scholarly journals Validation of reference tissue modelling for [11C]flumazenil positron emission tomography following head injury

2011 ◽  
Vol 25 (6) ◽  
pp. 396-405 ◽  
Author(s):  
Thomas Geeraerts ◽  
Jonathan P. Coles ◽  
Franklin I. Aigbirhio ◽  
John D. Pickard ◽  
David K. Menon ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Head Injury ◽  
Emission Tomography ◽  
Reference Tissue ◽  
Positron Emission ◽  
Tissue Modelling

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 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 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 Validation and Quantification of [18F]Altanserin Binding in the Rat Brain Using Blood Input and Reference Tissue Modeling

2011 ◽  
Vol 31 (12) ◽  
pp. 2334-2342 ◽  
Author(s):  
Patrick J Riss ◽  
Young T Hong ◽  
David Williamson ◽  
Daniele Caprioli ◽  
Sergey Sitnikov ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Emission Tomography ◽  
Brain Uptake ◽  
Reference Tissue ◽  
Tissue Modeling ◽  
Validation And Quantification ◽  
Positron Emission ◽  
Significant Uptake ◽  
Tissue Models ◽  
The Brain

The 5-hydroxytryptamine type 2a (5-HT2A) selective radiotracer [18F]altanserin has been subjected to a quantitative micro-positron emission tomography study in Lister Hooded rats. Metabolite-corrected plasma input modeling was compared with reference tissue modeling using the cerebellum as reference tissue. [18F]altanserin showed sufficient brain uptake in a distribution pattern consistent with the known distribution of 5-HT2A receptors. Full binding saturation and displacement was documented, and no significant uptake of radioactive metabolites was detected in the brain. Blood input as well as reference tissue models were equally appropriate to describe the radiotracer kinetics. [18F]altanserin is suitable for quantification of 5-HT2A receptor availability in rats.

scholarly journals In vivo evaluation of [11C]preladenant positron emission tomography for quantification of adenosine A2A receptors in the rat brain

2016 ◽  
Vol 37 (2) ◽  
pp. 577-589 ◽  
Author(s):  
Xiaoyun Zhou ◽  
Shivashankar Khanapur ◽  
Johan R de Jong ◽  
Antoon TM Willemsen ◽  
Rudi AJO Dierckx ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Receptor Occupancy ◽  
Compartment Model ◽  
Emission Tomography ◽  
Rat Striatum ◽  
Receptor Density ◽  
Reference Tissue ◽  
Tissue Compartment ◽  
Positron Emission ◽  
The Brain

[11C]Preladenant was developed as a novel adenosine A2A receptor positron emission tomography radioligand. The present study aims to evaluate the suitability of [11C]preladenant positron emission tomography for the quantification of striatal A2A receptor density and the assessment of striatal A2A receptor occupancy by KW-6002. Sixty- or ninety-minute dynamic positron emission tomography imaging was performed on rats. Tracer kinetics was quantified by the two-tissue compartment model, Logan graphical analysis and several reference tissue-based models. Test–retest reproducibility was assessed by repeated imaging on two consecutive days. Two-tissue compartment model and Logan plot estimated comparable distribution volume ( VT) values of ∼10 in the A2A receptor-rich striatum and substantially lower values in all extra-striatal regions (∼1.5–2.5). The simplified reference tissue model with midbrain or occipital cortex as the reference region proved to be the best non-invasive model for quantification of A2A receptor, showing a striatal binding potential ( BPND) value of ∼5.5, and a test–retest variability of ∼5.5%. The brain metabolite analysis showed that at 60-min post injection, 17% of the radioactivity in the brain was due to radioactive metabolites. The ED50 of KW-6002 in rat striatum for i.p. injection was 0.044–0.062 mg/kg. The study demonstrates that [11C]preladenant is a suitable tracer to quantify striatal A2A receptor density and assess A2A receptor occupancy by A2A receptor-targeting molecules.

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