Physiologically realistic and validated mathematical liver model reveals [corrected] hepatobiliary transfer rates for Gd-EOB-DTPA using human DCE-MRI data

PLoS One. 2014 Apr 18;9(4):e95700. doi: 10.1371/journal.pone.0095700. eCollection 2014.

Abstract

Objectives: Diffuse liver disease (DLD), such as non-alcoholic fatty liver disease (NASH) and cirrhosis, is a rapidly growing problem throughout the Westernized world. Magnetic resonance imaging (MRI), based on uptake of the hepatocyte-specific contrast agent (CA) Gd-EOB-DTPA, is a promising non-invasive approach for diagnosing DLD. However, to fully utilize the potential of such dynamic measurements for clinical or research purposes, more advanced methods for data analysis are required.

Methods: A mathematical model that can be used for such data-analysis was developed. Data was obtained from healthy human subjects using a clinical protocol with high spatial resolution. The model is based on ordinary differential equations and goes beyond local diffusion modeling, taking into account the complete system accessible to the CA.

Results: The presented model can describe the data accurately, which was confirmed using chi-square statistics. Furthermore, the model is minimal and identifiable, meaning that all parameters were determined with small degree of uncertainty. The model was also validated using independent data.

Conclusions: We have developed a novel approach for determining previously undescribed physiological hepatic parameters in humans, associated with CA transport across the liver. The method has a potential for assessing regional liver function in clinical examinations of patients that are suffering of DLD and compromised hepatic function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Contrast Media*
  • Gadolinium DTPA*
  • Humans
  • Liver Diseases / diagnosis*
  • Liver Diseases / pathology*
  • Magnetic Resonance Imaging*
  • Models, Theoretical*
  • Reproducibility of Results
  • Retrospective Studies
  • Sensitivity and Specificity

Substances

  • Contrast Media
  • gadolinium ethoxybenzyl DTPA
  • Gadolinium DTPA

Grants and funding

Funding sources: Swedish Research Council (VR/M, 2007-2884, http://www.vr.se/), the Medical Research Council of Southeast Sweden (FORSS, 12621, http://www.fou.nu/is/forss), the Linköping University, Linköping University Hospital Research Foundations, County Council of Östergötland. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.