complications after pediatric liver transplantation: A systematic review.

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.

Is work overload associated with diagnostic errors on 18F-FDG-PET/CT?

PURPOSE: To determine the association between workload and diagnostic errors on 18F-FDG-PET/CT. MATERIALS AND METHODS: This study included 103 18F-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 18F-FDG-PET/CT report was determined on the day the diagnostic error was made and normalized for his or her own average daily production (workloadnormalized). A workloadnormalized 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. Workloadnormalized 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: Workloadnormalized (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 18F-FDG-PET/CT. Diagnostic errors were encountered throughout the entire working day, without any upward trend towards the end of the day.

Head-to-head comparison of [11C]methionine PET, [11C]choline PET, and 4-dimensional CT as second-line scans for detection of parathyroid adenomas in primary hyperparathyroidism.

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 [11C]methionine PET/CT, [11C]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 99mTc-sestamibi. All patients underwent [11C]methionine PET/CT, [11C]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, [11C]choline PET/CT was positive in 28 patients (88%), [11C]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 [11C]choline PET/CT, [11C]methionine PET/CT, and 4D-CT was respectively 85%, 67%, and 39%. The sensitivity of [11C]choline PET/CT differed significantly from that of [11C]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, [11C]choline PET/CT is superior to [11C]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.

The radiology job market in the Netherlands: which subspecialties and other skills are in demand?

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.

Quantitative myelin imaging with MRI and PET: an overview of techniques and their validation status.

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.

Perinatal exposure to the immune-suppressant di-n-octyltin dichloride affects brain development in rats.

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 ([18F]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.

PET imaging of animal models with depressive-like phenotypes.

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.

[18F]FDG PET in conditions associated with hyperkinetic movement disorders and ataxia: a systematic review.

PURPOSE: To give a comprehensive literature overview of alterations in regional cerebral glucose metabolism, measured using [18F]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. [18F]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, [18F]FDG PET metabolic changes reflected the effect of treatment.

Non-invasive kinetic modelling approaches for quantitative analysis of brain PET studies.

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 (VT, DVR, or BPND for reversible tracers; Ki or CMRglu 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 (R2 = 0.59-1.00, R2 = 0.71-1.00, R2 = 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 (R2 = 0.71-1.00 and R2 = 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.

The validation of low-dose CT scans from the [18F]-FDG PET-CT scan to assess skeletal muscle mass in comparison with diagnostic neck CT scans.

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 [18F]-FDG PET-CT. This hampers SMI analysis in HNC patients without a diagnostic neck CT but with a [18F]-FDG PET-CT scan. Therefore, the aim was to study whether (low) SMI based on LD CT scan from [18F]-FDG PET-CT is comparable to those derived from diagnostic neck CT scans. METHODS: HNC patients with both diagnostic CT and [18F]-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 (cm2/m2) 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 cm2/m2), 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.

Quantification of P-glycoprotein function at the human blood-brain barrier using [18F]MC225 and PET.

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)-[11C]verapamil PET. (R)-[11C]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. [18F]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 [18F]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 [18F]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 (VT), Ki, and the rate constants K1 and k2). In addition, a reversible two-tissue compartment model with fixed k3/k4 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 (VB) showed the highest AIC weight score of 34.3 ± 17.6%. The TRVT of the VT for [18F]MC225 PET scans was 28.3 ± 20.4% for the whole brain grey matter region using this preferred model. CONCLUSION: [18F]MC225 VT, 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.

Towards in vivo characterization of thyroid nodules suspicious for malignancy using multispectral optoacoustic tomography.

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 (R2-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.

Optimisation of scan duration and image quality in oncological 89Zr immunoPET imaging using the Biograph Vision PET/CT.

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 89Zr 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 89Zr 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 89Zr 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 89Zr-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 89Zr 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.

Investigation of image-derived input functions for non-invasive quantification of myelin density using [11C]MeDAS PET.

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 [11C]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 [11C]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 (Ki) 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 [11C]MeDAS PET quantification, due to high inter-subject variability. Consequently, when unbiased quantification of [11C]MeDAS PET data is required, individual AIF needs to be used.

The integrated nuclear medicine and radiology residency program in the Netherlands: strengths and potential areas for improvement according to nuclear medicine physicians and radiologists.

PURPOSE: To evaluate the Dutch integrated nuclear medicine and radiology residency program from the perspective of nuclear medicine physicians and radiologists. METHODS: A survey was distributed among nuclear medicine physicians and radiologists in hospitals that participate in the Dutch integrated nuclear medicine and radiology training program. RESULTS: A total of 139 completed questionnaires were included. Nuclear medicine physicians (n = 36) assigned a mean score of 5.7 ± 2.0, and radiologists (n = 103) assigned a mean score of 6.5 ± 2.8 (on a 1-10 scale) to the success of the integrated training program in their hospital. On multiple regression, female gender of the survey participant (B = 2.22, P = 0.034), musculoskeletal radiology as subspecialty of the survey participant (B = 3.36, P = 0.032), and the survey participant's expectancy of resident's ability to handle workload after completion of residency were significantly associated with perceived success of the integrated training program (B = 1.16, P = 0.023). Perceived strengths of the integrated training program included broadening of expertise, a better preparation of future imaging specialists for hybrid imaging, increased efficiency in training residents, and increased efficiency in multidisciplinary meetings. Perceived weaknesses of the integrated training program included reduced exposure to nuclear medicine, less time for research and innovation, and concerns about its international recognition. CONCLUSION: This study provided insights into the experiences of nuclear medicine physicians and radiologists with the Dutch integrated nuclear medicine and radiology residency program, which may be helpful to improve the program and similar residency programs in other countries.

EARL compliance and imaging optimisation on the Biograph Vision Quadra PET/CT using phantom and clinical data.

PURPOSE: Current European Association of Nuclear Medicine (EANM) Research Ltd. (EARL) guidelines for the standardisation of PET imaging developed for conventional systems have not yet been adjusted for long axial field-of-view (LAFOV) systems. In order to use the LAFOV Siemens Biograph Vision Quadra PET/CT (Siemens Healthineers, Knoxville, TN, USA) in multicentre research and harmonised clinical use, compliance to EARL specifications for 18F-FDG tumour imaging was explored in the current study. Additional tests at various locations throughout the LAFOV and the use of shorter scan durations were included. Furthermore, clinical data were collected to further explore and validate the effects of reducing scan duration on semi-quantitative PET image biomarker accuracy and precision when using EARL-compliant reconstruction settings. METHODS: EARL compliance phantom measurements were performed using the NEMA image quality phantom both in the centre and at various locations throughout the LAFOV. PET data (maximum ring difference (MRD) = 85) were reconstructed using various reconstruction parameters and reprocessed to obtain images at shorter scan durations. Maximum, mean and peak activity concentration recovery coefficients (RC) were obtained for each sphere and compared to EARL standards specifications. Additionally, PET data (MRD = 85) of 10 oncological patients were acquired and reconstructed using various reconstruction settings and reprocessed from 10 min listmode acquisition into shorter scan durations. Per dataset, SUVs were derived from tumour lesions and healthy tissues. ANOVA repeated measures were performed to explore differences in lesion SUVmax and SUVpeak. Wilcoxon signed-rank tests were performed to evaluate differences in background SUVpeak and SUVmean between scan durations. The coefficient of variation (COV) was calculated to characterise noise. RESULTS: Phantom measurements showed EARL compliance for all positions throughout the LAFOV for all scan durations. Regarding patient data, EARL-compliant images showed no clinically meaningful significant differences in lesion SUVmax and SUVpeak or background SUVmean and SUVpeak between scan durations. Here, COV only varied slightly. CONCLUSION: Images obtained using the Vision Quadra PET/CT comply with EARL specifications. Scan duration and/or activity administration can be reduced up to a factor tenfold without the interference of increased noise.

Imaging of neuroinflammation due to repetitive head injury in currently active kickboxers.

PURPOSE: Chronic traumatic encephalopathy refers to a neurodegenerative disease resulting from repetitive head injury of participants in contact sports. Similar to other neurodegenerative diseases, neuroinflammation is thought to play a role in the onset and progression of the disease. Limited knowledge is available regarding the neuroinflammatory consequences of repetitive head injury in currently active contact sports athletes. PET imaging of the 18-kDa translocator protein (TSPO) allows quantification of microglial activation in vivo, a marker of neuroinflammation. METHODS: Eleven rank A kickboxers and 11 age-matched controls underwent TSPO PET using [11C]-PK11195, anatomical MRI, diffusion tensor imaging, and neuropsychological testing. Relevant imaging parameters were derived and correlated with the outcomes of the neuropsychological testing. RESULTS: On a group level, no statistically significant differences were detected in non-displaceable binding potential (BPND) using PET. Individually, 3 kickboxers showed increased BPNDs in widespread regions of the brain without a correlation with other modalities. Increased FA was observed in the superior corona radiata bilaterally. DTI parameters in other regions did not differ between groups. CONCLUSION: Despite negative results on a group level, individual results suggest that neuroinflammation may be present as a consequence of repetitive head injury in active kickboxers. Future studies using a longitudinal design may determine whether the observed TSPO upregulation is related to the future development of neuropsychiatric symptoms.

Quantitative assessment of myelin density using [11C]MeDAS PET in patients with multiple sclerosis: a first-in-human study.

PURPOSE: Multiple sclerosis (MS) is a disease characterized by inflammatory demyelinated lesions. New treatment strategies are being developed to stimulate myelin repair. Quantitative myelin imaging could facilitate these developments. This first-in-man study aimed to evaluate [11C]MeDAS as a PET tracer for myelin imaging in humans. METHODS: Six healthy controls and 11 MS patients underwent MRI and dynamic [11C]MeDAS PET scanning with arterial sampling. Lesion detection and classification were performed on MRI. [11C]MeDAS time-activity curves of brain regions and MS lesions were fitted with various compartment models for the identification of the best model to describe [11C]MeDAS kinetics. Several simplified methods were compared to the optimal compartment model. RESULTS: Visual analysis of the fits of [11C]MeDAS time-activity curves showed no preference for irreversible (2T3k) or reversible (2T4k) two-tissue compartment model. Both volume of distribution and binding potential estimates showed a high degree of variability. As this was not the case for 2T3k-derived net influx rate (Ki), the 2T3k model was selected as the model of choice. Simplified methods, such as SUV and MLAIR2 correlated well with 2T3k-derived Ki, but SUV showed subject-dependent bias when compared to 2T3k. Both the 2T3k model and the simplified methods were able to differentiate not only between gray and white matter, but also between lesions with different myelin densities. CONCLUSION: [11C]MeDAS PET can be used for quantification of myelin density in MS patients and is able to distinguish differences in myelin density within MS lesions. The 2T3k model is the optimal compartment model and MLAIR2 is the best simplified method for quantification. TRIAL REGISTRATION: NL7262. Registered 18 September 2018.

Impact of an Adenosine A2A Receptor Agonist and Antagonist on Binding of the Dopamine D2 Receptor Ligand [11C]raclopride in the Rodent Striatum.

Adenosine A2A and dopamine D2 receptors in the basal ganglia form heterotetrameric structures that are involved in the regulation of motor activity and neuropsychiatric functions. The present study examines the A2A receptor-mediated modulation of D2 receptor binding in vivo using positron emission tomography (PET) with the D2 antagonist tracer [11C]raclopride. Healthy male Wistar rats (n = 8) were scanned (60 min dynamic scan) with [11C]raclopride at baseline and 7 days later following an acute administration of the A2A agonist CGS21680 (1 mg/kg), using a MicroPET Focus-220 camera. Nondisplaceable binding potential (BPND) values were calculated using a simplified reference tissue model (SRTM), with cerebellum as the reference tissue. SRTM analysis did not show any significant changes in [11C]raclopride BPND (p = 0.102) in striatum after CGS21680 administration compared to the baseline. As CGS21680 strongly affects hemodynamics, we also used arterial blood sampling and a metabolite-corrected plasma input function for compartment modeling using the reversible two-tissue compartment model (2TCM) to obtain the BPND from the k3/k4 ratio and from the striatum/cerebellum volume of distribution ratio (DVR) in a second group of animals. These rats underwent dynamic [11C]raclopride scans after pretreatment with a vehicle (n = 5), a single dose of CGS21680 (1 mg/kg, n = 5), or a single dose of the A2A antagonist KW6002 (1 mg/kg, n = 5). The parent fraction in plasma was significantly higher in the CGS21680-treated group (p = 0.0001) compared to the vehicle-treated group. GCS21680 administration significantly reduced the striatal k3/k4 ratio (p < 0.01), but k3 and k4 estimates may be less reliable. The BPND (DVR-1) decreased from 1.963 ± 0.27 in the vehicle-treated group to 1.53 ± 0.55 (p = 0.080) or 1.961 ± 0.11 (p = 0.993) after the administration of CGS21680 or KW6002, respectively. Our study suggests that the A2A agonist CGS21680, but not the antagonist KW6002, may reduce the D2 receptor availability in the striatum.

Binding of the Dual-Action Anti-Parkinsonian Drug AG-0029 to Dopamine D2 and Histamine H3 Receptors: A PET Study in Healthy Rats.

Introduction: Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor dysfunction and a diverse range of nonmotor symptoms. Functional relationships between the dopaminergic and histaminergic systems suggest that dual-action pharmaceuticals like AG-0029 (D2/D3 agonist/H3 antagonist) could ameliorate both the motor and cognitive symptoms of PD. The current study aimed to demonstrate the interaction of AG-0029 with its intended targets in the mammalian brain using positron emission tomography (PET). Methods: Healthy male Wistar rats were scanned with a small-animal PET camera, using either the dopamine D2/D3 receptor ligand [11C]raclopride or the histamine H3 receptor ligand [11C]GSK-189254, before and after treatment with an intravenous, acute, single dose of AG-0029. Dynamic [11C]raclopride PET data (60 min duration) were analyzed using the simplified reference tissue model 2 (SRTM2) with cerebellum as reference tissue and the nondisplaceable binding potential as the outcome parameter. Data from dynamic [11C]GSK-189254 scans (60 min duration) with arterial blood sampling were analyzed using Logan graphical analysis with the volume of distribution (VT) as the outcome parameter. Receptor occupancy was estimated using a Lassen plot. Results: Dopamine D2/3 receptor occupancies in the striatum were 22.6 ± 18.0 and 84.0 ± 3.5% (mean ± SD) after administration of 0.1 and 1 mg/kg AG-0029, respectively. In several brain regions, the VT values of [11C]GSK-189254 were significantly reduced after pretreatment of rats with 1 or 10 mg/kg AG-0029. The H3 receptor occupancies were 11.9 ± 8.5 and 40.3 ± 11.3% for the 1 and 10 mg/kg doses of AG-0029, respectively. Conclusions: Target engagement of AG-0029 as an agonist at dopamine D2/D3 receptors and an antagonist at histamine H3 receptors could be demonstrated in the rat brain with [11C]raclopride and [11C]GSK-189254 PET, respectively. The measured occupancy values reflect the previously reported high (subnanomolar) affinity of AG-0029 to D2/D3 and moderate (submicromolar) affinity to H3 receptors.