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 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.

Cortical grey matter reductions associated with treatment-resistant chronic unipolar depression

1998 ◽  
Vol 172 (6) ◽  
pp. 527-532 ◽  
Author(s):  
Premal J. Shah ◽  
Klaus P. Ebmeier ◽  
Michael F. Glabus ◽  
Guy M. Goodwin
Keyword(s):  
Major Depression ◽  
Magnetic Resonance ◽  
Verbal Memory ◽  
Grey Matter ◽  
Temporal Cortex ◽  
Unipolar Depression ◽  
Magnetic Resonance Images ◽  
Matter Density ◽  
Treatment Resistant ◽  
Grey Matter Density

BackgroundThe aetiology of treatment-resistant major depression is little understood; its apparent intractability may reflect brain abnormality.MethodMagnetic resonance images of the brains of 20 subjects with major depression lasting for two years or more were compared with 20 healthy control subjects and 20 other subjects who had completely recovered from depression. Subjects were individually matched for age, gender, years of education and premorbid IQ. Grey matter was segmented from the images, and compared between groups on a voxel-by-voxel basis.ResultsSubjects with chronic depression showed reduced grey matter density in the left temporal cortex including the hippocampus. There was also a trend for reduction in the right hippocampus. Left hippocampal grey matter density was correlated with measures of verbal memory, supporting the functional significance of the observed magnetic resonance imaging changes.ConclusionsOur results potentially challenge the accepted view of depression as a functional and fully reversible illness, implying instead that more permanent brain changes may be associated with chronicity. Confirmatory longitudinal and prospective studies are required to determine whether these differences pre-date the onset of depression or are the result of the chronic illness process or its treatment.

scholarly journals Kinetics and 28-day test–retest repeatability and reproducibility of [11C]UCB-J PET brain imaging

2020 ◽  
pp. 0271678X2096424
Author(s):  
Hayel Tuncel ◽  
Ronald Boellaard ◽  
Emma M Coomans ◽  
Erik FJ de Vries ◽  
Andor WJM Glaudemans ◽  
...  
Keyword(s):  
Grey Matter ◽  
Volume Of Distribution ◽  
Reference Tissue ◽  
Positron Emission ◽  
Tracer Kinetic ◽  
Repeatability And Reproducibility ◽  
Simplified Reference Tissue Model ◽  
Tissue Models ◽  
Pet Scans ◽  
Brain Positron Emission Tomography

[11C]UCB-J is a novel radioligand that binds to synaptic vesicle glycoprotein 2A (SV2A). The main objective of this study was to determine the 28-day test–retest repeatability (TRT) of quantitative [11C]UCB-J brain positron emission tomography (PET) imaging in Alzheimer’s disease (AD) patients and healthy controls (HCs). Nine HCs and eight AD patients underwent two 60 min dynamic [11C]UCB-J PET scans with arterial sampling with an interval of 28 days. The optimal tracer kinetic model was assessed using the Akaike criteria (AIC). Micro-/macro-parameters such as tracer delivery (K1) and volume of distribution (VT) were estimated using the optimal model. Data were also analysed for simplified reference tissue model (SRTM) with centrum semi-ovale (white matter) as reference region. Based on AIC, both 1T2k_VB and 2T4k_VB described the [11C]UCB-J kinetics equally well. Analysis showed that whole-brain grey matter TRT for VT, DVR and SRTM BPND were –2.2% ± 8.5, 0.4% ± 12.0 and –8.0% ± 10.2, averaged over all subjects. [11C]UCB-J kinetics can be well described by a 1T2k_VB model, and a 60 min scan duration was sufficient to obtain reliable estimates for both plasma input and reference tissue models. TRT for VT, DVR and BPND was <15% (1SD) averaged over all subjects and indicates adequate quantitative repeatability of [11C]UCB-J PET.

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.

scholarly journals The applicability of SRTM in [18F]fallypride PET investigations: Impact of scan durations

2011 ◽  
Vol 31 (9) ◽  
pp. 1958-1966 ◽  
Author(s):  
Ingo Vernaleken ◽  
Lisa Peters ◽  
Mardjan Raptis ◽  
Robert Lin ◽  
Hans-Georg Buchholz ◽  
...  
Keyword(s):  
Temporal Cortex ◽  
Receptor Occupancy ◽  
Binding Potential ◽  
Reference Tissue ◽  
Scan Time ◽  
Positron Emission ◽  
Simplified Reference Tissue Model ◽  
Pet Scans ◽  
Drug Free ◽  
Time Point

The high-affinity radioligand [18F]fallypride (FP) is frequently used for quantification of striatal/extrastriatal D2/3 receptors and the receptor occupancies of antipsychotics (APs). Its 110 minutes half-life allows long scan durations. However, the optimum scan duration is a matter of debate. This investigation focuses on scan-duration-related effects on simplified reference tissue model (SRTM) results and the time point of transient equilibrium in a large sample of dynamic FP positron emission tomography (PET) scans. Fifty drug-free and 50 AP-treated subjects underwent FP-PET scans (180 minutes scan duration). The binding potential ( BPND) of the putamen, thalamus, and temporal cortex were calculated using the SRTM and the transient equilibrium model. Furthermore, receptor occupancies were calculated for AP-treated patients. Transient equilibrium in the unblocked putamen occurred after 121 ± 29.6 minutes. The transient equilibrium occurred much earlier in the extrastriatal regions or under AP treatment. Stepwise scan shortening caused BPND under-estimations of 0.58% for the first 10-minute reduction (putamen, SRTM), finally reaching 5.76% after 1 hour scan-time reduction. We observed preferential extrastriatal AP binding irrespective of the analytical method. [18F]fallypride scan durations of 180 minutes reliably reach equilibrium even in D2/3-receptor-rich regions. Moderate reductions in FP scan durations only caused small changes to SRTM results even in receptor-rich regions. Apparently, the D2/3 receptor occupancy results of APs, especially preferential extrastriatal binding observations, are not relevantly biased by inappropriate scan durations.

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

NeuroImage ◽  
2021 ◽  
pp. 117968
Author(s):  
Sandra Manninen ◽  
Tomi Karjalainen ◽  
Lauri J. Tuominen ◽  
Jarmo Hietala ◽  
Valtteri Kaasinen ◽  
...  
Keyword(s):  
Grey Matter ◽  
Matter Density ◽  
Grey Matter Density ◽  
Cerebral Grey Matter ◽  
Mri Study

scholarly journals The Simplified Reference Tissue Model: Model Assumption Violations and Their Impact on Binding Potential

2014 ◽  
Vol 35 (2) ◽  
pp. 304-311 ◽  
Author(s):  
Cristian A Salinas ◽  
Graham E Searle ◽  
Roger N Gunn
Keyword(s):  
Input Function ◽  
Binding Potential ◽  
Model Assumption ◽  
Reference Tissue ◽  
Tissue Model ◽  
Positron Emission ◽  
Assumption Violations ◽  
Quantitative Accuracy ◽  
Reference Tissue Model ◽  
Simplified Reference Tissue Model

Reference tissue models have gained significant traction over the last two decades as the methods of choice for the quantification of brain positron emission tomography data because they balance quantitative accuracy with less invasive procedures. The principal advantage is the elimination of the need to perform arterial cannulation of the subject to measure blood and metabolite concentrations for input function generation. In particular, the simplified reference tissue model (SRTM) has been widely adopted as it uses a simplified model configuration with only three parameters that typically produces good fits to the kinetic data and a stable parameter estimation process. However, the model's simplicity and its ability to generate good fits to the data, even when the model assumptions are not met, can lead to misplaced confidence in binding potential (BPND) estimates. Computer simulation were used to study the bias introduced in BPND estimates as a consequence of violating each of the four core SRTM model assumptions. Violation of each model assumption led to bias in BPND (both over and underestimation). Careful assessment of the bias in SRTM BPND should be performed for new tracers and applications so that an appropriate decision about its applicability can be made.

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