Positron Emission Tomography Compartmental Models

Gunn, Roger N.; Gunn, Steve R.; Cunningham, Vincent J.

doi:10.1097/00004647-200106000-00002

Cited by 433 publications

(391 citation statements)

References 24 publications

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“…These were an irreversible one-tissue model (M1T1K, i.e. one-tissue compartment with one kinetic rate constant), a reversible one-tissue model (M1T2K, one-tissue compartment with two kinetic rate constants), an irreversible twotissue model (M2T3K, two-tissue compartments with three kinetic rate constants), and a reversible two-tissue model (M2T4K, two-tissue compartments with four kinetic rate constants) [31]. Variants of these models with and without a blood volume (V b ) component were evaluated.…”

Section: Kinetic Analysismentioning

confidence: 99%

Quantification of (R)-[11C]PK11195 binding in rheumatoid arthritis

Kropholler

Boellaard

Elzinga

et al. 2008

Eur J Nucl Med Mol Imaging

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Purpose Rheumatoid arthritis (RA) involves migration of macrophages into inflamed areas. (R)-[11 C]PK11195 binds to peripheral benzodiazepine receptors, expressed on macrophages, and may be used to quantify inflammation using positron emission tomography (PET). This study evaluated methods for the quantification of (R)- Conclusion (R)-[11 C]PK11195 kinetics in the knee were best described by a reversible single-tissue compartment model including blood volume. Applying metabolite corrections did not increase sensitivity. Due to the high correlation with V d , SUV is a practical alternative for clinical use.

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Section: Kinetic Analysismentioning

confidence: 99%

Quantification of (R)-[11C]PK11195 binding in rheumatoid arthritis

Kropholler

Boellaard

Elzinga

et al. 2008

Eur J Nucl Med Mol Imaging

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“…Similarly, spectral analysis can also be used for the same purpose (Cunningham and Jones, 1993;Murase, 2003). Although it differs from compartmental modeling conceptually, it does not differ much technically, because in both cases, the solution for the tissue time activity curve (tTAC) consists of a linear combination of exponential functions and possibly a constant term, convolved with the input function (IF) (Gunn et al, 2001;Schmidt, 1999).…”

Section: Introductionmentioning

confidence: 99%

Cumulative Input Function Method for Linear Compartmental Models and Spectral Analysis in PET

Simončič

Jeraj

2010

J Cereb Blood Flow Metab

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Compartmental modeling and spectral analysis are often used for tracer kinetic modeling in positron emission tomography (PET). The concentrations in kinetic equations are usually considered to be instantaneous, whereas PET data are inherently integrated over time, which leads to uncertainties in the results. A new formalism for kinetic analysis that uses cumulative tracer concentrations and avoids approximating the image-derived input function and PET measurements with midframe instantanous values was developed. We assessed the improvements of the new formalism over the midframe approximation methods for three commonly used radiopharmaceuticals: [ ]raclopride ranged from 5% to 25%. Improvements in estimation accuracy of FDG and FLT microparameters ranged up to 25%. On the other hand, estimation of macroparameterfor FDG or FLT did not show significant benefit with the new method; only modest improvement up to 2% was observed. Assessment of the benefits of using new method is far from being exhaustive, but possibly significant improvement was demonstrated. Therefore, we consider the proposed algorithm a necessary component of any kinetic analysis software.

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“…In a previous study, it was demonstrated that this is the optimal plasma input model for [ 11 C](R)-PK11195 studies (Kropholler et al, 2005). The other plasma input model was a three-tissue compartment model with different compartments for specific and nonspecific binding (Gunn et al, 2001) and was used to generate tissue time-activity curves (TACs) for the Monte Carlo simulations. …”

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confidence: 99%

Evaluation of Reference Tissue Models for the Analysis of [¹¹C](R)-PK11195 Studies

Kropholler

Boellaard

Schuitemaker

et al. 2006

J Cereb Blood Flow Metab

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[ 11 C](R)-PK11195 is a marker of activated microglia, which can be used to measure inflammation in neurologic disorders. The purpose of the present study was to define the optimal reference tissue model based on a comparison with a validated plasma input model and using clinical studies and Monte Carlo simulations. Accuracy and reproducibility of reference tissue models were evaluated using Monte Carlo simulations. The effects of noise and variation in specific binding, nonspecific binding and blood volume were evaluated. Dynamic positron emission tomography scans were performed on 13 subjects, and radioactivity in arterial blood was monitored online. In addition, blood samples were taken to generate a metabolite corrected plasma input function. Both a (validated) two-tissue reversible compartment model with K 1 /k 2 fixed to whole cortex and various reference tissue models were fitted to the data. Finally, a simplified reference tissue model (SRTM) corrected for nonspecific binding using plasma input data (SRTM pl_corr ) was investigated. Correlations between reference tissue models (including SRTM pl_corr ) and the plasma input model were calculated. Monte Carlo simulations indicated that low-specific binding results in decreased accuracy and reproducibility. In this respect, the SRTM and SRTM pl_corr performed relatively well. Varying blood volume had no effect on performance. In the clinical evaluation, SRTM pl_corr and SRTM had the highest correlations with the plasma input model (R 2 = 0.82 and 0.78, respectively). SRTM pl_corr is optimal when an arterial plasma input curve is available. Simplified reference tissue model is the best alternative when no plasma input is available. Keywords: microglia; peripheral benzodiazepine receptor; PET (positron emission tomography); PK11195; reference tissue models; tracer kinetic modelling IntroductionCarbon-11 labeled (R)-PK11195 ((R)-1-(2-chlorophenyl)-N-[ 11 C]methyl-N-(1-methylpropyl)-3-isoquinoline carboxamide) is a ligand for the peripheral benzodiazepine receptor. In the brain, this receptor is mainly expressed on activated microglia (Banati et al, 1997). Both [ 11 C](R)-PK11195 and [ 11 C]PK11195 have been used as positron emmision tomography (PET) tracers to study activated microglia in various neurologic disorders. It has been used to study stroke (Ramsay et al, 1992;Pappata et al, 2000;Gerhard et al, 2000Gerhard et al, , 2005a), Alzheimer's disease (Groom et al, 1995; Cagnin et al, 2001a;Versijpt et al, 2003), multiple sclerosis (Banati et al, 2000;Debruyne et al, 2002Debruyne et al, , 2003Versijpt et al, 2005) and various other diseases (Pappata et al, 1991; Banati et al, 1999Banati et al, , 2001Goerres et al, 2001;Cagnin et al, 2001bCagnin et al, , 2004Cicchetti et al, 2002;Gerhard et al, 2003Gerhard et al, , 2004Gerhard et al, , 2005bTurner et al, 2004Turner et al, , 2005Venneti et al, 2004;Henkel et al, 2004;Ouchi et al, 2005). Most studies have used a reference tissue approach to quantify binding, either by applying the simplified reference tissue mod...

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Positron Emission Tomography Compartmental Models

Cited by 433 publications

References 24 publications

Quantification of (R)-[11C]PK11195 binding in rheumatoid arthritis

Quantification of (R)-[11C]PK11195 binding in rheumatoid arthritis

Cumulative Input Function Method for Linear Compartmental Models and Spectral Analysis in PET

Evaluation of Reference Tissue Models for the Analysis of [¹¹C](R)-PK11195 Studies

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Positron Emission Tomography Compartmental Models

Cited by 433 publications

References 24 publications

Quantification of (R)-[11C]PK11195 binding in rheumatoid arthritis

Quantification of (R)-[11C]PK11195 binding in rheumatoid arthritis

Cumulative Input Function Method for Linear Compartmental Models and Spectral Analysis in PET

Evaluation of Reference Tissue Models for the Analysis of [11C](R)-PK11195 Studies

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Evaluation of Reference Tissue Models for the Analysis of [¹¹C](R)-PK11195 Studies