Quantifying Regional and Global Liver Function Via Gadoxetic Acid Uptake

Abstract

Liver function is a dominant factor in the survival of patients with hepatocellular carcinoma (HCC). Measures of regional and global liver function are critical in guiding treatments for intrahepatic cancers. Regional and global liver function assessments important for defining the magnitude and spatial distribution of radiation dose to preserve functional liver parenchyma and reduce incidence of hepatotoxicity from radiation therapy (RT) for intrahepatic cancer treatment. This individualized liver function-guided RT strategy is critical for patients with heterogeneous and poor liver function, often observed in cirrhotic patients treated for HCC. Dynamic gadoxetic-acid enhanced (DGAE) magnetic resonance imaging (MRI) allows investigation of liver function through observation of the uptake of contrast agent into the hepatocytes.

This work seeks to determine if gadoxetic uptake rate can be used as a reliable measure of liver function, and to develop robust methods for uptake estimation with an interest in the therapeutic application of this knowledge in the case of intrahepatic cancers. Since voxel-by voxel fitting of the preexisting nonlinear dual-input two-compartment model is highly susceptible to over fitting, and highly dependent on data that is both temporally very well characterized and low in noise, this work proposes and validates a new model for quantifying the voxel-wise uptake rate of gadoxetic acid as a measure of regional liver function. A linearized single-input two-compartment (LSITC) model is a linearization of the pre-existing dual-input model but is designed to perform uptake quantification in a more robust, computationally simpler, and much faster manner. The method is validated against the preexisting dual-input model for both real and simulated data. Simulations are used to investigate the effects of noise as well as issues related to the sampling of the arterial peak in the characteristic input functions of DGAE MRI.

Further validation explores the relationship between gadoxetic acid uptake rate and two well established global measures of liver function, namely: Indocyanine Green retention (ICGR) and Albumin-Bilirubin (ALBI) score. This work also establishes the relationships between these scores and imaging derived measures of whole liver function using uptake rate. Additionally, the same comparisons are performed for portal venous perfusion, a pharmacokinetic parameter that has been observed to correlate with function in patients with relatively good liver function, and has been used as a guide for individualized liver function-guided RT. For the patients assessed, gadoxetic acid uptake rate performs significantly better as a predictor of whole liver function than portal venous perfusion.

This work also investigates the possible gains that could be introduced through use of gadoxetic uptake rate maps in the creation of function-guided RT plans. To this end, plans were created using both perfusion and uptake, and both were compared to plans that did not use functional guidance. While the plans were generally broadly similar, significant differences were observed in patients with severely compromised uptake that did not correspond with compromised perfusion.

This dissertation also deals with the problem of quantifying uptake rate in suboptimal very temporally sparse or short DGAE MRI acquisitions. In addition to testing the limits of the LSITC model for these limited datasets (both realistic and extreme), a neural network-based approach to quantification of uptake rate is developed, allowing for increased robustness over current models.