PurposeTo test the hypothesis that Pressure-Enabled Drug Delivery (PEDD) would improve the delivery of surrogate therapeutic glass microspheres (GMs) via hepatic artery infusion to liver tumors when compared with a conventional endhole microcatheter. Materials and MethodsThe study was conducted in transgenic pigs (Oncopigs) with induced liver tumors. Tumors were infused intra-arterially with fluorescently labeled GM. PEDD with a specialized infusion device (TriNav; TriSalus Life Sciences, Westminster, Colorado) was compared with conventional endhole microcatheter delivery in both lobar and selective infusions. Near-infrared imaging was used to detect GM fluorescent signal in tumors. Image analysis with a custom deep learning algorithm (Visiopharm A/S) was used to quantitate signal intensity in relation to the tumor border. ResultsWith lobar infusions, significant increases in GM signal intensity were observed in and around tumors after PEDD (n = 10) when compared with those after conventional delivery (n = 7), with PEDD increasing penetration into the tumor by 117% (P = .004). In selective infusions, PEDD (n = 9) increased penetration into the tumor by 39% relative to conventional delivery (n = 8, P = .032). Lobar PEDD of GMs to the tumor was statistically equivalent to conventional selective delivery (P = .497). ConclusionsPEDD with a TriNav device significantly improved GM uptake in liver tumors relative to conventional infusion in both lobar and selective procedures. Lobar GM delivery with PEDD was equivalent to conventional selective delivery with an endhole device, suggesting that proximal PEDD infusions may enable effective delivery without selection of distal target vessels.