Abstract
Liver tumors are common and imaging methods, particularly magnetic resonance imaging (MRI), play an important role in their non-invasive diagnosis. Previous studies have shown that detection of liver tumors can be improved by injection of two different MR contrast agents. Here, we developed a new contrast agent, Gd-manganese-doped magnetism-engineered iron oxide (Gd-MnMEIO), with enhancement effects on both T1- and T2-weighted MR images of the liver. A 3.0T clinical MR scanner equipped with transmit/receiver coil for mouse was used to obtain both T1-weighted spoiled gradient-echo and T2-weighted fast spin-echo axial images of the liver before and after intravenous contrast agent injection into Balb/c mice with and without tumors. After pre-contrast scanning, six mice per group were intravenously injected with 0.1 mmol/kg Gd-MnMEIO, or the control agents, i.e., Gd-DTPA or SPIO. The scanning time points for T1-weighted images were 0.5, 5, 10, 15, 20, 25, and 30 min after contrast administration. The post-enhanced T2-weighted images were then acquired immediately after T1-weighted acquisition. We found that T1-weighted images were positively enhanced by both Gd-DTPA and Gd-MnMEIO and negatively enhanced by SPIO. The enhancement by both Gd-DTPA and Gd-MnMEIO peaked at 0.5 min and gradually declined thereafter. Gd-MnMEIO (like Gd-DTPA) enhanced T1-weighted images and (like SPIO) T2-weighted images. Marked vascular enhancement was clearly visible on dynamic T1-weighted images with Gd-MnMEIO. In addition, the T2 signal was significantly decreased at 30 min after administration of Gd-MnMEIO. Whereas the effects of Gd-MnMEIO and SPIO on T2-weighted images were similar (p = 0.5824), those of Gd-MnMEIO and Gd-DTPA differed, with Gd-MnMEIO having a significant T2 contrast effect (p = 0.0086). Our study confirms the feasibility of synthesizing an MR contrast agent with both T1 and T2 shortening effects and using such an agent in vivo. This agent enables tumor detection and characterization in single liver MRI sections.
Highlights
Liver disease is a major worldwide health problem, in some developing countries [1, 2]
Analysis of transmission electron microscopy (TEM) images revealed that the average core diameter of magnetism-engineered iron oxide (MnMEIO) nanoparticles was 12.0 ± 2.0 nm and indicated that the methoxypoly(ethylene glycol) (mPEG)-modified nanoparticles were well-dispersed (Fig 1B)
The method of Gd-MnMEIO synthesis used in our study differs from methods used in previous studies [13, 14]
Summary
Liver disease is a major worldwide health problem, in some developing countries [1, 2]. Hepatocellular carcinoma (HCC) in patients with chronic liver disease or cirrhosis [4] or metastasis from extrahepatic primary malignancies, such as colorectal carcinoma [5] is associated with high mortality. Because early detection and diagnosis of liver tumors improve prognosis, great emphasis has been placed on developing methods to detect and diagnose liver tumors non-invasively. Tumor markers, such as α-fetoprotein (AFP), are relatively insensitive surveillance tools for the detection of chronic liver disease [6]. Imaging methods play an even more important role in the management of patients with these liver diseases and at risk of liver cancer
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