Dataset Information

PET imaging reveals lower kappa opioid receptor availability in alcoholics but no effect of age.

ABSTRACT: Opioid receptors are implicated in alcoholism, other addictions, withdrawal, and depression, and are considered potential pharmacological targets for treatment. Our goal in the present study was to compare the availability of kappa opioid receptors (KOR) between an alcohol-dependent cohort (AD) and a healthy control cohort (HC). Sixty-four participants-36 AD and 28 HC-underwent PET scans with [¹¹C]LY2795050, a selective kappa antagonist tracer. Partial-volume correction was applied to all PET data to correct for atrophy. Volume of distribution (V_T) of the tracer was estimated regionally as a measure of KOR availability. V_T values of AD versus HC were compared for 15 defined ROIs. Multivariate analysis showed a main effect of group on V_T across these 15 ROIs. Post hoc tests showed that AD had significantly lower V_T and thus a lower KOR availability than HC in amygdala and pallidum (corrected for multiple comparisons). Exploratory analysis of change in V_T with age was conducted; V_T was not found to vary significantly with age in any region. Our findings of lower V_T in AD versus HC in multiple regions are in contrast to findings in the mu and delta opioid receptor systems of higher V_T in AD versus HC. Although age-related decline in receptors has previously been observed in the mu opioid receptor system, we found that KOR availability does not change with age.

SUBMITTER: Vijay A

PROVIDER: S-EPMC6224533 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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PET imaging reveals lower kappa opioid receptor availability in alcoholics but no effect of age.

Vijay Aishwarya A Cavallo Dana D Goldberg Alissa A de Laat Bart B Nabulsi Nabeel N Huang Yiyun Y Krishnan-Sarin Suchitra S Morris Evan D ED

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 20180906 13

Opioid receptors are implicated in alcoholism, other addictions, withdrawal, and depression, and are considered potential pharmacological targets for treatment. Our goal in the present study was to compare the availability of kappa opioid receptors (KOR) between an alcohol-dependent cohort (AD) and a healthy control cohort (HC). Sixty-four participants-36 AD and 28 HC-underwent PET scans with [<sup>11</sup>C]LY2795050, a selective kappa antagonist tracer. Partial-volume correction was applied to ...[more]

PMID: 30188515

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Project description:Kappa opioid receptors (KORs) have been characterized as an aversive system in the brain and implicated in social behavior in preclinical models. This work investigated the effect of social status on the KOR system in humans using positron emission tomography (PET) imaging with the novel KOR agonist radiotracer [11C]EKAP. Eighteen healthy participants (mean age 41.2?±?9.3) completed the Barratt Simplified Measure of Social Status (BSMSS), an MRI and an [11C]EKAP PET scan on the High Resolution Research Tomograph. Arterial blood sampling and metabolite analysis were conducted to obtain the input function. Regions of interest were based upon an MR template and included the reward/aversion areas of the brain. The multilinear analysis-1 (MA1) method was applied to the regional time-activity curves (TACs) to calculate [11C]EKAP regional volume of distribution (VT). Mixed models and Pearson correlation coefficients were used for body mass index (BMI), gender and age, with age being dropped in subsequent analyses because of nonsignificance. An overall effect of primary ROIs (F7,?112 7.43, p?<?0.0001), BSMSS score (F1,?13 7.45, p?=?0.02), BMI (F1,?13 23.5, p?<?0.001), and gender (F1,?13 23.75, p?<?0.001), but not age (F1,?13 1.12, p?=?0.35) was observed. Regional [11C]EKAP VT and BSMSS were found to be negatively correlated in the amygdala (r?=?-0.69, p?<?0.01), anterior cingulate cortex (r?=?-0.56, p?=?0.02), caudate (r?=?-0.66, p?<?0.01), frontal cortex (r?=?-0.52, p?=?0.04), hippocampus (r?=?-0.60, p?=?0.01), pallidum (r?=?-0.59, p?=?0.02), putamen (r?=?-0.62, p?=?0.01), and ventral striatum (r?=?-0.66, p?<?0.01). In secondary (non-reward) regions, correlations of [11C]EKAP VT and BSMSS were nonsignificant with the exception of the insula. There was an inverse correlation between social status and KOR levels that was largely specific to the reward/aversion (e.g., saliency) areas of the brain. This finding suggests the KOR system may act as a mediator for the negative effects of social behaviors in humans.

Project description:We propose a novel approach for PET respiratory motion correction using tagged-MRI and simultaneous PET-MRI acquisitions.We use a tagged-MRI acquisition followed by motion tracking in the phase domain to estimate the nonrigid deformation of biological tissues during breathing. In order to accurately estimate motion even in the presence of noise and susceptibility artifacts, we regularize the traditional HARP tracking strategy using a quadratic roughness penalty on neighboring displacement vectors (R-HARP). We then incorporate the motion fields estimated with R-HARP in the system matrix of an MLEM PET reconstruction algorithm formulated both for sinogram and list-mode data representations. This approach allows reconstruction of all detected coincidences in a single image while modeling the effect of motion both in the emission and the attenuation maps. At present, tagged-MRI does not allow estimation of motion in the lungs and our approach is therefore limited to motion correction in soft tissues. Since it is difficult to assess the accuracy of motion correction approaches in vivo, we evaluated the proposed approach in numerical simulations of simultaneous PET-MRI acquisitions using the NCAT phantom. We also assessed its practical feasibility in PET-MRI acquisitions of a small deformable phantom that mimics the complex deformation pattern of a lung that we imaged on a combined PET-MRI brain scanner.Simulations showed that the R-HARP tracking strategy accurately estimated realistic respiratory motion fields for different levels of noise in the tagged-MRI simulation. In simulations of tumors exhibiting increased uptake, contrast estimation was 20% more accurate with motion correction than without. Signal-to-noise ratio (SNR) was more than 100% greater when performing motion-corrected reconstruction which included all counts, compared to when reconstructing only coincidences detected in the first of eight gated frames. These results were confirmed in our proof-of-principle PET-MRI acquisitions, indicating that our motion correction strategy is accurate, practically feasible, and is therefore ready to be tested in vivo.This work shows that PET motion correction using motion fields measured with tagged-MRI in simultaneous PET-MRI acquisitions can be made practical for clinical application and that doing so has the potential to remove motion blur in whole-body PET studies of the torso.

Dataset Information

PET imaging reveals lower kappa opioid receptor availability in alcoholics but no effect of age.

Publications

PET imaging reveals lower kappa opioid receptor availability in alcoholics but no effect of age.

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