In 2017, decompensated cirrhosis caused more than 1.32 million deaths globally and 62,943 deaths in the USA. A transjugular intrahepatic portosystemic shunt (TIPS), an intraparenchymal artificial shunt created between the hepatic vein (HV) and the portal vein (PV), is the most effective life-saving procedure to stop acute variceal bleeding (AVB) that cannot be controlled endoscopically. TIPS is also effective to decrease the risk of recurrence of tense ascites and improve renal dysfunction in patients with chronic liver disease. However, Intrahepatic puncture for TIPS creation remains one of the most challenging and radiation-intensive procedure, carrying high risks of various complications in up to 20% of cases even in the hands of experienced Interventional Radiologists. Intraperitoneal hemorrhage caused by liver and extrahepatic portal vein rupture is the most catastrophic major complication of TIPS creation. In children, TIPS has been employed to alleviate symptoms of refractory ascites and variceal bleeding, but only adult TIPS puncture sets are available for kids with portal hypertension. The intrahepatic puncture devices, complications and technical failure rate have not changed since TIPS was invented by interventional radiologists (IR). To address the critical issues described above, we are developing a novel in-plane IVUS/fiber optic imaging-integrated micro puncture balloon catheter system for TIPS creation. Tests of the fine needle/balloon catheter system in pig cadavers for TIPS creation resulted in 100% success of placing a 5Fr. catheter in the portal vein from the right hepatic vein. This novel fine needle(22G)/balloon catheter system is expected to eliminate the risk and significantly lower the difficulties of TIPS techniques, which will ultimately increase the availability of TIPS treatment. The in-plane IVUS and/or fiber optic imaging guidance will further facilitate TIPS creation. Therefore, we need to implement a series of experiments to bridge the gap between our laboratory innovation of a novel system for TIPS creation and clinical translation for treating patients with portal hypertension. At first, we will optimize the key components and parameters of the needle/balloon catheter systems using human excised cirrhotic liver specimens. Secondly, we will develop the technique of using fiber optic imaging and/or in-plane IVUS- integrated needle/balloon catheter system for TIPS creation in normal adult pigs, optimize the technical parameters, and further validate the technique of using the system for TIPS in pigs with liver cirrhosis and portal hypertension. At last, we will develop the technique of using this novel system for TIPS creation in baby and young pigs, optimize the technical parameters, and further validate the technique of using the system for TIPS in young pigs with portal hypertension. We are confident that the success of this project will lead to significant breakthroughs in the procedure of TIPS creation and benefit millions of patients with decompensated cirrhosis.

PROJECT NARRATIVE Our goal is to develop a novel in-plane IVUS/fiber optic imaging-integrated fine needle/ balloon catheter system for TIPS creation. Tests of the fine needle/balloon system in pig cadavers for TIPS creation resulted in 100% success of placing a 5Fr.catheter in portal vein from the right hepatic vein. This IVUS/fiber optic borescope-incorporated fine needle(22G)/balloon catheter system is expected to significantly lower the risk and difficulties of TIPS techniques, which will ultimately increase the availability of TIPS treatment and benefit millions of patients with decompensated cirrhosis, particularly those in underdeveloped countries.