Cortical β-amyloid burden, gray matter, and memory in adults at varying APOE ε4 risk for Alzheimer's disease.

Models of preclinical Alzheimer's disease (AD) propose that cerebral amyloidosis leads to neurodegeneration and subsequent cognitive decline. This study investigated whether APOE genotype is related to β-amyloid (Aβ) burden in brain regions preferentially affected by AD and whether Aβ burden is associated with gray-matter (GM) fraction (as a marker of neurodegeneration) and episodic memory performance in cognitively normal middle-aged individuals at varying genetic risk for AD. Three groups of cognitively normal participants aged 50-65 years with a first-degree family history of AD (APOE genotype ε4ε4 [n = 15], ε3ε4 [n = 15], and ε3ε3 [n = 15]) underwent [C]PiB positron emission tomography scans to quantify cortical Aβ, brain magnetic resonance imaging, and neuropsychological testing.

Direct 4-D PET list mode parametric reconstruction with a novel EM algorithm.

The production of images of kinetic parameters is often the ultimate goal of positron emission tomography (PET) imaging. The indirect method of PET parametric imaging, also called the frame-based method (FM), is performed by fitting the time-activity curve (TAC) for each voxel with an appropriate compartment model after image reconstruction. The indirect method is simple and easily implemented, however, it usually leads to some loss of accuracy or precision, due to the use of two separate steps.

Age effects on serotonin receptor 1B as assessed by PET.

Unlabelled: Previous imaging studies have suggested that there is an age-related decline in brain serotonin (5-hydroxytryptamine) measures in healthy subjects. This paper addresses whether the availability of 5-hydroxytryptamine receptor 1B (5-HT(1B)) is seen to decrease with aging via PET imaging.

Methods: Forty-eight healthy control subjects (mean age ± SD, 30 ± 10 y; age range, 18-61 y; 33 men, 15 women) underwent (11)C-P943 scanning on a high-resolution PET tomograph.

Glucose metabolism in the insula and cingulate is affected by systemic inflammation in humans.

Unlabelled: Depression is associated with systemic inflammation, and the systemic inflammation caused by endotoxin administration elicits mild depressive symptoms such as fatigue and reduced interest. The neural correlates of depressive symptoms that result from systemic inflammation are poorly defined. The aim of this study was to use (18)F-FDG PET to identify brain regions involved in the response to endotoxin administration in humans.

Serotonin 1B receptor imaging in pathological gambling.

Abstract Objectives. Although serotonergic mechanisms have been implicated in pathological gambling (PG), no ligand-based imaging studies have assessed serotonin receptors in individuals with PG. Given its role in substance addictions and its abundance in brain regions implicated in PG, we evaluated serotonin 1B receptors (5-HT1BRs) in PG.

The effect of early trauma exposure on serotonin type 1B receptor expression revealed by reduced selective radioligand binding.

Context: Serotonergic dysfunction is implicated in the pathogenesis of posttraumatic stress disorder (PTSD), and recent animal models suggest that disturbances in serotonin type 1B receptor function, in particular, may contribute to chronic anxiety. However, the specific role of the serotonin type 1B receptor has not been studied in patients with PTSD.

Objective: To investigate in vivo serotonin type 1B receptor expression in individuals with PTSD, trauma-exposed control participants without PTSD (TC), and healthy (non-trauma-exposed) control participants (HC) using positron emission tomography and the recently developed serotonin type 1B receptor selective radiotracer [(11)C]P943.

Clinically relevant doses of methylphenidate significantly occupy norepinephrine transporters in humans in vivo.

Background: Attention-deficit/hyperactivity disorder is a psychiatric disorder that starts in childhood. The mechanism of action of methylphenidate, the most common treatment for attention deficit hyperactivity disorder, is unclear. In vitro, the affinity of methylphenidate for the norepinephrine transporter (NET) is higher than that for the dopamine transporter (DAT).

Accuracy of Head Motion Compensation for the HRRT: Comparison of Methods.

Motion correction in PET has become more important as system resolution has improved. The purpose of this study was to evaluate the accuracy of three motion compensation methods, event-by-event motion compensation with list-mode reconstruction (MOLAR), frame-based motion correction, and post-reconstruction image registration. Motion compensated image reconstructions were carried out with simulated HRRT data, using a range of motion information based on human motion data.

A Multimodal Approach to Image-Derived Input Functions for Brain PET.

Many methods have been proposed for generating an image-derived input function (IDIF) exclusively from PET images. The purpose of this study was to assess the viability of a multimodality approach utilizing registered MR images. 3T-MR and HRRT-PET data were acquired from human subjects.

Reduced ventral striatal/ventral pallidal serotonin1B receptor binding potential in major depressive disorder.

Rationale: Although serotonin (5-HT) dysregulation is implicated in the pathophysiology of major depressive disorder (MDD), the role of specific receptor subtypes remains to be elucidated. Emerging preclinical research suggests an important role for the 5-HT(1B) receptor in behavioral regulation and depressive phenotypes. In particular, 5-HT(1B) heteroreceptors located within the striatum have been shown to play an essential role in antidepressant action.

Arterial transit time effects in pulsed arterial spin labeling CBF mapping: insight from a PET and MR study in normal human subjects.

Arterial transit time (ATT), a key parameter required to calculate absolute cerebral blood flow in arterial spin labeling (ASL), is subject to much uncertainty. In this study, ASL ATTs were estimated on a per-voxel basis using data measured by both ASL and positron emission tomography in the same subjects. The mean ATT increased by 260 +/- 20 (standard error of the mean) ms when the imaging slab shifted downwards by 54 mm, and increased from 630 +/- 30 to 1220 +/- 30 ms for the first slice, with an increase of 610 +/- 20 ms over a four-slice slab when the gap between the imaging and labeling slab increased from 20 to 74 mm.

Initial Evaluation of Direct 4D Parametric Reconstruction with Human PET Data.

Previously, we presented a direct EM method for producing kinetic parameter images from list mode PET data, where the time-activity curve for each voxel is described by a one-tissue compartment model (1T). The initial evaluations were performed with simulations, without motion, randoms, or scatter effects included. By extension of our previous frame-based physics correction methods, a practical direct 4D parametric reconstruction algorithm is now proposed and implemented for human data.

Kinetic modeling of the serotonin 5-HT(1B) receptor radioligand [(11)C]P943 in humans.

[(11)C]P943 is a new radioligand recently developed to image and quantify serotonin 5-Hydroxytryptamine (5-HT(1B)) receptors with positron emission tomography (PET). The purpose of this study was to evaluate [(11)C]P943 for this application in humans, and to determine the most suitable quantification method. Positron emission tomography data and arterial input function measurements were acquired in a cohort of 32 human subjects.

PET imaging of the effects of age and cocaine on the norepinephrine transporter in the human brain using (S,S)-[(11)C]O-methylreboxetine and HRRT.

Objectives: The role of the norepinephrine transporter (NET) in cocaine dependence has never been demonstrated via in vivo imaging due to the lack of suitable NET radioligands. Here we report our preliminary studies evaluting the NET in individuals with cocaine dependence (COC) in comparison to healthy controls (HC) using (S,S)-[(11)C]methylreboxetine ([(11)C]MRB), the most promising C-11 labeled positron-emission tomography (PET) radioligand for NET developed to date.

Methods: Twenty two human volunteers (10 COC and 12 HC) underwent dynamic (11)C-MRB-PET acquisition using a High Resolution Research Tomograph (HRRT).

Quantitative Accuracy of HRRT List-mode Reconstructions: Effect of Low Statistics.

Previous studies showed that iterative image reconstruction algorithms may produce overestimations of activity in low-activity regions in low-count frames. The purpose of this study was (1) to evaluate the quantitative accuracy of the MOLAR list-mode iterative reconstruction method in the context of ligand-receptor PET studies in low counts, and (2) to determine the minimum noise equivalent counts (NEC) per frame to avoid bias. Evaluation of clinical data was performed for 4 tracers using dynamic brain PET studies.

Direct 4D List Mode Parametric Reconstruction for PET with a Novel EM Algorithm.

We present a direct method for producing images of kinetic parameters from list mode PET data. The time-activity curve for each voxel is described by a one-tissue compartment, 2-parameter model. Extending previous EM algorithms, a new spatiotemporal complete data space was introduced to optimize the maximum likelihood function.

Cerebral metabolic effects of intravenous glycine in healthy human subjects.

Enhancing N-methyl-D-aspartate (NMDA) receptor function via increasing synaptic concentrations of glycine is currently investigated as a novel approach to treat schizophrenia. The neural correlates of enhanced NMDA receptor function in humans, however, are unclear to date. The present study determines the effects of intravenous administration of the glycine on regional cerebral metabolic rate of glucose (rCMRGlu) in healthy control subjects by using [18F]fluorodeoxyglucose and positron emission tomography and on neuropsychological behavioral measures.