Date of Award
Doctor of Philosophy
Dr. Ting-Yim Lee
In recent years, the incidence and mortality rate for hepatocellular carcinoma (HCC) have increased due to the emergence of hepatitis B, C and other diseases that cause cirrhosis. The progression from cirrhosis to HCC is characterized by abnormal vascularization and by a shift from a venous to an arterial blood supply. A knowledge of HCC vascularity which is manifested as alterations in liver blood flow may distinguish among different stages of liver disease and can be used to monitor response to treatment. Unfortunately, conventional diagnostic imaging techniques lack the ability to accurately quantify HCC vascularity. The purpose of this thesis was to validate and assess the diagnostic capabilities of dynamic contrast enhanced computed tomography (DCE-CT) and perfusion software designed to measure hepatic perfusion.
Chapter 2 described a study designed to evaluate the accuracy and precision of hepatic perfusion measurement. The results showed a strong correlation between hepatic artery blood flow measurement with DCE-CT and radioactive microspheres under steady state in a rabbit model for HCC (VX2 carcinoma). Using repeated measurements and Monte Carlo simulations, DCE-CT perfusion measurements were found to be precise; with the highest precision in the tumor rim.
In Chapter 3, we used fluorine-18 fluoro-2-deoxy-D-glucose (FDG) positron emission tomography and DCE-CT perfusion to determined an inverse correlation between glucose utilization and tumor blood flow; with an R of 0.727 (P < 0.05). This suggests a limited supply of oxygen (possibly hypoxia) and that the tumor cells were surviving via anaerobic glycolysis.
In Chapter 4, hepatic perfusion data showed that thalidomide caused a reduction of tumor perfusion in the responder group during the first 8 days after therapy, P < 0.05; while perfusion in the partial responder and control group remained unchanged, P > 0.05. These changes were attributed to vascular remodeling and maturation resulting in a more functional network of endothelial tubes lined with pericytes.
The results of this thesis demonstrate the accuracy and precision of DCE-CT hepatic perfusion measurements. It also showed that DCE-CT perfusion has the potential to enhance the functional imaging ability of hybrid PET/CT scanners and evaluate the efficacy of anti-angiogenesis therapy.
Stewart, Errol E., "Dynamic Contrast Enhanced Computed Tomography Measurement of Perfusion in Hepatic Cancer" (2009). Digitized Theses. 3943.