Dynamic PET of human liver inflammation: impact of kinetic modeling with optimization-derived dual-blood input function

The hallmark of nonalcoholic steatohepatitis is hepatocellular inflammation and injury in the setting of hepatic steatosis. Recent work has indicated that dynamic 18F-FDG PET with kinetic modeling has the potential to assess hepatic inflammation noninvasively, while static FDG-PET is less promising. Because the liver has dual blood supplies, kinetic modeling of dynamic liver PET data is challenging in human studies. This paper aims to identify the optimal dual-input kinetic modeling approach for dynamic FDG-PET of human liver inflammation. Fourteen patients with nonalcoholic fatty liver disease were included. Each patient underwent 1 h dynamic FDG-PET/CT scan and had liver biopsy within six weeks. Three models were tested for kinetic analysis: the traditional two-tissue compartmental model with an image-derived single-blood input function (SBIF), a model with population-based dual-blood input function (DBIF), and a new model with optimization-derived DBIF through a joint estimation framework. The three models were compared using Akaike information criterion (AIC), F test and histopathologic inflammation score. Results showed that the optimization-derived DBIF model improved liver time activity curve fitting and achieved lower AIC values and higher F values than the SBIF and population-based DBIF models in all patients. The optimization-derived model significantly increased FDG K1 estimates by 101% and 27% as compared with traditional SBIF and population-based DBIF. K1 by the optimization-derived model was significantly associated with histopathologic grades of liver inflammation while the other two models did not provide a statistical significance. In conclusion, modeling of DBIF is critical for dynamic liver FDG-PET kinetic analysis in human studies. The optimization-derived DBIF model is more appropriate than SBIF and population-based DBIF for dynamic FDG-PET of liver inflammation