scholarly journals Cerebral 5-HT release correlates with [11C]Cimbi36 PET measures of 5-HT2A receptor occupancy in the pig brain

2016 ◽  
Vol 37 (2) ◽  
pp. 425-434 ◽  
Author(s):  
Louise M Jørgensen ◽  
Pia Weikop ◽  
Jonas Villadsen ◽  
Tanel Visnapuu ◽  
Anders Ettrup ◽  
...  
Keyword(s):  
Spatial Information ◽  
Receptor Occupancy ◽  
The Novel ◽  
Imaging Data ◽  
Pig Brain ◽  
Positron Emission ◽  
Brain Neurotransmitter ◽  
Acute Changes ◽  
First Time ◽  
The Brain

Positron emission tomography (PET) can, when used with appropriate radioligands, non-invasively generate temporal and spatial information about acute changes in brain neurotransmitter systems. We for the first time evaluate the novel 5-HT2A receptor agonist PET radioligand, [11C]Cimbi-36, for its sensitivity to detect changes in endogenous cerebral 5-HT levels, as induced by different pharmacological challenges. To enable a direct translation of PET imaging data to changes in brain 5-HT levels, we calibrated the [11C]Cimbi-36 PET signal in the pig brain by simultaneous measurements of extracellular 5-HT levels with microdialysis and [11C]Cimbi-36 PET after various acute interventions (saline, citalopram, citalopram + pindolol, fenfluramine). In a subset of pigs, para-chlorophenylalanine pretreatment was given to deplete cerebral 5-HT. The interventions increased the cerebral extracellular 5-HT levels to 2–11 times baseline, with fenfluramine being the most potent pharmacological enhancer of 5-HT release, and induced a varying degree of decline in [11C]Cimbi-36 binding in the brain, consistent with the occupancy competition model. The observed correlation between changes in the extracellular 5-HT level in the pig brain and the 5-HT2A receptor occupancy indicates that [11C]Cimbi-36 binding is sensitive to changes in endogenous 5-HT levels, although only detectable with PET when the 5-HT release is sufficiently high.

scholarly journals Cerebral serotonin release correlates with [11C]AZ10419369 PET measures of 5-HT1B receptor binding in the pig brain

2017 ◽  
Vol 38 (7) ◽  
pp. 1243-1252 ◽  
Author(s):  
Louise M Jørgensen ◽  
Pia Weikop ◽  
Claus Svarer ◽  
Ling Feng ◽  
Sune H Keller ◽  
...  
Keyword(s):  
Spatial Information ◽  
Partial Agonist ◽  
Receptor Occupancy ◽  
Serotonin Release ◽  
Serotonin Level ◽  
Imaging Data ◽  
Pig Brain ◽  
Positron Emission ◽  
Acute Changes

Positron emission tomography (PET) can, when used with appropriate radioligands, non-invasively capture temporal and spatial information about acute changes in brain neurotransmitter systems. We here evaluate the 5-HT1B receptor partial agonist PET radioligand, [11C]AZ10419369, for its sensitivity to detect changes in endogenous cerebral serotonin levels, as induced by different pharmacological challenges. To enable a direct translation of PET imaging data to changes in brain serotonin levels, we compared the [11C]AZ10419369 PET signal in the pig brain to simultaneous measurements of extracellular serotonin levels with microdialysis after various acute interventions (saline, escitalopram, fenfluramine). The interventions increased the cerebral extracellular serotonin levels to two to six times baseline, with fenfluramine being the most potent pharmacological enhancer of serotonin release. The interventions induced a varying degree of decline in [11C]AZ10419369 binding in the brain, consistent with the occupancy competition model. The observed correlation between changes in the extracellular serotonin level in the pig brain and the 5-HT1B receptor occupancy indicates that [11C]AZ10419369 binding is sensitive to changes in endogenous serotonin levels to a degree equivalent to that reported of [11C]raclopride to dopamine, a much used approach to detect in vivo change in cerebral dopamine.

scholarly journals Preserved representations and decodability of diverse cognitive functions across the cortex, cerebellum, and subcortex

2021 ◽  
Author(s):  
Tomoya Nakai ◽  
Shinji Nishimoto
Keyword(s):  
Cognitive Functions ◽  
Principal Component ◽  
Cognitive Tasks ◽  
Sufficient Information ◽  
The Novel ◽  
Imaging Data ◽  
Functional Representations ◽  
Model Training ◽  
Task Representations ◽  
The Brain

Which part of the brain contributes to our complex cognitive processes? Studies have revealed contributions of the cerebellum and subcortex to higher-order cognitive functions; however it is unclear whether such functional representations are preserved across the cortex, cerebellum, and subcortex. In this study, we used functional magnetic resonance imaging data with 103 cognitive tasks and constructed three voxel-wise encoding and decoding models independently using cortical, cerebellar, and subcortical voxels. Representational similarity analysis revealed that the structure of task representations is preserved across the three brain parts. Principal component analysis visualized distinct organizations of abstract cognitive functions in each part of the cerebellum and subcortex. More than 90% of the cognitive tasks were decodable from the cerebellum and subcortical activities, even for the novel tasks not included in model training. Furthermore, we discovered that the cerebellum and subcortex have sufficient information to reconstruct activity in the cerebral cortex.

scholarly journals Predicting Brain Occupancy from Plasma Levels using PET: Superiority of Combining Pharmacokinetics with Pharmacodynamics while Modeling the Relationship

2011 ◽  
Vol 32 (4) ◽  
pp. 759-768 ◽  
Author(s):  
Euitae Kim ◽  
Oliver D Howes ◽  
Bo-Hyung Kim ◽  
Jae Min Jeong ◽  
Jae Sung Lee ◽  
...  
Keyword(s):  
Dopamine Receptor ◽  
Receptor Occupancy ◽  
Analysis Approach ◽  
Reliable Prediction ◽  
Positron Emission ◽  
Time Courses ◽  
The Relationship ◽  
The Brain ◽  
Serial Measurements ◽  
Hysteresis Characteristics

Positron emission tomography (PET) studies of dopamine receptor occupancy can be used to assess dosing of antipsychotics. Typically, studies of antipsychotics have applied pharmacodynamic (PD) modeling alone to characterize the relationship between antipsychotic dose and its effect on the brain. However, a limitation of this approach is that it does not account for the discrepancy between the time courses of plasma concentration and receptor occupancy by antipsychotics. Combined pharmacokinetic—PD (PK—PD) modeling, by incorporating the time dependence of occupancy, is better suited for the reliable analysis of the concentration—occupancy relationship. To determine the effect of time on the concentration—occupancy relationship as a function of analysis approach, we measured dopamine receptor occupancy after the administration of aripiprazole using [11C]raclopride PET and obtained serial measurements of the plasma aripiprazole concentration in 18 volunteers. We then developed a PK—PD model for the relationship, and compared it with conventional approach (PD modeling alone). The hysteresis characteristics were observed in the competitor concentration—occupancy relationship and the value of EC50 was different according to the analysis approach ( EC50 derived from PD modeling alone = 11.1 ng/mL (95% confidence interval (CI) = 10.1 to 12.1); while that derived from combined PK—PD modeling = 8.63 ng/mL (95% CI = 7.75 to 9.51)). This finding suggests that PK—PD modeling is required to obtain reliable prediction of brain occupancy by antipsychotics.

Positron Emission Tomography: A Technology Assessment

1986 ◽  
Vol 2 (4) ◽  
pp. 577-594 ◽  
Author(s):  
Nora D. Volkow ◽  
Laurence R. Tancredi
Keyword(s):  
Positron Emission Tomography ◽  
The Body ◽  
Emission Tomography ◽  
Positron Emission ◽  
Neurological Patients ◽  
Technological Assessment ◽  
A New Technique ◽  
First Time ◽  
Nuclear Medicine Technique ◽  
The Brain

Positron emission tomography (PET) is a new nuclear medicine technique that has recently entered the clinical realm of medicine. Although it is a technique that can be utilized for assessment of biochemical and physiological parameters of any organ in the body, it has particular utility in the investigation of the brain. PET poses unique advantages over previous imaging devices. For the first time, it is feasible to investigate directly various biological parameters of the brain in a noninvasive way. PET allows for investigating the functional, biochemical, physiological, and pharmacological characteristics of various areas within the brains of normal and psychiatric or neurological patients. Although it has already started to give promising results, it is too new a technique to obtain an accurate appraisal of its true potentials. This is a problem that seems always to surface when one tries to evaluate the utility of a new technique in a new area of research. The problem is accentuated in the case of PET where there is no other technique available with which to compare results. This paper will discuss the basic principles of PET, its relationship to other existing imaging devices, and the issues to be considered when making a technological assessment of positron emission tomography.

scholarly journals Semantic Grounding of Novel Spoken Words in the Primary Visual Cortex

2021 ◽  
Vol 15 ◽  
Author(s):  
Max Garagnani ◽  
Evgeniya Kirilina ◽  
Friedemann Pulvermüller
Keyword(s):  
Visual Cortex ◽  
Primary Visual Cortex ◽  
Semantic Information ◽  
Word Meaning ◽  
Familiar Object ◽  
The Novel ◽  
Brain Responses ◽  
Spoken Words ◽  
First Time ◽  
The Brain

Embodied theories of grounded semantics postulate that, when word meaning is first acquired, a link is established between symbol (word form) and corresponding semantic information present in modality-specific—including primary—sensorimotor cortices of the brain. Direct experimental evidence documenting the emergence of such a link (i.e., showing that presentation of a previously unknown, meaningless word sound induces, after learning, category-specific reactivation of relevant primary sensory or motor brain areas), however, is still missing. Here, we present new neuroimaging results that provide such evidence. We taught participants aspects of the referential meaning of previously unknown, senseless novel spoken words (such as “Shruba” or “Flipe”) by associating them with either a familiar action or a familiar object. After training, we used functional magnetic resonance imaging to analyze the participants’ brain responses to the new speech items. We found that hearing the newly learnt object-related word sounds selectively triggered activity in the primary visual cortex, as well as secondary and higher visual areas.These results for the first time directly document the formation of a link between the novel, previously meaningless spoken items and corresponding semantic information in primary sensory areas in a category-specific manner, providing experimental support for perceptual accounts of word-meaning acquisition in the brain.

scholarly journals Quantification of Human Opiate Receptor Concentration and Affinity Using High and Low Specific Activity [11C]Diprenorphine and Positron Emission Tomography

1991 ◽  
Vol 11 (2) ◽  
pp. 204-219 ◽  
Author(s):  
Bernard Sadzot ◽  
Julie C. Price ◽  
Helen S. Mayberg ◽  
Kenneth H. Douglass ◽  
Robert F. Dannals ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Specific Activity ◽  
Free Fraction ◽  
Receptor Occupancy ◽  
Occipital Cortex ◽  
Opiate Receptor ◽  
Emission Tomography ◽  
Positron Emission ◽  
Receptor Concentration ◽  
The Brain

[11C]Diprenorphine, a weak partial opiate agonist, and positron emission tomography were used to obtain noninvasive regional estimates of opiate receptor concentration ( Bmax) and affinity ( Kd) in human brain. Different compartmental models and fitting strategies were compared statistically to establish the most reliable method of parameter estimation. Paired studies were performed in six normal subjects using high (769–5,920 Ci/mmol) and low (27–80 Ci/mmol) specific activity (SA) [11C]diprenorphine. Two subjects were studied a third time using high SA [11C]diprenorphine after a pretreatment with 1–1.5 mg/kg of the opiate antagonist naloxone. After the plasma radioactivity was corrected for metabolites, the brain data were analyzed using a three-compartment model and nonlinear least-squares curve fitting. Linear differential equations were used to describe the high SA (low receptor occupancy) kinetics. The k3/ k4 ratio varied from 1.0 ± 0.2 (occipital cortex) to 8.6 ± 1.6 (thalamus). Nonlinear differential equations were used to describe the low SA (high receptor occupancy) kinetics and the curve fits provided the kon f2 product. The measured free fraction of [11C]diprenorphine in plasma ( f1) was 0.30 ± 0.03, the average K1/ k2 ratio from the two naloxone studies was 1.1 ± 0.2, and the calculated free fraction of [11C]diprenorphine in the brain ( f2) was 0.3. Using the paired SA studies, the estimated kinetic parameters, and f2, separate estimates of Bmax and Kd were obtained. Bmax varied from 2.3 ± 0.5 (occipital cortex) to 20.6 ± 7.3 (cingulate cortex) n M. The average Kd (eight brain regions) was 0.85 ± 0.17 n M.

scholarly journals In vivo evaluation of [11C]preladenant positron emission tomography for quantification of adenosine A2A receptors in the rat brain

2016 ◽  
Vol 37 (2) ◽  
pp. 577-589 ◽  
Author(s):  
Xiaoyun Zhou ◽  
Shivashankar Khanapur ◽  
Johan R de Jong ◽  
Antoon TM Willemsen ◽  
Rudi AJO Dierckx ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Receptor Occupancy ◽  
Compartment Model ◽  
Emission Tomography ◽  
Rat Striatum ◽  
Receptor Density ◽  
Reference Tissue ◽  
Tissue Compartment ◽  
Positron Emission ◽  
The Brain

[11C]Preladenant was developed as a novel adenosine A2A receptor positron emission tomography radioligand. The present study aims to evaluate the suitability of [11C]preladenant positron emission tomography for the quantification of striatal A2A receptor density and the assessment of striatal A2A receptor occupancy by KW-6002. Sixty- or ninety-minute dynamic positron emission tomography imaging was performed on rats. Tracer kinetics was quantified by the two-tissue compartment model, Logan graphical analysis and several reference tissue-based models. Test–retest reproducibility was assessed by repeated imaging on two consecutive days. Two-tissue compartment model and Logan plot estimated comparable distribution volume ( VT) values of ∼10 in the A2A receptor-rich striatum and substantially lower values in all extra-striatal regions (∼1.5–2.5). The simplified reference tissue model with midbrain or occipital cortex as the reference region proved to be the best non-invasive model for quantification of A2A receptor, showing a striatal binding potential ( BPND) value of ∼5.5, and a test–retest variability of ∼5.5%. The brain metabolite analysis showed that at 60-min post injection, 17% of the radioactivity in the brain was due to radioactive metabolites. The ED50 of KW-6002 in rat striatum for i.p. injection was 0.044–0.062 mg/kg. The study demonstrates that [11C]preladenant is a suitable tracer to quantify striatal A2A receptor density and assess A2A receptor occupancy by A2A receptor-targeting molecules.

scholarly journals PET-BIDS, an extension to the brain imaging data structure for positron emission tomography

2021 ◽  
Author(s):  
Martin Norgaard ◽  
Granville James Matheson ◽  
Hanne D Hansen ◽  
Adam G Thomas ◽  
Graham Searle ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Data Structure ◽  
Brain Imaging ◽  
Emission Tomography ◽  
Imaging Data ◽  
New Methods ◽  
Positron Emission ◽  
Neuroimaging Data ◽  
Brain Imaging Data ◽  
The Brain

The Brain Imaging Data Structure (BIDS) is a standard for organizing and describing neuroimaging datasets. It serves 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 (PET-BIDS). We describe the PET-BIDS standard in detail and share several open-access datasets curated following PET-BIDS. Additionally, we highlight several tools which are already available for converting, validating and analyzing PET-BIDS datasets.

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