Comparison of the DWI and Gd-EOB-DTPA-enhanced MRI on assessing the hepatic ischemia and reperfusion injury after partial hepatectomy
Introduction
Liver damage after ischemia and reperfusion is known to be a critical factor that induces cellular damage and causes cell death during the process of liver transplantation, tumor resection and veno-occlusive disease. It is also responsible for acute liver failure that is often associated with high morbidity and mortality. IRI itself leads the severe damage to the structure and function of liver cells particularly during the hepatectomy, addition to the loss of partial liver and blood during the hepatectomy causes difficulties to the rest of the liver to restore the regenerate ability in a short time. The degree of post-ischemic and postoperative tissue damage controlled by three main factors, which are hepatocellular damage, the range of hepatectomy and liver regeneration [1]. Degree of loss in liver function is usually estimated using laboratory data of serum parameters such as aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities have been frequently determined [2], [3], [4]. Although serum measurements have been considered to be reliable indicators for assessment of liver function, they do not afford 3-D information on the spatial distribution of liver injury. Information about spatial distribution which, combined with the laboratory test results, may impart useful basis for decision making on following surgical interventions.
Technetium–99 m galactosyl serum albumin (99mTc-GSA) scintigraphy has been taken for best solution on liver function assessment [5], [6], [7]. However, due to its poor image resolution and utilization of radioactive nuclide, popularity in clinical application has been limited. Since the first proposal of using gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) to assess liver function by Shimizu in 1999 [8], studies on evaluation of liver function have been deepen into various levels, with the remarkable achievements in continuous renewal of MRI or update in calculation of imaging parameters, which led to subsequent research provide more useful information for clinical diagnosis and treatment [9], [10], [11]. Diffusion-weighted imaging (DWI) is a technique for imaging molecular movement or diffusivity. Since the liver is a highly vascularized organ, perfusion-related effects are not negligible for diffusivity assessment by DWI. ADC value represents the diffusivity of the subjects observed by typical DWI [12], [13]. Since the histopathological structures of the liver tissue are vulnerable to the ischemia/reperfusion after hepatectomy, assessing the liver function by DWI or Gd-EOB-DTPA-enhanced MIR might largely affect the final evaluation.
In this study, we attempt to compare the efficiency of these two molecular imaging examinations via establishment of rat model with IRI + hepatoctemy for the purpose of comparison between variety of imaging parameters and to analyze the correlation of these parameters with the results of histological examination. Ultimately, we attempt to provide useful information for improvement of accuracy and specificity in assessing liver function.
Section snippets
Materials and methods
In this study, we aim to evaluate the liver function via changes indicated with variety of imaging parameters by DWI and Gd-EOB-DTPA-enhanced MRI, imaging IRI+ liver resections in rat model, and compare the MRI result with 99mTc-GSA imaging result to conduct histopathological analysis between these two imaging functions.
Animal model
Twenty-seven adult male healthy Wister rats weighing 220–270 g, which were provided by key laboratory of No.2 Affiliated Hospital of Harbin Medical University, were used in this study. The protocol was approved by the animal care committee of this institution. Experiments were performed in accordance with institutional guidelines. Before surgery, all rats fasted for 12 h with free access to water.
Surgical procedures and experimental groups
We used four animal groups, sham (n = 6), 30%hepatectomy (n = 7), 30% hepatectomy with IRI for 30 min (n = 7) and 30% hepatectomy with IRI for 60 min (n = 7). In brief, anesthesia was induced by intraperitoneal injection of 3% soluble pentobarbitone (30 mg/kg) before laparotomy via a middle incision to expose the lobes of the liver. After surgical exposure of the portal vein, the left portal vein and hepatic artery were occluded for 0, 30 and 60 min with a vascular clamp to produce the ischemia.
Scintigraphic imaging
In 24 h after hepatectomy, animals were subjected to Scintigraphic Imaging. 99mTc-GSA was injected intravenously, and dynamic images were recorded with the rats in the supine position using a SPECT (Millenium VG, GE Medical Systems, USA). Digital images (128 × 128 matrix) of an anterior abdominal view were acquired at a rate of 3 s/frame (40 frames) during the second minute after the bolus injection of 99mTc-GSA, followed by a rate of 1 min/frame (18 frames). Data acquisition was stopped 20 min
Magnetic resonance imaging (MRI)
In 10 min after completing the test, rats were subjected to MR imaging by using an 8- channel special coil for rats. IVIM imaging was acquired in the transverse plane by fat-saturated spin echo–echo planar imaging. The detailed imaging parameters were as follows: TR/TE/FA = 5100 ms/132.7 ms/90, matrix 384 × 288, NEX = 3.0 FOV 10 × 7.5 cm, RFOV 75%, slice thickness/gap = 2.5/0.5 mm. For testing DWI, SS-EP imaging was employed, parameters were TR/TE/FA = 2775/68.3 ms/90, slice thickness/gap = 2.5/0.5 mm, matrix 96 ×
Imaging analysis
To obtain diffusivity values, three regions of interest (ROI) were placed in liver parenchyma by two radiologists (S.I.) with 5 years of experience in abdominal radiology, who were blinded to the histopathologic data. They measured the signal intensities by placing the largest possible ROI on the liver parenchyma, as avoiding vessels and artifacts in a consensus fashion. ROIs were placed on an image with b = 0 s/mm2. The software automatically copied the ROI to each image (b = 10 to 1200 s/mm2) and
Liver enzyme chemistry and liver tissue histology
Blood samples were collected from the inferior vena cava right after the MRI was completed to determine serum ALT, AST and prothrombin time (PT) activities. The serum was separated from the whole blood by centrifugation at 3000 rpm for 10 min. It was aliquoted into small microcentrifuge tubes (0.5 mL) and stored in a freezer (–20 °C) under constant light protection. AST, ALT and PT levels were measured using standard clinical automated analysis; the results were expressed as international units per
Statistical analysis
All statistical analyses were performed by SPSS 17.0 program (SPSS Inc., Chicago IL). Data are presented as mean values ± standard deviation (SD). Normal distribution was assessed by Kolmogorov-Smirnov test. Comparison of changes within one group was performed by Student’s paired t test for normal distribution data. P values below 0.05 were considered to be statistically significant. For each imaging procedure group (99mTc-GSA SPECT, or MRI with Gd-EOB-DTPA), at least 5 animals were analyzed
The decreased HH15 and increased LHL15 in assessment of the 99mTc-GSA dynamics in vivo
The latter value for functional liver volume was experimentally chosen to agree with the liver volume measured by MRI in our hospital. 99mTc-GSA scintigraphy images of the blood pool were calculated by raw projection data, and 58 images of the liver distant from heart and large blood vessels were chosen. ROI lines were drawn for hepatic uptake rate and blood retention rate on 99mTc-GSA scintigraphy image by reference to the MRI images, and time-activity curve generated (Fig. 1). The ROI for the
Discussion
With the acknowledged fact that the asialoglycoprotein receptor (ASGPR) is present only in hepatocytes, which specifically binds to ASGP, the function of this receptor has been demonstrated to reflect the liver dysfunction [14]. A high level of ASGP in the blood and reduction of ASGPR on the surface of hepatocytes have been reported in patients who were diagnosed with chronic liver disease [15]. Hiroshi Toyama et al. [16] studied that after hepatic ischemia/reperfusion injury, the liver uptake
Conflicts of interest
None.
Funding
This research was supported by no funding.
Acknowledgement
None.
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