PET Brain Imaging Methodologies

2017 ◽  
Author(s):  
Ansel T. Hillmer ◽  
Kelly P. Cosgrove ◽  
Richard E. Carson
Keyword(s):  
Molecular Imaging ◽  
Brain Imaging ◽  
Volume Of Distribution ◽  
Group Differences ◽  
Binding Potential ◽  
Imaging Data ◽  
Imaging Studies ◽  
Standard Data ◽  
Positron Emission ◽  
Methodological Considerations

While quantitative and pharmacologically specific aspects distinguish molecular imaging, they also impose the need for considerable expertise to design, conduct, and analyze molecular imaging studies. Positron emission tomography (PET) brain imaging provides a powerful noninvasive tool for quantitative and pharmacologically specific clinical research. This chapter describes basic methodological considerations for PET brain imaging studies. First the physiological interpretation of the most common outcome measures of binding potential (BPND) and volume of distribution (VT) are described. Next, aspects of acquisition of PET imaging data and blood measurements for analysis are discussed, followed by a summary of standard data analysis techniques. Finally, various applications for the study of mental illness, including group differences, measurements of drug occupancy, and assay of acute neurotransmitter release are discussed.

scholarly journals Quantification of Ligand PET Studies using a Reference Region with a Displaceable Fraction: Application to Occupancy Studies with [11C]-DASB as an Example

2011 ◽  
Vol 32 (1) ◽  
pp. 70-80 ◽  
Author(s):  
Federico E Turkheimer ◽  
Sudhakar Selvaraj ◽  
Rainer Hinz ◽  
Venkatesha Murthy ◽  
Zubin Bhagwagar ◽  
...  
Keyword(s):  
Specific Binding ◽  
Normal Subjects ◽  
Volume Of Distribution ◽  
Binding Potential ◽  
Accurate Estimation ◽  
Data Sets ◽  
Reference Region ◽  
Reference Tissue ◽  
Positron Emission ◽  
Definition Of

This paper aims to build novel methodology for the use of a reference region with specific binding for the quantification of brain studies with radioligands and positron emission tomography (PET). In particular: (1) we introduce a definition of binding potential BPD = DVR–1 where DVR is the volume of distribution relative to a reference tissue that contains ligand in specifically bound form, (2) we validate a numerical methodology, rank-shaping regularization of exponential spectral analysis (RS-ESA), for the calculation of BPD that can cope with a reference region with specific bound ligand, (3) we demonstrate the use of RS-ESA for the accurate estimation of drug occupancies with the use of correction factors to account for the specific binding in the reference. [11C]-DASB with cerebellum as a reference was chosen as an example to validate the methodology. Two data sets were used; four normal subjects scanned after infusion of citalopram or placebo and further six test—retest data sets. In the drug occupancy study, the use of RS-ESA with cerebellar input plus corrections produced estimates of occupancy very close the ones obtained with plasma input. Test-retest results demonstrated a tight linear relationship between BPD calculated either with plasma or with a reference input and high reproducibility.

scholarly journals No Evidence for Additional Blood–Brain Barrier P-Glycoprotein Dysfunction in Alzheimer's Disease Patients with Microbleeds

2012 ◽  
Vol 32 (8) ◽  
pp. 1468-1471 ◽  
Author(s):  
Daniëlle ME van Assema ◽  
Jeroen DC Goos ◽  
Wiesje M van der Flier ◽  
Mark Lubberink ◽  
Ronald Boellaard ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Blood Brain Barrier ◽  
Volume Of Distribution ◽  
Brain Barrier ◽  
Binding Potential ◽  
Amyloid Angiopathy ◽  
P Glycoprotein ◽  
Blood Brain ◽  
Positron Emission

Decreased blood–brain barrier P-glycoprotein (Pgp) function has been shown in Alzheimer's disease (AD) patients using positron emission tomography (PET) with the radiotracer ( R)-[11C]verapamil. Decreased Pgp function has also been hypothesized to promote cerebral amyloid angiopathy (CAA) development. Here, we used PET and ( R)-[11C]verapamil to assess Pgp function in eighteen AD patients, of which six had microbleeds (MBs), presumably reflecting underlying CAA. No differences were found in binding potential and nonspecific volume of distribution of ( R)-[11C]verapamil between patient groups. These results provide no evidence for additional Pgp dysfunction in AD patients with MBs.

scholarly journals Higher HbA1c levels associate with lower hippocampal serotonin transporter availability in non-diabetic adults with obesity

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Rico Grundmann ◽  
Michael Rullmann ◽  
Julia Luthardt ◽  
Franziska Zientek ◽  
Georg-Alexander Becker ◽  
...  
Keyword(s):  
Glycosylated Hemoglobin ◽  
Binding Potential ◽  
Imaging Data ◽  
Appetite Control ◽  
High Blood Glucose ◽  
Glucose Levels ◽  
Positron Emission ◽  
The Right ◽  
Hba1c Levels

AbstractThe current study aimed to investigate whether the in vivo availability of central serotonin reuptake transporters (5-HTT) is associated with plasma levels of glycosylated hemoglobin (HbA1c) in non-diabetic humans with obesity. 5-HTT availability was measured by using positron emission tomography (PET) imaging with the 5-HTT selective radiotracer [11C]DASB in 23 non-diabetic individuals with obesity and 14 healthy, non-obesity controls. Parametric images of binding potential BPND were generated from the PET data and analyzed together with HbA1c levels by using volume of interest analysis for brain areas relevant to appetite control. Voxel-based morphometry (VBM) of individual magnetic resonance imaging data was further performed to correlate grey matter density (GMD) maps with HbA1c. We found significant negative correlations between HbA1c levels and BPND in right and left hippocampus in obesity (r = − 0.717, p < 0.001, and r = − 0.557, p = 0.006, respectively). VBM analyses revealed that higher HbA1c levels were associated with GMD in the right para-hippocampal area. Our results indicate that chronically high blood glucose levels may evoke changes in hippocampal 5-HTT levels that are in part tied to local microstructure.

Functional Magnetic Resonance Imaging and Spectroscopic Imaging of the Brain: Application of fmri and fmrs to Reading Disabilities and Education

2001 ◽  
Vol 24 (3) ◽  
pp. 189-203 ◽  
Author(s):  
Todd L. Richards
Keyword(s):  
Brain Imaging ◽  
Reading Disabilities ◽  
Imaging Techniques ◽  
Brain Activity ◽  
Diffusion Imaging ◽  
Functional Brain Imaging ◽  
Imaging Studies ◽  
Functional Brain ◽  
Positron Emission ◽  
Mr Diffusion

This tutorial/review covers functional brain-imaging methods and results used to study language and reading disabilities. Although the main focus is on functional MRI and functional MR spectroscopy, other imaging techniques are discussed briefly such as positron emission tomography (PET), electroencephalography (EEG), magnetoencepholography (MEG), and MR diffusion imaging. These functional brain-imaging studies have demonstrated that dyslexia is a brain-based disorder and that serial imaging studies can be used to study the effect of treatment on functional brain activity.

scholarly journals [11C]Befloxatone Distribution is well Correlated to Monoamine Oxidase a Protein Levels in the Human Brain

2014 ◽  
Vol 34 (12) ◽  
pp. 1951-1952 ◽  
Author(s):  
Paolo Zanotti-Fregonara ◽  
Michel Bottlaender
Keyword(s):  
Monoamine Oxidase ◽  
Human Brain ◽  
Volume Of Distribution ◽  
Monoamine Oxidase A ◽  
Binding Potential ◽  
Poor Correlation ◽  
Mrna Levels ◽  
Protein Levels ◽  
Positron Emission ◽  
Mao A

[11C]befloxatone is a positron emission tomography radioligand to image monoamine oxidase A (MAO-A) in the brain, which has been used in preclinical studies and in clinical protocols. However, a recent study found that [11C]befloxatone binding potential (k3/k4) has a poor correlation with MAO-A protein levels measured in the human brain. We here show that this poor correlation only depends on the choice of the parameter when performing kinetic modeling. In particular, the total volume of distribution of [11C]befloxatone shows a tight correlation with both protein and mRNA levels of MAO-A in the human brain.

scholarly journals Improved Models for Plasma Radiometabolite Correction and their Impact on Kinetic Quantification in PET Studies

2015 ◽  
Vol 35 (9) ◽  
pp. 1462-1469 ◽  
Author(s):  
Matteo Tonietto ◽  
Mattia Veronese ◽  
Gaia Rizzo ◽  
Paolo Zanotti-Fregonara ◽  
Talakad G Lohith ◽  
...  
Keyword(s):  
Model Misspecification ◽  
Simulated Data ◽  
Input Function ◽  
Volume Of Distribution ◽  
Binding Potential ◽  
Weighted Residuals ◽  
Injection Duration ◽  
Positron Emission ◽  
Reliable Quantification ◽  
The Impact

The quantification of dynamic positron emission tomography studies performed with arterial sampling usually requires correcting the input function for the presence of radiometabolites by using a model of the plasma parent fraction (PPf). Here, we show how to include the duration of radioligand injection in the PPf model formulations to achieve a more physiologic description of the plasma measurements. This formulation (here called convoluted model) was tested on simulated data and on three datasets with different parent kinetics: [11C]NOP-1A, [11C]MePPEP, and [11C](R)-rolipram. Results showed that convoluted PPf models better described the fraction of unchanged parent in the plasma compared with standard models for all three datasets (weighted residuals sum of squares up to 25% lower). When considering the effect on tissue quantification, the overall impact on the total volume of distribution (VT) was low. However, the impact was significant and radioligand-dependent on the binding potential (BP) and the microparameters ( K1, k2, k3, and k4). Simulated data confirmed that quantification is sensitive to different degrees to PPf model misspecification. Including the injection duration allows obtaining a more accurate correction of the input function for the presence of radiometabolites and this yields a more reliable quantification of the tissue parameters.

scholarly journals Determination of [11C]PBR28 Binding Potential in vivo: A First Human TSPO Blocking Study

2014 ◽  
Vol 34 (6) ◽  
pp. 989-994 ◽  
Author(s):  
David R Owen ◽  
Qi Guo ◽  
Nicola J Kalk ◽  
Alessandro Colasanti ◽  
Dimitra Kalogiannopoulou ◽  
...  
Keyword(s):  
Volume Of Distribution ◽  
Translocator Protein ◽  
Binding Potential ◽  
Healthy Human ◽  
Positron Emission ◽  
Dose Dependent ◽  
In Vitro Data

Positron emission tomography (PET) targeting the 18 kDa translocator protein (TSPO) is used to quantify neuroinflammation. Translocator protein is expressed throughout the brain, and therefore a classical reference region approach cannot be used to estimate binding potential ( BP ND). Here, we used blockade of the TSPO radioligand [11C]PBR28 with the TSPO ligand XBD173, to determine the non-displaceable volume of distribution ( V ND), and hence estimate the BP ND. A total of 26 healthy volunteers, 16 high-affinity binders (HABs) and 10 mixed affinity binders (MABs) underwent a [11C]PBR28 PET scan with arterial sampling. Six of the HABs received oral XBD173 (10 to 90 mg), 2 hours before a repeat scan. In XBD173-dosed subjects, V ND was estimated via the occupancy plot. Values of BP ND for all subjects were calculated using this V ND estimate. Total volume of distribution ( V T) of MABs (2.94 ± 0.31) was lower than V T of HABs (4.33 ± 0.29) ( P<0.005). There was dose-dependent occupancy of TSPO by XBD173 (ED50 = 0.34 ± 0.13 mg/kg). The occupancy plot provided a V ND estimate of 1.98 (1.69, 2.26). Based on these V ND estimates, BP ND for HABs is approximately twice that of MABs, consistent with predictions from in vitro data. Our estimates of [11C]PBR28 V ND and hence BP ND in the healthy human brain are consistent with in vitro predictions. XBD173 blockade provides a practical means of estimating V ND for TSPO targeting radioligands.

scholarly journals Molecular and Functional Imaging Studies of Psychedelic Drug Action in Animals and Humans

Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2451
Author(s):  
Paul Cumming ◽  
Milan Scheidegger ◽  
Dario Dornbierer ◽  
Mikael Palner ◽  
Boris B. Quednow ◽  
...  
Keyword(s):  
Molecular Imaging ◽  
Single Photon ◽  
Ex Vivo ◽  
Specific Binding ◽  
Photon Emission ◽  
Imaging Studies ◽  
Active Metabolites ◽  
Positron Emission ◽  
Imaging Research

Hallucinogens are a loosely defined group of compounds including LSD, N,N-dimethyltryptamines, mescaline, psilocybin/psilocin, and 2,5-dimethoxy-4-methamphetamine (DOM), which can evoke intense visual and emotional experiences. We are witnessing a renaissance of research interest in hallucinogens, driven by increasing awareness of their psychotherapeutic potential. As such, we now present a narrative review of the literature on hallucinogen binding in vitro and ex vivo, and the various molecular imaging studies with positron emission tomography (PET) or single photon emission computer tomography (SPECT). In general, molecular imaging can depict the uptake and binding distribution of labelled hallucinogenic compounds or their congeners in the brain, as was shown in an early PET study with N1-([11C]-methyl)-2-bromo-LSD ([11C]-MBL); displacement with the non-radioactive competitor ketanserin confirmed that the majority of [11C]-MBL specific binding was to serotonin 5-HT2A receptors. However, interactions at serotonin 5HT1A and other classes of receptors and pleotropic effects on second messenger pathways may contribute to the particular experiential phenomenologies of LSD and other hallucinogenic compounds. Other salient aspects of hallucinogen action include permeability to the blood–brain barrier, the rates of metabolism and elimination, and the formation of active metabolites. Despite the maturation of radiochemistry and molecular imaging in recent years, there has been only a handful of PET or SPECT studies of radiolabeled hallucinogens, most recently using the 5-HT2A/2C agonist N-(2[11CH3O]-methoxybenzyl)-2,5-dimethoxy- 4-bromophenethylamine ([11C]Cimbi-36). In addition to PET studies of target engagement at neuroreceptors and transporters, there is a small number of studies on the effects of hallucinogenic compounds on cerebral perfusion ([15O]-water) or metabolism ([18F]-fluorodeoxyglucose/FDG). There remains considerable scope for basic imaging research on the sites of interaction of hallucinogens and their cerebrometabolic effects; we expect that hybrid imaging with PET in conjunction with functional magnetic resonance imaging (fMRI) should provide especially useful for the next phase of this research.

scholarly journals A Two-Compartment Description and Kinetic Procedure for Measuring Regional Cerebral [11C]Nomifensine Uptake Using Positron Emission Tomography

1990 ◽  
Vol 10 (3) ◽  
pp. 307-316 ◽  
Author(s):  
Eric Salmon ◽  
David J. Brooks ◽  
Klaus L. Leenders ◽  
David R. Turton ◽  
Sue P. Hume ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Partition Coefficient ◽  
Cell Activity ◽  
Compartment Model ◽  
Input Function ◽  
Volume Of Distribution ◽  
Red Cells ◽  
Emission Tomography ◽  
Binding Potential ◽  
Positron Emission

S-[11C]Nomifensine ( S-[11C]NMF) is a positron-emitting tracer suitable for positron emission tomography, which binds to both dopaminergic and noradrenergic reuptake sites in the striatum and the thalamus. Modelling of the cerebral distribution of this drug has been hampered by the rapid appearance of glucuronide metabolites in the plasma, which do not cross the blood–brain barrier. To date, [11C]NMF uptake has simply been expressed as regional versus nonspecific cerebellar activity ratios. We have calculated a “free” NMF input curve from red cell activity curves, using the fact that the free drug rapidly equilibrates between red cells and plasma, while glucuronides do not enter red cells. With this free [11C]NMF input function, all regional cerebral uptake curves could be fitted to a conventional two-compartment model, defining tracer distribution in terms of [11C]NMF regional volume of distribution. Assuming that the cerebellar volume of distribution of [11C]NMF represents the nonspecific volume of distribution of the tracer in striatum and thalamus, we have calculated an equilibrium partition coefficient for [11C]NMF between freely exchanging specific and nonspecific compartments in these regions, representing its “binding potential” to dopaminergic or noradrenergic uptake sites (or complexes). This partition coefficient was lower in the striatum when the racemate rather than the active S-enantiomer of [11C]NMF was administered. In the striatum of patients suffering from Parkinson's disease and multiple-system atrophy, the specific compartmentation of S-[11C]NMF was significantly decreased compared with that of age-matched volunteers.

Conceptual, methodological, and statistical challenges in brain imaging studies of developmentally based psychopathologies

2003 ◽  
Vol 15 (3) ◽  
pp. 811-832 ◽  
Author(s):  
BRADLEY S. PETERSON
Keyword(s):  
Brain Imaging ◽  
Functional Imaging ◽  
Developmental Disorders ◽  
Imaging Modality ◽  
Effective Connectivity ◽  
Imaging Data ◽  
Scaling Effects ◽  
Imaging Studies ◽  
Brain Functions ◽  
The Brain

Brain imaging studies in developmentally based psychopathologies most often use magnetic resonance imaging (MRI) to study regional volumes, task-related activity, neurometabolite concentrations, or the paths of fiber tracts within the brain. Methodological challenges for the use of MRI in studying these disorders include understanding the ultrastructural correlates of brain structure and function that are below the limits of resolution of this imaging modality and developing better methods for approximating the anatomical boundaries of the cytoarchitectonic units that are defined by those ultrastructural characteristics. Conceptual challenges include distinguishing findings that represent pathophysiologically central causes from compensatory and epiphenomenal effects, a difficulty that stems directly from the inherently correlational nature of imaging data. The promise of functional imaging studies must capitalize on the specificity of the cognitive and behavioral probes that are used to illuminate core features of the pathophysiology of developmental disorders, while recognizing the assumptions and limitations of the subtraction paradigms that are used to isolate the brain functions of interest. Statistical challenges include incorporating adequate statistical models for scaling effects within the brain, as well as modeling important demographic correlates that contribute to the substantial interindividual variability inherent in most imaging data. Statistical analyses need to consider the substantial intercorrelation of measures across the brain and the importance of correcting for multiple statistical comparisons, as well as the need for improved methods for brain warping and for assessing effective connectivity in functional imaging studies.

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