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

被引:23
作者
Garbarino, Sara [1 ,2 ]
Vivaldi, Valentina [1 ,2 ]
Delbary, Fabrice [1 ]
Caviglia, Giacomo [1 ]
Piana, Michele [1 ,2 ]
Marini, Cecilia [3 ]
Capitanio, Selene [4 ]
Calamia, Iolanda [4 ]
Buschiazzo, Ambra [4 ]
Sambuceti, Gianmario [4 ,5 ]
机构
[1] Univ Genoa, Dipartimento Matemat, I-16146 Genoa, Italy
[2] CNR SPIN Genova, I-16146 Genoa, Italy
[3] CNR, Inst Mol Bioimaging & Physiol Milan, Sect Genova, Nucl Med, I-16132 Genoa, Italy
[4] Univ Genoa, IRCCS AOU San Martino IST, Nucl Med Unit, I-16132 Genoa, Italy
[5] Univ Genoa, Dipartimento Sci Salute, I-16132 Genoa, Italy
关键词
Compartmental analysis; Liver physiology; Dual input; FDG-PET; Metformin;
D O I
10.1186/s13550-015-0107-1
中图分类号
R8 [特种医学]; R445 [影像诊断学];
学科分类号
1002 ; 100207 ; 1009 ;
摘要
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 F-18-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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页数:9
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