The original version of this article, published on 22 March 2019, unfortunately contained a mistake. The following correction has therefore been made in the original: Affiliations 1 and 2 were presented incorrectly.

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Correction to: T1 mapping for liver function evaluation in gadoxetic acid-enhanced MR imaging: comparison of look-locker inversion recovery and B1 inhomogeneity-corrected variable flip angle method.

The introduction of hepatobiliary contrast agents, most notably gadoxetic acid (GA), has expanded the role of MRI, allowing not only a morphologic but also a functional evaluation of the hepatobiliary system. The mechanism of uptake and excretion of gadoxetic acid via transporters, such as organic anion transporting polypeptides (OATP1,3), multidrug resistance-associated protein 2 (MRP2) and MRP3, has been elucidated in the literature. Furthermore, GA uptake can be estimated on either static images or on dynamic imaging, for example, the hepatic extraction fraction (HEF) and liver perfusion. GA-enhanced MRI has achieved an important role in evaluating morphology and function in chronic liver diseases (CLD), allowing to distinguish between the two subgroups of nonalcoholic fatty liver diseases (NAFLD), simple steatosis and nonalcoholic steatohepatitis (NASH), and help to stage fibrosis and cirrhosis, predict liver transplant graft survival, and preoperatively evaluate the risk of liver failure if major resection is planned. Finally, because of its noninvasive nature, GA-enhanced MRI can be used for long-term follow-up and post-treatment monitoring. This review article aims to describe the current role of GA-enhanced MRI in quantifying liver function in a variety of hepatobiliary disorders.

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Quantification of liver function using gadoxetic acid-enhanced MRI

The need for extended liver resection is increasing due to the growing incidence of liver tumors in aging societies. Individualized surgical planning is the key for identifying the optimal resection strategy and to minimize the risk of postoperative liver failure and tumor recurrence. Current computational tools provide virtual planning of liver resection by taking into account the spatial relationship between the tumor and the hepatic vascular trees, as well as the size of the future liver remnant. However, size and function of the liver are not necessarily equivalent. Hence, determining the future liver volume might misestimate the future liver function, especially in cases of hepatic comorbidities such as hepatic steatosis. A systems medicine approach could be applied, including biological, medical, and surgical aspects, by integrating all available anatomical and functional information of the individual patient. Such an approach holds promise for better prediction of postoperative liver function and hence improved risk assessment. This review provides an overview of mathematical models related to the liver and its function and explores their potential relevance for computational liver surgery. We first summarize key facts of hepatic anatomy, physiology, and pathology relevant for hepatic surgery, followed by a description of the computational tools currently used in liver surgical planning. Then we present selected state-of-the-art computational liver models potentially useful to support liver surgery. Finally, we discuss the main challenges that will need to be addressed when developing advanced computational planning tools in the context of liver surgery.

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Computational Modeling in Liver Surgery.

Chronic injury to the liver leads to inflammation and hepatocyte necrosis, which when untreated can lead to myofibroblast activation and fibrogenesis with deposition of fibrous tissue. Over time, liver fibrosis can accumulate and lead to cirrhosis and end-stage liver disease with associated portal hypertension and liver failure. Detection and accurate measurement of the severity of liver fibrosis are important for assessing disease severity and progression, directing patient management, and establishing prognosis. Liver biopsy, generally considered the clinical standard of reference for detecting and measuring liver fibrosis, is invasive and has limitations, including sampling error, relatively high cost, and possible complications. For these reasons, liver biopsy is suboptimal for fibrosis screening, longitudinal monitoring, and assessing therapeutic efficacy. A variety of established and emerging qualitative and quantitative noninvasive MRI methods for detecting and staging liver fibrosis might ultimately serve these purposes. In this article, we review multiple MRI methods for detecting and measuring liver fibrosis and discuss the diagnostic performance and specific strengths and limitations of the various techniques.

Putting it all together: established and emerging MRI techniques for detecting and measuring liver fibrosis.

Noninvasive assessment of liver fibrosis via spleen stiffness measurement using acoustic radiation force impulse sonoelastography in patients with chronic hepatitis b or c

Assessing the liver function provides valuable information to evaluate surgical risk and plan accordingly. Current studies focus on whole liver function evaluation. However, assessment of segmental liver function is equally important in the clinical practice. The purpose of this study was to investigate whether Gd-EOB-DTPA-enhanced MRI can evaluate the liver function of each segment by using T1 mapping at 3 Tesla MRI. One hundred three patients were classified into one of 4 groups: a normal liver function (NLF) group (n = 38), a liver cirrhosis with Child-Pugh A (LCA) group (n = 33), a liver cirrhosis with Child-Pugh B (LCB) group (n = 21), and a liver cirrhosis with Child-Pugh C (LCC) group (n = 11). All patients underwent Gd-EOB-DTPA-enhanced MRI scans. T1 relaxation times were measured on the liver superimposing T1 mapping images. Reduction rate (△%) of T1 relaxation time of the liver parenchyma were calculated. After 20 min of Gd-EOB-DTPA enhancement, the T1 relaxation time of all liver segments in the LCC group were different from those in all the other groups, and more liver segments from the LCB and LCA groups different from the NLF group (p < 0.05). For the LCB group, the areas under the receiver operating characteristic curves (AUCs) of different liver segments for hepatobiliary phase (HBP) were 0.654-0.904 on T1 relaxation time, and 0.709-0.905 on △%. For the LCC group, the AUCs of different liver segments for HBP were 0.842–0.997 on T1 relaxation time, and 0.887–0.990 on △%. For LCB patients, segmental liver function evaluation is possible using Gd-EOB-DTPA-enhanced MRI T1 mapping. For LCC patients, all liver segments can be used to evaluate liver function and both T1 relaxation time and the △% of T1 relaxation time have good diagnostic performance.

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Evaluating segmental liver function using T1 mapping on Gd-EOB-DTPA-enhanced MRI with a 3.0 Tesla

To compare hepatobiliary phase (HBP) images obtained 10 and 20 min after Gd-EOB-DTPA-enhanced MRI for liver function assessment in clinic on 3.0 T MR imaging. 103 patients were separated into four groups: 38 patients for the normal liver function (NLF) group, 33 patients for the liver cirrhosis with Child–Pugh A (LCA) group, 21 patients for the liver cirrhosis with Child–Pugh B group, and 11 patients for a liver cirrhosis with Child–Pugh C group. T1 relaxation times (T1rt) were measured on T1 mapping and reduction rates of T1rt (rrT1rt) were calculated. HBP images were obtained at the 10- and 20-min mark after Gd-EOB-DTPA enhancement. T1rt on pre-enhancement imaging showed no significant difference (p > 0.05) among all four groups. T1rt for both the 10-min HBP and the 20-min HBP showed a significant difference (p   0.05) between the NLF group and the LCA group. T1rt and rrT1rt showed no significant difference (p > 0.05) between 10-min HBP and 20-min HBP among all groups. The ROC analysis on 10-min HBP and 20-min HBP showed a lower diagnostic performance between NLF group and LCA group (AUC from 0.532 to 0.582), but high diagnostic performance (AUC from 0.788 to 1.000) among others group. In comparing 10-min HBP and 20-min HBP T1 mapping after Gd-EOB-DTPA enhancement, our results suggest that 10-min HBP T1 mapping is a feasible option for quantitatively assessing liver function.

Wei-Jia Qiu

Papers

Evaluating segmental liver function using T1 mapping on Gd-EOB-DTPA-enhanced MRI with a 3.0 Tesla

Comparison of 10- and 20-min hepatobiliary phase images on Gd-EOB-DTPA-enhanced MRI T1 mapping for liver function assessment in clinic.