Characterizing the microvascular branching geometry of the dual blood supply to the liver with micro-CT

Abstract

Microvascular branching geometries determine the efficacy of the transport of nutrients and metabolic products to and from tissues in large-bodied organisms. The general `plan' is that an artery supplies oxygen, nutrients, and hormones to the tissue and a vein removes metabolic products from that tissue. The blood flow to the organ is controlled by the metabolic demand of the organ by a feedback mechanism controlling the arterial lumen diameter. The liver differs from other organs by having two vascular systems delivering its blood - the hepatic artery and the portal vein. The hepatic artery supplies the oxygen needed by liver cells, and the portal vein delivers the molecules absorbed by the gut which need to be processed by the liver tissue for use by other organs in the body. However, how the hepatic artery and portal vein interact is not fully understood in terms of how their relative flows are adjusted, either passively and/or actively, to meet the needs of the liver tissue. This dissertation explores the hypothesis that the hepatic artery's blood mixes with the portal vein's proximal to the hepatic sinusoids (where their mixing is traditionally thought to occur). This is performed utilizing micro-CT to image rat liver lobes injected with a contrast polymer. During the process of exploring this hypothesis, a number of image analysis tools needed to be developed. For one, understanding the level of accuracy by which geometrical measurements can be made by micro-CT is very important because vascular resistance to flow is proportional to the interbranch segment length, as well as inversely proportional to the fourth power of the lumen diameter. Moreover, a single vessel tree contained in a micro-CT image has hundreds, if not thousands of individual interbranch segments and knowledge of the interconnectivity relationship between the segments is important for modeling such properties as pressure distributions and relative blood flow rates. For these reasons, the development of automated measurement methods to measure the length and diameter of interbranch segments and extract the hierarchical structure of vascular trees was performed. These methods were then compared to a gold-standard measurement (obtained by measuring the lengths and diameters of interbranch segments of a microvascular cast by `hand' under a microscope) to understand the level of accuracy obtainable by micro-CT. Having successfully developed accurate automated measurement algorithms (thereby replacing the time-consuming gold standard measurement method), the algorithms were then used to compare and validate other algorithmic approaches, particularly those that quickly extract geometrical information regarding a vascular bed composed of many vessel trees within a micro-CT image. Because the hepatic artery and portal vein are in close proximity to one another as they distribute throughout the liver, the development of a special segmentation method was needed to allow separation of these concomitant vessel systems that may have `false' connections resulting from blurring of the micro-CT image. Finally, an anatomic study of the vasculature of the liver was performed which offered insight into the interaction between the hepatic artery and portal vein. In the case of specimens where only the portal vein was injected with contrast, only the portal vein was opacified, whereas in hepatic artery injections, both the hepatic artery and portal vein were opacified. Also, when different contrast agents were injected into the hepatic artery and the portal vein, the hepatic artery's contrast agent was observed to be mixed in with the different contrast injected into the portal vein. In addition, in high-resolution scans (5$\mu$m cubic voxels) anatomic evidence for hepatic arteriolo-portal venular shunts occurring between the hepatic artery and portal vein branches were found. Simulations were performed in order to rule out the possibility of the observed shunts being artifacts caused by image blurring. Thus, mixing of the hepatic artery and portal vein can occur proximal to the sinusoidal level, and hepatic arteriolo-portal venular shunts may function as a one-way valve-like mechanism, allowing flow only from the hepatic artery to the portal vein (and not the other way around).