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- ]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.

Connecting the dots: approaching a standardized nomenclature for molecular connectivity in positron emission tomography.

Positron emission tomography (PET)-based connectivity analysis provides a molecular perspective that complements fMRI-derived functional connectivity. However, lack of standardized terminology and diverse methodologies in PET connectivity studies has resulted in inconsistencies, complicating the interpretation and comparison of results across studies. A standardized nomenclature is thus needed to reduce ambiguity, enhance reproducibility, and facilitate interpretability across radiotracers, imaging modalities and studies.

Building Multivariate Molecular Imaging Brain Atlases Using the NeuroMark PET Independent Component Analysis Framework.

Molecular imaging analyses using positron emission tomography (PET) data often rely on macro-anatomical regions of interest (ROI), which may not align with chemo-architectural boundaries and obscure functional distinctions. While methods such as independent component analysis (ICA) have been useful to address this limitation, the fully data-driven nature can make it challenging to compare results across studies. Here, we introduce the NeuroMark PET approach, utilizing spatially constrained independent component analysis to define overlapping regions that may reflect the brain's molecular architecture.

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.

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.

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.

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.

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.

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.

Guidelines for the content and format of PET brain data in publications and archives: A consensus paper.

It is a growing concern that outcomes of neuroimaging studies often cannot be replicated. To counteract this, the magnetic resonance (MR) neuroimaging community has promoted acquisition standards and created data sharing platforms, based on a consensus on how to organize and share MR neuroimaging data. Here, we take a similar approach to positron emission tomography (PET) data.

AKT1 and genetic vulnerability to bipolar disorder.

AKT1 encodes a serine/threonine kinase that has as one of its best-known substrates glycogen synthase kinase-3 (GSK3), a primary target for lithium. AKT1 has been previously been implicated as a vulnerability gene for bipolar disorder (BD). We aimed to associate genetic variants in the AKT1 gene with subgroups of BD.