BackgroundOpen laparotomy hepatic portal vein injection is a well‐used pre‐clinical technique for transplantation of cell therapies to the liver in mice, including islet transplantation studies for type 1 diabetes. We hypothesised that ultrasound‐guided hepatic portal vein injection in mice would provide reproducible and reliable results, as is currently obtained via open laparotomy techniques, and offer a surgical refinement to emulate islet transplantation in humans.MethodsFluorescent‐polymer microparticles (20 μm) were injected (27G‐needle) into the hepatic portal vein via open laparotomy (n=4) or under ultrasound‐guidance (n=4) using an MX550D‐transducer with a Vevo3100‐scanner (FUJIFILM VisualSonics, Inc., Canada). Mice were culled 24‐hours post injection; organs were frozen, step sectioned (10 μm‐slices,) and 10 sections/mouse (50 μm‐spacing) were quantified for microparticles in the liver and other organs by fluorescent microscopy.ResultsMurine hepatic portal vein injection, via open laparotomy‐route, resulted in widespread distribution of microparticles in the liver, lungs and spleen; ultrasound‐guided injection resulted in reduced microparticle delivery (p<0.0001) and microparticle clustering in distinct areas of the liver at the site of needle penetration, with very few/no microparticles being seen in lung and spleen tissues, hypothesised to be due to flow into the body cavity: liver median(IQR) 4.15(0.00‐4.15) versus 0.00(0.00‐0.00) particle‐count mm‐2, respectively.ConclusionsUltrasound‐guided injection results in microparticle clustering in the liver, with an overall reduction in microparticle number when compared to open laparotomy hepatic portal vein injection, and high variability in microparticle‐counts detected between mice. Ultrasound‐guided injection is not currently a technique that can replace open laparotomy hepatic portal vein injection of islet transplantation in mice.