Effects of Citalopram Infusion on the Serotonin Transporter Binding of [11C]DASB in Healthy Controls

2008 ◽  
Vol 28 (8) ◽  
pp. 1478-1490 ◽  
Author(s):  
Rainer Hinz ◽  
Sudhakar Selvaraj ◽  
N Venkatesha Murthy ◽  
Zubin Bhagwagar ◽  
Matthew Taylor ◽  
...  
Keyword(s):  
Spectral Analysis ◽  
Serotonin Transporter ◽  
Area Under The Curve ◽  
Input Function ◽  
Brain Regions ◽  
Time Activity ◽  
Quantitative Studies ◽  
Logan Plot ◽  
Positron Emission ◽  
Arterial Plasma

The positron emission tomography (PET) ligand [11C]DASB is currently the most widely used imaging agent for quantitative studies of the serotonin transporter (SERT) in human brain. The aim of this work was to assess the effects of an intravenous infusion of 10 mg citalopram, a selective serotonin reuptake inhibitor (SSRI), before the PET scan on the kinetics of [11C]DASB in arterial plasma and in selected brain regions. Four healthy male volunteers underwent two PET scans with a mean of 523 MBq injected activity after either placebo or Citalopram infusion in a randomised design. The Citalopram infusion led to a substantial increase of the area under the curve of the metabolite-corrected arterial plasma input function. Total volumes of distribution VT were estimated applying the Logan plot to regional time—activity curves or by generating parametric maps with spectral analysis. A mean reduction of the cerebellar VT of 19% with Logan analysis and of 24% with spectral analysis was observed after Citalopram infusion, which confirms previous findings of displaceable SERT ligand binding in cerebellar grey matter. The SERT occupancy for six target regions with moderate to high binding was 60% derived from BPND and 69% derived from BPP.

scholarly journals Characterisation of the Contribution of the GABA-Benzodiazepine α1 Receptor Subtype to [11C]Ro15-4513 PET Images

2012 ◽  
Vol 32 (4) ◽  
pp. 731-744 ◽  
Author(s):  
James FM Myers ◽  
Lula Rosso ◽  
Ben J Watson ◽  
Sue J Wilson ◽  
Nicola J Kalk ◽  
...  
Keyword(s):  
Spectral Analysis ◽  
A Priori ◽  
Benzodiazepine Receptor ◽  
Brain Regions ◽  
Complex Model ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Time Activity ◽  
Positron Emission ◽  
The Impact

This positron emission tomography (PET) study aimed to further define selectivity of [11C]Ro15-4513 binding to the GABARα5 relative to the GABARα1 benzodiazepine receptor subtype. The impact of zolpidem, a GABARα1-selective agonist, on [11C]Ro15-4513, which shows selectivity for GABARα5, and the nonselective benzodiazepine ligand [11C]flumazenil binding was assessed in humans. Compartmental modelling of the kinetics of [11C]Ro15-4513 time-activity curves was used to describe distribution volume ( VT) differences in regions populated by different GABA receptor subtypes. Those with low α5 were best fitted by one-tissue compartment models; and those with high α5 required a more complex model. The heterogeneity between brain regions suggested spectral analysis as a more appropriate method to quantify binding as it does not a priori specify compartments. Spectral analysis revealed that Zolpidem caused a significant VT decrease (~10%) in [11C]flumazenil, but no decrease in [11C]Ro15-4513 binding. Further analysis of [11C]Ro15-4513 kinetics revealed additional frequency components present in regions containing both α1 and α5 subtypes compared with those containing only α1. Zolpidem reduced one component (mean ± s.d.: 71% ± 41%), presumed to reflect α1-subtype binding, but not another (13% ± 22%), presumed to reflect α5. The proposed method for [11C]Ro15-4513 analysis may allow more accurate selective binding assays and estimation of drug occupancy for other nonselective ligands.

scholarly journals Kinetic Analysis of the 5-HT2A Ligand [11C]MDL 100,907

2000 ◽  
Vol 20 (6) ◽  
pp. 899-909 ◽  
Author(s):  
Hiroshi Watabe ◽  
Michael A. Channing ◽  
Margaret G. Der ◽  
H. Richard Adams ◽  
Elaine Jagoda ◽  
...  
Keyword(s):  
Kinetic Analysis ◽  
Specific Binding ◽  
Compartment Model ◽  
Input Function ◽  
Brain Regions ◽  
Time Activity ◽  
Tissue Compartment ◽  
Arterial Blood ◽  
Fixed Parameter ◽  
Mdl 100,907

The goal of this study was to develop a suitable kinetic analysis method for quantification of 5-HT2A receptor parameters with [11C]MDL 100,907. Twelve control studies and four preblocking studies (400 nmol/kg unlabeled MDL 100,907) were performed in isoflurane-anesthetized rhesus monkeys. The plasma input function was determined from arterial blood samples with metabolite measurements by extraction in ethyl acetate. The preblocking studies showed that a two-tissue compartment model was necessary to fit the time activity curves of all brain regions including the cerebellum—in other words, the need for two compartments is not proof of specific binding. Therefore, a three-tissue compartment model was used to analyze the control studies, with three parameters fixed based on the preblocking data. Reliable fits of control data could be obtained only if no more than three parameters were allowed to vary. For routine use of [11C]MDL 100,907, several simplified methods were evaluated. A two-tissue (2T‘) compartment with one fixed parameter was the most reliable compartmental approach; a one-compartment model failed to fit the data adequately. The Logan graphical approach was also tested and produced comparable results to the 2T’ model. However, a simulation study showed that Logan analysis produced a larger bias at higher noise levels. Thus, the 2T' model is the best choice for analysis of [11C]MDL 100,907 studies.

scholarly journals Arterial Input Function Derived from Pairwise Correlations Between PET-image Voxels

2013 ◽  
Vol 33 (7) ◽  
pp. 1058-1065 ◽  
Author(s):  
Martin Schain ◽  
Simon Benjaminsson ◽  
Katarina Varnäs ◽  
Anton Forsberg ◽  
Christer Halldin ◽  
...  
Keyword(s):  
Arterial Input Function ◽  
Pearson Correlation ◽  
Invasive Procedure ◽  
Compartmental Analysis ◽  
Input Function ◽  
Time Activity ◽  
Pairwise Correlation ◽  
Positron Emission ◽  
Using Data ◽  
Suitable Reference

A metabolite corrected arterial input function is a prerequisite for quantification of positron emission tomography (PET) data by compartmental analysis. This quantitative approach is also necessary for radioligands without suitable reference regions in brain. The measurement is laborious and requires cannulation of a peripheral artery, a procedure that can be associated with patient discomfort and potential adverse events. A non invasive procedure for obtaining the arterial input function is thus preferable. In this study, we present a novel method to obtain image-derived input functions (IDIFs). The method is based on calculation of the Pearson correlation coefficient between the time-activity curves of voxel pairs in the PET image to localize voxels displaying blood-like behavior. The method was evaluated using data obtained in human studies with the radioligands [ 11 C]flumazenil and [ 11 C]AZ10419369, and its performance was compared with three previously published methods. The distribution volumes ( VT) obtained using IDIFs were compared with those obtained using traditional arterial measurements. Overall, the agreement in VT was good (~3% difference) for input functions obtained using the pairwise correlation approach. This approach performed similarly or even better than the other methods, and could be considered in applied clinical studies. Applications to other radioligands are needed for further verification.

Brain serotonin transporter binding in former users of MDMA (‘ecstasy’)

2009 ◽  
Vol 194 (4) ◽  
pp. 355-359 ◽  
Author(s):  
Sudhakar Selvaraj ◽  
Rosa Hoshi ◽  
Zubin Bhagwagar ◽  
Naga Venkatesha Murthy ◽  
Rainer Hinz ◽  
...  
Keyword(s):  
Serotonin Transporter ◽  
Experimental Studies ◽  
Public Health Problem ◽  
Brain Regions ◽  
Brain Serotonin ◽  
Binding Potential ◽  
Major Public Health Problem ◽  
Positron Emission ◽  
Significant Difference ◽  
Serotonin Neurons

BackgroundAnimal experimental studies have prompted concerns that widespread use of 3,4-methylenedioxymethamphetamine (MDMA; ‘ecstasy’) by young people may pose a major public health problem in terms of persistent serotonin neurotoxicity.AimsTo determine the status of brain serotonin neurons in a group of abstinent MDMA users.MethodWe assessed the integrity of brain serotonin neurons by measuring serotonin transporter (SERT) binding using positron emission tomography (PET) and [11C]DASB in 12 former MDMA users, 9 polydrug users who had never taken MDMA and 19 controls who reported no history of illicit drug use.ResultsThere was no significant difference in the binding potential of [11C]DASB between the groups in any of the brain regions examined.ConclusionsTo the extent that [11C]DASB binding provides an index of the integrity of serotonin neurons, our findings suggest that MDMA use may not result in long-term damage to serotonin neurons when used recreationally in humans.

scholarly journals Estimation of input function from dynamic PET brain data using Bayesian blind source separation

2015 ◽  
Vol 12 (4) ◽  
pp. 1273-1287
Author(s):  
Ondřej Tichý ◽  
Václav Smídl
Keyword(s):  
Blind Source Separation ◽  
Source Separation ◽  
Input Function ◽  
Time Activity ◽  
Probability Modeling ◽  
Arterial Blood ◽  
Positron Emission ◽  
Manual Interaction ◽  
Brain Data ◽  
Estimation Of Time

Selection of regions of interest in an image sequence is a typical prerequisite step for estimation of time-activity curves in dynamic positron emission tomography (PET). This procedure is done manually by a human operator and therefore suffers from subjective errors. Another such problem is to estimate the input function. It can be measured from arterial blood or it can be searched for a vascular structure on the images which is hard to be done, unreliable, and often impossible. In this study, we focus on blind source separation methods with no needs of manual interaction. Recently, we developed sparse blind source separation and deconvolution (S-BSS-vecDC) method for separation of original sources from dynamic medical data based on probability modeling and Variational Bayes approximation methodology. In this paper, we extend this method and we apply the methods on dynamic brain PET data and application and comparison of derived algorithms with those of similar assumptions are given. The S-BSS-vecDC algorithm is publicly available for download.

scholarly journals In vivo evidence for dysregulation of mGluR5 as a biomarker of suicidal ideation

2019 ◽  
Vol 116 (23) ◽  
pp. 11490-11495 ◽  
Author(s):  
Margaret T. Davis ◽  
Ansel Hillmer ◽  
Sophie E. Holmes ◽  
Robert H. Pietrzak ◽  
Nicole DellaGioia ◽  
...  
Keyword(s):  
Suicidal Ideation ◽  
Suicide Risk ◽  
Potential Role ◽  
Input Function ◽  
Brain Regions ◽  
Volume Of Distribution ◽  
Regions Of Interest ◽  
Emission Tomography ◽  
Positron Emission

Recent evidence implicates dysregulation of metabotropic glutamatergic receptor 5 (mGluR5) in pathophysiology of PTSD and suicidality. Using positron emission tomography and [18F]FPEB, we quantified mGluR5 availability in vivo in individuals with PTSD (n = 29) and MDD (n = 29) as a function of suicidal ideation (SI) to compare with that of healthy comparison controls (HC; n = 29). Volume of distribution was computed using a venous input function in the five key frontal and limbic brain regions. We observed significantly higher mGluR5 availability in PTSD compared with HC individuals in all regions of interest (P’s = 0.001–0.01) and compared with MDD individuals in three regions (P’s = 0.007). mGluR5 availability was not significantly different between MDD and HC individuals (P = 0.17). Importantly, we observed an up-regulation in mGluR5 availability in the PTSD-SI group (P’s = 0.001–0.007) compared with PTSD individuals without SI. Findings point to the potential role for mGluR5 as a target for intervention and, potentially, suicide risk management in PTSD.

scholarly journals Quantification of [11C]yohimbine Binding to α2 Adrenoceptors in Rat Brain in vivo

2015 ◽  
Vol 35 (3) ◽  
pp. 501-511 ◽  
Author(s):  
Jenny-Ann Phan ◽  
Anne M Landau ◽  
Dean F Wong ◽  
Steen Jakobsen ◽  
Adjmal Nahimi ◽  
...  
Keyword(s):  
Rat Brain ◽  
Volume Of Distribution ◽  
Sprague Dawley ◽  
Logan Plot ◽  
Positron Emission ◽  
Amphetamine Administration ◽  
Sprague Dawley Rats ◽  
Extracellular Level ◽  
Arterial Plasma

We quantified the binding potentials ( BPND) of [11C]yohimbine binding in rat brain to alpha-2 adrenoceptors to evaluate [11C]yohimbine as an in vivo marker of noradrenergic neurotransmission and to examine its sensitivity to the level of noradrenaline. Dual [11C]yohimbine dynamic positron emission tomography (PET) recordings were applied to five Sprague Dawley rats at baseline, followed by acute amphetamine administration (2 mg/kg) to induce elevation of the endogenous level of noradrenaline. The volume of distribution ( VT) of [11C]yohimbine was obtained using Logan plot with arterial plasma input. Because alpha-2 adrenoceptors are distributed throughout the brain, the estimation of the BPND is complicated by the absence of an anatomic region of no displaceable binding. We used the Inhibition plot to acquire the reference volume, VND, from which we calculated the BPND. Acute pharmacological challenge with amphetamine induced a significant decline of [11C]yohimbine BPND of ∼38% in all volumes of interest. The BPND was greatest in the thalamus and striatum, followed in descending order by, frontal cortex, pons, and cerebellum. The experimental data demonstrate that [11C]yohimbine binding is sensitive to a challenge known to increase the extracellular level of noradrenaline, which can benefit future PET investigations of pathologic conditions related to disrupted noradrenergic neurotransmission.

scholarly journals Initial Cerebral HM-PAO Distribution Compared to LCBF: Use of a Model Which Considers Cerebral HM-PAO Trapping Kinetics

1988 ◽  
Vol 8 (1_suppl) ◽  
pp. S31-S37 ◽  
Author(s):  
James L. Lear
Keyword(s):  
Arterial Input Function ◽  
Input Function ◽  
Brain Regions ◽  
Male Rats ◽  
Type Model ◽  
Emission Computed Tomography ◽  
Intravenous Injections ◽  
Positron Emission ◽  
Uptake Pattern ◽  
The Brain

The cerebral uptake of [99mTc]– d,l-hexamethylpropyleneamine oxime complex (HM-PAO) was compared to LCBF determined simultaneously with [14C]iodoantipyrine (IAP) using double radionuclide quantitative digital autoradiography. Awake male rats were given intravenous injections of a mixture of 50 μCi IAP and 15 mCi of HM-PAO and killed 20 s after tracer activity had first reached the brain. Two separate autoradiograms were produced from each 20 μm brain section. The autoradiograms were digitized, corrected for cross-contamination, and then converted into images of individual tracer concentration. The diffusible tracer model was used to convert the IAP concentration images into LCBF images. Regional HM-PAO concentration was found not to be linearly related to LCBF as determined with the IAP, and therefore a simple microsphere type model was inadequate in relating HM-PAO uptake to LCBF. A better HM-PAO uptake–LCBF correlation was obtained when the HM-PAO arterial input function was corrected for very rapidly produced, non-cerebrally extracted, metabolites and a kinetic model was used that considered the rate of intracerebral metabolism of HM-PAO to a retained metabolite. Even using this model, however, some differences between HM-PAO uptake and LCBF occurred in certain brain regions. Because these differences were small and the HM-PAO uptake pattern has been shown to be constant for many minutes, HM-PAO can probably be used to estimate LCBF in patients with single positron emission computed tomography (SPECT) imaging.

scholarly journals Reference Region Modeling Approaches for Amphetamine Challenge Studies with [11C]FLB 457 and PET

2015 ◽  
Vol 35 (4) ◽  
pp. 623-629 ◽  
Author(s):  
Christine M Sandiego ◽  
Jean-Dominique Gallezot ◽  
Keunpoong Lim ◽  
Jim Ropchan ◽  
Shu-fei Lin ◽  
...  
Keyword(s):  
Arterial Input Function ◽  
Input Function ◽  
Brain Regions ◽  
Reference Region ◽  
Reference Tissue ◽  
Modeling Approaches ◽  
Positron Emission ◽  
Dopaminergic Dysfunction ◽  
Induced Changes ◽  
Tissue Models

Detecting fluctuations in synaptic dopamine levels in extrastriatal brain regions with [11C]FLB 457 and positron emission tomography (PET) is a valuable tool for studying dopaminergic dysfunction in psychiatric disorders. The evaluation of reference region modeling approaches would eliminate the need to obtain arterial input function data. Our goal was to explore the use of reference region models to estimate amphetamine-induced changes in [11C]FLB 457 dopamine D2/D3 binding. Six healthy tobacco smokers were imaged with [11C]FLB 457 at baseline and at 3 hours after amphetamine (0.4  to 0.5 mg/kg, per os) administration. Simplified reference tissue models, SRTM and SRTM2, were evaluated against the 2-tissue compartmental model (2TC) to estimate [11C]FLB 457 binding in extrastriatal regions of interest (ROIs), using the cerebellum as a reference region. No changes in distribution volume were observed in the cerebellum between scan conditions. SRTM and SRTM2 underestimated binding, compared with 2TC, in ROIs by 26% and 9%, respectively, with consistent bias between the baseline and postamphetamine scans. Postamphetamine, [11C]FLB 457 binding significantly decreased across several brain regions as measured with SRTM and SRTM2; no significant change was detected with 2TC. These data support the sensitivity of [11C]FLB 457 for measuring amphetamine-induced dopamine release in extrastriatal regions with SRTM and SRTM2.

scholarly journals Towards quantitative [18F]FDG-PET/MRI of the brain: Automated MR-driven calculation of an image-derived input function for the non-invasive determination of cerebral glucose metabolic rates

2018 ◽  
Vol 39 (8) ◽  
pp. 1516-1530 ◽  
Author(s):  
Lalith KS Sundar ◽  
Otto Muzik ◽  
Lucas Rischka ◽  
Andreas Hahn ◽  
Ivo Rausch ◽  
...  
Keyword(s):  
Fdg Pet ◽  
Arterial Input Function ◽  
Area Under The Curve ◽  
Input Function ◽  
Absolute Quantification ◽  
Brain Regions ◽  
Metabolic Rates ◽  
Imaging Protocol ◽  
Percentage Difference ◽  
18F Fdg

Absolute quantification of PET brain imaging requires the measurement of an arterial input function (AIF), typically obtained invasively via an arterial cannulation. We present an approach to automatically calculate an image-derived input function (IDIF) and cerebral metabolic rates of glucose (CMRGlc) from the [18F]FDG PET data using an integrated PET/MRI system. Ten healthy controls underwent test–retest dynamic [18F]FDG-PET/MRI examinations. The imaging protocol consisted of a 60-min PET list-mode acquisition together with a time-of-flight MR angiography scan for segmenting the carotid arteries and intermittent MR navigators to monitor subject movement. AIFs were collected as the reference standard. Attenuation correction was performed using a separate low-dose CT scan. Assessment of the percentage difference between area-under-the-curve of IDIF and AIF yielded values within ±5%. Similar test–retest variability was seen between AIFs (9 ± 8) % and the IDIFs (9 ± 7) %. Absolute percentage difference between CMRGlc values obtained from AIF and IDIF across all examinations and selected brain regions was 3.2% (interquartile range: (2.4–4.3) %, maximum < 10%). High test–retest intravariability was observed between CMRGlc values obtained from AIF (14%) and IDIF (17%). The proposed approach provides an IDIF, which can be effectively used in lieu of AIF.

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