Toward Imaging of the GABA Transporter Type 1 In Vivo: Quantitative Evaluation of 4 Novel PET Radiotracers in Nonhuman Primates.

The main inhibitory neurotransmitter in the central nervous system is γ-aminobutyric acid (GABA). GABA transporter type 1 (GAT-1) is the principal GABA transporter in the brain, and it plays a crucial role in modulating GABA signaling. Its potential role in several neuropsychiatric disorders makes it an important target to study.

Markerless head motion tracking and event-by-event correction in brain PET.

Head motion correction (MC) is an essential process in brain positron emission tomography (PET) imaging. We have used the Polaris Vicra, an optical hardware-based motion tracking (HMT) device, for PET head MC. However, this requires attachment of a marker to the subject's head.

Dopamine D receptor availability in cocaine use disorder individuals with obesity as measured by [C]PHNO PET.

Background: Positron emission tomography (PET) work with the dopamine D3 receptor (DR) preferring ligand [C]PHNO in obese individuals has demonstrated higher binding and positive correlations with body mass index (BMI) in otherwise healthy individuals. These findings implicated brain reward areas including the substantia nigra/ventral tegmental area (SN/VTA) and pallidum. In cocaine use disorder (CUD), similar SN/VTA binding profiles have been found compared to healthy control subjects.

Effects of TOF Resolution Models on Edge Artifacts in PET Reconstruction from Limited-Angle Data.

Limited-angle data, such as data obtained from a dual-panel Breast-PET scanner, result in substantial image blur in directions coinciding with the missing cone of the image spectrum. On systems with time-of-flight (TOF) capabilities, this blur is reduced as given by the TOF uncertainty, with the image spectrum being correspondingly expanded into the missing spectral cone. Modeling of the TOF uncertainty in the reconstruction is expected to deconvolve this residual TOF blurring.

Dopaminergic Plasticity in the Bilateral Hippocampus Following Threat Reversal in Humans.

When a cue no longer predicts a threat, a diminished ability to extinguish or reverse this association is thought to increase risk for stress-related disorders. Despite the clear clinical relevance, the mediating neurochemical mechanisms of threat reversal have received relatively little study. One neurotransmitter implicated in rodent research of changing associations with threat is dopamine.

Spatially-variant image-based modeling of PSF deformations with application to a limited angle geometry from a dual-panel breast-PET imager.

Dual-panel PET system configuration can lead to spatially variable point-spread functions (PSF) of considerable deformations due to depth-of-interaction effects and limited angular coverage. If not modelled properly, these effects result in decreased and inconsistent recovery of lesion activity across the field-of-view (FOV), as well as mispositioning of lesions in the reconstructed image caused by strong PSF asymmetries. We implemented and evaluated models of such PSF deformations with spatially-variant image-based resolution modeling (IRM) within reconstruction (varRM) using the Direct Image REConstruction for Time-of-flight (DIRECT) method and within post-reconstruction deconvolution methods.

Brain serotonin synthesis capacity in obsessive-compulsive disorder: effects of cognitive behavioral therapy and sertraline.

Cognitive behavioral therapy (CBT) and selective serotonin reuptake inhibitors (SSRIs) are both effective treatments for some patients with obsessive-compulsive disorder (OCD), yet little is known about the neurochemical changes related to these treatment modalities. Here, we used positron emission tomography and the α-[C]methyl-L-tryptophan tracer to examine the changes in brain regional serotonin synthesis capacity in OCD patients following treatment with CBT or SSRI treatment. Sixteen medication-free OCD patients were randomly assigned to 12 weeks of either CBT or sertraline treatment.

Altered Regional Cerebral Blood Flow in Idiopathic Hypersomnia.

Study Objectives: Idiopathic hypersomnia is characterized by excessive daytime sleepiness, despite normal or long sleep time. Its pathophysiological mechanisms remain unclear. This pilot study aims at characterizing the neural correlates of idiopathic hypersomnia using single photon emission computed tomography.

Posterior dopamine D2/3 receptors and brain network functional connectivity.

Recent studies suggest that dopaminergic tone influences resting state activity in multiple brain networks. Although dopamine receptors and transporters have been identified in the posteromedial and parietal cortices, which are linked to functional networks such as the default mode network (DMN), the relationship between dopamine receptor distribution in these posterior regions and resting-state connectivity has yet to be explored. Here, we used a multi-modal neuroimaging strategy, combining resting-state functional magnetic resonance imaging (rsfMRI) and [18 F]-fallypride high-resolution positron emission tomography (PET), to examine the association between within-network functional connectivity and the dopamine D2/3 receptor distribution in the posterior portion of the brain in 13 healthy adults.

Cocaine cue-induced dopamine release in the human prefrontal cortex.

Background: Accumulating evidence indicates that drug-related cues can induce dopamine (DA) release in the striatum of substance abusers. Whether these same cues provoke DA release in the human prefrontal cortex remains unknown.

Methods: We used high-resolution positron emission tomography with [18F]fallypride to measure cortical and striatal DA D2/3 receptor availability in the presence versus absence of drug-related cues in volunteers with current cocaine dependence.

Direct 4D PET MLEM reconstruction of parametric images using the simplified reference tissue model with the basis function method for [¹¹C]raclopride.

This work assesses the one-step late maximum likelihood expectation maximization (OSL-MLEM) 4D PET reconstruction algorithm for direct estimation of parametric images from raw PET data when using the simplified reference tissue model with the basis function method (SRTM-BFM) for the kinetic analysis. To date, the OSL-MLEM method has been evaluated using kinetic models based on two-tissue compartments with an irreversible component. We extend the evaluation of this method for two-tissue compartments with a reversible component, using SRTM-BFM on simulated 3D + time data sets (with use of [(11)C]raclopride time-activity curves from real data) and on real data sets acquired with the high resolution research tomograph.

Brain serotonin synthesis in MDMA (ecstasy) polydrug users: an alpha-[(11) C]methyl-l-tryptophan study.

3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) use may have long-term neurotoxic effects. In this study, positron emission tomography with the tracer alpha-[(11) C]methyl-l-tryptophan ((11) C-AMT) was used to compare human brain serotonin (5-HT) synthesis capacity in 17 currently drug-free MDMA polydrug users with that in 18 healthy matched controls. Gender differences and associations between regional (11) C-AMT trapping and characteristics of MDMA use were also examined.

Stress-induced dopamine release in human medial prefrontal cortex--18F-fallypride/PET study in healthy volunteers.

Background: In laboratory animals, environmental stressors markedly activate the mesocortical dopamine system. The present study tested whether this occurs in humans.

Methods: The effects of a laboratory psychological stressor (Montreal Imaging Stress Task, MIST) on mesocortical dopamine release in healthy young adults (11 males, mean age ± SD, 20.

Cocaine cue-induced dopamine release in amygdala and hippocampus: a high-resolution PET [¹⁸F]fallypride study in cocaine dependent participants.

Drug-related cues are potent triggers for relapse in people with cocaine dependence. Dopamine (DA) release within a limbic network of striatum, amygdala and hippocampus has been implicated in animal studies, but in humans it has only been possible to measure effects in the striatum. The objective here was to measure drug cue-induced DA release in the amygdala and hippocampus using high-resolution PET with [(18)F]fallypride.

GABA(A) receptors in visual and auditory cortex and neural activity changes during basic visual stimulation.

Recent imaging studies have demonstrated that levels of resting γ-aminobutyric acid (GABA) in the visual cortex predict the degree of stimulus-induced activity in the same region. These studies have used the presentation of discrete visual stimulus; the change from closed eyes to open also represents a simple visual stimulus, however, and has been shown to induce changes in local brain activity and in functional connectivity between regions. We thus aimed to investigate the role of the GABA system, specifically GABA(A) receptors, in the changes in brain activity between the eyes closed (EC) and eyes open (EO) state in order to provide detail at the receptor level to complement previous studies of GABA concentrations.

3D PET image reconstruction including both motion correction and registration directly into an MR or stereotaxic spatial atlas.

This work explores the feasibility and impact of including both the motion correction and the image registration transformation parameters from positron emission tomography (PET) image space to magnetic resonance (MR), or stereotaxic, image space within the system matrix of PET image reconstruction. This approach is motivated by the fields of neuroscience and psychiatry, where PET is used to investigate differences in activation patterns between different groups of participants, requiring all images to be registered to a common spatial atlas. Currently, image registration is performed after image reconstruction which introduces interpolation effects into the final image.

External awareness and GABA--a multimodal imaging study combining fMRI and [18F]flumazenil-PET.

Awareness is an essential feature of the human mind that can be directed internally, that is, toward our self, or externally, that is, toward the environment. The combination of internal and external information is crucial to constitute our sense of self. Although the underlying neuronal networks, the so-called intrinsic and extrinsic systems, have been well-defined, the associated biochemical mechanisms still remain unclear.

Perinatal effects on in vivo measures of human brain serotonin synthesis in adulthood: a 27-year longitudinal study.

There is an increasing evidence that prenatal and early postnatal stressors have life long impacts on physical and mental health problems. Animal studies have shown that this could include enduring changes to brain serotonin neurotransmission. In the present study, we tested whether perinatal adversity in humans has a long-term impact on brain serotonin neurotransmission in adulthood.

Brain regional α-[11C]methyl-L-tryptophan trapping in medication-free patients with obsessive-compulsive disorder.

Context: The hypothesis of a serotonin (5-hydroxytryptamine [5-HT]) dysfunction in obsessive-compulsive disorder (OCD) stems largely from the clinical efficacy of 5-HT reuptake inhibitors. Serotonergic abnormalities in the unmedicated symptomatic state, however, remain to be fully characterized.

Objective: To investigate brain regional 5-HT synthesis, as indexed by positron emission tomography and the α-[(11)C]methyl-L-tryptophan trapping constant (K*), in treatment-free adults meeting criteria for OCD.

Task-oriented quantitative image reconstruction in emission tomography for single- and multi-subject studies.

Task-based selection of image reconstruction methodology in emission tomography is a critically important step when designing a PET study. This paper concerns optimizing, given the measured data of the study only, reconstruction performance for a range of quantification tasks: finding the mean radioactivity concentration for different regions of interests (ROIs), different ROI sizes and different group sizes (i.e.

Where in-vivo imaging meets cytoarchitectonics: the relationship between cortical thickness and neuronal density measured with high-resolution [18F]flumazenil-PET.

MRI-based measurements of surface cortical thickness (SCT) have become a sensitive tool to quantify changes in cortical morphology. When comparing SCT to histological cortical thickness maps, a good correspondence can be found for many but not all human brain areas. Discrepancies especially arise in the sensory motor cortex, where histological cortical thickness is high, but SCT is very low.

Brain serotonin synthesis in adult males characterized by physical aggression during childhood: a 21-year longitudinal study.

Background: Adults exhibiting severe impulsive and aggressive behaviors have multiple indices of low serotonin (5-HT) neurotransmission. It remains unclear though whether low 5-HT mediates the behavior or instead reflects a pre-existing vulnerability trait.

Methodology/principal Findings: In the present study, positron emission tomography with the tracer alpha-[(11)C]methyl-L-tryptophan ((11)C-AMT) was used to compare 5-HT synthesis capacity in two groups of adult males from a 21-year longitudinal study (mean age +/- SD: 27.

Improved work-up procedure for the production of [(18)F]flumazenil and first results of its use with a high-resolution research tomograph in human stroke.

Introduction: The central benzodiazepine receptor (cBZR)-gamma-aminobutyric acid (GABA(A)) receptor complex in the human brain plays an important role in many neurological and psychiatric disorders. (18)F-Labeled flumazenil ([(18)F]FZ) provides a potentially useful tracer to investigate those disorders by means of positron emission tomography (PET).

Methods: [(18)F]Flumazenil was synthesized from its nitro-precursor Ro 15-2344 in DMF at high temperatures between 150 degrees C and 160 degrees C.