The broad, long-term objective of this proposal is to improve the prognosis of patients with unresectable hepatocellular carcinoma (HCC). These patients commonly undergo transcatheter arterial embolization (TAE) as a form of palliative therapy. TAE is currently performed using x-ray DSA to estimate blood flow reductions after each injection of embolic material. However, DSA flow estimates may be highly subjective and poorly reflective of tumor perfusion. The objective of this proposal is to develop a new magnetic resonance imaging (MRI) technique to iteratively monitor liver tumor perfusion during TAE procedures. The proposed transcatheter intra-arterial perfusion MRI (TRIP-MRI) techniques offer the potential to monitor perfusion changes during TAE procedures within hybrid DSA/MRI procedure suites. For TRIP-MRI, small contrast doses are infused directly through the TAE catheter permitting iterative pharmacokinetic measurements to estimate perfusion changes after each injection of embolic material. Technical challenges must be resolved to permit serial quantitative TRIP-MRI measurements and further studies are required to validate TRIP-MRI measurements by comparison to invasive gold-standard methods. Proposed studies will address the following Specific Aims in a liver tumor animal model (Aims 1 and 2) and clinical patients with hepatocellular carcinoma (Aim 3):
Specific Aim 1 : Technical Development of TRIP-MRI Methodology Task 1: To test the hypothesis that intra-arterial injections permit quantitative estimation of contrast pharmacokinetics without needing to directly measure the arterial input function within distal hepatic arteries. Task 2: To test the hypothesis that TRIP-MRI contrast dose can be optimized intra-procedurally to permit short wash-out times and measurement repetition intervals conducive to TAE monitoring.
Specific Aim 2 : Quantitative Validation of TRIP-MRI Measurements Task 1: To test the hypothesis that TRIP-MRI measurements can accurately quantify intra-procedural perfusion reductions during liver tumor embolization. Task 2: To test the hypothesis that intra-procedural TRIP-MRI measurements can accurately predict the final fractional reduction to tumor perfusion after post-procedural catheter withdrawal.
Specific Aim 3 : Clinical Comparison of TRIP-MRI and DSA Monitored Embolic Endpoints Task 1: To test hypothesis that quantitative TRIP-MRI perfusion measurements provide a more reproducible estimation of TAE embolic endpoints than conventional DSA monitoring approaches. Task 2: To test the hypothesis that DSA flow estimates are poorly reflective of tumor perfusion reduction by comparison to quantitative intra-procedural TRIP-MRI perfusion measurements. ? ? ?
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