title: A new compartmental method for the analysis of liver FDG kinetics in small animal models.
abstract: 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.
authors.affiliation: Dipartimento di Matematica, Università di Genova, via Dodecaneso 35, 16146, Genova, Italy, garbarino@dima.unige.it.
authors.forename: Sara
authors.initials: S
authors.lastname: Garbarino
authors.forename: Valentina
authors.initials: V
authors.lastname: Vivaldi
authors.forename: Fabrice
authors.initials: F
authors.lastname: Delbary
authors.forename: Giacomo
authors.initials: G
authors.lastname: Caviglia
authors.forename: Michele
authors.initials: M
authors.lastname: Piana
authors.forename: Cecilia
authors.initials: C
authors.lastname: Marini
authors.forename: Selene
authors.initials: S
authors.lastname: Capitanio
authors.forename: Iolanda
authors.initials: I
authors.lastname: Calamia
authors.forename: Ambra
authors.initials: A
authors.lastname: Buschiazzo
authors.forename: Gianmario
authors.initials: G
authors.lastname: Sambuceti