The broad, long-term objective of this application is to improve the prognosis of patients with unresectable hepatocellular carcinoma (HCC). Magnetic resonance imaging (MRI) is proposed to monitor transcatheter arterial chemoembolization (TACE) of patients with HCC. A 4-dimensional transcatheter intraarterial perfusion weighted (TRIP)-MRI technique, using 3 spatial and 1 time dimension, will be used to measure quantitative changes in tumor perfusion at the time of therapy. These quantitative, absolute changes in perfusion will be correlated with clinical outcomes, x-ray digital subtraction angiography (DSA) endpoints, and tumor angiogenic markers on tissue specimens. The rationale is to determine the pivotal role that perfusion plays during TACE as a means of determining endpoints for therapy. Studies will be performed within the same prospective cohort of 100 patients with HCC already scheduled to undergo TACE using a hybrid MR-interventional radiology DSA procedure suite. This suite contains both a 1.5T MRI scanner and a DSA unit.
Specific Aim 1 will correlate tumor perfusion changes during TACE with clinical outcomes. It is hypothesized that baseline and interval reductions in quantitative 4D TRIP-MRI perfusion levels during TACE can predict future clinical outcomes. These clinical outcomes will be assessed by conventional anatomic size changes on MRI; functional changes in water mobility using an improved diffusion weighted MRI technique; survival; and toxicity. The health relevance will be to optimize TACE outcomes by measuring absolute perfusion changes for therapy.
Specific Aim 2 will correlate DSA endpoints during TACE with perfusion changes and clinical outcomes. It is hypothesized that DSA endpoints during TACE do not correlate with quantitative 4D TRIP-MRI perfusion changes and do not predict clinical outcomes. The health relevance is to use external objective standards to see if a specific DSA endpoint can and should be targeted during therapy.
Specific Aim 3 will correlate perfusion changes during TACE with tumor angiogenesis and clinical outcomes. Angiogenic proteins-- vascular endothelial growth factor (VEGF) and hypoxia inducible factor-11 (HIF-11) will be measured on pre-TACE liver biopsy specimens and on available liver explants. It is hypothesized that baseline tissue levels of VEGF and HIF-11 correlate with clinical outcomes after TACE; and that 4D TRIP-MRI perfusion changes during TACE predict future expression of tissue VEGF and HIF-11 on liver explants.
The health relevance is to see how baseline tissue angiogenic markers affect outcome and to determine which TACE endpoints are most likely to induce angiogenesis. The relevance to public health is to determine the central role that blood flow to tumors plays during treatment of liver cancer. We postulate that measurement of this blood flow during treatment can be used to help predict response to therapy. This information might improve the prognosis of future patients with liver cancer. ? ? ?
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