Reconstruction of [¹¹C]Glucose dual input function for quantitative metabolic imaging of the liver

Objectives The liver plays a central role in the metabolic fate of glucose through glycolytic (GLY) metabolism, formation of glycogen through glycogenesis (GGN), or glycogen metabolism through glycogenolysis (GGL) with deficiencies in these processes attributed to several diseases. We characterize arterial (ART) and portal-vein (PV) differences in the dual-input to the liver as well as optimize an ART-to-PV transfer function (TF) to facilitate quantitative imaging of liver processes such as GGN, GGL, and GLY using [¹¹C]Glucose.

Methods Zucker Lean rats (N=13) at the age of 14weeks were divided into groups of 12hr fasted, 24hr fasted and those fed with normal diet, and high fructose diet to expand the dynamic range of GGN, GGL, and GLY. Small animal PET was performed using [¹¹C]Glucose in series with [¹⁵O]H₂O to characterize liver metabolism and flow contributions of hepatic-ART and PV for reconstruction of DIF. Typically about 8 to 10 blood samples were obtained from ART and PV for blood profiling and analysis of substrate levels (insulin, fatty acids, triglycerides, glucose), while about 6 samples were obtained for metabolite analysis. [¹¹C]Glucose metabolism was modeled by examining two gut models: the traditional and a segregated-flow models, with the gut subdivided into vascular (intestinal blood), tissue and lumen compartments, which were evaluated as TF. These models were optimized against PV blood and metabolite data using Nonlinear Least Squares (NLS) algorithm to obtain metabolic parameters of glucose metabolism in the gut and the TF under varying diet interventions.

Results Significant differences were found in ART and PV blood and metabolism profiles under various dietary conditions. The intestinal model was able to sufficiently describe the metabolism of [¹¹C]Glucose. The TF was able to accurately predict PV activity from given ART input in all dietary interventions.

Conclusions These results facilitate metabolic imaging of the liver in rodents to characterize GGN, GGL, and GLY using [¹¹C]Glucose with potential application in human imaging.

Research Support This work was supported by NIDDK Grant 5R01DK085298