DESCRIPTION (provided by applicant): The objective of this proposal is to develop and test a microcatheter that creates a partial arterial occlusion during injection of embolic agents into tumors in the liver and thereby improve efficacy and reproducibility of the method. In the US over 30,000 people will be diagnosed with primary liver cancer and over 140,000 people will be diagnosed with colorectal cancer each year, of which 75% will metastasize to the liver. Embolization therapy, or the transvascular injection of drug and/or embolic agents directly into the tumor vasculature using a microcatheter, was established as a standard of care for intermediate stage hepatocellular carcinoma in 2006. However, clinical study results are remarkably inconsistent. Embolx aims to develop a delivery microcatheter, including a balloon, comprised of longitudinal channels that regulate anterograde arterial flow into the tumor and one-way valves that prevent retrograde flow. The proposed device will allow pressure measurement in the vascular compartment distal to the occlusion and enable a quantitative pressure- mediated endpoint. When the occlusion balloon is inflated at the site of injection, the pressure distal to the balloon immediately drops, causing distal hepatoenteric arteries to reverse direction, thereby producing hepatofugal flow which provides anterograde protection. We hypothesize that this device will eliminate reflux of embolic agents into proximal arterial branches, reduce or eliminate anterograde bypass of embolic agents into distal hepatoenteric arteries and maintain a controlled flow rate of blood into the tumor, thereby delaying pressure elevation and enabling improved embolic distribution. Further, isolation of the arterial space distal to the occlusion from the general circulation enables a pressure measurement to be a reliable signal of endpoint and support standardization of the method. If the proposed aims are achieved, this development will open a new channel of investigation leading to a change in the paradigm of embolization therapy and improve outcomes and quality of life for patients living with cancers. In Specific Aim #1, the device development includes, a detailed multi-variable flow simulation (Task 1), development of the catheter (Task 2), and development of the partial occlusion balloon (Task 3). At the completion of this Aim, the fully functional device is ready for testing and device assembly of Specific Aim #2, wherein 30 devices are tested for functionality, most importantly, anterograde flow, retrograde retention and catheter over-the-wire trackability in a tortuous vasculature anatomy fixture. Following completion of testing, 30 devices will be assembled and packaged in a class 10,000 clean room and E-beam sterilized for animal testing. In Specific Aim #3, the device will be tested in the porcine liver model. The goals of the animal studies are to establish: (1) safety, (2) pressure drop distal to the occlusion balloon (3) flow reversal of the gastroenteric artery and (4) elimination of retrograde reflux. At the conclusion of these studies, we hope to have a functional, validated microcatheter device, ready for advanced animal testing, FDA submission, clinical studies and market introduction.

PUBLIC HEALTH RELEVANCE: Transvascular infusion of embolic agents directly into the tumor using a microcatheter was established as the standard of care for treatment of hepatocellular carcinoma in 2006. However, its use is hindered by remarkably inconsistent outcomes. The objective of this proposal is to develop and test a microcatheter that creates a partial arterial occlusion during injection of embolic agents into tumors in the liver and thereby improve efficacy and reproducibility of the method. This enables a quantitative pressure measurement as an endpoint which supports standardization of the method.