Contrast agents in magnetic resonance imaging of the liver: Present and future

doi:10.1016/S0753-3322(98)80003-6

Biomedicine & Pharmacotherapy

Volume 52, Issue 2, March 1998, Pages 51-58

https://doi.org/10.1016/S0753-3322(98)80003-6 Get rights and content

Summary

New contrast agents are being developed by drug companies to better image the liver magnetic resonance imaging (MRI). They can be divided into hepatobiliary agents (Gd-EOB-DTPA. Gd-BOPTA, Mangafodipir) and nanoparticulate agents directed to the reticulo-endothelial system (ferumoxides, SHU 555A). After intravenous injection, all these agents concentrate in the liver and induce profound signal changes. Particulate agents induce predominantly a darkening of the liver parenchyma, while hepatobiliary agents induce a brightening. In both cases, liver-lesion conspicuity is enhanced, leading to a better visualization of the lesion. After a description of the principal pharmacokinetic characteristics of the compounds, this review paper summarizes the utility of the agents in the detection and characterization of focal liver diseases.

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Cited by (33)

Liver function quantification of patients with portal vein embolization using dynamic contrast-enhanced MRI for assessment of hepatocyte uptake and elimination
2020, Physica Medica
We evaluated pharmacokinetic models which quantify liver function including biliary elimination based on a dynamic Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI) technique with sparse data collection feasible in clinical routine.
Twelve patients with embolized liver segments following interventional treatment of primary liver cancer or hepatic metastasis underwent MRI. During Gd-EOB-DTPA bolus administration, a 3D dynamic gradient-echo (GRE) MRI examination was performed over approx. 28 min. Interrupted data sampling was started approx. 5 min after contrast agent administration. Different implementations of dual-inlet models were tested, namely the Euler method (DE) and convolution with residue functions (C). A simple uptake model (U) and an uptake- elimination model (UE) extended by incorporating the biliary contrast agent elimination rate ( $K_{e}$ ) were evaluated.
The uptake-elimination model, calculated via the simple Euler method (UE- DE) and by convolution (UE-C), yielded similar overall estimates in terms of fitting quality and agreement with published values. The Euler method was approx. 50 times faster and yielded a mean elimination rate of $K_{e} = 1.8 \pm 1.2$ mL/(min $\cdot$ 100 mL) in nonembolized liver tissue, which was significantly higher ( $p = 8.8 \cdot 10^{- 4}$ ) than in embolized tissue $K_{e} = 0.4 \pm 0.4$ mL/(min $\cdot$ 100 mL). Fractional hepatocyte volume $v_{h}$ was not significantly higher in nonembolized tissue (52.4 ± 13.4 mL/100 mL) compared to embolized tissue (44.4 ± 26.1 mL/100 mL).
Interrupted late enhancement MRI data sampling in conjunction with the uptake-elimination model, deconvolved by integration of the differential rate equation and combined with the simple uptake model implemented with the Euler method (U-DE), turned out to be a stable and practical method for reliable noninvasive assessment of liver function.
On the use of superparamagnetic hydroxyapatite nanoparticles as an agent for magnetic and nuclear in vivo imaging
2018, Acta Biomaterialia
Citation Excerpt :
For both NPs, the contrast enhancement achieved in the liver was measured at different time points. The choice of this target organ was motivated by the fact that liver imaging was the first clinical application of MNPs as CAs in the form of Ferumoxides (AMI-25, Endorem® and Feridex IV®) as widely documented [2,24,31–33,42]. Mice were administered with ∼140 μL of both FeHA and Endorem® solutions to obtain an equivalent dose of 1 mg of Fe per kg of mouse as already reported by other works on SPION-based CAs [43,44].
The identification of alternative biocompatible magnetic NPs for advanced clinical application is becoming an important need due to raising concerns about iron accumulation in soft issues associated to the administration of superparamagnetic iron oxide nanoparticles (NPs). Here, we report on the performance of previously synthetized iron-doped hydroxyapatite (FeHA) NPs as contrast agent for magnetic resonance imaging (MRI). The MRI contrast abilities of FeHA and Endorem® (dextran coated iron oxide NPs) were assessed by ¹H nuclear magnetic resonance relaxometry and their performance in healthy mice was monitored by a 7 Tesla scanner. FeHA applied a higher contrast enhancement, and had a longer endurance in the liver with respect to Endorem® at iron equality. Additionally, a proof of concept of FeHA use as scintigraphy imaging agent for positron emission tomography (PET) and single photon emission computed tomography (SPECT) was given labeling FeHA with ^99mTc-MDP by a straightforward surface functionalization process. Scintigraphy/x-ray fused imaging and ex vivo studies confirmed its dominant accumulation in the liver, and secondarily in other organs of the mononuclear phagocyte system. FeHA efficiency as MRI-T₂ and PET-SPECT imaging agent combined to its already reported intrinsic biocompatibility qualifies it as a promising material for innovative nanomedical applications.
The ability of iron-doped hydroxyapatite nanoaprticles (FeHA) to work in vivo as imaging agents for magnetic resonance (MR) and nuclear imaging is demonstrated. FeHA applied an higher MR contrast in the liver, spleen and kidneys of mice with respect to Endorem®. The successful radiolabeling of FeHA allowed for scintigraphy/X-ray and ex vivo biodistribution studies, confirming MR results and envisioning FeHA application for dual-imaging.
Assessment of Liver Function and Liver Fibrosis with Dynamic Gd-EOB-DTPA-Enhanced MRI
2015, Academic Radiology
To evaluate the ability of segmental linear fitting analysis of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid liver perfusion magnetic resonance imaging (MRI) to assess liver function and liver fibrosis.
Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid liver perfusion MRI was performed in 41 patients, and perfusion estimates were generated by segmental linear fitting analysis of the time-intensity curves. The relationships of T_in, T_out, K_up, and the ratio between the signal intensities of the peak and the last phase with liver fibrosis stage and laboratory measurements of liver function were evaluated.
Serum prealbumin concentration was significantly positively correlated with K_up and the signal intensity ratio and was significantly negatively correlated with T_in and T_out. T_in and T_out were significantly higher and K_up and the signal intensity ratio were significantly lower in patients with advanced fibrosis than those without. T_out was the best predictor of advanced fibrosis, with an area under the receiving operating characteristic curve of 0.843, a sensitivity of 100%, and a specificity of 80%.
A new procedure of quantifying the hepatocyte-specific uptake of a T1-enhancing contrast agent can be used to assess impaired hepatobiliary function. The parameters obtained from perfusion MRI have the potential to predict advanced fibrosis.
Magnetic nanoparticles in MR imaging and drug delivery
2008, Advanced Drug Delivery Reviews
Magnetic nanoparticles (MNPs) possess unique magnetic properties and the ability to function at the cellular and molecular level of biological interactions making them an attractive platform as contrast agents for magnetic resonance imaging (MRI) and as carriers for drug delivery. Recent advances in nanotechnology have improved the ability to specifically tailor the features and properties of MNPs for these biomedical applications. To better address specific clinical needs, MNPs with higher magnetic moments, non-fouling surfaces, and increased functionalities are now being developed for applications in the detection, diagnosis, and treatment of malignant tumors, cardiovascular disease, and neurological disease. Through the incorporation of highly specific targeting agents and other functional ligands, such as fluorophores and permeation enhancers, the applicability and efficacy of these MNPs have greatly increased. This review provides a background on applications of MNPs as MR imaging contrast agents and as carriers for drug delivery and an overview of the recent developments in this area of research.
Small molecular gadolinium(III) complexes as MRI contrast agents for diagnostic imaging
2007, Coordination Chemistry Reviews
Magnetic resonance imaging (MRI) contrast agents that contain the gadolinium ion are widely used in biomedical research and diagnosis. The relaxation mechanism of these T₁-agents highlights their sensitivity towards the proximal environment. Greater knowledge of the structurally related relaxation mechanism, particularly factors that govern relaxivity, leads to scrutinized chelate designs that improve contrast enhancement. Cyclic and acyclic polyaminocarboxylate gadolinium complexes, especially those have favourable water exchange and tumbling rate for relaxation, have been reported to improve relaxivity and specificity.
The criteria for a large relaxivity gain upon protein binding, such as the human serum albumin (HSA), are elucidated through the relaxometric study of the protein–chelate adduct. This adduct is an important model for the development of contrast agents, which may allow the in vivo visualization of proteins. The strength of HSA binding and the observed relaxivity are related to the pharmacokinetic profile of the contrast agents and give insight in the sensitivity of the agents after intravenous administration. By using animal models, an understanding of the physiology of contrast agents, including their biodistribution, excretion, and possible site of interaction, is acquired. The in vitro studies of contrast agents have demonstrated the feasibility of imaging various disease-related proteins, cell types, and gene delivery and expression. Imaging at the molecular level can be achieved through this integrative approach and the incorporation of nanotechnology in drug delivery.
Direct evidence of the temperature dependence of Gd-BOPTA transport in the intact rat liver
2005, Applied Radiation and Isotopes
The aim was to study the influence of temperature on the transport of the hepatobiliary contrast agent Gadobenate dimeglumine (Gd-BOPTA). Rat livers were isolated and perfused with Gd-BOPTA at 12, 25, 30, 36 and 38 °C. After the perfusion period, biopsies were collected and the MR signal intensity was measured. Uptake and biliary excretion were quantified with radiolabeled Gd-BOPTA. MR signal intensity decreased with temperature of perfusion. This phenomenon was appropriately quantified with ¹⁵³Gd and ¹⁵³Sm labeling, in contrast to ⁶⁷Ga.

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View full text

Contrast agents in magnetic resonance imaging of the liver: Present and future

Summary

Magn Keson Imaging Clin N Am

Magn Reson Imag

Liver metastases: safety and efficacy of detection with superparamagnetic iron oxide in MR imaging

Radiology

Hepatic MR imaging with Mn-DPDP: safety, image quality, and sensitivity

Radiology

Liver tumors in cirrhosis: experimental study with SPIO-enhanced MR Imaging

Radiology

Hepatic tumors: detection and characterization at 1-T MR imaging enhanced with AMI-25

Radiology

Benign hepatocellular tumors: MRI after superparamagnetic iron oxide administration

J Comput Assist Tomogr

Enhancement of liver hemangiomas on T1-weighted MR SE images by superparamagnetic iron oxide particles

J Comput Assist Tomogr

Detection of liver metastases: comparison of superparamagnetic iron oxide-enhanced and unenhanced MR imaging at 1.5, T with dynamic CT, intraoperative US, and percutaneous US

Radiology

Focal liver lesions: MR imaging with Mn-DPDP-initial clinical results in 40 patients

Radiology

Peripheral washout: a sign of malignancy on dynamic gadolinium-enhanced MR images of focal liver lesions

Radiology

Liver metastases: improved detection with gadolinium-enhanced MR imaging?

Radiology

Focal nodular hyperplasia of the liver: assessment with contrast-enhanced turboflash MR imaging

Radiology

Hepatocellular carcinoma: MR imaging with mangafodipir trisodium (Mn-DPDP)

Radiology