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Page 10 of 17 Marasco et al. Hepatoma Res 2020;6:32 I http://dx.doi.org/10.20517/2394-5079.2019.54

specific contrast agent that shows up to 50% hepatocyte uptake and is then excreted into the bile ducts. In
non-cirrhotic livers, it has peak enhancement on T1-W images at about 20-30 min after injection [138,139] .
Uptake and metabolism of this contrast agent is related to hepatocyte function [140,141] . Therefore, hepatic
parenchymal enhancement is affected by the severity of cirrhosis [138] . The mean signal intensity (SI) of liver
parenchyma on HBP reflects a quantitative measure of hepatocyte contrast agent uptake [114] . Watanabe et
al .[142] found that liver SI on Gd-EOB-DTPA MRI is strongly correlated with fibrosis stage and concluded
that it is more reliable for staging hepatic fibrosis than DWI or hematologic and clinical parameters.
Moreover, many recent studies [143,144] have reported the usefulness of relative liver enhancement [RLE = (SI
HBP - SI PRE)/SI PRE] in predicting PHLF in patients with hepatic metastases or with HCC because of the
superiority of pre-operative RLE over both the 50-50 criteria and ISGLS grading system [67,143] . Pre-operative
RLE measurement is considered reliable and reproducible with high inter-observer variability [145] . However,
further studies are necessary to understand the real role of RLE to predict PHLF.

Other parameters derived from Gd-EOB-DTPA MRI have been evaluated as predictors of PHLF with modest
success. Contrast enhancement ratio (CER= [(SIHBP - SIPRE)/(SITP - SIPRE] where SITP is measured on
transitional phases, about 3 min post-contrast injection) is less affected by the hemodynamics of a patient
than RLE, and better reflects Gd-EOB-DTPA uptake by hepatocytes. CER can also be multiplied by TLV/
SLV ratio (total CER, tCER) and by RLV/SLV ratio (remnant CER, rCER) [138] . A recent study demonstrated
that rCER correlates with the development of PHLF better than volumetry (cut off ≤ 1.23) and that tCER is
an independent predictive factor for PHLF (cut off ≤1.42) [114] . The prognostic value of CER, in predicting
PHLF, seems to be stronger than the ADC value and TVL/SLV ratio in cirrhotic patients [114] . Therefore,
patients with a relatively small tCER should preferably go under local treatment rather than resection [114] .
Asenbaum et al. [146] combined functional and morphological parameters (functional FLR, functFLR) by
measuring remnant RLE on Gd-EOB-DTPA MRI and the RLV by the formula: (RLV*remnantRLE)/body
weight (BW). A decreased functFLR (< 8.73 mL/kg) demonstrated a strong correlation with the development
of PHLF in patients that underwent major liver resection [146] .

[67]
Kim et al. verified the correlation between the remnant hepatocellular uptake index (rHUI = RVL × [(L20/
S20)-1]) and PHLF, where L20 is the mean SI of the FLR, and S20 is the mean SI of the spleen on HBP
images. A lower rHUI (< 0.89) and a lower body weighted and corrected rHUI (rHUI-BW < 12.38) showed
a statistically significant correlation with the development of PHLF in patients undergoing major liver
resection, and predicted PHLF better than ICG related parameters. In this study, the severity of PHLF also
[67]
showed a statistically significant association with rHUI-BW . Nevertheless, despite numerous promising
findings, MRI still represents an expensive, not immediate and not widely available technique, and careful
evaluation about its use needs to be performed according to each hospital setting. Thus, pre-operative MRI
parameters could be useful in predicting PHLF when available, otherwise, cheaper and faster techniques
should be used.

Single photon emission computed tomography
Single photon emission computed tomography (SPECT) using 99 metastable technetium diethylenetriamine-
pentaacetic acid-galactosyl human serum albumin (99mTc-GSA) is of increasing interest for the pre-
operative evaluation of cirrhotic patients. The molecule 99mTc-GSA is taken up rapidly by the liver, reflecting
accurately the volume of functional liver and FLR; indeed, it is correlated to bilirubin levels, INR, and ICG
clearance [147] . Liver 99mTc-GSA SPECT has been reported to be more useful than CT in predicting remnant
liver function before hepatic resection [148] . This technique is thought to be a substitute for ICG rate. It can
be used for patients whose liver function cannot be fully estimated using multimodal algorithms, such as
patients with jaundice, portal hypertension, or ICG intolerance [149] . However, as for MRI, there has not been
real-life application of this technique for predicting PHLF to date.