This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.MR microscopy - 9T, with gadolinium contrast agentWe have an initial simple approach that will involve simple immersion staining to see if the vessels will fill. Since the portal and arterial sides are both dead ended in the hepatocytes, it is not clear that we would have the necessary flow path required. So we will start simply. Some earlier results many years ago give me encouragement.The humanized mouse livers were perfusion-fixed with paraformaldehyde after first heparin-flushing them and dilating them with a vasodilator via the portal vein. Human hepatocytes account for roughly 70% of the mouse liver but the distribution is not uniform by lobe. If we could perfuse the fixed liver through the portal vein with a contrast material then MRI should tell us how disrupted the vascular supply is to the humanized areas. In some nodular areas, this should be easy to visualize at 25-50u resolution. I don't know that I can find the common bile duct but a retrograde look at the biliary system might also be worth a try.
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