Assessment of liver function with Dynamic Contrast-Enhanced MRI in patients scheduled for liver resection - a pilot study.

Surgical resection remains the most effective treatment in patients with
hepatic malignancies. In the last decades the number of extended surgical
resections has increased. Extended resection can result in a small
postoperative future remnant liver (FRL) leading to postoperative liver failure
and mortality. Therefore, preoperative assessment of FRL is of great
importance. Computed tomography (CT) volumetry is considered the gold standard
in the preoperative assessment of patients scheduled for major liver resection.
However, FRL volume is not per se representative for FRL function, especially
in patients with a compromised (i.e. steatosis, fibrosis, cholestasis) liver
parenchyma. Liver function can be divided in uptake, biotransformation,
synthesis and excretion. Clinically used serum liver function tests provide an
indirect evidence of only one of these processes and all of them lack the
possibility to assess regional liver function. 99mTc labelled mebrofenin
hepatobiliary scintigraphy with single emission proton CT (99mTc-HBS with
SPECT) has been validated as a tool to assess total and regional liver function
and is part of standard preoperative work-up at our centre. Nonetheless,
99mTc-HBS has disadvantages as well: radiation burden for the patient and
inferior quality of the SPECT images for use in the diagnostic process.

In the last decades the use of Gd-EOB-DTPA-enhanced MRI has been introduced as
an imaging technique in the diagnostic work-up in patients suspected of liver
malignancies, providing high sensitivity for the detection of liver lesions.
The pharmacokinetic properties of Gd-EOB-DTPA are similar to those of
mebrofenin used in 99mTc-HBS. Applying the dynamic contrast enhanced-MRI
(DCE-MRI) technique with Gd-EOB-DTPA allows assessment of its pharmacokinetic
behaviour in liver parenchyma including the FRL, allowing a functional
evaluation.

In this pilot study we will test this hypothesis by comparing DCE-MRI with
Gd-EOB-DTPA with 99mTc-HBS. Furthermore we plan to measure the effect of
Gd-EOB-DTPA on the intrinsic T1 relaxation times. This will allow the
extraction of absolute concentrations of Gd-EOB-DTPA in the liver with a high
resolution. Finally, liver fibrosis, steatosis and microperfusion can now
reliably be assessed with MRI, allowing a regional comparison of liver function
with liver fibrosis, steatosis and microperfusion levels. As we will obtain
histological results of both the resected liver tissue as well as the future
remnant liver (peroperative liver biopsy), these MRI parameter will be
correlected with histological characteristics as well.

To compare DCE-MRI of the liver with the liver-specific contrast agent
Gd-EOB-DTPA with 99mTC-HBS in patients scheduled for liver resection in
estimation of (regional) liver function.

Single-centre observational study

Participating in this study leads to no immediate advantage for the individual
participant. However, it is important to evaluate whether DCE-MRI of the liver
using Gd-EOB-DTPA can be used to derive information on total and future remnant
liver parenchyma function similar to that which the 99mTc-HBS can provide but
with better spatial resolution. In the future, this may lead to better
stratification of patients scheduled for possible liver resection into those
who are eligible, those who may require portal vein embolization and those who
are not eligible for resection. If this can be achieved, patients with focal
liver disease may then benefit considerably.

Additionally, knowledge of individual liver and steatosis (measured with
MRI-fatmaps) can be beneficial for future follow-up.

The burden for subjects consists of one extra visit to the hospital (if the
sessions can not be scheduled on the same day) in which one extra MRI
examination is performed which will take approximately 50 minutes in the
MR-scanner. Subjects are asked to fast for at least 4 hours before the MR
examination. Routine dosages of contrast agent (Gd-EOB-DTPA) are administered
to subjects. Adverse reactions to contrast agent administration are rare. 10 mL
of blood will be drawn from each subject prior to MRI examination at the
placement of the I.V. line. In the unlikely case of unexpected findings on the
MR images (e.g. hitherto undiagnosed liver lesions), the consulting surgeon
will be notified as this may have consequences for the treatment strategy.

The burden for subjects additionally consists of a perioperative liver biopsy
of the future remnant liver (circa 1 cm3), which is considered a safe
procedure, as any bleeding that could occur at the biopsy site can be inspected
visually by the surgeon and stemmed if necessary.