title: Astrocytic tracer dynamics estimated from [1-¹¹C]-acetate PET measurements.
abstract: We address the problem of estimating the unknown parameters of a model of tracer kinetics from sequences of positron emission tomography (PET) scan data using a statistical sequential algorithm for the inference of magnitudes of dynamic parameters. The method, based on Bayesian statistical inference, is a modification of a recently proposed particle filtering and sequential Monte Carlo algorithm, where instead of preassigning the accuracy in the propagation of each particle, we fix the time step and account for the numerical errors in the innovation term. We apply the algorithm to PET images of [1-¹¹C]-acetate-derived tracer accumulation, estimating the transport rates in a three-compartment model of astrocytic uptake and metabolism of the tracer for a cohort of 18 volunteers from 3 groups, corresponding to healthy control individuals, cirrhotic liver and hepatic encephalopathy patients. The distribution of the parameters for the individuals and for the groups presented within the Bayesian framework support the hypothesis that the parameters for the hepatic encephalopathy group follow a significantly different distribution than the other two groups. The biological implications of the findings are also discussed.
authors.affiliation: Center for Quantitative Sciences in Biomedicine, North Carolina State University, Campus Box 8213, 2700 Stinson Drive, 308 Cox Hall, Raleigh, NC 27695-8213, USA and Department of Mathematics, North Carolina State University, Campus Box 8205, 2108 SAS Hall, 2311 Stinson Drive, Raleigh, NC 27695-8205, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Arnold
authors.affiliation: Department of Mathematics, Applied Mathematics and Statistics, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA dxc57@case.edu daniela.calvetti@case.edu.
authors.forename: Daniela
authors.initials: D
authors.lastname: Calvetti
authors.affiliation: Department of Neuroscience and Pharmacology, University of Copenhagen, Blegdamsvej 3B, DK-2200, Copenhagen, Denmark and Department of Nuclear Medicine and PET Centre, Aarhus University Hospitals, Aarhus, Nørrebrogade 44 DK-8000, Denmark.
authors.forename: Albert
authors.initials: A
authors.lastname: Gjedde
authors.affiliation: Department of Nuclear Medicine and PET Centre, Aarhus University Hospitals, Aarhus, Nørrebrogade 44 DK-8000, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Iversen
authors.affiliation: Department of Mathematics, Applied Mathematics and Statistics, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA.
authors.forename: Erkki
authors.initials: E
authors.lastname: Somersalo
mesh_terms: D000328:Adult; D001253:Astrocytes / Q000000981:diagnostic imaging*; D001499:Bayes Theorem; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics*; D006801:Humans; D015233:Models, Statistical; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*
chemical_list: D002250:Carbon Radioisotopes; D019275:Radiopharmaceuticals
keywords: PET imaging; parameter estimation; particle filters; sequential Monte Carlo (SMC); tracer kinetics