Abstract
It was widely reported that 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) could not detect 40-50% of hepatocellular carcinoma (HCC), one of the most common malignancies worldwide. Recent research had demonstrated that 11C-acetate (ACT) was a complementary tracer to FDG and these 2 tracers together could maximize the detection accuracy of this tumor. Quantitative functional imaging techniques were, therefore, conducted to further characterize the underlying kinetic basis of this tracer in the detection of HCC. To describe the 11C-acetate molecular kinetic behavior in liver, a three-compartment model with fixed-weight dual-input function was initially proposed, together with a new physiologic parameter defined as the "local hepatic metabolic rate-constant of acetate (LHMRAct)". Preliminary results had shown that the LHMRAct of HCC was significantly higher than that of the non-tumor liver tissue. This tracer kinetic modeling technique provided the first quantitative and kinetic evidence that 11C-acetate was indeed metabolically incorporated in certain types of HCC. In real pathology, however, both tumor and non-tumor liver tissues were actually quite heterogeneous in the distribution and proportion of the two hepatic blood supplies: hepatic artery (HA) and portal vein (PV). To further improve the accuracy of our previous quantitative analysis, the individual proportion of HA/PV in different regions of interest (ROIs) was further studied. An extra parameter called "av", defined as the "relative portal venous contribution to the hepatic blood flow", was proposed (in substitute of the previously fixed weight HA:PV contribution) for the 11C-acetate dual-input liver model. Ten ROIs extracted from six patients were used to test the models with fixed/non-fixed weight dual-input function. The weighted non-linear least squares (NLS) algorithm was used to estimate all the parameters. Results showed that the new model structure could provide better characterization of the 11Cacetate kinetic behavior in liver by statistical study. The analysis was also able to provide a better understanding of the blood supply mechanism in the liver, proposing that the new parameter av, as a quantitatively derived vascular factor, might also provide useful diagnostic information for detection of HCC, particularly in situations when confounding hyperaemic variables such as dysplastic and regenerative nodules coexist in the setting of severe cirrhosis.
Keywords: 11C-acetate, dual-input function, local hepatic metabolic rate-constant of acetate (LHMRAct), modeling, parameter estimation, positron emission tomography (PET)
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