scholarly journals Reference Region Automatic Extraction in Dynamic [11C]PIB

2013 ◽  
Vol 33 (11) ◽  
pp. 1725-1731 ◽  
Author(s):  
Yoko Ikoma ◽  
Paul Edison ◽  
Anil Ramlackhansingh ◽  
David J Brooks ◽  
Federico E Turkheimer
Keyword(s):  
Gray Matter ◽  
Specific Binding ◽  
Amyloid Plaque ◽  
Blood Pool ◽  
Binding Potential ◽  
Automatic Extraction ◽  
Reference Region ◽  
Supervised Clustering ◽  
Plaque Deposition ◽  
Positron Emission

The positron emission tomography (PET) radiotracer [11C]Pittsburgh Compound B (PIB) is a marker of amyloid plaque deposition in brain, and binding potential is usually quantified using the cerebellum as a reference where the specific binding is negligible. The use of the cerebellum as a reference, however, has been questioned by the reported cerebellar [11C]PIB retention in familial Alzheimer's disease (AD) subjects. In this work, we developed a supervised clustering procedure for the automatic extraction of a reference region in [11C]PIB studies. Supervised clustering models each gray matter voxel as the linear combination of three predefined kinetic classes, normal and lesion gray matter, and blood pool, and extract reference voxels in which the contribution of the normal gray matter class is high. In the validation with idiopathic AD subjects, supervised clustering extracted reference voxels mostly in the cerebellum that indicated little specific [11C]PIB binding, and total distribution volumes of the extracted region were lower than those of the cerebellum. Next, the methodology was applied to the familial AD cohort where the cerebellar amyloid load had been demonstrated previously, resulting in higher binding potential compared with that obtained with the cerebellar reference. The supervised clustering method is a useful tool for the accurate quantification of [11C]PIB studies.

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 Assessment of a white matter reference region for 11C-UCB-J PET quantification

2019 ◽  
Vol 40 (9) ◽  
pp. 1890-1901 ◽  
Author(s):  
Samantha Rossano ◽  
Takuya Toyonaga ◽  
Sjoerd J Finnema ◽  
Mika Naganawa ◽  
Yihuan Lu ◽  
...  
Keyword(s):  
Gray Matter ◽  
Specific Binding ◽  
Region Of Interest ◽  
Volume Of Distribution ◽  
Reference Region ◽  
Synaptic Density ◽  
Positron Emission ◽  
The Difference ◽  
Density Marker

11C-UCB-J is a positron emission tomography (PET) radioligand that has been used in humans for synaptic vesicle glycoprotein 2A (SV2A) imaging and as a potential synaptic density marker. The centrum semiovale (CS) is a proposed reference region for noninvasive quantification of 11C-UCB-J, due to negligible concentrations of SV2A in this region in baboon brain assessed by in vitro methods. However, in displacement scans with SV2A-specific drug levetiracetam in humans, a decrease in 11C-UCB-J concentration was observed in the CS, consistent with some degree of specific binding. The current study aims to validate the CS as a reference region by (1) optimizing CS region of interest (ROI) to minimize spill-in from gray matter with high radioactivity concentrations; (2) investigating convergence of CS ROI values using ordered subset expectation maximization (OS-EM) reconstruction, and (3) comparing baseline CS volume of distribution ( VT) to nondisplaceable uptake in gray matter, VND. Improving ROI definition and increasing OS-EM iterations during reconstruction decreased the difference between CS VT and VND. However, even with these corrections, CS VT overestimated VND by ∼35–40%. These measures showed significant correlation, suggesting that, though biased, the CS may be a useful estimate of nondisplaceable uptake, allowing for noninvasive quantification for SV2A PET.

scholarly journals Quantitation of Translocator Protein Binding in Human Brain with the Novel Radioligand [18F]-FEPPA and Positron Emission Tomography

2011 ◽  
Vol 31 (8) ◽  
pp. 1807-1816 ◽  
Author(s):  
Pablo M Rusjan ◽  
Alan A Wilson ◽  
Peter M Bloomfield ◽  
Irina Vitcu ◽  
Jeffrey H Meyer ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Human Brain ◽  
Specific Binding ◽  
Compartment Model ◽  
Distribution Volume ◽  
Translocator Protein ◽  
Emission Tomography ◽  
Binding Potential ◽  
Specific Distribution ◽  
Positron Emission

This article describes the kinetic modeling of [18F]-FEPPA binding to translocator protein 18 kDa in the human brain using high-resolution research tomograph (HRRT) positron emission tomography. Positron emission tomography scans were performed in 12 healthy volunteers for 180 minutes. A two-tissue compartment model (2-CM) provided, with no exception, better fits to the data than a one-tissue model. Estimates of total distribution volume ( VT), specific distribution volume ( VS), and binding potential ( BPND) demonstrated very good identifiability (based on coefficient of variation ( COV)) for all the regions of interest (ROIs) in the gray matter ( COV VT < 7%, COV VS < 8%, COV BPND < 11%). Reduction of the length of the scan to 2 hours is feasible as VS and VT showed only a small bias (6% and 7.5%, respectively). Monte Carlo simulations showed that, even under conditions of a 500% increase in specific binding, the identifiability of VT and VS was still very good with COV<10%, across high-uptake ROIs. The excellent identifiability of VT values obtained from an unconstrained 2-CM with data from a 2-hour scan support the use of VT as an appropriate and feasible outcome measure for [18F]-FEPPA.

scholarly journals Measuring Drug Occupancy in the Absence of a Reference Region: The Lassen Plot Re-Visited

2009 ◽  
Vol 30 (1) ◽  
pp. 46-50 ◽  
Author(s):  
Vincent J Cunningham ◽  
Eugenii A Rabiner ◽  
Mark Slifstein ◽  
Marc Laruelle ◽  
Roger N Gunn
Keyword(s):  
Graphical Method ◽  
Quantitative Estimation ◽  
Specific Binding ◽  
Volume Of Distribution ◽  
Distribution Volume ◽  
Emission Tomography ◽  
Reference Region ◽  
Site Specific ◽  
Positron Emission ◽  
Regional Estimates

Quantitative estimation of neuroreceptor occupancy by exogenous drugs using positron emission tomography is based on the reduction in the total volume of distribution ( VT) of site-specific radioligands after drug administration. An estimate of the distribution volume of free and nonspecifically bound radioligand ( VND) is also required to distinguish specific from total binding. However, a true reference region, devoid of specific binding, is often not available. We present a transformation of a graphical method, originally introduced by Lassen, using regional estimates of VT alone to determine occupancy, together with an extension that does not require baseline data.

scholarly journals Confirmation of Fenfluramine Effect on 5-HT1B Receptor Binding of [11C]AZ10419369 using an Equilibrium Approach

2011 ◽  
Vol 32 (4) ◽  
pp. 685-695 ◽  
Author(s):  
Sjoerd J Finnema ◽  
Andrea Varrone ◽  
Tzung-Jeng Hwang ◽  
Christer Halldin ◽  
Lars Farde
Keyword(s):  
Specific Binding ◽  
Occipital Cortex ◽  
Serotonin Release ◽  
Binding Potential ◽  
Bolus Administration ◽  
Positron Emission ◽  
Equilibrium Approach ◽  
Induced Changes ◽  
Dose Dependent

Assessment of serotonin release in the living brain with positron emission tomography (PET) may have been hampered by the lack of suitable radioligands. We previously reported that fenfluramine caused a dose-dependent reduction in specific binding in monkeys using a classical displacement paradigm with bolus administration of [11C]AZ10419369. The aim of this study was to confirm our previous findings using an equilibrium approach in monkey. A total of 24 PET measurements were conducted using a bolus infusion protocol of [11C]AZ10419369 in three cynomolgus monkeys. Initial PET measurements were performed to assess suitable Kbol values. The fenfluramine effect on [11C]AZ10419369 binding was evaluated in a displacement and pretreatment paradigm. The effect of fenfluramine on [11C]AZ10419369 binding potential ( BPND) was dose-dependent in the displacement paradigm and confirmed in the pretreatment paradigm. After pretreatment administration of fenfluramine (5.0 mg/kg), the mean BPND of the occipital cortex decreased by 39%, from 1.38 ± 0.04 to 0.84 ± 0.09. This study confirms that the new 5-HT1B receptor radioligand [11C]AZ10419369 is sensitive to fenfluramine-induced changes in endogenous serotonin levels in vivo. The more advanced methodology is suitable for exploring the sensitivity limit to serotonin release as measured using [11C]AZ10419369 and PET.

scholarly journals Validation of an automatic reference region extraction for the quantification of [18F]DPA-714 in dynamic brain PET studies

2017 ◽  
Vol 38 (2) ◽  
pp. 333-346 ◽  
Author(s):  
Daniel García-Lorenzo ◽  
Sonia Lavisse ◽  
Claire Leroy ◽  
Catriona Wimberley ◽  
Benedetta Bodini ◽  
...  
Keyword(s):  
Gray Matter ◽  
Clustering Algorithm ◽  
Arterial Input Function ◽  
Neurological Diseases ◽  
Input Function ◽  
Translocator Protein ◽  
Reference Region ◽  
Supervised Clustering ◽  
Region Extraction ◽  
Highly Correlated

There is a great need for a non-invasive methodology enabling the quantification of translocator protein overexpression in PET clinical imaging. [18F]DPA-714 has emerged as a promising translocator protein radiotracer as it is fluorinated, highly specific and returned reliable quantification using arterial input function. Cerebellum gray matter was proposed as reference region for simplified quantification; however, this method cannot be used when inflammation involves cerebellum. Here we adapted and validated a supervised clustering (supervised clustering algorithm (SCA)) for [18F]DPA-714 analysis. Fourteen healthy subjects genotyped for translocator protein underwent an [18F]DPA-714 PET, including 10 with metabolite-corrected arterial input function and three for a test–retest assessment. Two-tissue compartmental modelling provided [Formula: see text] estimates that were compared to either [Formula: see text] or [Formula: see text] generated by Logan analysis (using supervised clustering algorithm extracted reference region or cerebellum gray matter). The supervised clustering algorithm successfully extracted a pseudo-reference region with similar reliability using classes that were defined using either all subjects, or separated into HAB and MAB subjects. [Formula: see text], [Formula: see text] and [Formula: see text] were highly correlated (ICC of 0.91 ± 0.05) but [Formula: see text] were ∼26% higher and less variable than [Formula: see text]. Reproducibility was good with 5% variability in the test–retest study. The clustering technique for [18F]DPA-714 provides a simple, robust and reproducible technique that can be used for all neurological diseases.

scholarly journals Supervised clustering for TSPO PET imaging

2021 ◽  
Author(s):  
Julia Schubert ◽  
Matteo Tonietto ◽  
Federico Turkheimer ◽  
Paolo Zanotti-Fregonara ◽  
Mattia Veronese
Keyword(s):  
Clustering Algorithm ◽  
Specific Binding ◽  
Technical Note ◽  
Translocator Protein ◽  
Experimental Medicine ◽  
Reference Region ◽  
Supervised Clustering ◽  
Pet Tracer ◽  
Tspo Expression

Abstract Purpose This technical note seeks to act as a practical guide for implementing a supervised clustering algorithm (SVCA) reference region approach and to explain the main strengths and limitations of the technique in the context of 18-kilodalton translocator protein (TSPO) positron emission tomography (PET) studies in experimental medicine. Background TSPO PET is the most widely used imaging technique for studying neuroinflammation in vivo in humans. Quantifying neuroinflammation with PET can be a challenging and invasive procedure, especially in frail patients, because it often requires blood sampling from an arterial catheter. A widely used alternative to arterial sampling is SVCA, which identifies the voxels with minimal specific binding in the PET images, thus extracting a pseudo-reference region for non-invasive quantification. Unlike other reference region approaches, SVCA does not require specification of an anatomical reference region a priori, which alleviates the limitation of TSPO contamination in anatomically-defined reference regions in individuals with underlying inflammatory processes. Furthermore, SVCA can be applied to any TSPO PET tracer across different neurological and neuropsychiatric conditions, providing noninvasivequantification of TSPO expression. Methods We provide an overview of the development of SVCA as well as step-by-step instructions for implementing SVCA with suggestions for specific settings. We review the literature on SVCAapplications using first- and second- generation TSPO PET tracers and discuss potential clinically relevant limitations and applications. Conclusions The correct implementation of SVCA can provide robust and reproducible estimates of brain TSPO expression. This review encourages the standardisation of SVCA methodology in TSPO PET analysis, ultimately aiming to improve replicability and comparability across study sites.

scholarly journals 11C-DPA-713 has much greater specific binding to translocator protein 18 kDa (TSPO) in human brain than 11C-(R)-PK11195

2017 ◽  
Vol 38 (3) ◽  
pp. 393-403 ◽  
Author(s):  
Masato Kobayashi ◽  
Teresa Jiang ◽  
Sanjay Telu ◽  
Sami S Zoghbi ◽  
Roger N Gunn ◽  
...  
Keyword(s):  
Second Generation ◽  
Specific Binding ◽  
Translocator Protein ◽  
Emission Tomography ◽  
Binding Potential ◽  
Arterial Blood ◽  
Plot Analysis ◽  
Positron Emission ◽  
Translocator Protein 18 Kda ◽  
Pet Scans

Positron emission tomography (PET) radioligands for translocator protein 18 kDa (TSPO) are widely used to measure neuroinflammation, but controversy exists whether second-generation radioligands are superior to the prototypical agent 11C-( R)-PK11195 in human imaging. This study sought to quantitatively measure the “signal to background” ratio (assessed as binding potential ( BPND)) of 11C-( R)-PK11195 compared to one of the most promising second-generation radioligands, 11C-DPA-713. Healthy subjects had dynamic PET scans and arterial blood measurements of radioligand after injection of either 11C-( R)-PK11195 (16 subjects) or 11C-DPA-713 (22 subjects). To measure the amount of specific binding, a subset of these subjects was scanned after administration of the TSPO blocking drug XBD173 (30–90 mg PO). 11C-DPA-713 showed a significant sensitivity to genotype in brain, whereas 11C-( R)-PK11195 did not. Lassen occupancy plot analysis revealed that the specific binding of 11C-DPA-713 was much greater than that of 11C-( R)-PK11195. The BPND in high-affinity binders was about 10-fold higher for 11C-DPA-713 (7.3) than for 11C-( R)-PK11195 (0.75). Although the high specific binding of 11C-DPA-713 suggests it is an ideal ligand to measure TSPO, we also found that its distribution volume increased over time, consistent with the accumulation of radiometabolites in brain.

scholarly journals Analysis of Four Dopaminergic Tracers Kinetics Using Two Different Tissue Input Function Methods

2000 ◽  
Vol 20 (4) ◽  
pp. 653-660 ◽  
Author(s):  
V. Sossi ◽  
J. E. Holden ◽  
G. Chan ◽  
M. Krzywinski ◽  
A. J. Stoessl ◽  
...  
Keyword(s):  
Dopaminergic System ◽  
Specific Binding ◽  
Input Function ◽  
D1 Receptors ◽  
Binding Potential ◽  
Intrasubject Variability ◽  
Reference Tissue ◽  
Good Reliability ◽  
Positron Emission ◽  
And Performance

The integrity of the dopaminergic system can be studied using positron emission tomography. The presynaptic tracers [11C]-methylphenidate and [11C]dihydrotetrabenazine (DTBZ) are used to investigate the dopamine transporter availability, the dopamine vesicular transporter integrity; the post-synaptic tracers [11C]-raclopride and [11C]-Schering 23990 (SCH) are used to probe the D2 and D1 receptors. These are reversible tracers, where the binding potential (BP) = Bmax/Kd often is used to quantify the amount of their specific binding to the sites of interest. The simplified tissue input methods to calculate BP are attractive, since they do not require a blood input function. The suitability and performance of two such methods were evaluated: the Logan graphical tissue method, and the Lammertsma reference tissue method (RTM). The BP estimates obtained with the two methods were nearly identical in most cases, with similar reliability and reproducibility indicating that all four tracers satisfy the assumptions required by each method. The correlations among the fitted parameters obtained from the RTM were estimated and were found not to introduce noticeable bias in the RTM BP and R1 estimates. R1 showed low intersubject and intrasubject variability. The k2 estimate showed good reliability for SCH with cerebellar input function and DTBZ with occipital input function.

scholarly journals Corrigendum

2018 ◽  
Vol 38 (6) ◽  
pp. 1120-1120
Keyword(s):  
Blood Flow ◽  
Partial Volume Correction ◽  
Automatic Extraction ◽  
Reference Region ◽  
Partial Volume ◽  
Volume Correction ◽  
Cereb Blood Flow ◽  
Reproducibility Study ◽  
Positron Emission ◽  
Myelin Imaging

Grecchi E, Veronese M, Bodini B, et al. Multimodal partial volume correction: Application to [11C]PIB PET/MRI myelin imaging in multiple sclerosis. J Cereb Blood Flow Metab 2017; 37: 3803–3817. Three references in the above article appeared with typesetting coding when published online and in print. The references should have appeared as follows: 8. Aston JAD, Cunningham VJ, Asselin M-C, et al. Positron emission tomography partial volume correction: estimation and algorithms. J Cereb Blood Flow Metab 2002; 22: 1019–1034. 20. Veronese M, Bodini B, García-Lorenzo D, et al. Quantification of [11C]PIB PET for imaging myelin in the human brain: a test–retest reproducibility study in high-resolution research tomography. J Cereb Blood Flow Metab 2015; 35: 1771–1782. 30. Ikoma Y, Edison P, Ramlackhansingh A, et al. Reference region automatic extraction in dynamic [11C]PIB. J Cereb Blood Flow Metab 2013; 33: 1725–1731.

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