Measuring Liver Function-Technical Aspects
Steven Sourbron1

1Leeds Imaging Biomarkers Group, University of Leeds, United Kingdom

Synopsis

This talk will provide a broad introduction of MRI methods to measure the function of liver parenchyma, with more in-depth treatment of Dynamic Gadoxetate-Enhanced MRI for the quantification of hepatocellular transporter function. We will also cover some basic facts about the liver, review competing non-MRI techniques for assessing liver function, and present examples of applications in basic science, drug development and clinical practice.

Overview

This talk will provide a broad introduction of MRI methods to measure the function of liver parenchyma, with more in-depth treatment of Dynamic Gadoxetate-Enhanced MRI for the quantification of hepatocellular transporter function.

We will review of the basic facts about liver anatomy, structure, function and pathophysiology, as well as the main competing, non-MRI methods to measure liver function including blood tests and non-MRI imaging methods such as hepatobiliary scintigraphy [1].

The main classes of functional MRI methods will be introduced, including iron [2] and fat [3] quantification with spectroscopic and relaxometry methods, fibrosis assessment through elastography [4] and relaxometry [5], and measurement of perfusion and hepatocellular function with dynamic contrast-enhanced MRI (DCE-MRI) [6].

We will then discuss in more detail the technical aspects of DCE-MRI with the liver-specific contrast agent Gadoxetate (Dynamic Gadoxetate-Enhanced MRI or DGE-MRI). This will cover an overview of the hepatocyte transporters and our current understanding of Gadoxetate transport into- and out of the cells [7]. We will discuss possible acquisition, modelling and analysis approaches of DGE-MRI in some detail, and review current limitations and open problems.

The talk will conclude by illustrating the use of these methods in some typical application areas, in particular as a replacement of histopathology [8], in predicting and assessing drug toxicity [9] as currently investigated by the EU-wide TRISTAN project [10], and to predict post-operative liver function after partial hepatectomy [11].

Syllabus

Quick facts about the liver

  • Functions of the liver
  • Meso- and microstructure
  • Macrostructure and blood supply
  • Diseases of the liver
  • Regeneration

Non-MRI measurements of liver function

  • Scores based on blood tests
  • Indocyanine Green (ICG)
  • LiMax Test
  • Histopathology
  • Hepatobiliary Scintigraphy
  • Ultrasound Elastography

MRI measurements of liver function

  • Fat fraction and iron content: spectroscopy and relaxometry
  • Fibrosis scores: relaxometry and elastography
  • Perfusion and hepatocellular function: dynamic-contrast enhanced MRI

A closer look at hepatocellular transporter function measurement with MRI

  • Hepatocyte transporters - intracellular uptake and excretion
  • Transporter affinities and pharmacokinetics of Gadoxetate
  • Acquisition strategies for dynamic Gadoxetate-enhanced MRI
  • Modelling and analysis strategies for dynamic Gadoxetate-enhanced MRI
  • Limitations and current challenges

Example applications of liver function measurement

  • The "virtual biopsy"
  • The TRISTAN project: Predicting Drug-Induced Liver Injury (DILI)
  • Risk assessment for partial hepatectomy

Acknowledgements

Steven Sourbron is partly funded by the Innovative Medicines Initiative 2 Joint Undertaking, Grant Agreement number 116106-IB4SD-TRISTAN

References

[1] K.P. CieĊ›lak. Scintigraphic assessment of liver function in patients requiring liver surgery. PhD thesis, University of Amsterdam, 18 January 2018 (ISBN 978-94-6361-043-8).

[2] P. Nasr, et al. Using a 3% Proton Density Fat Fraction as a Cut-Off Value Increases Sensitivity of Detection of Hepatic Steatosis, Based on Results From Histopathology Analysis. Gastroenterology 2017 Jul;153(1):53-55.e7

[3] D. Hernando, et al. Quantification of Liver Iron with MRI: State of the Art and Remaining Challenges. J Magn Reson Imaging. 2014 Nov; 40(5): 1003–1021.

[4] K. Venkatesh, et al. Magnetic Resonance Elastography of Liver: Clinical Applications. J Comput Assist Tomogr. 2013 Nov-Dec; 37(6): 887-896.

[5] M Pavlides, et al. Multiparametric magnetic resonance imaging predicts clinical outcomes in patients with chronic liver disease. J Hepatol. 2016 Feb; 64(2): 308–315.

[6] Sourbron, et al. Combined quantification of liver perfusion and function with dynamic gadoxetic acid-enhanced MR imaging. Radiology. 2012 Jun;263(3):874-83.

[7] https://www.unige.ch/hepatocyte-transporter-network/home/

[8] Mikael Forsgren. The Non-Invasive Liver Biopsy: Determining Hepatic Function in Diffuse and Focal Liver Disease. PhD thesis, Linköping University, 23 May 2017 (DOI: 10.3384/diss.diva-136545)

[9] Kenna J.G. et al. (2018) Noninvasive Preclinical and Clinical Imaging of Liver Transporter Function Relevant to Drug-Induced Liver Injury. In: Chen M., Will Y. (eds) Drug-Induced Liver Toxicity. Methods in Pharmacology and Toxicology. Humana Press, New York, N [OPEN ACCESS].

[10] https://www.imi-tristan.eu/en/liver/

[11] Nilsson H, et al. The inhomogeneous distribution of liver function: possible impact on the prediction of post-operative remnant liver function. HPB (Oxford). 2015 Mar;17(3):272-7.

Proc. Intl. Soc. Mag. Reson. Med. 26 (2018)