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The purpose of this study was to assess the 1-year skeletal stability of the osteotomized maxilla after Le Fort I surgery, comparing conventional osteosynthesis with patient-specific osteosynthesis. Patients were assigned to a conventional or patient-specific osteosynthesis group using prospective randomization. The primary outcome was the three-dimensional change in postoperative skeletal position of the maxilla between the 2-week and 1-year follow-up cone beam computed tomography scans. Fifty-eight patients completed the protocol for the 2-week postoperative analysis, and 27 patients completed the 1-year follow-up study protocol. Of the 27 patients completing the entire protocol, 13 were in the conventional group and 14 in the patient-specific osteosynthesis group. The three-dimensional translation analysis showed that the use of the patient-specific osteosynthesis resulted in a skeletally stable result, comparable to that of conventional miniplate fixation. For both the patient-specific osteosynthesis and conventional miniplate fixation groups, median translations of less than 1 mm and median rotations of less than 1° were observed, indicating that both methods of fixation resulted in a stable result for the 27 patients examined. For the Le Fort I osteotomy, the choice between patient-specific osteosynthesis and conventional osteosynthesis did not affect the postoperative skeletal stability after 1 year of follow-up.

Background: Obesity is becoming more prevalent in the end-stage renal disease population. Bariatric surgery (BS) is increasingly considered as an approach to become eligible for kidney transplant (KT) or reduce obesity-related morbidities.Objectives: To assess the short- and long-term outcomes of patients who underwent both BS and KT and to determine the optimal timing of BS.Methods: Patients who underwent both KT and BS between January 2000 and December 2020 were included and stratified according to the sequence of the 2 operations. The primary outcomes were patient and graft survival. The secondary outcomes were postoperative complications and efficacy of weight loss.Results: Twenty-two patients were included in the KT first group and 34 in the BS first group. Death-uncensored graft survival in the KT first group was significantly higher than in the BS first group (90.9% versus 71.4%, P = .009), without significant difference in patient survival and death-censored graft survival (100% versus 90.5%, P = .082; 90.9% versus 81.0%, P = .058). There was no significant difference in 1-year total weight loss (1-yr TWL: median [interquartile range {IQR}], 36.0 [28.0–42.0] kg versus 29.6 [21.5–40.6] kg, P = .424), 1-year percentage of excess weight loss (1-yr %EWL: median [IQR], 74.9 [54.1–99.0] versus 57.9 [47.5–79.4], P = .155), and the incidence of postoperative complications (36.4% versus 50.0%, P = .316) between the KT first and BS first groups.Conclusion: Both pre- and posttransplant BS are effective and safe. Different conditions of each transplant candidate should be considered in detail to determine the optimal timing of BS.

Purpose The composition of thrombi retrieved during endovascular thrombectomy (EVT) in acute ischemic stroke (AIS) due to large vessel occlusion (LVO) may differ depending on their origin. In this study, we investigated the association between thrombus composition and stroke etiology in a large population of patients from the Dutch MR CLEAN Registry treated with EVT in daily clinical practice. Methods The thrombi of 332 patients with AIS were histologically analyzed for red blood cells (RBC), fibrin/platelets (F/P), and white blood cells (leukocytes) using a machine learning algorithm. Stroke etiology was assessed using the Trial of Org 10,172 in acute stroke treatment (TOAST) classification. Results The thrombi of cardioembolic origin contained less RBC and more F/P than those of non-cardioembolic origin (25.8% vs 41.2% RBC [p = 0.003] and 67.1% vs 54.5% F/P [p = 0.004]). The likelihood of a non-cardioembolic source of stroke increased with increasing thrombus RBC content (OR 1.02; [95% CI 1.00–1.06] for each percent increase) and decreased with a higher F/P content (OR 1.02; [95% CI 1.00–1.06]). Thrombus composition in patients with a cardioembolic origin and undetermined origin was similar. Conclusion Thrombus composition is significantly associated with stroke etiology, with an increase in RBC and a decrease in F/P raising the odds for a non-cardioembolic cause. No difference between composition of cardioembolic thrombi and of undetermined origin was seen. This emphasizes the need for more extensive monitoring for arrhythmias and/or extended cardiac analysis in case of an undetermined origin.

BACKGROUND: Endovascular treatment for anterior circulation ischaemic stroke is effective and safe within a 6 h window. MR CLEAN-LATE aimed to assess efficacy and safety of endovascular treatment for patients treated in the late window (6-24 h from symptom onset or last seen well) selected on the basis of the presence of collateral flow on CT angiography (CTA).METHODS: MR CLEAN-LATE was a multicentre, open-label, blinded-endpoint, randomised, controlled, phase 3 trial done in 18 stroke intervention centres in the Netherlands. Patients aged 18 years or older with ischaemic stroke, presenting in the late window with an anterior circulation large-vessel occlusion and collateral flow on CTA, and a neurological deficit score of at least 2 on the National Institutes of Health Stroke Scale were included. Patients who were eligible for late-window endovascular treatment were treated according to national guidelines (based on clinical and perfusion imaging criteria derived from the DAWN and DEFUSE-3 trials) and excluded from MR CLEAN-LATE enrolment. Patients were randomly assigned (1:1) to receive endovascular treatment or no endovascular treatment (control), in addition to best medical treatment. Randomisation was web based, with block sizes ranging from eight to 20, and stratified by centre. The primary outcome was the modified Rankin Scale (mRS) score at 90 days after randomisation. Safety outcomes included all-cause mortality at 90 days after randomisation and symptomatic intracranial haemorrhage. All randomly assigned patients who provided deferred consent or died before consent could be obtained comprised the modified intention-to-treat population, in which the primary and safety outcomes were assessed. Analyses were adjusted for predefined confounders. Treatment effect was estimated with ordinal logistic regression and reported as an adjusted common odds ratio (OR) with a 95% CI. This trial was registered with the ISRCTN, ISRCTN19922220.FINDINGS: Between Feb 2, 2018, and Jan 27, 2022, 535 patients were randomly assigned, and 502 (94%) patients provided deferred consent or died before consent was obtained (255 in the endovascular treatment group and 247 in the control group; 261 [52%] females). The median mRS score at 90 days was lower in the endovascular treatment group than in the control group (3 [IQR 2-5] vs 4 [2-6]), and we observed a shift towards better outcomes on the mRS for the endovascular treatment group (adjusted common OR 1·67 [95% CI 1·20-2·32]). All-cause mortality did not differ significantly between groups (62 [24%] of 255 patients vs 74 [30%] of 247 patients; adjusted OR 0·72 [95% CI 0·44-1·18]). Symptomatic intracranial haemorrhage occurred more often in the endovascular treatment group than in the control group (17 [7%] vs four [2%]; adjusted OR 4·59 [95% CI 1·49-14·10]).INTERPRETATION: In this study, endovascular treatment was efficacious and safe for patients with ischaemic stroke caused by an anterior circulation large-vessel occlusion who presented 6-24 h from onset or last seen well, and who were selected on the basis of the presence of collateral flow on CTA. Selection of patients for endovascular treatment in the late window could be primarily based on the presence of collateral flow.FUNDING: Collaboration for New Treatments of Acute Stroke consortium, Dutch Heart Foundation, Stryker, Medtronic, Cerenovus, Top Sector Life Sciences & Health, and the Netherlands Brain Foundation.

Systemic vasculitides comprise a group of autoimmune diseases affecting blood vessels, including large vessel vasculitis (LVV) and medium-sized vessel vasculitis such as giant cell arteritis (GCA) and Takayasu arteritis (TAK). GCA frequently overlaps with polymyalgia rheumatica (PMR), a rheumatic inflammatory condition affecting bursae, tendons or tendon sheaths, and joints. 18F-FDG PET/CT plays an important role in the diagnostic work-up of GCA, PMR, and TAK and is increasingly used to monitor treatment response. This continuing education article provides up-to-date guidance on the role of 18F-FDG PET/CT in patients with LVV, medium-sized vessel vasculitis, and PMR. It provides a general introduction on the clinical presentation and challenges in the diagnostic work-up of LVV and medium-sized vessel vasculitis, with a focus on the 2 major LVV subtypes: GCA, including PMR, and TAK. Next, practice points to perform and interpret the results of 18F-FDG PET/CT are described in line with the published procedure recommendations. Furthermore, the diagnostic performance and its role for treatment monitoring are discussed, taking into account recent international recommendations for the use of imaging in LVV and medium-sized vessel vasculitis in clinical practice. This is illustrated by several clinically representative PET/CT scan examples. Lastly, knowledge of limitations and pitfalls is essential to understand the role of 18F-FDG PET/CT in LVV, medium-sized vessel vasculitis, and PMR. Challenges and opportunities, as well as future research and conclusions, are highlighted. Learning objectives provide up-to-date guidance for the role of 18F-FDG PET/CT in patients with suspected LVV, medium-sized vessel vasculitis, and PMR.

We report the evolution of mScarlet3, a cysteine-free monomeric red fluorescent protein with fast and complete maturation, as well as record brightness, quantum yield (75%) and fluorescence lifetime (4.0 ns). The mScarlet3 crystal structure reveals a barrel rigidified at one of its heads by a large hydrophobic patch of internal residues. mScarlet3 behaves well as a fusion tag, displays no apparent cytotoxicity and it surpasses existing red fluorescent proteins as a Förster resonance energy transfer acceptor and as a reporter in transient expression systems.

BACKGROUND: Fenestrated endovascular aortic aneurysm repair (FEVAR) is used in pararenal abdominal aortic aneurysms to achieve a durable proximal seal. This study investigated the mid-term course of the proximal fenestrated stent graft (FSG) sealing zone on the first and latest available post-FEVAR computed tomographic angiography (CTA) scan in a single-center series.METHODS: In 61 elective FEVAR patients, the shortest length of circumferential apposition between the FSG and the aortic wall (shortest apposition length [SAL]) was retrospectively assessed on the first and last available postoperative CTA scans. Patient records were reviewed for FEVAR-related procedural details, complications, and reinterventions.RESULTS: The median (interquartile range) time between the FEVAR procedure and the first and last CTA scan was 35 (30-48) days and 2.6 (1.2-4.3) years, respectively. The median (interquartile range) SAL was 38 (29-48) mm, and 44 (34-59) mm on the first and last CTA scans, respectively. During follow-up, the SAL increased >5 mm in 32 patients (52%), and decreased >5 mm in six patients (10%). Reintervention was performed for a type 1a endoleak in one patient. Twelve other patients needed 17 reinterventions for other FEVAR-related complications.CONCLUSIONS: Good mid-term apposition of the FSG in the pararenal aorta was achieved post-FEVAR, and the occurrence of type 1a endoleaks was low. The number of reinterventions was substantial, however, but for reasons other than loss of proximal seal.

Sodium-glucose co-transporter 2 (SGLT2) inhibitors, including canagliflozin, reduce the risk of cardiovascular and kidney outcomes in patients with and without type 2 diabetes, albeit with a large inter-individual variation. The underlying mechanisms for this variation in response might be attributed to differences in SGLT2 occupancy, resulting from individual variation in plasma and tissue drug exposure and receptor availability. We performed a feasibility study for the use of [ 18 F]Canagliflozin positron emission tomography (PET) imaging to determine the association between clinical canagliflozin doses and SGLT2 occupancy in patients with type 2 diabetes. We obtained two 90-min dynamic PET scans with diagnostic intravenous [ 18 F]Canagliflozin administration and a full kinetic analysis in seven patients with type 2 diabetes. Patients received 50, 100 or 300mg oral canagliflozin (n=2:4:1) 2.5 hours before the second scan. Canagliflozin pharmacokinetics and urinary glucose excretion were measured. The apparent SGLT2 occupancy was derived from the difference between the apparent volume of distribution of [ 18 F]Canagliflozin in the baseline and post-drug PET scans. Individual canagliflozin area under the curve from oral dosing until 24-hours (AUC P0-24h ) varied largely (range 1715-25747 μg/L*h, mean 10580 μg/L*h) and increased dose dependently with mean values of 4543, 6525 and 20012 μg/L*h for 50, 100 and 300mg respectively (P=0.046). SGLT2 occupancy ranged between 65 and 87%, but did not correlate with canagliflozin dose, plasma exposure or urinary glucose excretion. We report the feasibility of [ 18 F]Canagliflozin PET imaging to determine canagliflozin kidney disposition and SGLT2 occupancy. This suggests the potential of [ 18 F]Canagliflozin as a tool to visualize and quantify clinically SGLT2 tissue binding.

Background: Previous interim data from a phase I study of AKS-452, a subunit vaccine comprising an Fc fusion of the respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein receptor binding domain (SP/RBD) emulsified in the water-in-oil adjuvant, Montanide™ ISA 720, suggested a good safety and immunogenicity profile in healthy adults. This phase I study was completed and two dosing regimens were further evaluated in this phase II study.Methods: This phase II randomized, open-labelled, parallel group study was conducted at a single site in The Netherlands with 52 healthy adults (18 – 72 years) receiving AKS-452 subcutaneously at one 90 µg dose (cohort 1, 26 subjects) or two 45 µg doses 28 days apart (cohort 2, 26 subjects). Serum samples were collected at the first dose (day 0) and at days 28, 56, 90, and 180. Safety and immunogenicity endpoints were assessed, along with induction of IgG isotypes, cross-reactive immunity against viral variants, and IFN-γ T cell responses.Results: All AEs were mild/moderate (grades 1 or 2), and no SAEs were attributable to AKS-452. Seroconversion rates reached 100% in both cohorts, although cohort 2 showed greater geometric mean IgG titers that were stable through day 180 and associated with enhanced potencies of SP/RBD-ACE2 binding inhibition and live virus neutralization. AKS-452-induced IgG titers strongly bound mutant SP/RBD from several SARS-CoV-2 variants (including Omicrons) that were predominantly of the favorable IgG1/3 isotype and IFN-γ-producing T cell phenotype.Conclusion: These favorable safety and immunogenicity profiles of the candidate vaccine as demonstrated in this phase II study are consistent with those of the phase I study (ClinicalTrials.gov: NCT04681092) and suggest that a total of 90 µg received in 2 doses may offer a greater duration of cross-reactive neutralizing titers than when given in a single dose.

Purpose In selected ADPKD patients, a nephrectomy is required in the work-up for a kidney transplantation. Because the impact of this procedure is unknown, we investigated the effect of pre-transplantation nephrectomy on quality of life in this group. Methods In this retrospective cohort study all ADPKD patients, ≥ 18 years, who received a kidney transplantation in 2 ADPKD expertise centers between January 2000 and January 2016, were asked to participate. Quality of life was assessed using three validated questionnaires on three time points. Nephrectomy was performed in preparation for transplantation. Results Two hundred seventy-six ADPKD patients (53 ± 9 years, 56.2% male) were included. 98 patients (35.5%) underwent native nephrectomy in preparation for transplantation, of which 43 underwent bilateral nephrectomy. Pre-transplantation, ADPKD-IS scores were worse in the nephrectomy group vs. no-nephrectomy group (physical: 2.9 vs. 2.3, p p = 0.03; fatigue: 3.0 vs. 2.3, p = 0.01). Post-transplantation and post-nephrectomy, ADPKD-IS scores improved significantly in both groups, with a significantly higher improvement in the nephrectomy group. During follow-up, all scores were still better compared to pre-transplantation. Observed physical QoL (ADPKD-IS physical 1.3 vs. 1.7, p = 0.04; SF-36 physical 50.0 vs. 41.3, p = 0.03) was better post-transplantation after bilateral nephrectomy compared to unilateral nephrectomy. In retrospect, 19.7% of patients would have liked to undergo a nephrectomy, while the decision not to perform nephrectomy was made by the treating physician. Conclusion This study shows that pre-transplantation nephrectomy improves quality of life in selected ADPKD patients. Bilateral nephrectomy may be preferred, although the risk of additional complications should be weighted.

This review aims to summarize key articles published in the Journal of Cardiovascular Computed Tomography (JCCT) in 2022, focusing on those that had the most scientific and educational impact. The JCCT continues to expand; the number of submissions, published manuscripts, cited articles, article downloads, social media presence, and impact factor continues to grow. The articles selected by the Editorial Board of the JCCT in this review highlight the role of cardiovascular computed tomography (CCT) to detect subclinical atherosclerosis, assess the functional relevance of stenoses, and plan invasive coronary and valve procedures. A section is dedicated to CCT in infants and other patients with congenital heart disease, in women, and to the importance of training in CT. In addition, we highlight key consensus documents and guidelines published in JCCT last year. The Journal values the tremendous work by authors, reviewers, and editors to accomplish these contributions.

Background: The aim of this study was to evaluate the long-term patient satisfaction and quality of life 9 to 13 years after autologous versus alloplastic breast reconstruction and compare the data to those of an earlier study.Methods: This is a 9-year follow-up study of 92 women who underwent breast reconstruction (47 autologous and 45 alloplastic) between 2006 and 2010 and filled out the BREAST-Q questionnaire in 2010. Changes in BREAST-Q scores were analyzed by using a change score from baseline (2010) to follow-up (2019), which was presented by a mean change score with 95% confidence intervals. Linear regression analyses were performed to test which patient characteristics were related to the BREAST-Q change scores.Results: The response rate at follow-up was 60% (25 autologous and 30 alloplastic). Responders at follow-up had a lower body mass index and had less frequently undergone unilateral breast reconstruction compared to the nonresponders. Women undergoing both autologous and alloplastic breast reconstruction had significantly decreased satisfaction with breasts (-4 points), satisfaction with outcome (-8 points), and satisfaction with nipples (-20 points) over time. None of the patient characteristics, including reconstruction technique, were related to the BREAST-Q change scores.Conclusions: Satisfaction with breasts, satisfaction with outcome, and satisfaction with nipples decreased slightly over time for women undergoing alloplastic and autologous breast reconstruction. Women undergoing autologous breast reconstruction seemed to remain more satisfied with their breasts 9 to 13 years after breast reconstruction compared to women undergoing alloplastic breast reconstruction. Because of the small sample size, conclusions should be carefully drawn. However, the results were in line with the expectations based on previous literature.

BackgroundTo ensure optimal utilization of deceased donor kidneys, it is important to understand the precise reasons why kidneys are discarded. In this study we aimed to obtain a comprehensive overview of kidney utilization and discard during the entire donation process in the Netherlands.MethodsIn this retrospective cohort study we analysed kidney utilization of 3856 kidneys in the Netherlands between 1 January 2015 and 31 December 2020. For every kidney that was not transplanted, we determined the moment of and reason for discard through a unique case-by-case assessment.ResultsKidney discard according to the traditional definition (procured but not transplanted) was 7.8%. However, when kidneys that seemed medically suitable at the beginning of the donation process were also included, many more potential donor kidneys were lost and the total non-utilization was 24.4%. Subjectively presumed impaired organ quality was responsible for 34.2% of all discarded kidneys. Two-thirds of kidneys discarded due to acute kidney injury (AKI) had only AKI stage 1 or 2.ConclusionThe classical definition of organ discard underestimates the non-utilization of deceased donor kidneys. Strategies to improve kidney utilization could be a revision of the maximum allowed agonal time in donation after circulatory death, careful consideration in reporting and accepting kidneys from donors with AKI and a prospectively filled registry of detailed organ discard reasons, including the ‘silent’ non-utilization before procurement.

Endovascular revascularization is the preferred treatment for peripheral arterial disease. Restenosis often occurs as a response to procedure-induced arterial damage. Reducing vascular injury during endovascular revascularization may improve its success rate. This study developed and validated an ex vivo flow model using porcine iliac arteries, obtained from a local abattoir. Twenty arteries (of 10 pigs) were equally allocated to two groups: a mock-treated control group and an endovascular intervention group. Arteries of both groups were perfused with porcine blood for 9 min, including 3 min of balloon angioplasty in the intervention group. Vessel injury was assessed by calculating the presence of endothelial cell denudation, vasomotor function, and histopathological analysis. MR imaging displayed balloon positioning and inflation. Endothelial cell staining showed 76% of denudation after ballooning compared to 6% in the control group (p < 0.001). This was confirmed by histopathological analysis, showing a significantly reduced endothelial nuclei count after ballooning compared to the controls (median: 22 vs. 37 nuclei/mm, p = 0.022). In the intervention group, vasoconstriction and endothelium-dependent relaxation were significantly reduced (p < 0.05).We present an ex vivo flow model to test the effects of endovascular therapy on the vessel’s wall morphology, endothelial denudation, and endothelial-dependent vasomotor function under physiological conditions. Additionally, it allows the future testing of human arterial tissue.

Background: Differentiation between uncomplicated and complicated postoperative wound drainage after arthroplasty is crucial to prevent unnecessary reoperation. Prospective data about the duration and amount of postoperative wound drainage in patients with and without prosthetic joint infection (PJI) are currently absent. Methods: A multicentre cohort study was conducted to assess the duration and amount of wound drainage in patients after arthroplasty. During 30 postoperative days after arthroplasty, patients recorded their wound status in a previously developed wound care app and graded the amount of wound drainage on a 5-point scale. Data about PJI in the follow-up period were extracted from the patient files. Results: Of the 1019 included patients, 16 patients (1.6 %) developed a PJI. Minor wound drainage decreased from the first to the fourth postoperative week from 50 % to 3 %. Both moderate to severe wound drainage in the third week and newly developed wound drainage in the second week after a week without drainage were strongly associated with PJI (odds ratio (OR) 103.23, 95 % confidence interval (CI) 26.08 to 408.57, OR 80.71, 95 % CI 9.12 to 714.52, respectively). The positive predictive value (PPV) for PJI was 83 % for moderate to heavy wound drainage in the third week. Conclusion: Moderate to heavy wound drainage and persistent wound drainage were strongly associated with PJI. The PPV of wound drainage for PJI was high for moderate to heavy drainage in the third week but was low for drainage in the first week. Therefore, additional parameters are needed to guide the decision to reoperate on patients for suspected acute PJI.

Background: Poor glycemic control prior to cancer diagnosis for patients with preexisting type 2 diabetes (T2DM) may predict a worse cancer diagnosis. We investigated the association between pre-diagnosis glycemic control and all-cause mortality in patients with T2DM who develop cancer. Methods: This prospective cohort study linked data from three sources covering 1989 to 2019: a T2DM benchmarking database, the Netherlands Cancer Registry, and the Personal Records Database. We included patients with T2DM and incident primary breast, colorectal, or prostate cancer (stage 0–III), with target glycemic control defined according to Dutch guidelines. Analysis involved estimating the association between glycemic control and all-cause mortality with Cox proportional hazard models, accounting for individual expected survival relative to the general population and relevant disease (e.g., diabetes duration and medications) and individual (e.g., age and gender) characteristics. Results: Of the 71,648 linked cases, 620 had breast cancer, 774 had colorectal cancer, and 438 had prostate cancer, with follow-up data available for 6.4 (4.2–8.4), 5.6 (2.7–7.6), and 6.3 (4.5–8.2) years, respectively. Compared with patients with pre-diagnosis glycemic control at target, the HRs and 95% confidence intervals for mortality among those with pre-diagnosis glycemic control not at target were 1.40 (1.00–1.96) for breast cancer, 1.45 (1.12–1.88) for colorectal cancer, and 1.39 (0.98–1.98) for prostate cancer. Conclusions: Among patients with T2DM in Dutch primary care, poor glycemic control before diagnosis with breast and colorectal cancer can increase mortality compared with good control. Impact: Glycemic control prior to cancer diagnosis is of prognostic value.

Background Coronary computed tomography angiography (CCTA) is widely used in the diagnostic work-up of patients with stable chest pain. CCTA has an excellent negative predictive value, but a moderate positive predictive value for detecting coronary stenosis. Computed tomography-derived fractional flow reserve (FFRct) is a non-invasive, well-validated technique that provides functional assessment of coronary stenosis, improving the positive predictive value of CCTA. However, to determine the value of FFRct in routine clinical practice, a pragmatic randomised, controlled trial (RCT) is required. We will conduct an RCT to investigate the impact of adding FFRct analysis in the diagnostic pathway of patients with a coronary stenosis on CCTA on the rate of unnecessary invasive coronary angiography, cost-effectiveness, quality of life and clinical outcome. Methods The FUSION trial is a prospective, multicentre RCT that will randomise 528 patients with stable chest pain and anatomical stenosis of ≥ 50% but Conclusion The FUSION trial will evaluate the use of FFRct in stable chest pain patients from the Dutch perspective. The trial is funded by the Dutch National Health Care Institute as part of the research programme ‘Potentially Promising Care’ and the results will be used to assess if FFRct reimbursement should be included in the standard health care package.

IntroductionThe efficacy and safety of local intra-arterial (IA) thrombolytics during endovascular thrombectomy (EVT) for large-vessel occlusions is uncertain. We analysed how often IA thrombolytics were administered in the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN) Registry, whether it was associated with improved functional outcome and assessed technical and safety outcomes compared with EVT without IA thrombolytics.MethodsIn this observational study, we included patients undergoing EVT for an acute ischaemic stroke in the anterior circulation from the MR CLEAN Registry (March 2014–November 2017). The primary endpoint was favourable functional outcome, defined as an modified Rankin Scale score ≤2 at 90 days. Secondary endpoints were reperfusion status, early neurological recovery and symptomatic intracranial haemorrhage (sICH). Subgroup analyses for IA thrombolytics as primary versus adjuvant revascularisation attempt were performed.ResultsOf the 2263 included patients, 95 (4.2%) received IA thrombolytics during EVT. The IA thrombolytics administered were urokinase (median dose, 250 000 IU (IQR, 1 93 750–2 50 000)) or alteplase (median dose, 20 mg (IQR, 12–20)). No association was found between IA thrombolytics and favourable functional outcome (adjusted OR (aOR), 1.16; 95% CI 0.71 to 1.90). Successful reperfusion was less often observed in those patients treated with IA thrombolytics (aOR, 0.57; 95% CI 0.36 to 0.90). The odds of sICH (aOR, 0.82; 95% CI 0.32 to 2.10) and early neurological recovery were comparable between patients treated with and without IA thrombolytics. For primary and adjuvant revascularisation attempts, IA thrombolytics were more often administered for proximal than for distal occlusions. Functional outcomes were comparable for patients receiving IA thrombolytics as a primary versus adjuvant revascularisation attempt.ConclusionLocal IA thrombolytics were rarely used in the MR CLEAN Registry. In the relatively small study sample, no statistical difference was observed between groups in the rate of favourable functional outcome or sICH. Patients whom required and underwent IA thrombolytics were patients less likely to achieve successful reperfusion, probably due to selection bias.

The paper describes the numerical coupling challenges in multiphysics problems like the simulation of blood flow in compliant arteries. In addition to an iterative coupling between the fluid flow and elastic vessel walls, i.e. fluid-structure interaction, also the coupling between a detailed 3D local (arterial) flow model and a more global 0D model (representing a global circulation) is analyzed. Most of the coupling analysis is formulated in the more abstract setting of electrical-network models. Both, weak (segregated) and strong (monolithic) coupling approaches are studied, and their numerical stability limitations are discussed. Being a hybrid combination, the quasi-simultaneous coupling method, developed for partitioned problems in aerodynamics, is shown to be a robust and flexible approach for hemodynamic applications too.

Rationale: Tumor visualization with near-infrared fluorescence (NIRF) imaging could aid exploration and resection of pancreatic cancer by visualizing the tumor in real time. Conjugation of the near-infrared fluorophore IRDye800CW to the monoclonal antibody bevacizumab enables targeting of vascular endothelial growth factor-A (VEGF-A). The aim of this study was to determine if intraoperative tumor-specific imaging of pancreatic cancer with the fluorescent tracer bevacizumab-800CW is feasible and safe. Materials and Methods: In this multicenter, dose escalation phase I trial patients with suspicion of pancreatic ductal adenocarcinoma (PDAC) were administered bevacizumab-800CW (4.5mg, 10mg or 25mg) three days before surgery. Safety monitoring encompassed allergic or anaphylactic reactions and serious adverse events attributed to bevacizumab-800CW. Intraoperative NIRF imaging was performed immediately after laparotomy, just before and after resection of the specimen. Postoperatively, fluorescence signals on the axial slices and formalin-fixed paraffin-embedded tissue blocks from the resected specimens were correlated to histology. Subsequently, tumor-to-background ratios (TBR) were calculated. Results: Ten patients with clinically suspected PDAC were enrolled in the study. Four of the resected specimens were confirmed PDACs; other malignancies were distal cholangiocarcinoma, ampullary carcinoma and neuroendocrine tumors. No serious adverse events were related to bevacizumab-800CW. In vivo tumor visualization with NIRF imaging differed per tumor type and was non-conclusive. Ex vivo TBRs were 1.3, 1.5 and 2.5 for 4.5mg, 10mg and 25mg groups, respectively. Conclusion: NIRF guided surgery in patients with suspect PDAC using bevacizumab-IRDye800CW is feasible and safe. However, suboptimal TBRs were obtained because no clear distinction between pancreatic cancer from normal or inflamed pancreatic tissue was achieved. Therefore, a more tumor-specific tracer other than bevacizumab-IRDye800CW for PDAC is preferred.

BACKGROUND: The shortage of donor organs for transplantation remains a worldwide problem. The utilization of suboptimal deceased donors enlarges the pool of potential organs, yet consequently, clinicians face the difficult decision of whether these sub-optimal organs are of sufficient quality for transplantation. Novel technologies could play a pivotal role in making pre-transplant organ assessment more objective and reliable.METHODS: Ex vivo normothermic machine perfusion (NMP) at temperatures around 35-37°C allows organ quality assessment in a near-physiological environment. Advanced magnetic resonance imaging (MRI) techniques convey unique information about an organ's structural and functional integrity. The concept of applying magnetic resonance imaging during renal normothermic machine perfusion is novel in both renal and radiological research and we have developed the first MRI-compatible NMP setup for human-sized kidneys.RESULTS: We were able to obtain a detailed and real-time view of ongoing processes inside renal grafts during ex vivo perfusion. This new technique can visualize structural abnormalities, quantify regional flow distribution, renal metabolism, and local oxygen availability, and track the distribution of ex vivo administered cellular therapy.CONCLUSION: This platform allows for advanced pre-transplant organ assessment, provides a new realistic tool for studies into renal physiology and metabolism, and may facilitate therapeutic tracing of pharmacological and cellular interventions to an isolated kidney.

Rationale: An effective absorbed dose response relationship is yet to be established for Lutetium-177 based radionuclide therapies such as 177Lu-DOTATATE and 177Lu-PSMA. The inherent biological heterogeneity of neuroendocrine and prostate cancers may make the prospect of establishing cohort-based dose-response relationships unobtainable. Instead, an individual-based approach, monitoring the dose-response within each tumor could provide the necessary metric to monitor treatment efficacy. Methods: We developed a dual isotope SPECT imaging strategy to monitor the change over time in the relationship between 177Lu-DOTATATE and 111In-anti-γH2AX-TAT, a modified radiolabelled antibody that allows imaging of DNA double strand breaks, in mice bearing rat pancreatic cancer xenografts. The dynamics of γH2AX foci, apoptosis and senescence following exposure to 177Lu-DOTATATE was further investigated in vitro and in ex vivo tumor sections. Results: The change in slope of the 111In-anti-γH2AX-TAT to 177Lu signal between days 5 and 7 was found to be highly predictive of survival (r = 0.955, P < 0.0001). This pivotal timeframe was investigated further in vitro: clonogenic survival correlated with the number of γH2AX foci at day 6 (r = -0.995, P < 0.0005). While there was evidence of continuously low levels of apoptosis, delayed induction of senescence in vitro appeared to better account for the γH2AX response to 177Lu. The induction of senescence was further investigated by ex vivo analysis and corresponded with sustained retention of 177Lu within tumor regions. Conclusions: Dual isotope SPECT imaging can provide individualized tumor dose-responses that can be used to predict lutetium-177 treatment efficacy. This bio-dosimeter metric appears to be dependent upon the extent of senescence induction and suggests an integral role that senescence plays in lutetium-177 treatment efficacy.

Aims Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by ventricular dysfunction and ventricular arrhythmias (VA). Adequate arrhythmic risk assessment is important to prevent sudden cardiac death. We aimed to study the incremental value of strain by feature-tracking cardiac magnetic resonance imaging (FT-CMR) in predicting sustained VA in ARVC patients. Methods and results CMR images of 132 ARVC patients (43% male, 40.6 ± 16.0 years) without prior VA were analysed for global and regional right and left ventricular (RV, LV) strain. Primary outcome was sustained VA during follow-up. We performed multivariable regression assessing strain, in combination with (i) RV ejection fraction (EF); (ii) LVEF; and (iii) the ARVC risk calculator. False discovery rate adjusted P-values were given to correct for multiple comparisons and c-statistics were calculated for each model. During 4.3 (2.0–7.9) years of follow-up, 19% of patients experienced sustained VA. Compared to patients without VA, those with VA had significantly reduced RV longitudinal (P ≤ 0.03) and LV circumferential (P ≤ 0.04) strain. In addition, patients with VA had significantly reduced biventricular EF (P ≤ 0.02). After correcting for RVEF, LVEF, and the ARVC risk calculator separately in multivariable analysis, both RV and LV strain lost their significance [hazard ratio 1.03–1.18, P > 0.05]. Likewise, while strain improved the c-statistic in combination with RVEF, LVEF, and the ARVC risk calculator separately, this did not reach statistical significance (P ≥ 0.18). Conclusion Both RV longitudinal and LV circumferential strain are reduced in ARVC patients with sustained VA during follow-up. However, strain does not have incremental value over RVEF, LVEF, and the ARVC VA risk calculator.

Artificial intelligence (AI) is coming into the field of nuclear medicine, and it is likely here to stay. As a society, EANM can and must play a central role in the use of AI in nuclear medicine. In this position paper, the EANM explains the preconditions for the implementation of AI in NM and takes position.

Objective: This study demonstrates intravascular micro-agent visualization by utilizing robotic ultrasound-based tracking and visual servoing in clinically-relevant scenarios. Methods: Visual servoing path is planned intraoperatively using a body surface point cloud acquired with a 3D camera and the vessel reconstructed from ultrasound (US) images, where both the camera and the US probe are attached to the robot end-effector. Developed machine vision algorithms are used for detection of micro-agents from minimal size of 250μm inside the vessel contour and tracking with error recovery. Finally, real-time positions of the micro-agents are used for servoing of the robot with the attached US probe. Constant contact between the US probe and the surface of the body is accomplished by means of impedance control. Results: Developed algorithms are tested in clinically relevant scenarios which include anthropomorphic phantom, biological tissue, simulation of physiological movement and simulation of fluid flow through the vessels. Breathing motion is compensated to keep constant contact between the US probe and the body surface, with minimal measured force of 2.02N. Anthropomorphic phantom vessels are segmented with an Intersection-Over-Union (IOU) score of 0.93±0.05, while micro-agent tracking is performed with up to 99.8% success rate at 28-36 frames per second. Path planning, tracking and visual servoing are realized over 80mm and 120mm long surface paths. Conclusion: Experiments performed using anthropomorphic surfaces, biological tissue, simulation of physiological movement and simulation of fluid flow through the vessels indicate that robust visualization and tracking of micro-agents involving human patients is an achievable goal.

Background and purpose: Xerostomia remains a common side effect of radiotherapy (RT) for patients with head and neck (H&N) cancer despite advancements in treatment planning and delivery. Secretory salivary gland cells express the prostate-specific membrane antigen (PSMA), and show significant uptake on PET scans using 68Ga/18F-PSMA-ligands. We aimed to objectively quantify the dose–response of salivary glands to RT using PSMA PET. Methods and materials: 28H&N cancer patients received RT with 70 Gy in 35 fractions over 7 weeks. PSMA PET/CT was acquired at baseline (BL), during treatment (DT) and at 1-&6-months post-treatment (PT1M/PT6M). Dose, BL- PT1M- and PT6M-SUV were extracted for every voxel inside each parotid (PG) and submandibular (SMG) gland. The PT1M/6M data was analysed using a generalised linear mixed effects model. Patient-reported xerostomia and DT-PSMA loss was also analysed. Results: Dose had a relative effect on BL SUV. For a population average gland (BL-SUV of 10), every 1 Gy increment, decreased the PT1M/PT6M-SUV by 1.6 %/1.6 % for PGs and by 0.9 %/1.8 % for SMGs. TD50 of the population curves was 26.5/31.3 Gy for PGs, and 22.9/27.8 Gy for SMGs at PT1M /PT6M. PSMA loss correlated well with patient-reported xerostomia at DT/PT1M (Spearman's ρ = -0.64, −0.50). Conclusion: A strong relationship was demonstrated between radiation dose and loss of secretory cells in salivary glands derived using PSMA PET/CT. The population curve could potentially be used as a dose planning objective, by maximising the predicted post-treatment SUV. BL scans could be used to further tailor this to individual patients.

The angiotensin receptor blocker telmisartan slows progression of kidney disease in patients with type 2 diabetes (T2D), yet many patients remain at high risk for progressive kidney function loss. The underlying mechanisms for this response variation might be attributed to differences in angiotensin-1 receptor occupancy (RO), resulting from individual variation in plasma drug exposure, tissue drug exposure, and receptor availability. Therefore, we first assessed the relationship between plasma telmisartan exposure and urinary-albumin-to-creatinine-ratio (UACR) in 10 patients with T2D and albuminuria (mean age 66 years, median UACR 297 mg/g) after 4 weeks treatment with 80 mg telmisartan once daily. Increasing telmisartan exposure associated with a larger reduction in UACR (Pearson correlation coefficient (PCC) = -0.64, P = 0.046, median change UACR: -40.1%, 95% confidence interval (CI): -22.9 to -77.4%, mean telmisartan area under the curve (AUC) = 2927.1 ng center dot hour/mL, 95% CI: 723.0 to 6501.6 ng center dot hour/mL). Subsequently, we assessed the relation among plasma telmisartan exposure, kidney distribution, and angiotensin-1 RO in five patients with T2D (mean age 60 years, median UACR 72 mg/g) in a separate positron emission tomography imaging study with [C-11]Telmisartan. Individual plasma telmisartan exposure correlated with telmisartan distribution to the kidneys (PCC = 0.976, P = 0.024). A meaningful RO could be calculated in three patients receiving 120 mg oral telmisartan, and although high exposure seems related to higher RO, with AUC(0-last) of 31, 840, and 274 ng center dot hour/mL and corresponding RO values 5.5%, 44%, and 59%, this was not significant (P = 0.64). Together these results indicate, for the first time, a relationship among interindividual differences in plasma exposure, kidney tissue distribution, RO, and ultimately UACR response after telmisartan administration.

OBJECTIVES: Differentiating benign gallbladder diseases from gallbladder cancer (GBC) remains a radiological challenge because they can appear very similar on imaging. This study aimed at investigating whether CT-based radiomic features of suspicious gallbladder lesions analyzed by machine learning algorithms could adequately discriminate benign gallbladder disease from GBC. In addition, the added value of machine learning models to radiological visual CT-scan interpretation was assessed.METHODS: Patients were retrospectively selected based on confirmed histopathological diagnosis and available contrast-enhanced portal venous phase CT-scan. The radiomic features were extracted from the entire gallbladder, then further analyzed by machine learning classifiers based on Lasso regression, Ridge regression, and XG Boosting. The results of the best-performing classifier were combined with radiological visual CT diagnosis and then compared with radiological visual CT assessment alone.RESULTS: In total, 127 patients were included: 83 patients with benign gallbladder lesions and 44 patients with GBC. Among all machine learning classifiers, XG boosting achieved the best AUC of 0.81 (95% CI 0.72-0.91) and the highest accuracy rate of 73% (95% CI 65-80%). When combining radiological visual interpretation and predictions of the XG boosting classifier, the highest diagnostic performance was achieved with an AUC of 0.98 (95% CI 0.96-1.00), a sensitivity of 91% (95% CI 86-100%), a specificity of 93% (95% CI 90-100%), and an accuracy of 92% (95% CI 90-100%).CONCLUSIONS: Machine learning analysis of CT-based radiomic features shows promising results in discriminating benign from malignant gallbladder disease. Combining CT-based radiomic analysis and radiological visual interpretation provided the most optimal strategy for GBC and benign gallbladder disease differentiation.KEY POINTS: Radiomic-based machine learning algorithms are able to differentiate benign gallbladder disease from gallbladder cancer. Combining machine learning algorithms with a radiological visual interpretation of gallbladder lesions at CT increases the specificity, compared to visual interpretation alone, from 73 to 93% and the accuracy from 85 to 92%. Combined use of machine learning algorithms and radiological visual assessment seems the most optimal strategy for GBC and benign gallbladder disease differentiation.

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.

Purpose Doppler ultrasound (DUS) is widely used to detect vascular complications after pediatric liver transplantation (LT). This study aimed to assess the moment of first detection of vascular complications with DUS, and to determine the positive predictive value (PPV) of DUS. Materials and Methods Patients aged 0–18 years who underwent LT between 2015 and 2019 were retrospectively included. 92 LTs in 83 patients were included (median age: 3.9 years, interquartile range: 0.7–10.5). Patients underwent perioperative (intra-operative and immediately postoperative) and daily DUS surveillance during the first postoperative week, and at 1, 3, and 12 months. Vascular complications were categorized for the hepatic artery, portal vein, and hepatic veins. DUS findings were compared to surgical or radiological findings during the 1-year follow-up. Results 52 vascular complications were diagnosed by DUS in 35/92 LTs (38%). 15 out of 52 (28.8%) were diagnosed perioperatively, 29/52 (55.8%) were diagnosed on postoperative days 1–7, and 8/52 (15.4%) after day 7. The PPV for all vascular complications diagnosed with DUS was 92.3%. During the 1-year follow-up, 18/19 (94.7%) hepatic artery complications, 19/26 (73.1%) portal vein complications, and 7/7 (100%) hepatic vein complications were diagnosed perioperatively or during the first week. Conclusion The majority of vascular complications during the first year after pediatric LT were diagnosed by DUS perioperatively or during the first week, with a high PPV. Our findings provide important information regarding when to expect different types of vascular complications on DUS, which might improve DUS post-LT surveillance protocols.

Parathyroid diseases are characterized by dysregulation of calcium homeostasis and alterations in parathyroid hormone (PTH) excretion. The development of parathyroid-targeted treatment and imaging tracers could benefit from in vitro models. Therefore, we aim to establish a patient-derived parathyroid organoid model representing human parathyroid tissue. Hyperplastic parathyroid tissue was dispersed, and parathyroid organoids (PTOs) were cultured and characterized. PTO-derived cells exhibited self-renewal over several passages, indicative of the presence of putative stem cells. Immunofluorescence and RNA sequencing confirmed that PTOs phenocopy hyperplastic parathyroid tissue. Exposure of PTOs to increasing calcium concentrations and PTH-lowering drugs resulted in significantly reduced PTH excretion. PTOs showed specific binding of the imaging tracers 11C-methionine and 99mTc-sestamibi. These data show the functionality of PTOs resembling the parathyroid. This PTO model recapitulates the originating tissue on gene and protein expression and functionality, paving the way for future physiology studies and therapeutic target and tracer discovery.

Different types of medical imaging are increasingly being used to explain specific aspects of injuries to patients during consultations. However, there are no validated questionnaires available yet that specifically measure patients’ satisfaction with the use of such images. The objective of this study was to develop and evaluate a patient-centred measure of satisfaction with the use of medical imaging modalities in clinical treatment. A preliminary 22-item version of the Questionnaire for Patient Satisfaction with Imaging (QPSI) was developed based on extant literature and interviews with trauma patients. Final item selection and psychometric evaluations were conducted amongst a sample of 106 hospital trauma patients who were shown medical images of their injuries. The psychometric analyses resulted in a final 13-item questionnaire comprising two subscales that measure the importance of seeing the images (9 items) and the clearness of the image (4 items). Both subscales showed adequate internal consistency (α = 0.84 and 0.75). The subscales were weakly intercorrelated (ρ = 0.34) and were both significantly and independently associated with patients’ global ratings of satisfaction with the use of imaging. The final two-dimensional QPSI is an innovative, reliable and valid questionnaire for measuring patients’ satisfaction with imaging-based information during clinical consultations.

Continuum manipulators coupled with magnetic actuation have great potential as steerable instruments for diverse surgical applications. They can be maneuvered inside the human body to reach difficult-to-access surgical sites with contactless actuation. This paper presents a new design of a compliant continuum manipulator of diameter 3 mm and length 70 mm, capable of spatial bending under magnetic actuation. A quasi-static model is developed to estimate the 3D motion of the manipulator. Experiments report an overall mean error in whole shape estimation of the manipulator between the model and the ground truth of 1.7 mm and 4.8 mm, when suspended vertically and horizontally from its base, respectively. Furthermore, fiber Bragg grating (FBG) sensors are integrated with the manipulator to enable shape sensing. Closed-loop control is demonstrated to trace different trajectories with the tip of the manipulator. A square trajectory and a straight line trajectory are generated with an average error in tip position of 4.1 mm between the desired and estimated positions. The potential of the manipulator as a steerable instrument is validated by maneuvering it inside phantoms of a bifurcating arterial system and a heart with visual guidance from a miniature camera.

Objectives Thrombus computed tomography (CT) characteristics might be used to assess histopathologic thrombus composition in patients treated with endovascular thrombectomy (EVT) for acute ischemic stroke (AIS). We aimed to assess the variability in thrombus composition that could be predicted with combined thrombus CT characteristics. Methods Thrombi of patients enrolled in the MR CLEAN Registry between March 2014 and June 2016 were histologically analyzed with hematoxylin-eosin staining and quantified for percentages of red blood cells (RBCs) and fibrin/platelets. We estimated the association between general qualitative characteristics (hyperdense artery sign [HAS], occlusion location, clot burden score [CBS]) and thrombus composition with linear regression, and quantified RBC variability that could be explained with individual and combined characteristics with R2. For patients with available thin-slice (≤ 2.5 mm) imaging, we performed similar analyses for general and quantitative characteristics (HAS, occlusion location, CBS, [relative] thrombus density, thrombus length, perviousness, distance from ICA-terminus). Results In 332 included patients, the presence of HAS (aβ 7.8 [95% CI 3.9–11.7]) and shift towards a more proximal occlusion location (aβ 3.9 [95% CI 0.6–7.1]) were independently associated with increased RBC and decreased fibrin/platelet content. With general characteristics, 12% of RBC variability could be explained; HAS was the strongest predictor. In 94 patients with available thin-slice imaging, 30% of RBC variability could be explained; thrombus density and thrombus length were the strongest predictors. Conclusions Quantitative thrombus CT characteristics on thin-slice admission CT improve prediction of thrombus composition and might be used to further guide clinical decision-making in patients treated with EVT for AIS in the future. Key Points • With hyperdense artery sign and occlusion location, 12% of variability in thrombus RBC content can be explained. • With hyperdense artery sign, occlusion location, and quantitative thrombus characteristics on thin-slice (≤ 2.5 mm) non-contrast CT and CTA, 30% of variability in thrombus RBC content can be explained. • Absolute thrombus density and thrombus length were the strongest predictors for thrombus composition.

Contains fulltext : 287508.pdf (Publisher’s version ) (Closed access) BACKGROUND: Pooled analyses of previous randomised studies have suggested that very early treatment with glyceryl trinitrate (also known as nitroglycerin) improves functional outcome in patients with acute ischaemic stroke or intracerebral haemorrhage, but this finding was not confirmed in a more recent trial (RIGHT-2). We aimed to assess whether patients with presumed acute stroke benefit from glyceryl tr initrate started within 3 h after symptom onset. METHODS: MR ASAP was a phase 3, randomised, open-label, blinded endpoint trial done at six ambulance services serving 18 hospitals in the Netherlands. Eligible participants (aged ≥18 years) had a probable diagnosis of acute stroke (as assessed by a paramedic), a face-arm-speech-time test score of 2 or 3, systolic blood pressure of at least 140 mm Hg, and could start treatment within 3 h of symptom onset. Participants were randomly assigned (1:1) by ambulance personnel, using a secure web-based electronic application with random block sizes stratified by ambulance service, to receive either transdermal glyceryl trinitrate 5 mg/day for 24 h plus standard care (glyceryl trinitrate group) or to standard care alone (control group) in the prehospital setting. Informed consent was deferred until after arrival at the hospital. The primary outcome was functional outcome assessed with the modified Rankin Scale (mRS) at 90 days. Safety outcomes included death within 7 days, death within 90 days, and serious adverse events. Analyses were based on modified intention to treat, and treatment effects were expressed as odds ratios (ORs) or common ORs, with adjustment for baseline prognostic factors. We separately analysed the total population and the target population (ie, patients with intracerebral haemorrhage, ischaemic stroke, or transient ischaemic attack). The target sample size was 1400 patients. The trial is registered as ISRCTN99503308. FINDINGS: On June 24, 2021, the MR ASAP trial was prematurely terminated on the advice of the data and safety monitoring board, with recruitment stopped because of safety concerns in patients with intracerebral haemorrhage. Between April 4, 2018, and Feb 12, 2021, 380 patients were randomly allocated to a study group. 325 provided informed consent or died before consent could be obtained, of whom 170 were assigned to the glyceryl trinitrate group and 155 to the control group. These patients were included in the total population. 201 patients (62%) had ischaemic stroke, 34 (10%) transient ischaemic attack, 56 (17%) intracerebral haemorrhage, and 34 (10%) a stroke-mimicking condition. In the total population (n=325), the median mRS score at 90 days was 2 (IQR 1-4) in both the glyceryl trinitrate and control groups (adjusted common OR 0·97 [95% CI 0·65-1·47]). In the target population (n=291), the 90-day mRS score was 2 (2-4) in the glyceryl trinitrate group and 3 (1-4) in the control group (0·92 [0·59-1·43]). In the total population, there were no differences between the two study groups with respect to death within 90 days (adjusted OR 1·07 [0·53-2·14]) or serious adverse events (unadjusted OR 1·23 [0·76-1·99]). In patients with intracerebral haemorrhage, 12 (34%) of 35 patients allocated to glyceryl trinitrate versus two (10%) of 21 allocated to the control group died within 7 days (adjusted OR 5·91 [0·78-44·81]); death within 90 days occurred in 16 (46%) of 35 in the glyceryl trinitrate group and 11 (55%) of 20 in the control group (adjusted OR 0·87 [0·18-4·17]). INTERPRETATION: We found no sign of benefit of transdermal glyceryl trinitrate started within 3 h of symptom onset in the prehospital setting in patients with presumed acute stroke. The signal of potential early harm of glyceryl trinitrate in patients with intracerebral haemorrhage suggests that glyceryl trinitrate should be avoided in this setting. FUNDING: The Collaboration for New Treatments of Acute Stroke consortium, the Brain Foundation Netherlands, the Ministry of Economic Affairs, Stryker, Medtronic, Cerenovus, and the Dutch Heart Foundation.

PURPOSE Determining the estrogen receptor (ER) status is essential in metastatic breast cancer (MBC) management. Whole-body ER imaging with 16α-[18F]fluoro-17β-estradiol positron emission tomography ([18F]FES-PET) is increasingly used for this purpose. To establish the clinical validity of the [18F]FES-PET, we studied the diagnostic accuracy of qualitative and quantitative [18F]FES-PET assessment to predict ER expression by immunohistochemistry in a metastasis. METHODS In a prospective multicenter trial, 200 patients with newly diagnosed MBC underwent extensive workup including molecular imaging. For this subanalysis, ER expression in the biopsied metastasis was related to qualitative whole-body [18F]FES-PET evaluation and quantitative [18F]FES uptake in the corresponding metastasis. A review and meta-analysis regarding [18F]FES-PET diagnostic performance were performed. RESULTS Whole-body [18F]FES-PET assessment predicted ER expression in the biopsied metastasis with good accuracy: a sensitivity of 95% (95% CI, 89 to 97), a specificity of 80% (66 to 89), a positive predictive value (PPV) of 93% (87 to 96), and a negative predictive value (NPV) of 85% (72 to 92) in 181 of 200 evaluable patients. Quantitative [18F]FES uptake predicted ER immunohistochemistry in the corresponding metastasis with a sensitivity/specificity of 91%/69% and a PPV/NPV of 90%/71% in 156 of 200 evaluable patients. For bone metastases, PPV/NPV was 92%/81%. Meta-analysis with addition of our data has increased diagnostic performance and narrowed the 95% CIs compared with previous studies with a sensitivity/specificity of both 86% (81 to 90 and 73 to 93, respectively). CONCLUSION In this largest prospective series so far, we established the clinical validity of [18F]FES-PET to determine tumor ER status in MBC. In view of the high diagnostic accuracy of qualitatively assessed whole-body [18F]FES-PET, this noninvasive imaging modality can be considered a valid alternative to a biopsy of a metastasis to determine ER status in newly MBC (ClinicalTrials.gov identifier: NCT01957332 ).

Background: We aimed to assess whether the effect of intravenous alteplase treatment (IVT) before endovascular treatment (EVT) on outcome is modified by first-line technique during EVT in IVT eligible patients. Methods: This was a post hoc analysis from MR CLEAN-NO IV (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands - Intravenous Treatment Followed by Intra-Arterial Treatment Versus Direct Intra-Arterial Treatment for Acute Ischemic Stroke Caused by a Proximal Intracranial Occlusion), a randomized trial of IVT followed by EVT versus EVT alone in patients presenting directly to EVT-capable centers. We included data from all patients who underwent EVT with a thrombectomy attempt. We compared patients treated with stent retriever (with or without aspiration) to aspiration alone as first-line EVT technique and assessed the interaction of first-line EVT technique with IVT treatment. Primary outcome was the 90-day modified Rankin Scale score, analyzed with mixed model ordinal regression for a shift towards better outcome. Secondary outcomes included successful reperfusion (extended Thrombolysis in Cerebral Infarction score 2b–3). Results: Of 473 included patients, 102 (21.6%) were treated with aspiration alone as first-line technique. In the full population, functional outcome was similar for patients treated with stent retriever versus aspiration only (adjusted common odds ratio [acOR]‚ 1.07 [95% CI, 0.69–1.66]). We observed a significant interaction between IVT and first-line EVT technique ( P =0.03). In the aspiration-only group, patients treated with EVT alone had worse functional outcome compared to those treated with IVT and EVT (acOR, 0.44 [95% CI, 0.21–0.90]). In the stent retriever group, functional outcome did not differ between patients treated with or without IVT (acOR, 1.08 [95% CI, 0.74–1.57]). There was no statistically significant interaction for successful reperfusion. Conclusions: In MR CLEAN-NO IV, the treatment effect of IVT was modified by first-line EVT technique. Patients treated with aspiration only as first-line technique had worse clinical outcomes if they did not receive IVT. No such difference was observed in patients treated with stent retrievers. Confirmation by pooling with results from other trials is needed to confirm these findings.

Biogenesis of nuclear pore complexes (NPCs) includes the formation of the permeability barrier composed of phenylalanine-glycine-rich nucleoporins (FG-Nups) that regulate the selective passage of biomolecules across the nuclear envelope. The FG-Nups are intrinsically disordered and prone to liquid–liquid phase separation and aggregation when isolated. How FG-Nups are protected from making inappropriate interactions during NPC biogenesis is not fully understood. Here we find that DNAJB6, a molecular chaperone of the heat shock protein network, forms foci in close proximity to NPCs. The number of these foci decreases upon removal of proteins involved in the early steps of interphase NPC biogenesis. Conversely, when this process is stalled in the last steps, the number of DNAJB6-containing foci increases and these foci are identified as herniations at the nuclear envelope. Immunoelectron tomography shows that DNAJB6 localizes inside the lumen of the herniations arising at NPC biogenesis intermediates. Loss of DNAJB6 results in the accumulation of cytosolic annulate lamellae, which are structures containing partly assembled NPCs, a feature associated with disturbances in NPC biogenesis. We find that DNAJB6 binds to FG-Nups and can prevent the aggregation of the FG region of several FG-Nups in cells and in vitro. Together, our data show that the molecular chaperone DNAJB6 provides quality control during NPC biogenesis and is involved in the surveillance of native intrinsically disordered FG-Nups.

Objective To evaluate the methodological rigor of radiomics-based studies using noninvasive imaging in ovarian setting. Methods Multiple medical literature archives (PubMed, Web of Science, and Scopus) were searched to retrieve original studies focused on computed tomography (CT), magnetic resonance imaging (MRI), ultrasound (US), or positron emission tomography (PET) radiomics for ovarian disorders’ assessment. Two researchers in consensus evaluated each investigation using the radiomics quality score (RQS). Subgroup analyses were performed to assess whether the total RQS varied according to first author category, study aim and topic, imaging modality, and journal quartile. Results From a total of 531 items, 63 investigations were finally included in the analysis. The studies were greatly focused (94%) on the field of oncology, with CT representing the most used imaging technique (41%). Overall, the papers achieved a median total RQS 6 (IQR, −0.5 to 11), corresponding to a percentage of 16.7% of the maximum score (IQR, 0–30.6%). The scoring was low especially due to the lack of prospective design and formal validation of the results. At subgroup analysis, the 4 studies not focused on oncological topic showed significantly lower quality scores than the others. Conclusions The overall methodological rigor of radiomics studies in the ovarian field is still not ideal, limiting the reproducibility of results and potential translation to clinical setting. More efforts towards a standardized methodology in the workflow are needed to allow radiomics to become a viable tool for clinical decision-making. Key Points • The 63 included studies using noninvasive imaging for ovarian applications were mostly focused on oncologic topic (94%). • The included investigations achieved a median total RQS 6 (IQR, −0.5 to 11), indicating poor methodological rigor. • The RQS was low especially due to the lack of prospective design and formal validation of the results.

Tetra-ortho-fluoro-azobenzenes are a class of photoswitches useful for the construction of visible-light-controlled molecular systems. They can be used to achieve spatio-temporal control over the properties of a chosen bioactive molecule. However, the introduction of different substituents to the tetra-fluoro-azobenzene core can significantly affect the photochemical properties of the switch and compromise biocompatibility. Herein, we explored the effect of useful substituents, such as functionalization points, attachment handles, and water-solubilizing groups, on the photochemical properties of this photochromic system. In general, all the tested fluorinated azobenzenes exhibited favorable photochemical properties, such as high photostationary state distribution and long half-lives, both in organic solvents and in water. One of the azobenzene building blocks was functionalized with a trehalose group to enable the uptake of the photoswitch into mycobacteria. Following metabolic uptake and incorporation of the trehalose-based azobenzene in the mycobacterial cell wall, we demonstrated photoswitching of the azobenzene in the isolated total lipid extract.

Purpose To investigate if serum inflammatory markers or nuclear imaging can accurately diagnose a chronic spinal instrumentation infection (SII) prior to surgery. Methods All patients who underwent revision of spinal instrumentation after a scoliosis correction between 2017 and 2019, were retrospectively evaluated. The diagnostic accuracy of serum C-reactive protein (CRP) and Erythrocyte Sedimentation Rate (ESR), 18F-fluorodeoxyglucose positron emission tomography combined with computed tomography (FDG–PET/CT) and Technetium-99m-methylene diphosphonate (99mTc-MDP) 3-phase bone scintigraphy (TPBS) to diagnose infection were studied. Patients with an acute infection or inadequate culture sampling were excluded. SII was diagnosed if ≥ 2 of the same microorganism(s) were isolated from intra-operative tissue cultures. Results 30 patients were included. The indication for revision surgery was pseudoarthrosis in the majority of patients (n = 15). 22 patients (73%) were diagnosed with SII. In all infected cases, Cutibacterium acnes was isolated, including 5 cases with a polymicrobial infection. The majority of patients had low inflammatory parameters preoperatively. For CRP > 10.0 mg/L, the sensitivity was 9.1% and specificity 100%; for ESR > 30 mm/h, the sensitivity was 9.1% and specificity 100%. The diagnostic accuracy for nuclear imaging was 64% for the FDG–PET/CT and 67% for the TPBS to diagnose infection. Conclusions The prevalence of SII in patients undergoing revision spinal surgery is high, with Cutibacterium acnes as the main pathogen. No diagnostic tests could be identified that could accurately diagnose or exclude SII prior to surgery. Future studies should aim to find more sensitive diagnostic modalities to detect low-grade inflammation.

Deformable models are widely used in medical image segmentation methods, to find not only single but also multiple objects within an image. They have the ability to follow the contours of an object of interest, define the boundary of ROI (Region Of Interest) and improve shape recovery. However, these methods still have limitations in cases of low image quality or clutter.This paper presents a new deformable model, the Spring-Charged Particles Model (SCPM). It simulates the movement of positively charged particles connected by springs, attracted towards the contour of objects of interest which is charged negatively, according to the gradient-magnitude image. Springs prevent the particles from moving away and keep the particles at appropriate distances without reducing their flexibility. SCPM was tested on simple shape images and on frontal X-ray images of scoliosis patients. Artificial noise was added to the simple images to examine the robustness of the method. Several configurations of springs and positively charged-particles were evaluated by determining the best spinal segmentation result. The performance of SCPM was compared to the Charged Fluid Model (CFM), Active Contours, and a convolutional neural network (CNN) with U-Net architecture to measure its ability for determining the curvature of the spinal column from frontal X-Ray images. The results show that SCPM is better at segmenting the spine and determining its curvature, as indicated by the highest Area Score value of 0.837, and the lowest standard deviation value of 0.028.

BACKGROUND: Survival of kidney transplant recipients (KTR) is low compared with the general population. Low muscle mass and muscle strength may contribute to lower survival, but practical measures of muscle status suitable for routine care have not been evaluated for their association with long-term survival and their relation with each other in a large cohort of KTR.METHODS: Data of outpatient KTR ≥ 1 year post-transplantation, included in the TransplantLines Biobank and Cohort Study (ClinicalTrials.gov Identifier: NCT03272841), were used. Muscle mass was determined as appendicular skeletal muscle mass indexed for height 2 (ASMI) through bio-electrical impedance analysis (BIA), and by 24-h urinary creatinine excretion rate indexed for height 2 (CERI). Muscle strength was determined by hand grip strength indexed for height 2 (HGSI). Secondary analyses were performed using parameters not indexed for height 2. Cox proportional hazards models were used to investigate the associations between muscle mass and muscle strength and all-cause mortality, both in univariable and multivariable models with adjustment for potential confounders, including age, sex, body mass index (BMI), estimated glomerular filtration rate (eGFR) and proteinuria. RESULTS: We included 741 KTR (62% male, age 55 ± 13 years, BMI 27.3 ± 4.6 kg/m 2), of which 62 (8%) died during a median [interquartile range] follow-up of 3.0 [2.3-5.7] years. Compared with patients who survived, patients who died had similar ASMI (7.0 ± 1.0 vs. 7.0 ± 1.0 kg/m 2; P = 0.57), lower CERI (4.2 ± 1.1 vs. 3.5 ± 0.9 mmol/24 h/m 2; P < 0.001) and lower HGSI (12.6 ± 3.3 vs. 10.4 ± 2.8 kg/m 2; P < 0.001). We observed no association between ASMI and all-cause mortality (HR 0.93 per SD increase; 95% confidence interval [CI] [0.72, 1.19]; P = 0.54), whereas CERI and HGSI were significantly associated with mortality, independent of potential confounders (HR 0.57 per SD increase; 95% CI [0.44, 0.81]; P = 0.002 and HR 0.47 per SD increase; 95% CI [0.33, 0.68]; P < 0.001, respectively), and associations of CERI and HGSI with mortality remained independent of each other (HR 0.68 per SD increase; 95% CI [0.47, 0.98]; P = 0.04 and HR 0.53 per SD increase; 95% CI [0.36, 0.76]; P = 0.001, respectively). Similar associations were found for unindexed parameters. CONCLUSIONS: Higher muscle mass assessed by creatinine excretion rate and higher muscle strength assessed by hand grip strength are complementary in their association with lower risk of all-cause mortality in KTR. Muscle mass assessed by BIA is not associated with mortality. Routine assessment using both 24-h urine samples and hand grip strength is recommended, to potentially target interdisciplinary interventions for KTR at risk for poor survival to improve muscle status.

Yu Pu,1,&ast; Xiuxiu Zhou,1,&ast; Di Zhang,1,&ast; Yu Guan,1,&ast; Yi Xia,1 Wenting Tu,1 Yang Lu,2 Weidong Zhang,2 Chi-Cheng Fu,2 Qu Fang,2 Geertruida H de Bock,3 Shiyuan Liu,1 Li Fan1 1Department of Radiology, Changzheng Hospital, Naval Medical University, Shanghai, People’s Republic of China; 2Department of Scientific Research, Shanghai Aitrox Technology Corporation Limited, Shanghai, People’s Republic of China; 3Department of Epidemiology, University Medical Center Groningen, Groningen, the Netherlands&ast;These authors contributed equally to this workCorrespondence: Shiyuan Liu; Li Fan, Department of Radiology, ChangZheng Hospital, Naval Medical University, No. 415 Fengyang Road, Shanghai, 200003, People’s Republic of China, Tel +86 21 81886012 ; Tel +86 21 81886012, Fax +86 21 63587668, Email cjr.liushiyuan@vip.163.com; fanli0930@163.comPurpose: To explore optimal threshold of FEV1% predicted value (FEV1%pre) for high-risk chronic obstructive pulmonary disease (COPD) using the parameter response mapping (PRM) based on machine learning classification model.Patients and Methods: A total of 561 consecutive non-COPD subjects who were screened for chest diseases in our hospital between August and October 2018 and who had complete questionnaire surveys, pulmonary function tests (PFT), and paired respiratory chest CT scans were enrolled retrospectively. The CT quantitative parameter for small airway remodeling was PRM, and 72 parameters were obtained at the levels of whole lung, left and right lung, and five lobes. To identify a more reasonable thresholds of FEV1% predicted value for distinguishing high-risk COPD patients from the normal, 80 thresholds from 50% to 129% were taken with a partition of 1% to establish a random forest classification model under each threshold, such that novel PFT-parameter-based high-risk criteria would be more consistent with the PRM-based machine learning classification model.Results: Machine learning-based PRM showed that consistency between PRM parameters and PFT was better able to distinguish high-risk COPD from the normal, with an AUC of 0.84 when the threshold was 72%. When the threshold was 80%, the AUC was 0.72 and when the threshold was 95%, the AUC was 0.64.Conclusion: Machine learning-based PRM is feasible for redefining high-risk COPD, and setting the optimal FEV1% predicted value lays the foundation for redefining high-risk COPD diagnosis.Keywords: chronic obstructive pulmonary disease, computed tomography, pulmonary function test, quantitative imaging, artificial intelligence

Purpose Prenatal infection during pregnancy is a risk factor for schizophrenia, as well as for other developmental psychiatric disorders, such as autism and bipolar disorder. Schizophrenia patients were reported to have altered brain metabolism and neuroinflammation. However, the link between prenatal infection, altered brain inflammation and metabolism, and schizophrenia remains unclear. In this project, we aimed to evaluate whether there are changes in brain glucose consumption and microglia activation in the offspring of pregnant rats exposed to maternal immune activation (MIA), and if so, whether these changes occur before or after the initiation of schizophrenia-like behaviour. Procedures Pregnant rats were treated with the viral mimic polyinosinic-polycytidylic acid (MIA group) or saline (control group) on gestational day 15. Static PET scans of the male offspring were acquired on postnatal day (PND) 21, 60, and 90, using [11C]-PK11195 and deoxy-2-[18F]fluoro-D-glucose ([18F]-FDG) as tracers to measure TSPO expression in activated microglia and brain glucose consumption, respectively. On PND60 and PND90, anxiety-like behaviour, recognition memory, and sensorimotor gating were measured using the open field test (OFT), novel object recognition test (NOR), and prepulse inhibition test (PPI). Results [18F]-FDG PET demonstrated that MIA offspring displayed higher brain glucose consumption in the whole brain after weaning (p = 0.017), and in the frontal cortex during late adolescence (p = 0.001) and adulthood (p = 0.037) than control rats. [11C]-PK11195 PET did not reveal any changes in TSPO expression in MIA offspring. Prenatal infection induced age-related behavioural alterations. Adolescent MIA offspring displayed a more anxious state in the OFT than controls (p = 0.042). Adult MIA offspring showed recognition memory deficits in the NOR (p = 0.003). Our study did not show any PPI deficits. Conclusions Our results suggest that prenatal immune activation changed neurodevelopment, resulting in increased brain glucose consumption, but not in microglia activation. The increased brain glucose consumption in the frontal cortex of MIA offspring remained until adulthood and was associated with increased anxiety-like behaviour during adolescence and recognition memory deficits in adulthood.

Free radical generation plays a key role in killing bacteria by antibiotics. However, radicals are short-lived and reactive, and thus difficult to detect for the state of the art. Here we use a technique which allows optical nanoscale magnetic resonance imaging (MRI) to detect radical generation on the scale of single bacteria. We demonstrate that the radical generation in Staphylococcus aureus increases in the presence of UV irradiation as well as vancomycin and is dependent on the antibiotic's dose. With a method based on ensembles of nitrogen vacancy (NV) centers in diamond, we were able to follow the radical formation near individual bacteria over the whole duration of the experiment to reveal the dynamics of radical generation. Using this new approach, we observed free radical concentrations within nanoscale voxels around the diamond particles and determined its exact timing depending on the antibiotic dose. Since changes in the response to antibiotics emerge in only a few bacteria of the entire population, such a single-cell approach can prove highly valuable for research into drug resistance.

Purpose: Total body positron emission tomography (TB-PET) has recently been introduced in nuclear medicine departments. There is a large interest in these systems, but for many centers, the high acquisition cost makes it very difficult to justify their current operational budget. Here, we propose medium-cost long axial FOV scanners as an alternative.Methods: Several medium-cost long axial FOV designs are described with their advantages and drawbacks. We describe their potential for higher throughput, more cost-effective scanning, a larger group of indications, and novel research opportunities. The wider spread of TB-PET can also lead to the fast introduction of new tracers (at a low dose), new methodologies, and optimized workflows.Conclusions: A medium-cost TB-PET would be positioned between the current standard PET-CT and the full TB-PET systems in investment but recapitulate most advantages of full TB-PET. These systems could be more easily justified financially in a standard academic or large private nuclear medicine department and still have ample research options.

Objectives The aim of this study was to determine mono-energetic (monoE) level–specific photon-counting CT (PCCT) Agatston thresholds, to yield monoE level independent Agatston scores validated with a dynamic cardiac phantom. Also, we examined the potential of dose reduction for PCCT coronary artery calcium (CAC) studies, when reconstructed at low monoE levels. Methods Theoretical CAC monoE thresholds were calculated with data from the National Institute of Standards and Technology (NIST) database. Artificial CAC with three densities were moved in an anthropomorphic thorax phantom at 0 and 60–75 bpm, and scanned at full and 50% dose on a first-generation dual-source PCCT. For all densities, Agatston scores and maximum CT numbers were determined. Agatston scores were compared with the reference at full dose and 70 keV monoE level; deviations (95% confidence interval) < 10% were deemed to be clinically not-relevant. Results Averaged over all monoE levels, measured CT numbers deviated from theoretical CT numbers by 6%, 13%, and − 4% for low-, medium-, and high-density CAC, respectively. At 50% reduced dose and 60–75 bpm, Agatston score deviations were non-relevant for 60 to 100 keV and 60 to 120 keV for medium- and high-density CAC, respectively. Conclusion MonoE level–specific Agatston score thresholds resulted in similar scores as in standard reconstructions at 70 keV. PCCT allows for a potential dose reduction of 50% for CAC scoring using low monoE reconstructions for medium- and high-density CAC. Key Points • Mono-energy level–specific Agatston thresholds allow for reproducible coronary artery calcium quantification on mono-energetic images. • Increased calcium contrast-to-noise ratio at reduced mono-energy levels allows for coronary artery calcium quantification at 50% reduced radiation dose for medium- and high-density calcifications.

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.