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.

Relationships between serotonin 1A receptor DNA methylation, self-reported history of childhood abuse and gray matter volume in major depression.

Background: Early life adversity is a risk factor for psychopathology and is associated with epigenetic alterations in the 5-HT receptor gene promoter. The 5-HT receptor mediates neurotrophic effects, which could affect brain structure and function. We examined relationships between self-reported early childhood abuse, 5-HT receptor promoter DNA methylation, and gray matter volume (GMV) in Major Depressive Disorder (MDD).

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.

Functional support vector machine.

Linear and generalized linear scalar-on-function modeling have been commonly used to understand the relationship between a scalar response variable (e.g. continuous, binary outcomes) and functional predictors.

Dynamic Human Brain Imaging with a Portable PET Camera: Comparison to a Standard Scanner.

Portable, cost-effective PET cameras can radically expand the applicability of PET. We present here a within-participant comparison of fully quantified [F]FDG dynamic scans in healthy volunteers using the standard Biograph mCT scanner and portable CerePET scanner. Each of 20 healthy volunteers underwent dynamic [F]FDG imaging with both scanners (1-154 d apart) and concurrent arterial blood sampling.

Permutation-Based Inference for Function-on-Scalar Regression With an Application in PET Brain Imaging.

The density of various proteins throughout the human brain can be studied through the use of positron emission tomography (PET) imaging. We report here on data from a study of serotonin transporter (5-HTT) binding. While PET imaging data analysis is most commonly performed on data that are aggregated into several discrete regions of interest, in this study, primary interest is on measures of 5-HTT binding potential that are made at many locations along a continuous anatomically defined tract, one that was chosen to follow serotonergic axons.

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.

Kinetic models for estimating occupancy from single-scan PET displacement studies.

The traditional design of PET target engagement studies is based on a baseline scan and one or more scans after drug administration. We here evaluate an alternative design in which the drug is administered during an on-going scan (i.e.

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.

Mature parvalbumin interneuron function in prefrontal cortex requires activity during a postnatal sensitive period.

In their seminal findings, Hubel and Wiesel identified sensitive periods in which experience can exert lasting effects on adult visual cortical functioning and behavior via transient changes in neuronal activity during development. Whether comparable sensitive periods exist for non-sensory cortices, such as the prefrontal cortex, in which alterations in activity determine adult circuit function and behavior is still an active area of research. Here, using mice we demonstrate that inhibition of prefrontal parvalbumin (PV)-expressing interneurons during the juvenile and adolescent period, results in impairments in adult prefrontal circuit connectivity, in vivo network function, and behavioral flexibility that can be reversed by targeted activation of PV interneurons in adulthood.

The Temporal Dynamics of Emotion Regulation in Subjects With Major Depression and Healthy Control Subjects.

Background: Emotion regulation (ER) processes help support well-being, but ineffective ER is implicated in several psychiatric disorders. Engaging ER flexibly by going online and offline as needs and capacities shift may be more effective than engaging ER rigidly across time. Here, we sought to observe the neural temporal dynamics of an ER process, reappraisal, during regulation of responses to negative memories in healthy control subjects (n = 33) and subjects with major depressive disorder (n = 36).

Mu Opioid Receptor Dynamics in Healthy Volunteers with a History of Childhood Maltreatment.

Evidence suggests that adults with a history of childhood maltreatment, the experience of emotional or physical neglect and/or abuse within the family during childhood, have blunted reward and stress processing, and higher risk of depression. The mu opioid receptor rich nucleus accumbens and amygdala are critical to reward and stress processing respectively. We hypothesized that nucleus accumbens and amygdala mu opioid receptor densities and activity (change in receptor binding due to endogenous opioid release or receptor conformation change) were negatively associated with childhood maltreatment in healthy young adults.

Designing drug occupancy studies with PET neuroimaging: Sample size, occupancy ranges and analytical methods.

Molecular neuroimaging is today considered essential for evaluation of novel CNS drugs; it is used to quantify blood-brain barrier permeability, verify interaction with key target and determine the drug dose resulting in 50% occupancy, IC. In spite of this, there has been limited data available to inform on how to optimize study designs. Through simulations, we here evaluate how IC estimation is affected by the (i) range of drug doses administered, (ii) number of subjects included, and (iii) level of noise in the plasma drug concentration measurements.

Rejection sensitivity and mu opioid receptor dynamics associated with mood alterations in response to social feedback.

Rejection sensitivity (RS) is the heightened expectation or perception of social rejection and is a feature of many psychiatric disorders. As endogenous opioid pathways have been implicated in response to social rejection and reward, we hypothesize that RS will be negatively associated with mu opioid receptor (MOR) baseline binding and activity during rejection and acceptance stimuli. In exploratory analyses, we assessed the relationships between MOR activity and changes in mood and self-esteem before and after stimuli.

Serotonin transporter binding in major depressive disorder: impact of serotonin system anatomy.

Serotonin transporter (5-HTT) binding deficits are reported in major depressive disorder (MDD). However, most studies have not considered serotonin system anatomy when parcellating brain regions of interest (ROIs). We now investigate 5-HTT binding in MDD in two novel ways: (1) use of a 5-HTT tract-based analysis examining binding along serotonergic axons; and (2) using the Copenhagen University Hospital Neurobiology Research Unit (NRU) 5-HT Atlas, based on brain-wide binding patterns of multiple serotonin receptor types.

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.

Source-to-Target Automatic Rotating Estimation (STARE) - A publicly-available, blood-free quantification approach for PET tracers with irreversible kinetics: Theoretical framework and validation for [F]FDG.

Introduction: Full quantification of positron emission tomography (PET) data requires an input function. This generally means arterial blood sampling, which is invasive, labor-intensive and burdensome. There is no current, standardized method to fully quantify PET radiotracers with irreversible kinetics in the absence of blood data.

Multiple domain and multiple kernel outcome-weighted learning for estimating individualized treatment regimes.

Individualized treatment rules (ITRs) recommend treatments that are tailored specifically according to each patient's own characteristics. It can be challenging to estimate optimal ITRs when there are many features, especially when these features have arisen from multiple (e.g.