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Background: Over the last decades, many brain imaging studies have contributed to new insights in the pathogenesis of psychiatric disease. However, in spite of these developments, progress in the development of novel therapeutic drugs for prevalent psychiatric health conditions has been limited. Objective: In this review, we discuss translational, diagnostic and methodological issues that have hampered drug development in CNS disorders with a particular focus on psychiatry. The role of preclinical models is critically reviewed and opportunities for brain imaging in early stages of drug development using PET and fMRI are discussed. The role of PET and fMRI in drug development is reviewed emphasizing the need to engage in collaborations between industry, academia and phase I units. Conclusion: Brain imaging technology has revolutionized the study of psychiatric illnesses, and during the last decade, neuroimaging has provided valuable insights at different levels of analysis and brain organization, such as effective connectivity (anatomical), functional connectivity patterns and neurochemical information that may support both preclinical and clinical drug development. Since there is no unifying pathophysiological theory of individual psychiatric syndromes and since many symptoms cut across diagnostic boundaries, a new theoretical framework has been proposed that may help in defining new targets for treatment and thus enhance drug development in CNS diseases. In addition, it is argued that new proposals for data-mining and mathematical modelling as well as freely available databanks for neural network and neurochemical models of rodents combined with revised psychiatric classification will lead to new validated targets for drug development.

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.

Objective To investigate how patients experience a radiologist-patient consultation of imaging findings directly after neck ultrasonography (US), and how much time this consumes. Materials and methods This prospective randomized study included 109 consecutive patients who underwent neck US, of whom 44 had a radiologist-patient consultation of US results directly after the examination, and 65 who had not. Results The median ratings of all healthcare quality metrics (friendliness of the radiologist, explanation of the radiologist, skill of the radiologist, radiologist's concern for comfort during the examination, radiologist's concern for patient questions/worries, overall rating of the examination, and likelihood of recommending the examination) were either good/high or very good/very high, without any significant differences between both patient groups. Patients who did not discuss the US results with the radiologist, were significantly more worried during the examination (P = 0.040) and had significantly higher anxiety levels after completion of the US examination (P = 0.027) than patients who discussed the US results with the radiologist. Fifty-one out of 55 responding patients (92.7%) indicated a radiologist-patient consultation of US results to be important. The median duration of US examinations that included a radiologist-patient consultation of US results was 7.57 min (range: 5.15–12.10 min), while the median duration of US examinations without a radiologist-patient consultation of US results was 7.34 min (range: 3.45–14.32 min), without any significant difference (P = 0.637). Conclusion A radiologist-patient consultation of imaging findings after neck US decreases patient anxiety, is desired by most patients, and does not significantly prolong total examination time.

In this contribution, several opportunities and challenges for long axial field of view (LAFOV) PET are described. It is an anthology in which the main issues have been highlighted. A consolidated overview of the camera system implementation, business and financial plan, opportunities and challenges is provided. What the nuclear medicine and molecular imaging community can expect from these new PET/CT scanners is the delivery of more comprehensive information to the clinicians for advancing diagnosis, therapy evaluation and clinical research.

Introduction Portal vein obstruction (PVO) is a significant vascular complication after liver transplantation (LT) in pediatric patients. Current treatment strategies include percutaneous transluminal angioplasty (PTA), with or without stent placement, mesorex bypass (MRB), splenorenal shunt, mesocaval shunt, endovascular recanalization (EVR), splenic artery embolization and splenectomy. However, specific characteristics of patients undergoing intervention and selection of individual treatment and its efficacy have remained unclear. This review systematically analyzed biochemical and clinical characteristics, selection of treatment, efficacy, and post-procedural complications. Methods We systematically searched PubMed and Embase between January 1995 and March 2021 for studies on the management of PVO after LT. We analyzed the reports for biochemical and clinical characteristics at the timing of the intervention in different patients, selection of treatment, and reported efficacies. Results We found 22 cohort studies with 362 patients who had the following characteristics: biliary atresia (83%), living-donor LT (85%), thrombocytopenia (73%), splenomegaly (40%), ascites (16%), or gastrointestinal bleeding (26%). The 3-year primary patency of PTA without stent placement was similar to that with stent placement (70%–80% and 43%–94%, respectively). MRB was used as an initial treatment with a 3-year patency of 75% to 100%. One study showed that 5-year primary patency of EVR was 80%. Secondary patency was 90% to 100% after 3 years in all studies with PTA alone, PTA/stent placement, and stent placement alone. Conclusion This is the first review of all treatment protocols in PVO after pediatric LT. We showed that an important group of patients has severe symptoms of portal hypertension. Efficacy of all treatment modalities was high in the included studies which make them important modalities for these patients.

Purpose The aim of this review is to give an overview of the current status of targeted optical fluorescence imaging in the field of oncology, cardiovascular, infectious and inflammatory diseases to further promote clinical translation. Methods A meta-narrative approach was taken to systematically describe the relevant literature. Consecutively, each field was assigned a developmental stage regarding the clinical implementation of optical fluorescence imaging. Results Optical fluorescence imaging is leaning towards clinical implementation in gastrointestinal and head and neck cancers, closely followed by pulmonary, neuro, breast and gynaecological oncology. In cardiovascular and infectious disease, optical imaging is in a less advanced/proof of concept stage. Conclusion Targeted optical fluorescence imaging is rapidly evolving and expanding into the clinic, especially in the field of oncology. However, the imaging modality still has to overcome some major challenges before it can be part of the standard of care in the clinic, such as the provision of pivotal trial data. Intensive multidisciplinary (pre-)clinical joined forces are essential to overcome the delivery of such compelling phase III registration trial data and subsequent regulatory approval and reimbursement hurdles to advance clinical implementation of targeted optical fluorescence imaging as part of standard practice.

BACKGROUND AND PURPOSE: Second opinion reports of neurologic head and neck imaging are requested with increased regularity, and they may contain a recommendation to the clinician. Our aim was to investigate the frequency and determinants of the presence of a recommendation and the adherence by the referring physician to the recommendation in a second opinion neurology head and neck imaging report and the diagnostic yield of these recommendations.MATERIALS AND METHODS: This retrospective study included 994 consecutive second opinion reports of neurology head and neck imaging examinations performed at a tertiary care center.RESULTS: Of the 994 second opinion reports, 12.2% (121/994) contained a recommendation. An oncologic imaging indication was significantly (P = .030) associated with a lower chance of a recommendation in the second opinion report (OR = .67; 95% CI, 0.46?0.96). Clinicians followed 65.7% (88/134) of the recommendations. None of the investigated variables (patient age, sex, hospitalization status, indication for the second opinion report, experience of the radiologist who signed the second opinion report, strength of the recommendation, and whether the recommendation was made due to apparent quality issues of the original examination) were significantly associated with the compliance of the referring physician to this recommendation. The 134 individual recommendations eventually led to the establishment of 52 (38.2%) benign diagnoses and 28 (20.6%) malignant diagnoses, while no definitive diagnosis could be established in 56 (41.2%) cases.CONCLUSIONS: Recommendations are relatively common in second opinion reports of neurology head and neck imaging examinations, though less for oncologic indications. They are mostly followed by requesting physicians, thus affecting patient management. In most cases, they also lead to the establishment of a diagnosis, hence adding value to patient care.

Purpose Reactive microglia are an important hallmark of neuroinflammation. Reactive microglia release various inflammatory mediators, such as cytokines, chemokines, and prostaglandins, which are produced by enzymes like cyclooxygenases (COX). The inducible COX-2 subtype has been associated with inflammation, whereas the constitutively expressed COX-1 subtype is generally considered as a housekeeping enzyme. However, recent evidence suggests that COX-1 can also be upregulated and may play a prominent role in the brain during neuroinflammation. In this review, we summarize the evidence that supports this involvement of COX-1. Methods Five databases were used to retrieve relevant studies that addressed COX-1 in the context of neuroinflammation. The search resulted in 32 articles, describing in vitro, in vivo, post mortem, and in vivo imaging studies that specifically investigated the COX-1 isoform under such conditions. Results Reviewed literature generally indicated that the overexpression of COX-1 was induced by an inflammatory stimulus, which resulted in an increased production of prostaglandin E2. The pharmacological inhibition of COX-1 was shown to suppress the induction of inflammatory mediators like prostaglandin E2. Positron emission tomography (PET) imaging studies in animal models confirmed the overexpression of COX-1 during neuroinflammation. The same imaging method, however, could not detect any upregulation of COX-1 in patients with Alzheimer's disease. Conclusion Taken together, studies in cultured cells and living rodents suggest that COX-1 is involved in neuroinflammation. Most postmortem studies on human brains indicate that the concentration of COX-1-expressing microglial cells is increased near sites of inflammation. However, evidence for the involvement of COX-1 in neuroinflammation in the living human brain is still largely lacking.

16 beta-F-18-fluoro-5 alpha-dihydrotestosterone (F-18-FDHT) is a radiopharmaceutical that has been investigated as a diagnostic agent for the assessment of androgen receptor (AR) density in prostate cancer using PET. However, F-18-FDHT is rapidly metabolized in humans and excreted via the kidneys into the urine, potentially compromising the detection of tumor lesions close to the prostate. Enzalutamide is an AR signaling inhibitor currently used in different stages of prostate cancer. Enzalutamide and its primary metabolite N-desmethylenzalutamide have an AR affinity comparable to that of FDHT but are excreted mainly via the hepatic route. Radiolabeled enzalutamide could thus be a suitable candidate PET tracer for AR imaging. Here, we describe the radiolabeling of enzalutamide with F-18. Moreover, the in vitro and in vivo behavior of F-18-enzalutamide was evaluated and compared with the current standard, F-18-FDHT. Methods: F-18-enzalutamide was obtained by fluorination of the nitro precursor. In vitro cellular uptake studies with F-18-enzalutamide and F-18-FDHT were performed in LNCaP (AR-positive) and HEK293 (AR-negative) cells. Competition assays with both tracers were conducted on the LNCaP (AR-positive) cell line. In vivo PET imaging, ex vivo biodistribution, and metabolite studies with F-18-enzalutamide and F-18-FDHT were conducted on athymic nude male mice bearing an LNCaP xenograft in the shoulder. Results: F-18-enzalutamide was obtained in 1.4% +/- 0.9% radiochemical yield with an apparent molar activity of 6.2 +/- 10.3 GBq/mu mol. F-18-FDHT was obtained in 1.5% +/- 0.8% yield with a molar activity of more than 25 GBq/mu mol. Coincubation with an excess of 5 alpha-dihydrotestosterone or enzalutamide significantly reduced the cellular uptake of F-18-enzalutamide and F-18-FDHT to about 50% in AR-positive LNCaP cells but not in AR-negative HEK293 cells. PET and biodistribution studies on male mice bearing a LnCaP xenograft showed about 3 times higher tumor uptake for F-18-enzalutamide than for F-18-FDHT. Sixty minutes after tracer injection, 93% of F-18-enzalutamide in plasma was still intact, compared with only 3% of F-18-FDHT. Conclusion: Despite its lower apparent molar activity, F-18-enzalutamide shows higher tumor uptake and better metabolic stability than F-18-FDHT and thus seems to have more favorable properties for imaging of AR with PET. However, further evaluation in other oncologic animal models and patients is warranted to confirm these results.

P-Glycoprotein (P-gp) is an efflux pump located at the blood-brain barrier (BBB) that contributes to the protection of the central nervous system by transporting neurotoxic compounds out of the brain. A decline in P-gp function has been related to the pathogenesis of neurodegenerative diseases. P-gp inducers can increase the P-gp function and are considered as potential candidates for the treatment of such disorders. The P-gp inducer MC111 increased P-gp expression and function in SW480 human colon adenocarcinoma and colo-320 cells, respectively. Our study aims to evaluate the P-gp inducing effect of MC111 in the whole brain in vivo, using the P-gp tracer [F-18]MC225 and positron emission tomography (PET). Eighteen Wistar rats were treated with either vehicle solution, 4.5 mg/kg of MC111 (low-dose group), or 6 mg/kg of MC111 (high-dose group). Animals underwent a 60 min dynamic PET scan with arterial-blood sampling, 24 h after treatment with the inducer. Data were analyzed using the 1-tissue-compartment model and metabolite-corrected plasma as the input function. Model parameters such as the influx constant (K-1) and volume of distribution (V-T) were calculated, which reflect the in vivo P-gp function. P-gp and pregnane xenobiotic receptor (PXR) expression levels of the whole brain were assessed using western blot. The administration of MC111 decreased K-1 and V-T of [F-18]MC225 in the whole brain and all of the selected brain regions. In the high-dose group, whole-brain K-1 was decreased by 34% (K-1-high-dose = 0.20 +/- 0.02 vs K-1-control = 0.30 +/- 0.02; p < 0.001) and in the low-dose group by 7% (K-1-low-dose = 0.28 +/- 0.02 vs K-1-control = 0.30 +/- 0.02; p = 0.42) compared to controls. Whole-brain V-T was decreased by 25% in the high-dose group (V-T-high-dose = 5.92 +/- 0.41 vs V-T-control = 7.82 +/- 0.38; p < 0.001) and by 6% in the low-dose group (V-T-low-dose = 7.35 +/- 0.38 vs V-T-control = 7.82 +/- 0.37; p = 0.38) compared to controls. k(2) values did not vary after treatment. The treatment did not affect the metabolism of [F-18]MC225. Western blot studies using the wholebrain tissue did not detect changes in the P-gp expression, however, preliminary results using isolated brain capillaries found an increasing trend up to 37% in treated rats. The decrease in K1 and VT values after treatment with the inducer indicates an increase in the P-gp functionality at the BBB of treated rats. Moreover, preliminary results using brain endothelial cells also sustained the increase in the P-gp expression. In conclusion, the results verify that MC111 induces P-gp expression and function at the BBB in rats. An increasing trend regarding the P-gp expression levels is found using western blot and an increased P-gp function is confirmed with [F-18]MC225 and PET.

Objective To determine the association between medical knowledge relevant to radiology practice (as measured by the Dutch radiology progress test [DRPT]) and clinical productivity during radiology residency. Methods This study analyzed the results of 6 DRPTs and time period–matched clinical production points of radiology residents affiliated to a tertiary care academic medical center between 2013 and 2016. The Spearman correlation analysis was performed to determine the association between DRPT percentile scores and average daily clinical production points. Linear regression analyses were performed to determine the association of DRPT percentile scores with average daily clinical production points, adjusted for age and gender of the radiology resident, and postgraduate year. Results Eighty-four DRPTs with time period–matched clinical production points were included. These 84 DRPTs were made by 29 radiology residents (18 males and 11 females) with a median age of 31 years (range: 26–38 years). The Spearman correlation coefficient between DRPT percentile scores and average daily clinical production points was 0.550 (95% confidence interval: 0.381–0.694) (p < 0.001), indicating a significant moderate positive association. On multivariate analysis, average daily clinical production points (β coefficient of 0.035, p = 0.003), female gender of the radiology resident (β coefficient of 12.690, p = 0.001), and postgraduate year (β coefficient of 10.179, p < 0.001) were significantly associated with DRPT percentile scores. These three independent variables achieved an adjusted R2 of 0.527. Conclusion Clinical productivity is independently associated with medical knowledge relevant to radiology practice during radiology residency. These findings indicate that clinical productivity of a resident could be a potentially relevant metric in a radiology training program. Key Points • There is a significant moderate correlation between medical knowledge relevant to radiology practice and clinical productivity during radiology residency. • Medical knowledge relevant to radiology practice remains independently associated with clinical productivity during radiology residency after adjustment for postgraduate year and gender. • Clinical productivity of a resident may be regarded as a potentially relevant metric in a radiology training program.

Purpose: To explore reasons that influence a resident's choice for the nuclear medicine subspecialty in the integrated nuclear medicine and radiology residency program in the Netherlands. Methods: A web questionnaire was developed and distributed among residents in the Dutch integrated nuclear medicine and radiology training. Results: A total of 114 residents were included. The survey results revealed four categories of incentives to choose the nuclear medicine subspecialty: 1) Expertise of nuclear medicine physicians and their quality of supervision in the training hospital, 2) Opportunities to do scientific research during and after residency, 3) Diversity of pathology, radiotracers, examinations and therapies in the training hospital, and 4) The expectation that the role of hybrid imaging will increase in the future. They also revealed four groups of disincentives to choose the nuclear medicine subspecialty: 1) Lack of collaboration and integration between nuclear medicine and radiology in some training hospitals, 2) Imbalance between nuclear medicine and radiology during the first 2.5 years of basic training during residency at the expense of nuclear medicine, 3) Uncertainty regarding the international recognition of the nuclear medicine subspecialty training, and 4) Uncertain future of nuclear medicine regarding the chances of employment and the ratio of work activities of nuclear medicine to radiology. Conclusion: This study provided insight into residents' motives to pursue or refrain from nuclear medicine subspecialization in an integrated nuclear medicine and radiology residency program. Medical imaging specialists in training hospitals and developers of curricula for nuclear medicine and radiology training should take these motives into account to ensure a sufficient outflow of newly graduated nuclear medicine specialists.

Objectives Cross-sectional area (CSA) measurements of the neck musculature at the level of third cervical vertebra (C3) on CT scans are used to diagnose radiological sarcopenia, which is related to multiple adverse outcomes in head and neck cancer (HNC) patients. Alternatively, these assessments are performed with neck MRI, which has not been validated so far. For that, the objective was to evaluate whether skeletal muscle mass and sarcopenia can be assessed on neck MRI scans. Methods HNC patients were included between November 2014 and November 2018 from a prospective data-biobank. CSAs of the neck musculature at the C3 level were measured on CT (n = 125) and MRI neck scans (n = 92 on 1.5-T, n = 33 on 3-T). Measurements were converted into skeletal muscle index (SMI), and sarcopenia was defined (SMI 2/m2). Pearson correlation coefficients, Bland–Altman plots, McNemar test, Cohen’s kappa coefficients, and interclass correlation coefficients (ICCs) were estimated. Results CT and MRI correlated highly on CSA and SMI (r = 0.958–0.998, p 2/m2). There was no significant difference between CT and MRI in diagnosing sarcopenia (McNemar, p = 0.5–1.0). Agreement on sarcopenia diagnosis was good with κ = 0.956–0.978 and κ = 0.870–0.933, for 1.5-T and 3-T respectively. Observer ICCs in MRI were excellent. In general, T2-weighted images had the best correlation and agreement with CT. Conclusions Skeletal muscle mass and sarcopenia can interchangeably be assessed on CT and 1.5-T and 3-T MRI neck scans. This allows future clinical outcome assessment during treatment irrespective of used modality. Key Points • Screening for low amount of skeletal muscle mass is usually measured on neck CT scans and is highly clinical relevant as it is related to multiple adverse outcomes in head and neck cancer patients. • We found that skeletal muscle mass and sarcopenia determined on CT and 1.5-T and 3-T MRI neck scans at the C3 level can be used interchangeably. • When CT imaging of the neck is missing for skeletal muscle mass analysis, patients can be assessed with 1.5-T or 3-T neck MRIs.

Objectives Currently, multiple sclerosis is treated with anti-inflammatory therapies, but these treatments lack efficacy in progressive disease. New treatment strategies aim to repair myelin damage and efficacy evaluation of such new therapies would benefit from validated myelin imaging techniques. Several MRI methods for quantification of myelin density are available now. This systematic review aims to analyse the performance of these MRI methods. Methods Studies comparing myelin quantification by MRI with histology, the current gold standard, or assessing reproducibility were retrieved from PubMed/MEDLINE and Embase (until December 2019). Included studies assessed both myelin histology and MRI quantitatively. Correlation or variance measurements were extracted from the studies. Non-parametric tests were used to analyse differences in study methodologies. Results The search yielded 1348 unique articles. Twenty-two animal studies and 13 human studies correlated myelin MRI with histology. Eighteen clinical studies analysed the reproducibility. Overall bias risk was low or unclear. All MRI methods performed comparably, with a mean correlation between MRI and histology of R2=0.54 (SD=0.30) for animal studies, and R2=0.54 (SD=0.18) for human studies. Reproducibility for the MRI methods was good (ICC=0.75–0.93, R2=0.90–0.98, COV=1.3–27%), except for MTR (ICC=0.05–0.51). Conclusions Overall, MRI-based myelin imaging methods show a fairly good correlation with histology and a good reproducibility. However, the amount of validation data is too limited and the variability in performance between studies is too large to select the optimal MRI method for myelin quantification yet.

(R)-[(11)C]verapamil is a radiotracer widely used for the evaluation of the P-glycoprotein (P-gp) function at the blood-brain barrier (BBB). Several studies have evaluated the pharmacokinetics of (R)-[(11)C]verapamil in rats and humans under different conditions. However, to the best of our knowledge, the pharmacokinetics of (R)-[(11)C]verapamil have not yet been evaluated in nonhuman primates. Our study aims to establish (R)-[(11)C]verapamil as a reference P-gp tracer for comparison of a newly developed P-gp positron emission tomography (PET) tracer in a species close to humans. Therefore, the study assesses the kinetics of (R)-[(11)C]verapamil and evaluates the effect of scan duration and P-gp inhibition on estimated pharmacokinetic parameters. Three nonhuman primates underwent two dynamic 91 min PET scans with arterial blood sampling, one at baseline and another after inhibition of the P-gp function. The (R)-[(11)C]verapamil data were analyzed using 1-tissue compartment model (1-TCM) and 2-tissue compartment model fits using plasma-corrected for polar radio-metabolites or non-corrected for radio-metabolites as an input function and with various scan durations (10, 20, 30, 60, and 91 min). The preferred model was chosen according to the Akaike information criterion and the standard errors (SE %) of the estimated parameters. 1-TCM was selected as the model of choice to analyze the (R)-[(11)C]verapamil data at baseline and after inhibition and for all scan durations tested. The volume of distribution (V(T)) and the efflux constant k(2) estimations were affected by the evaluated scan durations, whereas the influx constant K(1) estimations remained relatively constant. After P-gp inhibition (tariquidar, 8 mg/kg), in a 91 min scan duration, the whole-brain V(T) increased significantly up to 208% (p < 0.001) and K(1) up to 159% (p < 0.001) compared with baseline scans. The k(2) values decreased significantly after P-gp inhibition in all the scan durations except for the 91 min scans. This study suggests the use of K(1), calculated with 1-TCM and using short PET scans (10 to 30 min), as a suitable parameter to measure the P-gp function at the BBB of nonhuman primates

Objective: Patients with peripheral arterial occlusive disease (PAOD) have a poor prognosis and a high prevalence of comorbidity. This study investigated whether sarcopenia and/or myosteatosis negatively affect long-term survival in patients with PAOD.Methods: This was a single-center, retrospective cohort study of 686 consecutive patients diagnosed and treated for PAOD and who underwent computed tomography scanning. Cross-sectional muscle measurements were obtained at the level of the third lumbar vertebra. Optimal stratification was used to define sex-specific and body mass index-specific cutoff values for sarcopenia and myosteatosis, respectively. The Cox proportional hazards model was used to determine the effect of sarcopenia and myosteatosis on overall survival.Results: Sarcopenia was associated with age, body mass index, myosteatosis, malignancy, congestive heart failure, hemodialysis, and Fontaine 4 classification. Myosteatosis was associated with age, sarcopenia, type 2 diabetes mellitus, hypertension, chronic obstructive pulmonary disease, malignancy, congestive heart failure, ischemic stroke, and Fontaine 4 classification. Sarcopenia (hazard ratio [HP], 2.82; 95% confidence interval [CI], 2.05-3.86; P Conclusions: Muscle depletion is independently associated with a poorer overall survival in patients with PAOD. Myosteatosis is a stronger predictor than sarcopenia, which indicates that quality is more important than quantity. Results should be interpreted with caution owing to missing data on medication usage.

[18F]MC225 has been developed as a weak substrate of P-glycoprotein (P-gp) aimed to measure changes in the P-gp function at the blood-brain barrier with positron emission tomography. This study evaluates [18F]MC225 kinetics in non-human primates and investigates the effect of both scan duration and P-gp inhibition. Three rhesus monkeys underwent two 91-min dynamic scans with blood sampling at baseline and after P-gp inhibition (8 mg/kg tariquidar). Data were analyzed using the 1-tissue compartment model (1-TCM) and 2-tissue compartment model (2-TCM) fits using metabolite-corrected plasma as the input function and for various scan durations (10, 20, 30, 60, and 91 min). The preferred model was chosen according to the Akaike information criterion and the standard errors (%) of the estimated parameters. For the 91-min scan duration, the influx constant K1 increased by 40.7% and the volume of distribution (VT) by 30.4% after P-gp inhibition, while the efflux constant k2 did not change significantly. Similar changes were found for all evaluated scan durations. K1 did not depend on scan duration (10 min - K1 = 0.2191 vs 91 min - K1 = 0.2258), while VT and k2 did. A scan duration of 10 min seems sufficient to properly evaluate the P-gp function using K1 obtained with 1-TCM. For the 91-min scan, VT and K1 can be estimated with a 2-TCM, and both parameters can be used to assess P-gp function.

Purpose Radiotherapy is a frequently applied treatment modality for brain tumors. Concomitant irradiation of normal brain tissue can induce various physiological responses. The aim of this study was to investigate whether acute and early-delayed effects of brain irradiation on glial activation and brain metabolism can be detected with positron emission tomography (PET) and whether these effects are correlated with behavioral changes. Procedures Rats underwent 0-, 10-, or 25-Gy whole-brain irradiation. At 3 and 31 days post irradiation, 1-(2-chlorophenyl)-N-[11C]methyl-(1-methylpropyl)-3-isoquinoline carboxamide ([11C]PK11195) and 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) PET scans were acquired to detect changes in glial activation (neuroinflammation) and glucose metabolism, respectively. The open-field test (OFT) was performed on days 6 and 27 to assess behavioral changes. Results Twenty-five-gray-irradiated rats showed higher [11C]PK11195 uptake in most brain regions than controls on day 3 (striatum, hypothalamus, accumbens, septum p p 11C]PK11195 uptake than controls and 10-Gy-irradiated group (p 11C]PK11195 uptake in individual brain regions of 25-Gy treated rats remained stable or slightly increased between days 3 and 31. In contrast, a significant reduction (p 18F]FDG uptake on day 3 (p 18F]FDG uptake decreased between days 3 and 31 in all groups; no significant differences between groups were observed anymore on day 31, except for increased uptake in the hypothalamus in the 10-Gy group. The OFT did not show any significant differences between groups. Conclusions Non-invasive PET imaging indicated that brain irradiation induces neuroinflammation and a metabolic flare, without causing acute or early-delayed behavioral changes.

Purpose: [18F]Fluoroethoxybenzovesamicol ([18F]FEOBV) is a radioligand for the vesicular acetylcholine transporter (VAChT), a marker of the cholinergic system. We evaluated the quantification of [18F]FEOBV in rats in control conditions and after partial saturation of VAChT using plasma and reference tissue input models and test-retest reliability. Procedure: Ninety-minute dynamic [18F]FEOBV PET scans with arterial blood sampling were performed in control rats and rats pretreated with 10 μg/kg FEOBV. Kinetic analyses were performed using one- (1TCM) and two-tissue compartmental models (2TCM), Logan and Patlak graphical analyses with metabolite-corrected plasma input, reference tissue Patlak with cerebellum as reference tissue, standard uptake value (SUV) and SUV ratio (SUVR) using 60- or 90-min acquisition. To assess test-retest reliability, two dynamic [18F]FEOBV scans were performed 1 week apart. Results: The 1TCM did not fit the data. Time-activity curves were more reliably estimated by the irreversible than the reversible 2TCM for 60 and 90 min as the influx rate Ki showed a lower coefficient of variation (COV, 14–24 %) than the volume of distribution VT (16–108 %). Patlak graphical analysis showed a good fit to the data for both acquisition times with a COV (12–27 %) comparable to the irreversible 2TCM. For 60 min, Logan analysis performed comparably to both irreversible models (COV 14–32 %) but showed lower sensitivity to VAChT saturation. Partial saturation of VAChT did not affect model selection when using plasma input. However, poor correlations were found between irreversible 2TCM and SUV and SUVR in partially saturated VAChT states. Test-retest reliability and intraclass correlation for SUV were good. Conclusion: [18F]FEOBV is best modeled using the irreversible 2TCM or Patlak graphical analysis. SUV should only be used if blood sampling is not possible.

Introduction Depression is characterized by behavioral, cognitive and physiological changes, imposing a major burden on the overall wellbeing of the patient. Some evidence indicates that social stress, changes in growth factors (e.g., brain-derived neurotrophic factor (BDNF)), and neuroinflammation are involved in the development and progression of the disease. The monoamine oxidase A inhibitor drug harmine was suggested to have both antidepressant and anti-inflammatory properties and may, therefore, be a potential candidate for treatment of depression. Aim The goal of this study was to assess the effects of harmine on behavior, brain BDNF levels, and microglia activation in control rats and a rat model of social stress. Material and methods Rats were submitted to 5 consecutive days of repeated social defeat (RSD) or control conditions. Animals were treated daily with harmine (15 mg/kg) or vehicle from day 3 until the end of the experiment. To assess the effects of harmine treatment on behavior, the sucrose preference test (SPT) was performed on days 1, 6, and 15, the open field test (OFT) on days 6 and 14, and the novel object recognition test (NOR) on day 16. Brain microgliosis was assessed using [11C]PBR-28 PET on day 17. Animals were terminated on day 17, and BDNF protein concentrations in the hippocampus and frontal cortex were analyzed using ELISA. Results RSD significantly decreased bodyweight and increased anxiety and anhedonia-related parameters in the OFT and SPT on day 6, but these behavioral effects were not observed anymore on day 14/15. Harmine treatment caused a significant reduction in bodyweight gain in both groups, induced anhedonia in the SPT on day 6, and significantly reduced the mobility and exploratory behavior of the animals in the OFT mainly on day 14. PET imaging and the NOR test did not show any significant effects on microglia activation and memory, respectively. BDNF protein concentrations in the hippocampus and frontal cortex were not significantly affected by either RSD or harmine treatment. Discussion Harmine was not able to reverse the acute effects of RSD on anxiety and anhedonia and even aggravated the effect of RSD on bodyweight loss. Moreover, harmine treatment caused unexpected side effects on general locomotion, both in RSD and control animals, but did not influence glial activation status and BDNF concentrations in the brain. In this model, RSD-induced stress was not strong enough to induce long-term effects on the behavior, neuroinflammation, or BDNF protein concentration. Thus, the efficacy of harmine treatment on these delayed parameters needs to be further evaluated in more severe models of chronic stress.

The interaction of dopaminergic and cholinergic neurotransmission in, e.g., Parkinson's disease has been well established. Here, D2 receptor antagonists were used to assess changes in [18F]-FEOBV binding to the vesicular acetylcholine transporter (VAChT) in rodents using positron emission tomography (PET). After pretreatment with either 10 mg/kg haloperidol, 1 mg/kg raclopride, or vehicle, 90 min dynamic PET scans were performed with arterial blood sampling. The net influx rate (Ki) was obtained from Patlak graphical analysis, using a metabolite-corrected plasma input function and dynamic PET data. [18F]-FEOBV concentration in whole-blood or plasma and the metabolite-corrected plasma input function were not significantly changed by the pretreatments (adjusted p > 0.07, Cohen's d 0.28-1.89) while the area-under-the-curve (AUC) of the parent fraction of [18F]-FEOBV was significantly higher after haloperidol treatment (adjusted p = 0.022, Cohen's d = 2.51) than in controls. Compared to controls, the AUC of [18F]-FEOBV, normalized for injected dose and body weight, was nonsignificantly increased in the striatum after haloperidol (adjusted p = 0.4, Cohen's d = 1.77) and raclopride (adjusted p = 0.052, Cohen's d = 1.49) treatment, respectively. No changes in the AUC of [18F]-FEOBV were found in the cerebellum (Cohen's d 0.63-0.74). Raclopride treatment nonsignificantly increased Ki in the striatum 1.3-fold compared to control rats (adjusted p = 0.1, Cohen's d = 1.1) while it reduced Ki in the cerebellum by 28% (adjusted p = 0.0004, Cohen's d = 2.2) compared to control rats. Pretreatment with haloperidol led to a nonsignificant reduction in Ki in the striatum (10%, adjusted p = 1, Cohen's d = 0.44) and a 40-50% lower Ki than controls in all other brain regions (adjusted p < 0.0005, Cohen's d = 3.3-4.7). The changes in Ki induced by the selective D2 receptor antagonist raclopride can in part be quantified using [18F]-FEOBV PET imaging. Haloperidol, a nonselective D2/σ receptor antagonist, either paradoxically decreased cholinergic activity or blocked off-target [18F]-FEOBV binding to σ receptors. Hence, further studies evaluating the binding of [18F]-FEOBV to σ receptors using selective σ receptor ligands are necessary.

In May 2018, the Biograph Vision PET/CT system was installed at the University Medical Center Groningen. This study evaluated the initial experiences with this new PET/CT system in terms of perceived image quality and semiquantitative analysis in comparison to the Biograph mCT as a reference. Methods: In total, 20 oncologic patients were enrolled and received a single 3 MBq/kg injected dose of 18F-FDG followed by a dual-imaging PET scan. Ten patients were scanned on the Biograph mCT first, whereas the other 10 patients were scanned on the Biograph Vision first. The locally preferred clinically reconstructed images were blindly reviewed by 3 nuclear medicine physicians and scored (using a Likert scale of 1–5) on tumor lesion demarcation, overall image quality, and image noise. In addition, these clinically reconstructed images were used for semiquantitative analysis by measurement of SUVs in tumor lesions. Images acquired using reconstructions conform with the European Association of Nuclear Medicine Research Ltd. (EARL) specifications were also used for measurements of SUV in tumor lesions and healthy tissues for comparison between systems. Results: The 18F-FDG dose received by the 14 men and 6 women (age range, 36–84; mean ± SD, 61 ± 16 y) ranged from 145 to 405 MBq (mean ± SD, 268 ± 59.3). Images acquired on the Biograph Vision were scored significantly higher on tumor lesion demarcation, overall image quality, and image noise than images acquired on the Biograph mCT (P < 0.001). The overall interreader agreement showed a Fleiss κ of 0.61 (95% confidence interval, 0.53–0.70). Furthermore, the SUVs in tumor lesions and healthy tissues agreed well (within 95%) between PET/CT systems, particularly when EARL-compliant reconstructions were used on both systems. Conclusion: In this initial study, the Biograph Vision showed improved image quality compared with the Biograph mCT in terms of lesion demarcation, overall image quality, and visually assessed signal-to-noise ratio. The 2 systems are comparable in semiquantitatively assessed image biomarkers in both healthy tissues and tumor lesions. Improved quantitative performance may, however, be feasible using the clinically optimized reconstruction settings.

Purpose Ventricle contact is associated with a worse prognosis and more aggressive tumor characteristics in glioblastoma (GBM). This is hypothesized to be a result of neural stem cells located around the lateral ventricles, in the subventricular zone. 11C Methionine positron emission tomography (metPET) is an indicator for increased proliferation, as it shows uptake of methionine, an amino acid needed for protein synthesis. This study is the first to study metPET characteristics of GBM in relation to ventricle contact. Methods A total of 12 patients with IDH wild-type GBM were included. Using MRI, the following regions were determined: primary tumor (defined as contrast enhancing lesion on T1) and peritumoral edema (defined as edema visible on FLAIR excluding the enhancement). PET parameters in these areas were extracted using PET fused with MRI imaging. Parameters extracted from the PET included maximum and mean tumor-to-normal ratio (TNRmax and TNRmean) and metabolic tumor volume (MTV). Results TNRmean of the primary tumor showed significantly higher values for the ventricle-contacting group compared to that for the non-contacting group (4.44 vs 2.67, p = 0.030). Other metPET parameters suggested higher values for the ventricle-contacting group, but these differences did not reach statistical significance. Conclusion GBM with ventricle contact demonstrated a higher methionine uptake and might thus have increased proliferation compared with GBM without ventricle contact. This might explain survival differences and should be considered in treatment decisions.

in press

Abstract Whole-body Patlak images can be obtained from an acquisition of first 6 min of dynamic imaging over the heart to obtain the arterial input function (IF), followed by multiple whole-body sweeps up to 60 min pi. The use of a population-averaged IF (PIF) could exclude the first dynamic scan and minimize whole-body sweeps to 30–60 min pi. Here, the effects of (incorrect) PIFs on the accuracy of the proposed Patlak method were assessed. In addition, the extent of mitigating these biases through rescaling of the PIF to image-derived IF values at 30–60 min pi was evaluated. Methods Using a representative IF and rate constants from the literature, various tumour time-activity curves (TACs) were simulated. Variations included multiplication of the IF with a positive and negative gradual linear bias over 60 min of 5, 10, 15, 20, and 25% (generating TACs using an IF different from the PIF); use of rate constants (K1, k3, and both K1 and k2) multiplied by 2, 1.5, and 0.75; and addition of noise (μ = 0 and σ = 5, 10 and 15%). Subsequent Patlak analysis using the original IF (representing the PIF) was used to obtain the influx constant (Ki) for the differently simulated TACs. Next, the PIF was scaled towards the (simulated) IF value using the 30–60-min pi time interval, simulating scaling of the PIF to image-derived values. Influence of variabilities in IF and rate constants, and rescaling the PIF on bias in Ki was evaluated. Results Percentage bias in Ki observed using simulated modified IFs varied from − 16 to 16% depending on the simulated amplitude and direction of the IF modifications. Subsequent scaling of the PIF reduced these Ki biases in most cases (287 out of 290) to Conclusions Simulations suggest that scaling of a (possibly incorrect) PIF to IF values seen in whole-body dynamic imaging from 30 to 60 min pi can provide accurate Ki estimates. Consequently, dynamic Patlak imaging protocols may be performed for 30–60 min pi making whole-body Patlak imaging clinically feasible.

Purpose P-glycoprotein (P-gp) function is altered in several brain disorders; thus, it is of interest to monitor the P-gp function in vivo using PET. (R)-[11C]verapamil is considered the gold standard tracer to measure the P-gp function; however, it presents some drawbacks that limit its use. New P-gp tracers have been developed with improved properties, such as [18F]MC225. This study compares the characteristics of (R)-[11C]verapamil and [18F]MC225 in the same subjects. Methods Three non-human primates underwent 4 PET scans: 2 with (R)-[11C]verapamil and 2 with [18F]MC225, at baseline and after P-gp inhibition. The 30-min PET data were analyzed using 1-Tissue Compartment Model (1-TCM) and metabolite-corrected plasma as input function. Tracer kinetic parameters at baseline and after inhibition were compared. Regional differences and simplified methods to quantify the P-gp function were also assessed. Results At baseline, [18F]MC225 VT values were higher, and k2 values were lower than those of (R)-[11C]verapamil, whereas K1 values were not significantly different. After inhibition, VT values of the 2 tracers were similar; however, (R)-[11C]verapamil K1 and k2 values were higher than those of [18F]MC225. Significant regional differences between tracers were found at baseline, which disappeared after inhibition. The positive slope of the SUV-TAC was positively correlated to the K1 and VT of both tracers. Conclusion [18F]MC225 and (R)-[11C]verapamil show comparable sensitivity to measure the P-gp function in non-human primates. Moreover, this study highlights the 30-min VT as the best parameter to measure decreases in the P-gp function with both tracers. [18F]MC225 may become the first radiofluorinated tracer able to measure decreases and increases in the P-gp function due to its higher baseline VT.

Objectives Deep learning has been proven to be able to stage liver fibrosis based on contrast-enhanced CT images. However, until now, the algorithm is used as a black box and lacks transparency. This study aimed to provide a visual-based explanation of the diagnostic decisions made by deep learning. Methods The liver fibrosis staging network (LFS network) was developed at contrast-enhanced CT images in the portal venous phase in 252 patients with histologically proven liver fibrosis stage. To give a visual explanation of the diagnostic decisions made by the LFS network, Gradient-weighted Class Activation Mapping (Grad-cam) was used to produce location maps indicating where the LFS network focuses on when predicting liver fibrosis stage. Results The LFS network had areas under the receiver operating characteristic curve of 0.92, 0.89, and 0.88 for staging significant fibrosis (F2–F4), advanced fibrosis (F3–F4), and cirrhosis (F4), respectively, on the test set. The location maps indicated that the LFS network had more focus on the liver surface in patients without liver fibrosis (F0), while it focused more on the parenchyma of the liver and spleen in case of cirrhosis (F4). Conclusions Deep learning methods are able to exploit CT-based information from the liver surface, liver parenchyma, and extrahepatic information to predict liver fibrosis stage. Therefore, we suggest using the entire upper abdomen on CT images when developing deep learning–based liver fibrosis staging algorithms. Key Points • Deep learning algorithms can stage liver fibrosis using contrast-enhanced CT images, but the algorithm is still used as a black box and lacks transparency. • Location maps produced by Gradient-weighted Class Activation Mapping can indicate the focus of the liver fibrosis staging network. • Deep learning methods use CT-based information from the liver surface, liver parenchyma, and extrahepatic information to predict liver fibrosis stage.

Background 6-[18F]fluoro-l-3,4-dihydroxyphenyl alanine ([18F]FDOPA) is a commonly used PET tracer for the detection and staging of neuroendocrine tumors. In neuroendocrine tumors, [18F]FDOPA is decarboxylated to [18F]dopamine via the enzyme amino acid decarboxylase (AADC), leading to increased uptake when there is increased AADC activity. Recently, in our hospital, a new GMP compliant multi-dose production of [18F]FDOPA has been developed, [18F]FDOPA-H, resulting in a higher activity yield, improved molar activity and a lower administered mass than the conventional method ([18F]FDOPA-L). Aims This study aimed to investigate whether the difference in molar activity affects the [18F]FDOPA uptake at physiological sites and in tumor lesions, in patients with NET. It was anticipated that the specific uptake of [18F]FDOPA-H would be equal to or higher than [18F]FDOPA-L. Methods We retrospectively analyzed 49 patients with pathologically confirmed NETs and stable disease who underwent PET scanning using both [18F]FDOPA-H and [18F]FDOPA-L within a time span of 5 years. A total of 98 [18F]FDOPA scans (49 [18F]FDOPA-L and 49 [18F]FDOPA-H with average molar activities of 8 and 107 GBq/mmol) were analyzed. The SUVmean was calculated for physiological organ uptake and SUVmax for tumor lesions in both groups for comparison, and separately in subjects with low tumor load (1–2 lesions) and higher tumor load (3–10 lesions). Results Comparable or slightly higher uptake was demonstrated in various physiological uptake sites in subjects scanned with [18F]FDOPA-H compared to [18F]FDOPA-L, with large overlap being present in the interquartile ranges. Tumor uptake was slightly higher in the [18F]FDOPA-H group with 3–10 lesion (SUVmax 6.83 vs. 5.19, p Conclusion [18F]FDOPA-H provides a higher activity yield, offering the possibility to scan more patients with one single production. Minor differences were observed in SUV’s, with slight increases in uptake of [18F]FDOPA-H in comparison to [18F]FDOPA-L. This finding is not a concern for clinical practice, but could be of importance when quantifying follow-up scans while introducing new production methods with a higher molar activity of [18F]FDOPA.

Automating cardiac function assessment on cardiac magnetic resonance short-axis cines is faster and more reproducible than manual contour-tracing; however, accurately tracing basal contours remains challenging. Three automated post-processing software packages (Level 1) were compared to manual assessment. Subsequently, automated basal tracings were manually adjusted using a standardized protocol combined with software package-specific relative-to-manual standard error correction (Level 2). All post-processing was performed in 65 healthy subjects. Manual contour-tracing was performed separately from Level 1 and 2 automated analysis. Automated measurements were considered accurate when the difference was equal or less than the maximum manual inter-observer disagreement percentage. Level 1 (2.1 & PLUSMN; 1.0 min) and Level 2 automated (5.2 & PLUSMN; 1.3 min) were faster and more reproducible than manual (21.1 & PLUSMN; 2.9 min) post-processing, the maximum inter-observer disagreement was 6%. Compared to manual, Level 1 automation had wide limits of agreement. The most reliable software package obtained more accurate measurements in Level 2 compared to Level 1 automation: left ventricular end-diastolic volume, 98% and 53%; ejection fraction, 98% and 60%; mass, 70% and 3%; right ventricular end-diastolic volume, 98% and 28%; ejection fraction, 80% and 40%, respectively. Level 1 automated cardiac function post-processing is fast and highly reproducible with varying accuracy. Level 2 automation balances speed and accuracy.

The human response to invading fungi includes a series of events that detect, kill, or clear the fungi. If the metabolic host response is unable to eliminate the fungi, an infection ensues. Some of the host response’s metabolic events to fungi can be imaged with molecules labelled with radionuclides. Several important clinical applications have been found with radiolabelled biomolecules of inflammation. 18F-fluorodeoxyglucose is the tracer that has been most widely investigated in the host defence of fungi. This tracer has added value in the early detection of infection, in staging and visualising dissemination of infection, and in monitoring antifungal treatment. Radiolabelled antimicrobial peptides showed promising results, but large prospective studies in fungal infection are lacking. Other tracers have also been used in imaging events of the host response, such as the migration of white blood cells at sites of infection, nutritional immunity in iron metabolism, and radiolabelled monoclonal antibodies. Many tracers are still at the preclinical stage. Some tracers require further studies before translation into clinical use. The application of therapeutic radionuclides offers a very promising clinical application of these tracers in managing drug-resistant fungi.

OBJECTIVE: To review the literature on the clinical application of radiolabeled somatostatin receptor scintigraphy (SRS) by SPECT and PET in adults with chronic inflammatory diseases.RESEARCH DESIGN: Systematic review of published observational studies between 1993 and 2017.DATA COLLECTION AND ANALYSIS: The Cochrane Central Register of Controlled Trials, MedLine, EMBASE, PubMed, Google Scholar, OVID, EBSCO, Scopus, and Web of Science were used to search for studies on the use of SRS in adults with chronic inflammatory diseases. A team of reviewers independently screened for eligible studies. Quality of evidence was assessed by QUADAS approach.RESULTS: Eligible papers included 38 studies. Studied populations were heterogeneous, and patients were classified according to the diagnosed disease: endothelial inflammation, rheumatoid arthritis, cardiac allograft rejection, granulomatous diseases, small vessel vasculitis, idiopathic pulmonary fibrosis, sarcoidosis, and thyroid exophthalmopathy. Because of many quality differences between studies, it was not possible to pool data, and a narrative synthesis is reported.CONCLUSION: Results highlight the value of SRS to detect active inflammation in several chronic inflammatory conditions, despite the bias related to the index test, showing lack of standardization of the scintigraphic technique and high variability of methods used to clinically evaluate inflammatory condition.

Background: Post-treatment high-grade gliomas are usually monitored with contrast-enhanced MRI, but its diagnostic accuracy is limited as it cannot adequately distinguish between true tumor progression and treatment-related changes. According to recent response assessment in neuro-oncology (RANO) recommendations PET overcomes this limitation. However, it is currently unknown which tracer yields the best results. Therefore, a systematic review and meta-analysis were performed to compare the diagnostic accuracy of the different PET tracers in differentiating tumor progression from treatment-related changes in high-grade glioma patients. Methods: Pubmed, Web of Science and Embase were searched systematically. Study selection, data extraction and quality assessment were performed independently by two authors. Meta-analysis was performed using a bivariate random effects model when ≥ 5 studies were included. Results: 39 studies (11 tracers) were included in the systematic review. 18F-FDG (12 studies, 171 lesions) showed a pooled sensitivity and specificity of 84% (95%CI 72-92) and 84% (69-93), respectively. 18F-FET (7 studies, 172 lesions) demonstrated a sensitivity of 90% (81-95) and specificity of 85% (71-93). 11C-MET (8 studies, 151 lesions) sensitivity was 93% (80-98) and specificity was 82% (68-91). The number of included studies for the other tracers were too low to combine, but sensitivity and specificity ranged between 93-100% and 0-100% for 18F-FLT, 85-100% and 72-100% for 18F-FDOPA and 100% and 70-88% for 11C-CHO, respectively. Conclusion:18F-FET and 11C-MET, both amino-acid tracers, showed a comparable higher sensitivity than 18F-FDG in the differentiation between tumor progression and treatment-related changes in high-grade glioma patients. The evidence for other tracers is limited, thus 18F-FET and 11C-MET are preferred when available. Our results support the incorporation of amino-acid PET tracers for the treatment evaluation of high-grade gliomas.

Medical magnetic resonance imaging (MRI) produces high-resolution anatomical images of the human body, but has limited capacity to provide useful molecular information. The light-responsive, liposomal MRI contrast agent described herein could be used to provide an intrinsic theranostic aspect to MRI and enable tracking the distribution and cargo release of drug delivery systems upon light-triggered activation.

18F-FDG and 68Ga-citrate PET/CT have both been shown to be useful in the management of tuberculosis (TB). We compared the abnormal PET findings of 18F-FDG- and 68Ga-citrate-PET/CT in patients with TB. Methods Patients with TB on anti-TB therapy were included. Patients had a set of PET scans consisting of both 18F-FDG and 68Ga-citrate. Abnormal lesions were identified, and the two sets of scans were compared. The scan findings were correlated to the clinical data as provided by the attending physician. Results 46 PET/CT scans were performed in 18 patients, 11 (61 %) were female, and the mean age was 35.7 ± 13.5 years. Five patients also had both studies for follow-up reasons during the use of anti-TB therapy. Thirteen patients were co-infected with HIV. 18F-FDG detected more lesions than 68Ga-citrate (261 vs. 166, p Conclusion Preliminary data shows 18F-FDG-PET detects more abnormal lesions in TB compared to 68Ga-citrate. However, 68Ga-citrate has better lesion definition in the brain and is therefore especially useful when intracranial TB is suspected.

PURPOSE: Post-transplant lymphoproliferative disorder (PTLD) is a serious complication after solid organ and hematopoietic stem cell transplantation, requiring a timely and accurate diagnosis. In this study, we evaluated the diagnostic performance of FDG-PET/CT in patients with suspected PTLD and examined if lactate dehydrogenase (LDH) levels, Epstein-Barr virus (EBV) load, or timing of FDG-PET/CT relate to detection performance of FDG-PET/CT.METHODS: This retrospective study included 91 consecutive patients with clinical suspicion of PTLD and a total of 97 FDG-PET/CT scans within an 8-year period. Pathology reports and a 2-year follow-up were used as the reference standard. Diagnostic performance of FDG-PET/CT for detection of PTLD as well as logistic regression analysis for factors expected to affect diagnostic yield were assessed.RESULTS: The diagnosis of PTLD was established in 34 patients (35%). Fifty-seven FDG-PET/CT scans (59%) were true negative, 29 (30%) were true positive, 6 (6%) false positive, and 5 (5%) false negative. Sensitivity of FDG-PET/CT for the detection of PTLD was 85%, specificity 90%, positive predictive value 83%, and negative predictive value 92%, with good inter-observer variability (k = 0.78). Of the parameters hypothesized to be associated with a true positive FDG-PET/CT result for the diagnosis of PTLD, only LDH was statistically significant (OR 1.03, p = 0.04).CONCLUSION: FDG-PET/CT has a good diagnostic performance in patients suspected of PTLD, with a good inter-observer agreement. Only LDH levels seemed to influence the detection performance of FDG-PET/CT. EBV-DNA load and timing of FDG-PET/CT after transplantation did not affect FDG-PET/CT diagnostic yield.

Objectives: Amyloid PET quantification can be affected by differences in image processing. For example, brain tissue segmentations can be performed in the subject- or standard-space (e.g. MNI), which might have an impact in regional and parametric analysis of the images. The aim of this study was to assess the effects of using different non-rigid image deformations (to standard-space) on quantitative PET metrics. Additionally, effects of using different grey matter masks, derived from population- or subject-based segmentations, were compared. Methods: Alzheimer’s Disease (AD, n=12) and healthy (HC, n=16) subjects underwent 70 min dynamic [11C]PiB PET scans and T1-weighted MRI scan. The 40–60 min of the [11C]PiB image were averaged and used for the registration to the individual MR scan (subject-space). Following, the MRI was used to calculate the transformation from subject-to-standard space using three different methods: preserving total amount (AMOUNT), preserving concentrations (CONCENTRATION), and with tissue probability maps (TPM). Grey matter probability maps were defined in subject-space (derived from the MRI) and in standard-space (population-based).Metrics were extracted for all the combinations of space, tissue segmentation, and transformation matrix, within grey matter. [11C]PiB SUV ratios (SUVR) were calculated using the cerebellum as reference. Two intensity metrics were extracted, one using the uptake in all grey matter (SUVRmeanall) and another including only amyloid-beta positive (Aβ+) voxels, with a SUVR≥1.5 threshold (SUVRmeanAβ+). Moreover, two volume-based metrics were defined: amyloid fractional volume (AFV, percentage of Aβ+ volume) and total amyloid burden (TAB, SUVRmeanAβ+ times Aβ+ volume). All image data were processed with SPM12, and the analysis was performed in R Studio (v1.1.456; R v3.5.1). Mean differences and standard deviations are shown. Results: When using the same spatial normalisation methodology and grey matter definition, small variations in the intensity metrics were found (0.4%±0.7%) between the subject- and standard-space results. However, within a specific space, grey matter definition had a greater impact in SUVRmeanall (5.67%±2.8%), but not on SUVRmeanAβ+ (0.7%±1.5%). Overall, normalisation methods AMOUNT and CONCENTRATION provided similar intensity metrics (0.7%±0.6%). Meanwhile, TPM was different than the other methods (7.5%±7.4%).Volumetric measurements showed larger differences between spaces when the spatial normalisation and grey matter were the same (AFV: 4.6%±6.8%; TAB:15%±10%). Within the same space and normalisation, large differences were observed for AFV and TAB depending of the grey matter segmentation method (4.6%±15% and 33%±14%, respectively). For spatial normalisation methods, CONCENTRATION and AMOUNT provided similar volume-based metrics (12%±9.5%), while TPM showed larger differences to the other methods (27%±21%). Conclusions: Intensity metrics were less affected by differences in PET image processing procedures while volumetric measurements depended more strongly on both space and spatial normalisation method applied and may thus only be valid when derived in subject-space.Therefore, only when SUVR are quantitative image analysis may be performed in either subject- or template-space, while volumetric measures should be performed in subject-space only.(This project is funded by European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 764458.)

OBJECTIVES: There is increased interest in various new quantitative uptake metrics beyond standardized uptake value (SUV) in oncology PET/CT studies. The purpose of this study is to investigate the variability and test-retest repeatability (TRT) of metabolically active tumor volume (MATV) measurements and several other new quantitative metrics in non-small cell lung cancer (NSCLC) using [18F]FDG PET/CT with different segmentation methods, user interactions, uptake intervals, and reconstruction protocols. METHODS: Ten advanced NSCLC patients received two whole-body [18F]FDG PET/CT scans at both 60 and 90 min post-injection. PET data were reconstructed with four different protocols. Eight segmentation methods were applied to delineate lesions with and without a tumor mask. MATV, maximum and mean SUV (SUVmax, SUVmean), total lesion glycolysis (TLG), and intralesional heterogeneity features were derived. Variability and repeatability were evaluated using a generalized estimating equations statistical model with Bonferroni correction for multiple comparisons. The statistical model, including interaction between uptake interval and reconstruction protocol, was applied individually to the data obtained from each segmentation method. RESULTS: Without masking, none of the segmentation methods could delineate all lesions correctly. MATV was affected by both uptake interval and reconstruction settings for most segmentation methods. Similar observations were obtained for the uptake metrics SUVmax, SUVmean, TLG, homogeneity, entropy, and zone percentage. No effect of uptake interval was observed on TRT metrics, while the reconstruction protocol affected the TRT of SUVmax. Overall, segmentation methods showing poor quantitative performance in one condition showed better performance in other (combined) conditions. For some metrics, a clear statistical interaction was found between the segmentation method and both uptake interval and reconstruction protocol. CONCLUSION: All segmentation results need to be reviewed critically. MATV and other quantitative uptake metrics, as well as their TRT, depend on segmentation method, uptake interval, and reconstruction protocol. To obtain quantitative reliable metrics, with good TRT performance, the optimal segmentation method depends on local imaging procedure, the PET/CT system and/or reconstruction protocol. Rigid harmonization of imaging procedure and PET/CT performance will be helpful in mitigating this variability.

Brain-derived neurotrophic factor (BDNF) is one of the most studied neurotrophins in the healthy and diseased brain. As a result, there is a large body of evidence that associates BDNF with neuronal maintenance, neuronal survival, plasticity, and neurotransmitter regulation. Patients with psychiatric and neurodegenerative disorders often have reduced BDNF concentrations in their blood and brain. A current hypothesis suggests that these abnormal BDNF levels might be due to the chronic inflammatory state of the brain in certain disorders, as neuroinflammation is known to affect several BDNF-related signaling pathways. Activation of glia cells can induce an increase in the levels of pro- and antiinflammatory cytokines and reactive oxygen species, which can lead to the modulation of neuronal function and neurotoxicity observed in several brain pathologies. Understanding how neuroinflammation is involved in disorders of the brain, especially in the disease onset and progression, can be crucial for the development of new strategies of treatment. Despite the increasing evidence for the involvement of BDNF and neuroinflammation in brain disorders, there is scarce evidence that addresses the interaction between the neurotrophin and neuroinflammation in psychiatric and neurodegenerative diseases. This review focuses on the effect of acute and chronic inflammation on BDNF levels in the most common psychiatric and neurodegenerative disorders and aims to shed some light on the possible biological mechanisms that may influence this effect. In addition, this review will address the effect of behavior and pharmacological interventions on BDNF levels in these disorders.

Introduction: This study aimed to determine the positive predictive value (PPV) of positron emission tomography/computed tomography (PET/CT) with an F-18-fluoro-2-deoxy-D-glucose (FDG)-avid presacral lesion for locally recurrent rectal cancer, and the additional value of magnetic resonance imaging (MRI), including diffusion-weighted imaging (DWI).Materials and methods: This retrospective study included 38 patients who completed primary rectal cancer treatment and who presented with a suspicious FDG-avid presacral lesion on PET/CT. Twenty-seven patients also underwent MRI, of whom 24 with DWI. PPV of FOG-PET/CT and additional value of MRI, including DWI, for the diagnosis of recurrent presacral cancer were determined.Results: The PPV of PET/CT with an FDG-avid presacral lesion for the diagnosis of locally recurrent rectal cancer was 58% (22/38). Air in the FDG-avid presacral lesion, as visible on the a component of the PET/CT examination, favoured the diagnosis of benign presacral tissue with a sensitivity of 56.3% (9/16) and a specificity 81.8% (18/22). Areas under the receiver operating characteristic curve (AUCs) of MRI without DWI for the diagnosis of locally recurrent rectal cancer in FDG-avid presacral tissue were 0.765 and 0.840, for observers 1 and 2. AUCs of MRI with DWI were 0.803 and 0.811, for observers 1 and 2. There were no significant differences among any of these AUCs (P=0.169 to 0.906).Conclusions: FOG-PET/CT has a poor PPV for locally recurrent rectal cancer in the presacral space. The observation of air in the FDG-avid presacral lesion and additional MRI assessment are diagnostically helpful, without a significant additional value of DWI. (C) 2018 Elsevier Ltd, BASO similar to The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Effective patient selection before or early during treatment is important to increasing the therapeutic benefits of anticancer treatments. This selection process is often predicated on biomarkers, predominantly biospecimen biomarkers derived from blood or tumour tissue; however, such biomarkers provide limited information about the true extent of disease or about the characteristics of different, potentially heterogeneous tumours present in an individual patient. Molecular imaging can also produce quantitative outputs; such imaging biomarkers can help to fill these knowledge gaps by providing complementary information on tumour characteristics, including heterogeneity and the microenvironment, as well as on pharmacokinetic parameters, drug- target engagement and responses to treatment. This integrative approach could therefore streamline biomarker and drug development, although a range of issues need to be overcome in order to enable a broader use of molecular imaging in clinical trials. In this Perspective article, we outline the multistage process of developing novel molecular imaging biomarkers. We discuss the challenges that have restricted the use of molecular imaging in clinical oncology research to date and outline future opportunities in this area.

Objective To determine the frequency, nature (using standardized coding taxonomy), and temporal trends of patient complaints about the radiological service provided in a European tertiary care center. Methods This retrospective study included all written patient complaints received by the department of radiology of a European tertiary care center within a 9-year period. Results A total of 94 written patient complaints were included. Overall complaint frequency was 14.4 per 100,000 radiological procedures. Complaint frequencies per 100,000 procedures were 103.7 for interventional radiology, 13.9 for MRI, 6.9 for ultrasonography, 6.5 for CT, 4.5 for fluoroscopy, and 1.2 for conventional radiography. Interventional radiology received significantly more complaints than all other radiological procedures (p

Background The value of magnetic resonance imaging (MRI) signs in differentiating Ewing sarcoma from osteomyelitis has not be thoroughly investigated. Purpose To investigate the value of various MRI signs in differentiating Ewing sarcoma from osteomyelitis. Material and Methods Forty-one patients who underwent MRI because of a bone lesion of unknown nature with a differential diagnosis that included both Ewing sarcoma and osteomyelitis were included. Two observers assessed several MRI signs, including the transition zone of the bone lesion, the presence of a soft-tissue mass, intramedullary and extramedullary fat globules, and the penumbra sign. Results Diagnostic accuracies for discriminating Ewing sarcoma from osteomyelitis were 82.4% and 79.4% for the presence of a soft-tissue mass, and 64.7% and 58.8% for a sharp transition zone of the bone lesion, for readers 1 and 2 respectively. Inter-observer agreement with regard to the presence of a soft-tissue mass and the transition zone of the bone lesion were moderate (κ = 0.470) and fair (κ = 0.307), respectively. Areas under the receiver operating characteristic curve of the diameter of the soft-tissue mass (if present) were 0.829 and 0.833, for readers 1 and 2 respectively. Mean inter-observer difference in soft-tissue mass diameter measurement ± limits of agreement was 35.0 ± 75.0 mm. Diagnostic accuracies of all other MRI signs were all Conclusion Presence and size of a soft-tissue mass, and sharpness of the transition zone, are useful MRI signs to differentiate Ewing sarcoma from osteomyelitis, but inter-observer agreement is relatively low. Other MRI signs are of no value in this setting.