A Reference Tissue Implementation of Simultaneous Multifactor Bayesian Analysis (SiMBA) of PET Time Activity Curve Data.

PET analysis is conventionally performed as a two-stage process of quantification followed by analysis. We recently introduced SiMBA (Simultaneous Multifactor Bayesian Analysis), a hierarchical model that performs quantification and analysis for all brain regions of all individuals at once, and in so doing improves both the accuracy of parameter estimation as well as inferential efficiency. However until now, SiMBA has only been implemented for the two-tissue compartment model.

Altered Serotonin 1B Receptor Binding After Escitalopram for Depression Is Correlated With Treatment Effect.

Background: Major depressive disorder (MDD) is commonly treated with selective serotonin reuptake inhibitors (SSRIs). SSRIs inhibit the serotonin transporter (5-HTT), but the downstream antidepressant mechanism of action of these drugs is poorly understood. The serotonin 1B (5-HT1B) receptor is functionally linked to 5-HTT and 5-HT1B receptor binding and 5-HT1B receptor mRNA is reduced in the raphe nuclei after SSRI administration in primates and rodents, respectively.

PET Imaging of the Serotonin 1A Receptor in Major Depressive Disorder: Hierarchical Multivariate Analysis of [C]WAY100635 Overcomes Outcome Measure Discrepancies.

The serotonin 1A receptor has been linked to both the pathophysiology of major depressive disorder (MDD) and the antidepressant action of serotonin reuptake inhibitors. Most PET studies of the serotonin 1A receptor in MDD used the receptor antagonist radioligand, [carbonyl-C]WAY100635; however the interpretation of the combined results has been contentious owing to reports of higher or lower binding in MDD with different outcome measures. The reasons for these divergent results originate from several sources, including properties of the radiotracer itself, which complicate its quantification and interpretation; as well as from previously reported differences between MDD and healthy volunteers in both reference tissue binding and plasma free fraction, which are typically assumed not to differ.

Parametric and non-parametric Poisson regression for modelling of the arterial input function in positron emission tomography.

Full quantification of Positron Emission Tomography (PET) requires an arterial input function (AIF) for measurement of certain targets, or using particular radiotracers, or for the quantification of specific outcome measures. The AIF represents the measurement of radiotracer concentrations in the arterial blood plasma over the course of the PET examination. Measurement of the AIF is prone to error as it is a composite measure created from the combination of multiple measurements of different samples with different equipment, each of which can be sources of measurement error.

Nonlinear Mixed-Effects Modeling Approach for Simplified Reference Tissue Model.

Objective: The conventional approach to the analysis of dynamic PET data can be described as a two-stage approach. In Stage 1, each individual's kinetic parameter estimates are obtained by modeling their PET data. Then in Stage 2, those parameter estimates are treated as though they are the observed data and compared across subjects and groups using standard statistical analyses.

Multivariate analysis of PET pharmacokinetic parameters improves inferential efficiency.

Purpose: In positron emission tomography quantification, multiple pharmacokinetic parameters are typically estimated from each time activity curve. Conventionally all but the parameter of interest are discarded before performing subsequent statistical analysis. However, we assert that these discarded parameters also contain relevant information which can be exploited to improve the precision and power of statistical analyses on the parameter of interest.

Striatal dopamine D2 receptor availability as a predictor of subsequent alcohol use in social drinkers.

Background And Aims: Whereas striatal dopamine D2 receptor (D2R) availability has shown to be altered in individuals with alcohol use disorder (AUD) and in healthy individuals with a family history of AUD, the role of D2R in the development of AUD is unknown. In this positron emission tomography (PET) study, we measured whether D2R availability is associated with subsequent alcohol use and alcohol-related factors, at a follow-up 8 to 16 years post-PET scan, in social drinkers.

Design: Longitudinal study investigating the association between PET data and later self-report measures in healthy individuals.

Experimental Sleep Deprivation Results in Diminished Perceptual Stability Independently of Psychosis Proneness.

Psychotic disorders as well as psychosis proneness in the general population have been associated with perceptual instability, suggesting weakened predictive processing. Sleep disturbances play a prominent role in psychosis and schizophrenia, but it is unclear whether perceptual stability diminishes with sleep deprivation, and whether the effects of sleep deprivation differ as a function of psychosis proneness. In the current study, we aimed to clarify this matter.

Evaluation of Sublethal Toxicity of Nitrite to a Suite of Aquatic Organisms in Support of the Derivation of a Chronic Environmental Water Quality Benchmark.

Nitrite is a naturally-occurring inorganic compound that occurs in aquatic environments as an intermediary between nitrate and ammonia in the nitrogen cycle. It is a contaminant of potential concern resulting from anthropogenic activities in some cases. While the acute toxicity of nitrite has been characterized in previous studies, its sublethal toxicity is less understood.

Simultaneous multifactor Bayesian analysis (SiMBA) of PET time activity curve data.

Positron emission tomography (PET) is an in vivo imaging method essential for studying the neurochemical pathophysiology of psychiatric and neurological disease. However, its high cost and exposure of participants to radiation make it unfeasible to employ large sample sizes. The major shortcoming of PET imaging is therefore its lack of power for studying clinically-relevant research questions.

PET-BIDS, an extension to the brain imaging data structure for positron emission tomography.

The Brain Imaging Data Structure (BIDS) is a standard for organizing and describing neuroimaging datasets, serving not only to facilitate the process of data sharing and aggregation, but also to simplify the application and development of new methods and software for working with neuroimaging data. Here, we present an extension of BIDS to include positron emission tomography (PET) data, also known as PET-BIDS, and share several open-access datasets curated following PET-BIDS along with tools for conversion, validation and analysis of PET-BIDS datasets.

Thalamic dopamine D2-receptor availability in schizophrenia: a study on antipsychotic-naive patients with first-episode psychosis and a meta-analysis.

Pharmacological and genetic evidence support a role for an involvement of the dopamine D2-receptor (D2-R) in the pathophysiology of schizophrenia. Previous molecular imaging studies have suggested lower levels of D2-R in thalamus, but results are inconclusive. The objective of the present study was to use improved methodology to compare D2-R density in whole thalamus and thalamic subregions between first-episode psychosis patients and healthy controls.

What do end-users want to know about managing the performance of healthcare delivery systems? Co-designing a context-specific and practice-relevant research agenda.

Background: Despite increasing interest in joint research priority-setting, few studies engage end-user groups in setting research priorities at the intersection of the healthcare and management disciplines. With health systems increasingly establishing performance management programmes to account for and incentivize performance, it is important to conduct research that is actionable by the end-users involved with or impacted by these programmes. The aim of this study was to co-design a research agenda on healthcare performance management with and for end-users in a specific jurisdictional and policy context.

Are current tissue-based selenium guidelines and criteria overly protective of freshwater fish populations? A critical review with recommendations.

Several decades after selenium impacts on wild fish populations were observed in freshwater reservoirs receiving fly ash effluents from electric power facilities at Belews Lake and Hyco Reservoir (North Carolina, USA), developments in selenium (Se) toxicology have led to a greater understanding of Se effects on freshwater fish. These latter advancements have allowed regulatory agencies in several jurisdictions to develop tissue-based toxicity benchmarks for the protection of aquatic life. These benchmarks were generally derived from datasets encompassing multiple fish species and designed to protect the most sensitive species (US Environmental Protection Agency [EPA] water quality criteria).

A positron emission tomography study of the serotonin1B receptor effect of electroconvulsive therapy for severe major depressive episodes.

Background: Electroconvulsive therapy (ECT) is an effective treatment for depressive disorders, although its molecular mechanism of action is unknown. The serotonin 1B (5-HT) receptor is a potential target for treatment of depression and low 5-HT receptor binding in limbic regions has been reported in previous positron emission tomography (PET) studies of depression.

Methods: The objective of this longitudinal PET study was to examine the effect of ECT for depression on 5-HT receptor binding.

Test-Retest Reliability and Consistency of HVPG and Impact on Trial Design: A Study in 289 Patients from 20 Randomized Controlled Trials.

Background And Aims: Portal hypertension (PH) is a major driver for cirrhosis complications. Portal pressure is estimated in practice by the HVPG. The assessment of HVPG changes has been used for drug development in PH.

Adenovirus Infection and Rhabdomyolysis as a Cause of Acute Liver Failure in a Healthy Collegiate Football Athlete: A Case Report and Proposed Return to Play Protocol for Rhabdomyolysis.

Adenovirus is a common cause of upper respiratory and gastrointestinal tract infections. Though cases of significant organ failure and death have been reported in young children and immunocompromised individuals, adenovirus infections in healthy individuals are typically self-limiting without significant morbidity or mortality. Exertional rhabdomyolysis is a pathologic condition resulting from repetitive, excessive, or prolonged exercise, often in a hot environment, leading to acute muscle injury, renal injury and, rarely, death.

Low convergent validity of [C]raclopride binding in extrastriatal brain regions: A PET study of within-subject correlations with [C]FLB 457.

Dopamine D2 receptors (D2-R) in extrastriatal brain regions are of high interest for research in a wide range of psychiatric and neurologic disorders. Pharmacological competition studies and test-retest experiments have shown high validity and reliability of the positron emission tomography (PET) radioligand [C]FLB 457 for D2-R quantification in extrastriatal brain regions. However, this radioligand is not available at most research centers.

Smooth Pursuit Eye-Movement Abnormalities Associated With Cervical Spine Whiplash: A Scientific Review and Case Report.

Whiplash injuries may disrupt normal cervical afferent and efferent projections. Oculomotor abnormalities have been reported in chronic whiplash cases, but there is limited knowledge of their presence in acute whiplash and how acute assessment may target early intervention. We present a literature review and case study of a 22-year-old female presenting with an acute concussion and whiplash secondary to a high-speed motor vehicle collision.

Reliability of dopamine transporter PET measurements with [F]FE-PE2I in patients with Parkinson's disease.

Background: Reliable quantification of dopamine transporter (DAT), a biomarker for Parkinson's disease (PD), is essential for diagnostic purposes as well as for evaluation of potential disease-modifying treatment. Due to degeneration of dopaminergic neurons and thus lower expected radioligand binding to DAT, higher measurement variability in PD patients might be expected than earlier reproducibility results in healthy controls. Therefore, we aimed to examine the test-retest properties of [F]FE-PE2I-PET in PD patients.

Kinfitr - an open-source tool for reproducible PET modelling: validation and evaluation of test-retest reliability.

Background: In positron emission tomography (PET) imaging, binding is typically estimated by fitting pharmacokinetic models to the series of measurements of radioactivity in the target tissue following intravenous injection of a radioligand. However, there are multiple different models to choose from and numerous analytical decisions that must be made when modelling PET data. Therefore, it is important that analysis tools be adapted to the specific circumstances, and that analyses be documented in a transparent manner.

Dopamine D1 receptor availability is not associated with delusional ideation measures of psychosis proneness.

The dopamine D1 receptor (D1R) is thought to play a role in psychosis and schizophrenia, however positron emission tomography studies comparing patients and controls have been inconsistent. To circumvent some of the limitations of clinical studies, such as antipsychotic exposure, an alternative approach is to examine subclinical psychotic symptoms within the general population, i.e.