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.

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 Cerebral grey matter density is associated with neuroreceptor and neurotransporter availability: A combined PET and MRI study

2020 ◽  
Author(s):  
Sandra Manninen ◽  
Tomi Karjalainen ◽  
Lauri J. Tuominen ◽  
Jarmo Hietala ◽  
Valtteri Kaasinen ◽  
...  
Keyword(s):  
Grey Matter ◽  
Magnetic Resonance Images ◽  
Matter Density ◽  
Binding Potential ◽  
Reference Tissue ◽  
Grey Matter Density ◽  
Positron Emission ◽  
Simplified Reference Tissue Model ◽  
Mri Study

AbstractPositron emission tomography (PET) can be used for in vivo measurement of specific neuroreceptors and transporters using radioligands, while voxel-based morphometric analysis of magnetic resonance images allows automated estimation of local grey matter densities. However, it is not known how regional neuroreceptor or transporter densities are reflected in grey matter densities. Here, we analyzed brain scans retrospectively from 325 subjects and compared grey matter density estimates with three different neuroreceptors and transporter availabilities. µ-opioid receptors (MORs) were measured with [11C]carfentanil (162 scans), dopamine D2 receptors with [11C]raclopride (91 scans) and serotonin transporters (SERT) with [11C]MADAM (72 scans). The PET data were modelled with simplified reference tissue model. Voxel-wise correlations between binding potential and grey matter density images were computed. Regional binding of all the used radiotracers was associated with grey matter density in region and ligand-specific manner independently of subjects’ age or sex. These data show that grey matter density and MOR and D2R neuroreceptor / SERT availability are correlated, with effect sizes (r2) ranging from 0.04 to 0.69. This suggests that future studies comparing PET outcome measure different groups (such as patients and controls) should take grey matter density differences between the groups into account.

scholarly journals High long-term test–retest reliability for extrastriatal 11C-raclopride binding in healthy older adults

2019 ◽  
Vol 40 (9) ◽  
pp. 1859-1868 ◽  
Author(s):  
Nina Karalija ◽  
Lars Jonassson ◽  
Jarkko Johansson ◽  
Goran Papenberg ◽  
Alireza Salami ◽  
...  
Keyword(s):  
Older Adults ◽  
Dopamine D2 Receptor ◽  
Intraclass Correlation ◽  
D2 Receptor ◽  
Binding Potential ◽  
Good Test ◽  
Retest Reliability ◽  
Healthy Older Adults ◽  
Test Retest Reliability

In vivo dopamine D2-receptor availability is frequently assessed with 11C-raclopride and positron emission tomography. Due to low signal-to-noise ratios for 11C-raclopride in areas with low D2 receptor densities, the ligand has been considered unreliable for measurements outside the dopamine-dense striatum. Intriguingly, recent studies show that extrastriatal 11C-raclopride binding potential (BPND) values are (i) reliably higher than in the cerebellum (where D2-receptor levels are negligible), (ii) correlate with behavior in the expected direction, and (iii) showed good test–retest reliability in a sample of younger adults. The present work demonstrates high seven-month test–retest reliability of striatal and extrastriatal 11C-raclopride BPND values in healthy, older adults (n = 27, age: 64–78 years). Mean 11C-raclopride BPND values were stable between test sessions in subcortical nuclei, and in frontal and temporal cortices (p > 0.05). Across all structures analyzed, intraclass correlation coefficients were high (0.85–0.96), absolute variability was low (mean: 4–8%), and coefficients of variance ranged between 9 and 25%. Furthermore, regional 11C-raclopride BPND values correlated with previously determined 18F-fallypride BPND values (ρ = 0.97 and 0.92 in correlations with and without striatal values, respectively, p < 0.01) and postmortem determined D2-receptor densities (including striatum: ρ = 0.92; p < 0.001; excluding striatum: ρ = 0.75; p = 0.067). These observations suggest that extrastriatal 11C-raclopride measurements represent a true D2 signal.

scholarly journals Imaging the Cannabinoid CB1 Receptor in Humans with [11C] OMAR: Assessment of Kinetic Analysis Methods, Test–Retest Reproducibility, and Gender Differences

2015 ◽  
Vol 35 (8) ◽  
pp. 1313-1322 ◽  
Author(s):  
Marc D Normandin ◽  
Ming-Qiang Zheng ◽  
Kuo-Shyan Lin ◽  
N Scott Mason ◽  
Shu-Fei Lin ◽  
...  
Keyword(s):  
Gender Differences ◽  
Kinetic Analysis ◽  
Human Subjects ◽  
Intraclass Correlation ◽  
Volume Of Distribution ◽  
Absolute Deviation ◽  
Retest Reliability ◽  
Analysis Methods ◽  
Test Retest Reliability

The Radiotracer [11C]OMAR was developed for positron emission tomography (PET) imaging of cannabinoid type-1 receptors (CB1R). The objectives of the present study were to evaluate kinetic analysis methods, determine test–retest reliability, and assess gender differences in receptor availability. Dynamic PET data were acquired in 10 human subjects, and analyzed with one-tissue (1T) and two-tissue (2T) compartment models and by the Logan and multilinear analysis (MA1) methods to estimate regional volume of distribution ( VT). The 2T model inclusive of a vascular component (2TV) and MA1 were the preferred techniques. Test–retest reliability of VT was good (mean absolute deviation ~ 9%; intraclass correlation coefficient ~ 0.7). Tracer parent fraction in plasma was lower in women ( P < 0.0001). Cerebral uptake normalized by body weight and injected dose was higher in men by 17% ( P < 0.0001), but VT was significantly greater in women by 23% ( P < 0.0001). These findings show that [11C]OMAR binding can be reliably quantified by the 2T model or MA1 method and demonstrate the utility of this tracer for in vivo imaging of CB1R. In addition, results from the present study indicate that gender difference in receptor binding should be taken into consideration when [11C]OMAR is used to quantify CB1R availability in neuropsychiatric disorders.

scholarly journals Quantification of [11C]PIB PET for Imaging Myelin in the Human Brain: A Test—Retest Reproducibility Study in High-Resolution Research Tomography

2015 ◽  
Vol 35 (11) ◽  
pp. 1771-1782 ◽  
Author(s):  
Mattia Veronese ◽  
Benedetta Bodini ◽  
Daniel García-Lorenzo ◽  
Marco Battaglini ◽  
Salvatore Bongarzone ◽  
...  
Keyword(s):  
High Resolution ◽  
High Reliability ◽  
Intraclass Correlation ◽  
Volume Ratio ◽  
Reference Region ◽  
Brain White Matter ◽  
Reproducibility Study ◽  
Pet Tracer ◽  
Positron Emission

An accurate in vivo measure of myelin content is essential to deepen our insight into the mechanisms underlying demyelinating and dysmyelinating neurological disorders, and to evaluate the effects of emerging remyelinating treatments. Recently [11C]PIB, a positron emission tomography (PET) tracer originally conceived as a beta-amyloid marker, has been shown to be sensitive to myelin changes in preclinical models and humans. In this work, we propose a reference-region methodology for the voxelwise quantification of brain white-matter (WM) binding for [11C]PIB. This methodology consists of a supervised procedure for the automatic extraction of a reference region and the application of the Logan graphical method to generate distribution volume ratio (DVR) maps. This approach was assessed on a test–retest group of 10 healthy volunteers using a high-resolution PET tomograph. The [11C]PIB PET tracer binding was shown to be up to 23% higher in WM compared with gray matter, depending on the image reconstruction. The DVR estimates were characterized by high reliability (outliers < 1%) and reproducibility (intraclass correlation coefficient (ICC) > 0.95). [11C]PIB parametric maps were also found to be significantly correlated ( R2 > 0.50) to mRNA expressions of the most represented proteins in the myelin sheath. On the contrary, no correlation was found between [11C]PIB imaging and nonmyelin-associated proteins.

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 The Reliability of Pharyngeal High Resolution Manometry with Impedance for Derivation of Measures of Swallowing Function in Healthy Volunteers

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Taher I. Omari ◽  
Johanna Savilampi ◽  
Karmen Kokkinn ◽  
Mistyka Schar ◽  
Kristin Lamvik ◽  
...  
Keyword(s):  
High Resolution ◽  
Intraclass Correlation ◽  
Correlation Coefficients ◽  
Interrater Agreement ◽  
Swallowing Function ◽  
Retest Reliability ◽  
High Resolution Manometry ◽  
Intraclass Correlation Coefficients ◽  
Test Retest Reliability ◽  
Swallow Function

Purpose. We evaluated the intra- and interrater agreement and test-retest reliability of analyst derivation of swallow function variables based on repeated high resolution manometry with impedance measurements.Methods. Five subjects swallowed10×10 mL saline on two occasions one week apart producing a database of 100 swallows. Swallows were repeat-analysed by six observers using software. Swallow variables were indicative of contractility, intrabolus pressure, and flow timing.Results. The average intraclass correlation coefficients (ICC) for intra- and interrater comparisons of all variable means showedsubstantialtoexcellentagreement (intrarater ICC 0.85–1.00; mean interrater ICC 0.77–1.00). Test-retest results were less reliable. ICC for test-retest comparisons ranged fromslighttoexcellentdepending on the class of variable. Contractility variables differed most in terms of test-retest reliability. Amongst contractility variables, UES basal pressure showedexcellenttest-retest agreement (mean ICC 0.94), measures of UES postrelaxation contractile pressure showedmoderatetosubstantialtest-retest agreement (mean Interrater ICC 0.47–0.67), and test-retest agreement of pharyngeal contractile pressure ranged fromslighttosubstantial(mean Interrater ICC 0.15–0.61).Conclusions. Test-retest reliability of HRIM measures depends on the class of variable. Measures of bolus distension pressure and flow timing appear to be more test-retest reliable than measures of contractility.

scholarly journals Quantitative Measurement of Cerebral Acetylcholinesterase Using [11C]physostigmine and Positron Emission Tomography

2001 ◽  
Vol 21 (2) ◽  
pp. 114-131 ◽  
Author(s):  
Gunnar Blomqvist ◽  
Bertrand Tavitian ◽  
Sabina Pappata ◽  
Christian Crouzel ◽  
Antoinette Jobert ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
White Matter ◽  
Good Description ◽  
Acetylcholinesterase Inhibitor ◽  
Emission Tomography ◽  
Late Time ◽  
Reference Tissue ◽  
Positron Emission ◽  
Simplified Reference Tissue Model

[11C]physostigmine, an acetylcholinesterase inhibitor, has been shown to be a promising positron emission tomography ligand to quantify the cerebral concentration of the enzyme in animals and humans in vivo. Here, a quantitative and noninvasive method to measure the regional acetylcholinesterase concentration in the brain is presented. The method is based on the observation that the ratio between regions rich in acetylcholinesterase and white matter, a region almost entirely deprived of this enzyme, was found to become approximately constant after 20 to 30 minutes, suggesting that at late time points the uptake mainly contains information about the distribution volume. Taking the white matter as the reference region, a simplified reference tissue model, with effectively one reversible tissue compartment and three parameters, was found to give a good description of the data in baboons. One of these parameters, the ratio between the total distribution volumes in the target and reference regions, showed a satisfactory correlation with the acetylcholinesterase concentration measured postmortem in two baboon brains. Eight healthy male subjects were also analyzed and the regional enzyme concentrations obtained again showed a good correlation with the known acetylcholinesterase concentrations measured in postmortem studies of human brain.

scholarly journals Quantification of [11C]Ro15-4513 GABAAα5 specific binding and regional selectivity in humans

2016 ◽  
Vol 37 (6) ◽  
pp. 2137-2148 ◽  
Author(s):  
Jim FM Myers ◽  
Robert A Comley ◽  
Roger N Gunn
Keyword(s):  
Compartmental Model ◽  
Specific Binding ◽  
Receptor Subtype ◽  
Reference Tissue ◽  
Positron Emission ◽  
Negative Allosteric Modulator ◽  
Band Pass ◽  
Simplified Reference Tissue Model ◽  
Regional Selectivity

[11C]Ro15-4513 has been introduced as a positron emission tomography radioligand to image the GABAAα5 receptor subtype thought to be important in learning, memory and addiction. However, the in vivo selectivity of the ligand remains unknown and a full assessment of different analysis approaches has yet to be performed. Using human heterologous competition data, with [11C]Ro15-4513 and the highly selective GABAAα5 selective negative allosteric modulator Basmisanil (RG1662), we quantify the GABAAα5 selectivity of [11C]Ro15-4513, assess the validity of reference tissues and evaluate the performance of four different kinetic analysis methods. The results show that [11C]Ro15-4513 has high but not complete selectivity for GABAAα5, with α5 representing around 60–70% of the specific binding in α5 rich regions. Competition data indicate that the cerebellum and pons are essentially devoid of α5 signal and might be used as reference regions under certain conditions. Off-target non-selective binding to other GABAA subtypes means that the choice of analysis method and the interpretation of outcome measures must be considered carefully. We discuss the merits of two tissue compartmental model analyses to derive both VT and VS, band-pass spectral analysis for estimation of [Formula: see text] and the simplified reference tissue model for estimation of [Formula: see text].

scholarly journals Optimization of Supervised Cluster Analysis for Extracting Reference Tissue Input Curves in (R)-[11C]PK11195 Brain PET Studies

2012 ◽  
Vol 32 (8) ◽  
pp. 1600-1608 ◽  
Author(s):  
Maqsood Yaqub ◽  
Bart NM van Berckel ◽  
Alie Schuitemaker ◽  
Rainer Hinz ◽  
Federico E Turkheimer ◽  
...  
Keyword(s):  
Cluster Analysis ◽  
Binding Potential ◽  
Reference Tissue ◽  
Time Activity ◽  
Positron Emission ◽  
Lower Blood ◽  
Activity Curve ◽  
Simplified Reference Tissue Model ◽  
Significant Concentration ◽  
Brain Positron Emission Tomography

Performance of two supervised cluster analysis (SVCA) algorithms for extracting reference tissue curves was evaluated to improve quantification of dynamic (R)-[11C]PK11195 brain positron emission tomography (PET) studies. Reference tissues were extracted from images using both a manually defined cerebellum and SVCA algorithms based on either four (SVCA4) or six (SVCA6) kinetic classes. Data from controls, mild cognitive impairment patients, and patients with Alzheimer's disease were analyzed using various kinetic models including plasma input, the simplified reference tissue model (RPM) and RPM with vascular correction (RPM V b). In all subject groups, SVCA-based reference tissue curves showed lower blood volume fractions ( V b) and volume of distributions than those based on cerebellum time-activity curve. Probably resulting from the presence of specific signal from the vessel walls that contains in normal condition a significant concentration of the 18 kDa translocation protein. Best contrast between subject groups was seen using SVCA4-based reference tissues as the result of a lower number of kinetic classes and the prior removal of extracerebral tissues. In addition, incorporation of V b in RPM improved both parametric images and binding potential contrast between groups. Incorporation of V b within RPM, together with SVCA4, appears to be the method of choice for analyzing cerebral (R)-[11C]PK11195 neurodegeneration studies.

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