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The neuronal correlate of tremor genesis and cognitive function in essential tremor (ET) and its modulation by deep brain stimulation (DBS) are poorly understood. To explore the underlying metabolic topography of motor and cognitive symptoms, sixteen ET patients (age 63.6 ± 49.1 years) and 18 healthy controls (HC) (61.1 ± 6.3 years) underwent tremor and cognitive assessments and 18 F-fluorodeoxyglucose PET of the brain. Multivariate spatial covariance analysis was applied for identifying ET related metabolic brain networks. For network validation and to explore DBS effects, 8 additional ET patients (68.1 ± 8.2 years) treated with DBS were assessed in both the ON and OFF state, respectively. The ET related metabolic spatial covariance pattern (ETRP) was characterized by relatively increased metabolism in the cerebellum, brainstem, and temporo-occipital cortices, accompanied by relative metabolic decreases mainly in fronto-temporal and motor cortices. Network expression showed inverse correlations with tremor severity and disease duration and positive correlations with cognitive dysfunction. DBS substantially alleviated tremor, but had only marginal effects on cognitive performance. There were no significant DBS effects on ETRP expression at the group level, but all but one subject showed higher scores in the ON state. Our findings suggest ET is characterized by an abnormal brain network associated with disease phenotype., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

The modification of biomaterials to comply with clinically employed monitoring techniques is a promising strategy to support clinical translation in regenerative medicine. Here, multimodal imaging of tissue-engineered vascular grafts (TEVG) was enabled by functionalizing the textile scaffold with ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles. The resulting MR-imageable grafts (iTEVG) were monitored non-invasively throughout their whole life-cycle, from initial quality control to longitudinal functional evaluation in an ovine model for up to 8 weeks. Crucial features such as the complete embedding of the textile mesh in the developing tissue and the grafts' structural stability were assessed in vitro using 1T-, 3T- and 7T-MRI scanners. In vivo, the grafts were imaged by 3T-MRI and PET-CT. Contrary to unlabeled constructs, iTEVG could be delineated from native arteries and precisely localized by MRI. USPIO labeling neither induced calcifications, nor negatively affected their remodeling with respect to tissue-specific extracellular matrix composition and endothelialization. Functionality was confirmed by MR-angiography. 18 F-FDG uptake (assessed via PET-CT) indicated only transient post-surgical inflammation. In conclusion, USPIO-labeling enables accurate localization of TEVG and opens up opportunities for multimodal imaging approaches to assess transplant acceptance and function. Thereby, it can support clinical decision-making on the need for further pharmacological or surgical interventions., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The short- and long-term success of intravascular stents depends on a proper re-endothelialisation after the intervention-induced endothelial denudation. The aim of this study was to evaluate the potential of in vivo molecular imaging of glutamate carboxypeptidase II (GCPII; identical with prostate-specific membrane antigen PSMA) expression as a marker of re-endothelialisation. Fifteen Sprague Dawley rats underwent unilateral balloon angioplasty of the common carotid artery (CCA). Positron emission tomography (PET) using the GCPII-targeting tracer [ 18 F]DCFPyL was performed after 5-21 days (scan 60-120 min post injection). In two animals, the GCPII inhibitor PMPA (23 mg/kg BW) was added to the tracer solution. After PET, both CCAs were removed, dissected, and immunostained with the GCPII specific antibody YPSMA-1. Difference of GCPII expression between both CCAs was established by PCR analysis. [ 18 F]DCFPyL uptake was significantly higher in the ipsilateral compared to the contralateral CCA with an ipsi-/contralateral ratio of 1.67 ± 0.39. PMPA blocked tracer binding. The selective expression of GCPII in endothelial cells of the treated CCA was confirmed by immunohistological staining. PCR analysis verified the site-specific GCPII expression. By using a molecular imaging marker of GCPII expression, we provide the first non-invasive in vivo delineation of re-endothelialisation after angioplasty.

Early life stress may have a lasting impact on the developmental programming of the dopamine (DA) system implicated in psychosis. Early adversity could promote resilience by calibrating the prefrontal stress-regulatory dopaminergic neurotransmission to improve the individual's fit with the predicted stressful environment. Aberrant reactivity to such match between proximal and distal environments may, however, enhance psychosis disease risk. We explored the combined effects of childhood adversity and adult stress by exposing 12 unmedicated individuals with a diagnosis of non-affective psychotic disorder (NAPD) and 12 healthy controls (HC) to psychosocial stress during an [18F]fallypride positron emission tomography. Childhood trauma divided into early (ages 0-11 years) and late (12-18 years) was assessed retrospectively using a questionnaire. A significant group x childhood trauma interaction on the spatial extent of stress-related [18F]fallypride displacement was observed in the mPFC for early (b = -8.45, t(1,23) = -3.35, p = .004) and late childhood trauma (b = -7.86, t(1,23) = -2.48, p = .023). In healthy individuals, the spatial extent of mPFC DA activity under acute psychosocial stress was positively associated with the severity of early (b = 7.23, t(11) = 3.06, p = .016) as well as late childhood trauma (b = -7.86, t(1,23) = -2.48, p = .023). Additionally, a trend-level main effect of early childhood trauma on subjective stress response emerged within this group (b = -.7, t(11) = -2, p = .07), where higher early trauma correlated with lower subjective stress response to the task. In the NAPD group, childhood trauma was not associated with the spatial extent of the tracer displacement in mPFC (b = -1.22, t(11) = -0.67), nor was there a main effect of trauma on the subjective perception of stress within this group (b = .004, t(11) = .01, p = .99). These findings reveal a potential mechanism of neuroadaptation of prefrontal DA transmission to early life stress and suggest its role in resilience and vulnerability to psychosis.

Cerebral dopamine (DA) transmission is thought to be an important modulator for the development and occurrence of aggressive behavior. However, the link between aggression and DA transmission in humans has not been investigated using molecular imaging and standardized behavioral tasks. We investigated aggression as a function of DA transmission in a group of (N = 21) healthy male volunteers undergoing 6-[18F]-fluoro-L-DOPA (FDOPA)-positron emission tomography (PET) and a modified version of the Point Subtraction Aggression Paradigm (PSAP). This task measures aggressive behavior during a monetary reward-related paradigm, where a putative adversary habitually tries to cheat. The participant can react in three ways (i.e., money substraction of the putative opponent [aggressive punishment], pressing a defense button, or continuing his money-making behavior). FDOPA-PET was analyzed using a steady-state model yielding estimates of the DA-synthesis capacity (K), the turnover of tracer DA formed in living brain (kloss), and the tracer distribution volume (Vd), which is an index of DA storage capacity. Significant negative correlations between PSAP aggressive responses and the DA-synthesis capacity were present in several regions, most prominently in the midbrain (r = -0.640; p = 0.002). Lower degrees of aggressive responses were associated with higher DA storage capacity in the striatum and midbrain. Additionally, there was a significant positive correlation between the investment into monetary incentive responses on the PSAP and DA-synthesis capacity, notably in the midbrain (r = +0.618, p = 0.003). The results suggest that individuals with low DA transmission capacity are more vulnerable to reactive/impulsive aggression in response to provocation.

A small positron-generating branch in 90-Yttrium ((90)Y) decay enables post-therapy dose assessment in liver cancer radioembolization treatment. The aim of this study was to validate clinical (90)Y positron emission tomography (PET) quantification, focusing on scanner linearity as well as acquisition and reconstruction parameter impact on scanner calibration. Data from three dedicated phantom studies (activity range: 55.2 MBq-2.1 GBq) carried out on a Philips Gemini TF 16 PET/CT scanner were analyzed after reconstruction with up to 361 parameter configurations. For activities above 200 MBq, scanner linearity could be confirmed with relative error margins 4%. An acquisition-time-normalized calibration factor of 1.04 MBq·s/CNTS was determined for the employed scanner. Stable activity convergence was found in hot phantom regions with relative differences in summed image intensities between -3.6% and +2.4%. Absolute differences in background noise artifacts between - 79.9% and + 350% were observed. Quantitative accuracy was dominated by subset size selection in the reconstruction. Using adequate segmentation and optimized acquisition parameters, the average activity recovery error induced by the axial scanner sensitivity profile was reduced to +2.4%±3.4% (mean ± standard deviation). We conclude that post-therapy dose assessment in (90)Y PET can be improved using adapted parameter setups.

The high-affinity radioligand [(18)F]fallypride (FP) is frequently used for quantification of striatal/extrastriatal D(2/3) receptors and the receptor occupancies of antipsychotics (APs). Its 110 minutes half-life allows long scan durations. However, the optimum scan duration is a matter of debate. This investigation focuses on scan-duration-related effects on simplified reference tissue model (SRTM) results and the time point of transient equilibrium in a large sample of dynamic FP positron emission tomography (PET) scans. Fifty drug-free and 50 AP-treated subjects underwent FP-PET scans (180 minutes scan duration). The binding potential (BP(ND)) of the putamen, thalamus, and temporal cortex were calculated using the SRTM and the transient equilibrium model. Furthermore, receptor occupancies were calculated for AP-treated patients. Transient equilibrium in the unblocked putamen occurred after 121±29.6 minutes. The transient equilibrium occurred much earlier in the extrastriatal regions or under AP treatment. Stepwise scan shortening caused BP(ND) underestimations of 0.58% for the first 10-minute reduction (putamen, SRTM), finally reaching 5.76% after 1 hour scan-time reduction. We observed preferential extrastriatal AP binding irrespective of the analytical method. [(18)F]fallypride scan durations of 180 minutes reliably reach equilibrium even in D(2/3)-receptor-rich regions. Moderate reductions in FP scan durations only caused small changes to SRTM results even in receptor-rich regions. Apparently, the D(2/3) receptor occupancy results of APs, especially preferential extrastriatal binding observations, are not relevantly biased by inappropriate scan durations.

Unlabelled: 8-cyclopentyl-3-(3-18F-fluoropropyl)-1-propylxanthine (18F-CPFPX) is a novel PET ligand for in vivo quantification of cerebral A1 adenosine receptors. The present study investigated the applicability of voxelwise graphical analysis to the generation of parametric images of the total volume of distribution (DVt) of 18F-CPFPX as a prerequisite for voxel-by-voxel statistical analysis. The benefit of spatial smoothing for reduction of noise-dependent negative bias in graphical analysis was examined. Additionally, the effect of scan duration on the accuracy of analyses based on volumes of interest (VOIs) and individual voxels was explored., Methods: Ten healthy male volunteers underwent bolus-injection 18F-CPFPX PET (90 min). The data were analyzed using a 2-tissue-compartment model and graphical analysis. Voxelwise graphical analysis was performed with and without preceding spatial gaussian smoothing., Results: Voxelwise graphical analysis yielded high-quality parametric images. However, voxelwise graphical analysis suffered from a negative bias (mean bias in cortical regions, -9.6% to -7.5%), which could be attenuated considerably by spatial smoothing (using a kernel of 5 mm in full width at half maximum, bias of -4.0% to -1.9%). Shortening the total scan duration to 60 min had minor effects on the accuracy of VOI-based analysis (15 VOIs x 10 subjects); the resulting error only occasionally exceeded +/-5% in individual regions (n = 6 for 2-tissue-compartment model, n = 10 for VOI-based graphical analysis, always within +/-7.5%). Quantification accuracy was acceptable with scan durations of 60 and 75 min in voxelwise graphical analysis with spatial smoothing (mean bias in cortical regions, -8.4% to -5.9%) and without spatial smoothing (bias, -9.2% to -11.6%), respectively., Conclusion: High-quality DVt parametric images of 18F-CPFPX can be generated by voxelwise graphical analysis. The noise-dependent negative bias of voxelwise graphical analysis is greatly reduced by spatial smoothing. A shortened scan of 60 min will enhance the clinical applicability of 18F-CPFPX PET.