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A new compartmental method for the analysis of liver FDG kinetics in small animal models

BACKGROUND: Compartmental analysis is a standard method to quantify metabolic processes using fluorodeoxyglucose-positron emission tomography (FDG-PET). For liver studies, this analysis is complex due to the hepatocyte capability to dephosphorylate and release glucose and FDG into the blood. Moreove...

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Autores principales: Garbarino, Sara, Vivaldi, Valentina, Delbary, Fabrice, Caviglia, Giacomo, Piana, Michele, Marini, Cecilia, Capitanio, Selene, Calamia, Iolanda, Buschiazzo, Ambra, Sambuceti, Gianmario
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2015
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4469683/
https://www.ncbi.nlm.nih.gov/pubmed/26077542
http://dx.doi.org/10.1186/s13550-015-0107-1
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author Garbarino, Sara
Vivaldi, Valentina
Delbary, Fabrice
Caviglia, Giacomo
Piana, Michele
Marini, Cecilia
Capitanio, Selene
Calamia, Iolanda
Buschiazzo, Ambra
Sambuceti, Gianmario
author_facet Garbarino, Sara
Vivaldi, Valentina
Delbary, Fabrice
Caviglia, Giacomo
Piana, Michele
Marini, Cecilia
Capitanio, Selene
Calamia, Iolanda
Buschiazzo, Ambra
Sambuceti, Gianmario
author_sort Garbarino, Sara
collection PubMed
description BACKGROUND: Compartmental analysis is a standard method to quantify metabolic processes using fluorodeoxyglucose-positron emission tomography (FDG-PET). For liver studies, this analysis is complex due to the hepatocyte capability to dephosphorylate and release glucose and FDG into the blood. Moreover, a tracer is supplied to the liver by both the hepatic artery and the portal vein, which is not visible in PET images. This study developed an innovative computational approach accounting for the reversible nature of FDG in the liver and directly computing the portal vein tracer concentration by means of gut radioactivity measurements. METHODS: Twenty-one mice were subdivided into three groups: the control group ‘CTR’ (n = 7) received no treatment, the short-term starvation group ‘STS’ (n = 7) was submitted to food deprivation with free access to water within 48 h before imaging, and the metformin group ‘MTF’ (n = 7) was treated with metformin (750 mg/Kg per day) for 1 month. All mice underwent a dynamic micro-PET study for 50 min after an (18)F-FDG injection. The compartmental analysis considered two FDG pools (phosphorylated and free) in both the gut and liver. A tracer was carried into the liver by the hepatic artery and the portal vein, and tracer delivery from the gut was considered as the sole input for portal vein tracer concentration. Accordingly, both the liver and gut were characterized by two compartments and two exchange coefficients. Each one of the two two-compartment models was mathematically described by a system of differential equations, and data optimization was performed by applying a Newton algorithm to the inverse problems associated to these differential systems. RESULTS: All rate constants were stable in each group. The tracer coefficient from the free to the metabolized compartment in the liver was increased by STS, while it was unaltered by MTF. By contrast, the tracer coefficient from the metabolized to the free compartment was reduced by MTF and increased by STS. CONCLUSIONS: Data demonstrated that our method was able to analyze FDG kinetics under pharmacological or pathophysiological stimulation, quantifying the fraction of the tracer trapped in the liver or dephosphorylated and released into the bloodstream.
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spelling pubmed-44696832015-06-18 A new compartmental method for the analysis of liver FDG kinetics in small animal models Garbarino, Sara Vivaldi, Valentina Delbary, Fabrice Caviglia, Giacomo Piana, Michele Marini, Cecilia Capitanio, Selene Calamia, Iolanda Buschiazzo, Ambra Sambuceti, Gianmario EJNMMI Res Original Research BACKGROUND: Compartmental analysis is a standard method to quantify metabolic processes using fluorodeoxyglucose-positron emission tomography (FDG-PET). For liver studies, this analysis is complex due to the hepatocyte capability to dephosphorylate and release glucose and FDG into the blood. Moreover, a tracer is supplied to the liver by both the hepatic artery and the portal vein, which is not visible in PET images. This study developed an innovative computational approach accounting for the reversible nature of FDG in the liver and directly computing the portal vein tracer concentration by means of gut radioactivity measurements. METHODS: Twenty-one mice were subdivided into three groups: the control group ‘CTR’ (n = 7) received no treatment, the short-term starvation group ‘STS’ (n = 7) was submitted to food deprivation with free access to water within 48 h before imaging, and the metformin group ‘MTF’ (n = 7) was treated with metformin (750 mg/Kg per day) for 1 month. All mice underwent a dynamic micro-PET study for 50 min after an (18)F-FDG injection. The compartmental analysis considered two FDG pools (phosphorylated and free) in both the gut and liver. A tracer was carried into the liver by the hepatic artery and the portal vein, and tracer delivery from the gut was considered as the sole input for portal vein tracer concentration. Accordingly, both the liver and gut were characterized by two compartments and two exchange coefficients. Each one of the two two-compartment models was mathematically described by a system of differential equations, and data optimization was performed by applying a Newton algorithm to the inverse problems associated to these differential systems. RESULTS: All rate constants were stable in each group. The tracer coefficient from the free to the metabolized compartment in the liver was increased by STS, while it was unaltered by MTF. By contrast, the tracer coefficient from the metabolized to the free compartment was reduced by MTF and increased by STS. CONCLUSIONS: Data demonstrated that our method was able to analyze FDG kinetics under pharmacological or pathophysiological stimulation, quantifying the fraction of the tracer trapped in the liver or dephosphorylated and released into the bloodstream. Springer Berlin Heidelberg 2015-06-11 /pmc/articles/PMC4469683/ /pubmed/26077542 http://dx.doi.org/10.1186/s13550-015-0107-1 Text en © Garbarino et al. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.
spellingShingle Original Research
Garbarino, Sara
Vivaldi, Valentina
Delbary, Fabrice
Caviglia, Giacomo
Piana, Michele
Marini, Cecilia
Capitanio, Selene
Calamia, Iolanda
Buschiazzo, Ambra
Sambuceti, Gianmario
A new compartmental method for the analysis of liver FDG kinetics in small animal models
title A new compartmental method for the analysis of liver FDG kinetics in small animal models
title_full A new compartmental method for the analysis of liver FDG kinetics in small animal models
title_fullStr A new compartmental method for the analysis of liver FDG kinetics in small animal models
title_full_unstemmed A new compartmental method for the analysis of liver FDG kinetics in small animal models
title_short A new compartmental method for the analysis of liver FDG kinetics in small animal models
title_sort new compartmental method for the analysis of liver fdg kinetics in small animal models
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4469683/
https://www.ncbi.nlm.nih.gov/pubmed/26077542
http://dx.doi.org/10.1186/s13550-015-0107-1
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