Imaging-Based Liver Function Tests – Past, Present and Future

Abstract

Preoperative assessment of liver function and?prediction of postoperative functional reserve are important in patients scheduled for liver resection. While determination of absolute liver function currently mostly relies on laboratory tests and clinical scores, postoperative remnant liver function is estimated volumetrically using imaging data obtained with computed tomography (CT) or magnetic resonance imaging (MRI). Accurate estimation of hepatic function is also relevant for intensive care patients, oncologic patients, and patients with diffuse liver disease. The indocyanine green (ICG) test is still the only established test for estimating true global liver function. However, more recent tools such as the LiMAx test also allow global assessment of hepatic function. These tests are limited when liver function is inhomogeneously distributed, which is the case in such conditions as unilateral cholestasis or after portal vein embolization. Imaging-based liver function tests were first developed in nuclear medicine and, compared with laboratory tests, have the advantage of displaying the spatial distribution of liver function. Nuclear medicine scans are obtained using tracers such as?99mTc galactosyl and 99mTc mebrofenin. Liver function is typically assessed using planar scintigraphy. However, three-dimensional volumetry is possible with single-photon emission computed tomography (SPECT-CT). Another technique for image-based liver function estimation is Gd-EOB-enhanced MRI. While metabolization of Gd-EOB in the body is similar to that of ICG and mebrofenin, its distribution in the liver can be displayed by MRI with higher temporal and spatial resolution. Moreover, MRI-based determination of liver function can be integrated into routine preoperative imaging. This makes MRI an ideal candidate for preoperative determination of?liver function, though the best pulse sequence and the parameter to be derived from the image information remain to be identified. Another question to be answered is how the results may be affected by renal function and the presence of hyperbilirubinemia. As more results from clinical evaluation including comparison with postoperative liver function data become available, image-based liver function tests, especially with use of Gd-EOB as the contrast medium, have the potential to add another dimension to preoperative imaging. Key Points: ??Liver function consists of a multitude of subfunctions such as biotransformation, excretion and storage. ??Global liver function tests are score-based tests such as Child-Pugh or MELD as well as the ICG- and LiMAx-test. ??Imaging-based liver function tests add spatial information. Current clinical standard is the 99mTc-Mebrofenin-scintigraphy. ??MRI-based function tests with Gd-EOB-DTPA have the potential to integrate seamlessly into clinical workup, feature a higher temporal and spatial resolution and do not rely on ionizing radiation. Citation Format: ??Geisel D, L?demann L, Hamm B et?al. Imaging-Based Liver Function Tests ? Past, Present and F...

ICG Clearance Test and 99mTc-GSA SPECT/CT Fusion Images

“…There are several 99mTc-GSA SPECT parameters such as the liver uptake ratio (LUR) [74,75], liver uptake density [74,76], liver uptake value corrected for body surface area (LUV) [77], or uptake index [78,79]; all these parameters basically depend on the regional strength of radioactivity in the liver. The parameter LUR correlates well with the extent of ASGPR expression immunohistochemically evaluated, and a parallel decrease in LUR and ASGPR protein expression was observed in the fibrotic liver [80].…”

“…Gd-EOBenhanced MRI can display regional liver function with good spatial resolution, which is critically useful for preoperative surgical decisions. For the evaluation of its usefulness as a liver functional test, the best conditional setting and the interpretation of the acquired data are currently under investigation [76].…”

Noninvasive Preclinical and Clinical Imaging of Liver Transporter Function Relevant to Drug-Induced Liver Injury

“…Such agents are taken up by normal hepatocytes (but not neoplasms), and appear in the biliary tree. Quantitation of their uptake and biliary excretion provides an assessment of liver function [17,18], and (through imaging) a functional liver volume. These tracers and contrast agents were optimized iteratively by medicinal chemists.…”

“…[ 99m Tc]sestamibi likely enters hepatocytes passively and undergoes partial fecal clearance, as efflux is modulated by hepatocyte P-gp and the tracer undergoes preferential basolateral efflux into the bile. [ 99m Tc]galactosyl-human serum albumin is also used in Japan [17,47] to assess liver function, but is not a known transporter substrate.…”

Lycopene treatment stalls the onset of experimentally induced hepatocellular carcinoma: a radioisotopic, physiological and biochemical analysis

“…Therefore, the development of non-invasive diagnostic techniques and identification of tumor specific serological markers linked to early stages of carcinogenesis would be of great clinical significance in the early management of HCC patients. This may be accomplished by 99m Tc-mebrofenin hepatobiliary functional test that mainly relies on functional perturbations in the tissue as functional alterations precede anatomical alterations [6] . The main rationale behind the identification of candidate biomarkers relevant for cancer risk is to find a link between biological alterations in nonspecific tissues, such as blood, and the occurrence of similar events in specific tissues involved in the carcinogenesis.…”