scholarly journals Reproducibility of Striatal and Thalamic Dopamine D2 Receptor Binding Using [11C]raclopride with High-Resolution Positron Emission Tomography

2010 ◽  
Vol 31 (1) ◽  
pp. 155-165 ◽  
Author(s):  
Kati Alakurtti ◽  
Sargo Aalto ◽  
Jarkko J Johansson ◽  
Kjell Någren ◽  
Terhi Tuokkola ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
High Resolution ◽  
Spatial Resolution ◽  
Receptor Binding ◽  
Dopamine D2 Receptor ◽  
Intraclass Correlation ◽  
Emission Tomography ◽  
Binding Potential ◽  
Reference Tissue ◽  
Positron Emission

Positron emission tomography (PET) imaging of small striatal brain structures such as the ventral striatum (VST) has been hampered by low spatial resolution causing partial-volume effects. The high-resolution research tomograph (HRRT) is a brain-dedicated PET scanner that has considerably better spatial resolution than its predecessors. However, its superior spatial resolution is associated with a lower signal-to-noise ratio. We evaluated the test–retest reliability of the striatal and thalamic dopamine D2 receptor binding using the HRRT scanner. Seven healthy male volunteers underwent two [11C]raclopride PET scans with a 2.5-hour interval. Dopamine D2 receptor availability was quantified as binding potential (BPND) using the simplified reference tissue model. To evaluate the reproducibility of repeated BPND estimations, absolute variability (VAR) and intraclass correlation coefficients (ICCs) were calculated. VAR values indicated fairly good reproducibility and were 3.6% to 4.5% for the caudate nucleus and putamen and 4.5% to 6.4% for the lateral and medial part of the thalamus. In the VST, the VAR value was 5.8% when the definition was made in the coronal plane. However, the ICC values were only moderate, in the range of 0.34 to 0.66, for all regions except the putamen (0.87). Experimental signal processing methods improved neither ICC nor VAR values significantly.

scholarly journals Imaging Human Mesolimbic Dopamine Transmission with Positron Emission Tomography: I. Accuracy and Precision of D2 Receptor Parameter Measurements in Ventral Striatum

2001 ◽  
Vol 21 (9) ◽  
pp. 1034-1057 ◽  
Author(s):  
Osama Mawlawi ◽  
Diana Martinez ◽  
Mark Slifstein ◽  
Allegra Broft ◽  
Rano Chatterjee ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
High Resolution ◽  
Ventral Striatum ◽  
Critical Role ◽  
Intraclass Correlation ◽  
Emission Tomography ◽  
Binding Potential ◽  
Positron Emission ◽  
Accuracy And Precision ◽  
Dopamine Transmission

Dopamine transmission in the ventral striatum (VST), a structure which includes the nucleus accumbens, ventral caudate, and ventral putamen, plays a critical role in the pathophysiology of psychotic states and in the reinforcing effects of virtually all drugs of abuse. The aim of this study was to assess the accuracy and precision of measurements of D2 receptor availability in the VST obtained with positron emission tomography on the high-resolution ECAT EXACT HR+ scanner (Siemens Medical Systems, Knoxville, TN, U.S.A.). A method was developed for identification of the boundaries of the VST on coregistered high-resolution magnetic resonance imaging scans. Specific-to-nonspecific partition coefficient (V3″) and binding potential (BP) of [11C]raclopride were measured twice in 10 subjects, using the bolus plus constant infusion method. [11C]Raclopride V3″ in the VST (1.86 ± 0.29) was significantly lower than in the dorsal caudate (DCA, 2.33 ± 0.28) and dorsal putamen (DPU, 2.99 ± 0.26), an observation consistent with postmortem studies. The reproducibility of V3″ and BP were appropriate and similar in VST (V3″ test–retest variability of 8.2% ± 6.2%, intraclass correlation coefficient = 0.83), DCA (7.7% ± 5.1%, 0.77), DPU (6.0% ± 4.1%, 0.71), and striatum as a whole (6.3% ± 4.1%, 0.78). Partial volume effects analysis revealed that activities in the VST were significantly contaminated by counts spilling over from the adjacent DCA and DPU: 70% ± 5% of the specific binding measured in the VST originated from D2 receptors located in the VST, whereas 12% ± 3% and 18% ± 3% were contributed by D2 receptors in the DCA and DPU, respectively. Thus, accuracy of D2 receptor measurement is improved by correction for partial voluming effects. The demonstration of an appropriate accuracy and precision of D2 receptor measurement with [11C]raclopride in the VST is the first critical step toward the use of this ligand in the study of synaptic dopamine transmission at D2 receptors in the VST using endogenous competition techniques.

scholarly journals Long-Term Test–Retest Reliability of Striatal and Extrastriatal Dopamine D2/3 Receptor Binding: Study with [11C]Raclopride and High-Resolution PET

2015 ◽  
Vol 35 (7) ◽  
pp. 1199-1205 ◽  
Author(s):  
Kati Alakurtti ◽  
Jarkko J Johansson ◽  
Juho Joutsa ◽  
Matti Laine ◽  
Lars Bäckman ◽  
...  
Keyword(s):  
High Resolution ◽  
Intraclass Correlation ◽  
Binding Potential ◽  
Reference Tissue ◽  
Retest Reliability ◽  
Positron Emission ◽  
Simplified Reference Tissue Model ◽  
Test Retest Reliability

We measured the long-term test–retest reliability of [11C]raclopride binding in striatal subregions, the thalamus and the cortex using the bolus-plus-infusion method and a high-resolution positron emission scanner. Seven healthy male volunteers underwent two positron emission tomography (PET) [11C]raclopride assessments, with a 5-week retest interval. D2/3 receptor availability was quantified as binding potential using the simplified reference tissue model. Absolute variability (VAR) and intraclass correlation coefficient (ICC) values indicated very good reproducibility for the striatum and were 4.5%/0.82, 3.9%/0.83, and 3.9%/0.82, for the caudate nucleus, putamen, and ventral striatum, respectively. Thalamic reliability was also very good, with VAR of 3.7% and ICC of 0.92. Test-retest data for cortical areas showed good to moderate reproducibility (6.1% to 13.1%). Our results are in line with previous test–retest studies of [11C]raclopride binding in the striatum. A novel finding is the relatively low variability of [11C]raclopride binding, providing suggestive evidence that extrastriatal D2/3 binding can be studied in vivo with [11C]raclopride PET to be verified in future studies.

A Double-Injection Technique for in vivo Measurement of Dopamine D2-Receptor Density in Monkeys with 3-(2'-[18F] Fluoroethyl)Spiperone and Dynamic Positron Emission Tomography

1989 ◽  
Vol 9 (6) ◽  
pp. 850-858 ◽  
Author(s):  
Sung-Cheng Huang ◽  
Mark M. Bahn ◽  
Jorge R. Barrio ◽  
John M. Hoffman ◽  
Nagichettiar Satyamurthy ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Receptor Binding ◽  
Dopamine D2 Receptor ◽  
D2 Receptor ◽  
Emission Tomography ◽  
Injection Technique ◽  
Receptor Density ◽  
Dopamine D2 ◽  
Positron Emission ◽  
Kinetics Of

Dopamine D2-receptor density in striatum of monkey was measured with 3-(2'-[18F]fluoroethyl)spiperone (FESP) and dynamic positron emission tomography (PET), using a double-injection technique. A first bolus of high specific activity (SA) FESP (5 mCi; ≃ 1 Ci/μmol) was injected i.v.; 90 min later, a second bolus of lower SA FESP (5 mCi; ≃ 0.04 Ci/μmol) was injected. A dynamic PET study was performed to measure the kinetics of FESP in striatum over 180 min, and the metabolite-corrected concentration of FESP in plasma as a function of time was obtained from arterial blood samples. A nonlinear compartmental model that took into account the saturability of the receptor binding was used to describe the kinetics of FESP in striatum. Model parameters were estimated by regression with a constraint based on information about the equilibrium dissociation constant of the ligand–receptor binding. Dopamine D2-receptor density in striatum was estimated to be 25.9 ± 12.7 pmol/g in seven Macaca nemestrina monkeys. The method does not require the use of cerebellum as a reference tissue region and an estimate of dopamine D2-receptor density can be obtained from a single study.

Positron emission tomography inter-scanner differences in dopamine D2 receptor binding measured with [11C]FLB457

2010 ◽  
Vol 24 (9) ◽  
pp. 671-677 ◽  
Author(s):  
Fumitoshi Kodaka ◽  
Hiroshi Ito ◽  
Miho Shidahara ◽  
Harumasa Takano ◽  
Hidehiko Takahashi ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Receptor Binding ◽  
Dopamine D2 Receptor ◽  
D2 Receptor ◽  
Emission Tomography ◽  
Dopamine D2 ◽  
Positron Emission

scholarly journals Kinetic Modeling of the Serotonin 5-HT1B Receptor Radioligand [11C]P943 in Humans

2009 ◽  
Vol 30 (1) ◽  
pp. 196-210 ◽  
Author(s):  
Jean-Dominique Gallezot ◽  
Nabeel Nabulsi ◽  
Alexander Neumeister ◽  
Beata Planeta-Wilson ◽  
Wendol A Williams ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Arterial Input Function ◽  
Human Subjects ◽  
Emission Tomography ◽  
Binding Potential ◽  
Noninvasive Methods ◽  
Reference Tissue ◽  
Positron Emission ◽  
Tissue Models

[11C]P943 is a new radioligand recently developed to image and quantify serotonin 5-Hydroxytryptamine (5-HT1B) receptors with positron emission tomography (PET). The purpose of this study was to evaluate [11C]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. Using arterial input functions, compartmental modeling, the Logan graphical analysis, and the multilinear method MA1 were tested. Both the two tissue-compartment model and MA1 provided good fits of the PET data and reliable distribution volume estimates. Using the cerebellum as a reference region, BPND binding potential estimates were computed. [11C]P943 BPND estimates were significantly correlated with in vitro measurements of the density of 5-HT1B receptors, with highest values in the occipital cortex and pallidum. To evaluate noninvasive methods, two- and three-parameter graphical analyses, Simplified Reference Tissue Models (SRTM and SRTM2), and Multilinear Reference Tissue Models (MRTM and MRTM2) were tested. The MRTM2 model provided the best correlation with MA1 binding-potential estimates. Parametric images of the volume of distribution or binding potential of [11C]P943 could be computed using both MA1 and MRTM2. The results show that [11C]P943 provides quantitative measurements of 5-HT1B binding potential.

scholarly journals Linearized Reference Tissue Parametric Imaging Methods: Application to [11C]DASB Positron Emission Tomography Studies of the Serotonin Transporter in Human Brain

2003 ◽  
Vol 23 (9) ◽  
pp. 1096-1112 ◽  
Author(s):  
Masanori Ichise ◽  
Jeih-San Liow ◽  
Jian-Qiang Lu ◽  
Akihiro Takano ◽  
Kendra Model ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Human Brain ◽  
Positron Emission Tomography Imaging ◽  
Emission Tomography ◽  
Binding Potential ◽  
Parametric Imaging ◽  
Reference Tissue ◽  
Parametric Images ◽  
Positron Emission ◽  
Tissue Models

The authors developed and applied two new linearized reference tissue models for parametric images of binding potential ( BP) and relative delivery ( R1) for [11C]DASB positron emission tomography imaging of serotonin transporters in human brain. The original multilinear reference tissue model (MRTMO) was modified (MRTM) and used to estimate a clearance rate ( k′2) from the cerebellum (reference). Then, the number of parameters was reduced from three (MRTM) to two (MRTM2) by fixing k′2. The resulting BP and R1 estimates were compared with the corresponding nonlinear reference tissue models, SRTM and SRTM2, and one-tissue kinetic analysis (1TKA), for simulated and actual [11C]DASB data. MRTM gave k′2 estimates with little bias (<1%) and small variability (<6%). MRTM2 was effectively identical to SRTM2 and 1TKA, reducing BP bias markedly over MRTMO from 12–70% to 1–4% at the expense of somewhat increased variability. MRTM2 substantially reduced BP variability by a factor of two or three over MRTM or SRTM. MRTM2, SRTM2, and 1TKA had R1 bias <0.3% and variability at least a factor of two lower than MRTM or SRTM. MRTM2 allowed rapid generation of parametric images with the noise reductions consistent with the simulations. Rapid parametric imaging by MRTM2 should be a useful method for human [11C]DASB positron emission tomography studies.

scholarly journals Serotonin 1B receptor density mapping of the human brainstem using positron emission tomography and autoradiography

2021 ◽  
pp. 0271678X2110491
Author(s):  
Emma R Veldman ◽  
Andrea Varrone ◽  
Katarina Varnäs ◽  
Marie M Svedberg ◽  
Zsolt Cselényi ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Receptor Binding ◽  
Healthy Subjects ◽  
Radioligand Binding ◽  
Emission Tomography ◽  
Binding Potential ◽  
Parametric Image ◽  
Individual Subject ◽  
Density Mapping ◽  
Positron Emission

The serotonin 1B (5-HT1B) receptor has lately received considerable interest in relation to psychiatric and neurological diseases, partly due to findings based on quantification using Positron Emission Tomography (PET). Although the brainstem is an important structure in this regard, PET radioligand binding quantification in brainstem areas often shows poor reliability. This study aims to improve PET quantification of 5-HT1B receptor binding in the brainstem. Volumes of interest (VOIs) were selected based on a 3D [3H]AZ10419369 Autoradiography brainstem model, which visualized 5-HT1B receptor distribution in high resolution. Two previously developed VOI delineation methods were tested and compared to a conventional manual method. For a method based on template data, a [11C]AZ10419369 PET template was created by averaging parametric binding potential (BPND) images of 52 healthy subjects. VOIs were generated based on a predefined volume and BPND thresholding and subsequently applied to test-retest [11C]AZ10419369 parametric BPND images of 8 healthy subjects. For a method based on individual subject data, VOIs were generated directly on each individual parametric image. Both methods showed improved reliability compared to a conventional manual VOI. The VOIs created with [11C]AZ10419369 template data can be automatically applied to future PET studies measuring 5-HT1B receptor binding in the brainstem.

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