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Reproducibility of quantitative (R)-[11C]verapamil studies

DOI: 10.1186/2191-219x-2-1

Keywords: Positron emission tomography, P-glycoprotein, reproducibility, (R)-[11C]verapamil

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Abstract:

Dynamic (R)-[11C]verapamil scans with arterial sampling were performed twice on the same day in 13 healthy controls. Data were reconstructed using both filtered back projection [FBP] and partial volume corrected ordered subset expectation maximization [PVC OSEM]. All data were analysed using single-tissue and two-tissue compartment models. Global and regional test-retest variability was determined for various outcome measures.Analysis using the Akaike information criterion showed that a constrained two-tissue compartment model provided the best fits to the data. Global test-retest variability of the volume of distribution was comparable for single-tissue (6%) and constrained two-tissue (9%) compartment models. Using a single-tissue compartment model covering the first 10 min of data yielded acceptable global test-retest variability (9%) for the outcome measure K1. Test-retest variability of binding potential derived from the constrained two-tissue compartment model was less robust, but still acceptable (22%). Test-retest variability was comparable for PVC OSEM and FBP reconstructed data.The model of choice for analysing (R)-[11C]verapamil data is a constrained two-tissue compartment model.P-glycoprotein [Pgp] is considered to be the most important efflux transporter at the human blood-brain barrier [BBB] because of its high expression and its ability to transport a wide range of substrates from the brain into the circulation and cerebrospinal fluid. Pgp plays an important role in protecting the brain from endogenous and exogenous toxic substances by removing them before they reach the parenchyma [1-5]. It has been hypothesised that decreased Pgp function and/or expression at the BBB are involved in several neurological disorders, such as Creutzfeldt-Jakob disease, Parkinson's disease and Alzheimer's disease [AD] [6-9]. On the other hand, increased Pgp function may be involved in drug-resistant epilepsy [10].Over the past years, several positron emission tomography [

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