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Quantifying differences in hepatic uptake of the liver specific contrast agents Gd-EOB-DTPA and Gd-BOPTA: a pilot study
Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Faculty of Health Sciences.
Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Radiology in Linköping.ORCID iD: 0000-0002-4111-1693
Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Radiology in Linköping.ORCID iD: 0000-0003-3124-8044
Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Surgery.
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2012 (English)In: European Radiology, ISSN 0938-7994, E-ISSN 1432-1084, Vol. 22, no 3, 642-653 p.Article in journal (Refereed) Published
Abstract [en]

Objectives   To develop and evaluate a procedure for quantifying the hepatocyte-specific uptake of Gd-BOPTA and Gd-EOB-DTPA using dynamic contrast-enhanced (DCE) MRI. Methods   Ten healthy volunteers were prospectively recruited and 21 patients with suspected hepatobiliary disease were retrospectively evaluated. All subjects were examined with DCE-MRI using 0.025 mmol/kg of Gd-EOB-DTPA. The healthy volunteers underwent an additional examination using 0.05 mmol/kg of Gd-BOPTA. The signal intensities (SI) of liver and spleen parenchyma were obtained from unenhanced and enhanced acquisitions. Using pharmacokinetic models of the liver and spleen, and an SI rescaling procedure, a hepatic uptake rate, K Hep, estimate was derived. The K Hep values for Gd-EOB-DTPA were then studied in relation to those for Gd-BOPTA and to a clinical classification of the patient’s hepatobiliary dysfunction. Results   K Hep estimated using Gd-EOB-DTPA showed a significant Pearson correlation with K Hep estimated using Gd-BOPTA (r = 0.64; P < 0.05) in healthy subjects. Patients with impaired hepatobiliary function had significantly lower K Hep than patients with normal hepatobiliary function (K Hep = 0.09 ± 0.05 min-1 versus K Hep = 0.24 ± 0.10 min−1; P < 0.01). Conclusions   A new procedure for quantifying the hepatocyte-specific uptake of T 1-enhancing contrast agent was demonstrated and used to show that impaired hepatobiliary function severely influences the hepatic uptake of Gd-EOB-DTPA. Key Points   • The liver uptake of contrast agents may be measured with standard clinical MRI.Calculation of liver contrast agent uptake is improved by considering splenic uptake.Liver function affects the uptake of the liver-specific contrast agent Gd-EOB-DTPA.Hepatic uptake of two contrast agents (Gd-EOB-DTPA, Gd-BOPTA) is correlated in healthy individuals.This method can be useful for determining liver function, e.g. before hepatic surgery

Place, publisher, year, edition, pages
Springer Berlin/Heidelberg, 2012. Vol. 22, no 3, 642-653 p.
Keyword [en]
Gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid – Gadobenate Dimeglumine – Dynamic contrast-enhanced MRI – Pharmacokinetics – Liver
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-73624DOI: 10.1007/s00330-011-2302-4ISI: 000299768000018PubMedID: 21984449OAI: oai:DiVA.org:liu-73624DiVA: diva2:475273
Funder
Swedish Research Council, VR/M 2007-2884Medical Research Council of Southeast Sweden (FORSS), 12621Linköpings universitet
Note

The previous status of this article was Manuscript and the working titles was Liver Specific Gd-EOB-DTPA vs. Gd-BOPTA Uptake in Healthy Subjects: A Novel and Quantitative MRI Analysis of Hepatic Uptake and Vascular Enhancement and Hepatic Uptake of Gd-EOB-DTPA in Patients with Varying Degree of Hepatobiliary Disease.

Available from: 2012-01-10 Created: 2012-01-10 Last updated: 2017-12-08
In thesis
1. Quantitative Evaluation of Contrast Agent Dynamics in Liver MRI
Open this publication in new window or tab >>Quantitative Evaluation of Contrast Agent Dynamics in Liver MRI
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The studies presented here evaluate the biliary, parenchymal and vascular enhancement effects of two T1-shortening liver-specific contrast agents, Gd-BOPTA and Gd-EOB-DTPA, in Magnetic Resonance Imaging (MRI) of healthy subjects and of patients.

Ten healthy volunteers were examined with both contrast agents in a 1.5 T MRI system using three-dimensional gradient echo sequences for dynamic imaging until five hours after injection. The enhancement of the common hepatic duct in contrast to the liver parenchyma was analyzed in the first study. This was followed by a study of the image contrasts of the hepatic artery, portal vein and middle hepatic vein versus the liver parenchyma.

While Gd-EOB-DTPA gave an earlier and more prolonged enhancement and image contrast of the bile duct, Gd-BOPTA achieved higher maximal enhancement and higher image contrast for all vessels studied during the arterial and portal venous phases. There was no significant difference in the maximal enhancement obtained in the liver parenchyma.

In a third study, another 10 healthy volunteers were examined with the same protocol in another 1.5 T MRI system. Using signal normalization and a more quantitative, pharmacokinetic analysis, the hepatocyte-specific uptake of Gd-EOB-DTPA and Gd-BOPTA was calculated. A significant between-subjects correlation of the uptake estimates was found and the ratio of these uptake rates was of the same magnitude as has been reported in pre-clinical studies. The procedure also enabled quantitative analysis of vascular enhancement properties of these agents. Gd-BOPTA was found to give higher vessel-to-liver contrast than Gd-EOB-DTPA when recommended doses were given.

In the final study, retrospectively gathered datasets from patients with hepatobiliary disease were analyzed using the quantitative estimation of hepatic uptake of Gd-EOB-DTPA described in the third study. The uptake rate estimate provided significant predictive ability in separating normal from disturbed hepatobiliary function, which is promising for future evaluations of regional and global liver disease.

In conclusion, the differing dynamic enhancement profiles of the liver-specific contrast agents presented here can be beneficial in one context and challenging in another. Diseases of the liver and biliary system may affect the vasculature, parenchyma or biliary excretion, or a combination of these. The clinical context in terms of the relative importance of vascular, hepatic parenchymal and biliary processes should therefore determine the contrast agent for each patient and examination. A quantitative approach to analysis of contrast-enhanced liver MRI examinations is feasible and may prove valuable for their interpretation.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2010. 93 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1196
Keyword
Liver, spleen, hepatobiliary system, liver function, MRI, DCE-MRI, Gd-EOBDTPA, Gd-BOPTA, pharmacokinetic, hepatocyte, relaxivity.
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-60264 (URN)978-91-7393-338-4 (ISBN)
Public defence
2010-11-05, Elsa Brändströmsalen, Hälsouniversitetet, Campus US, Linköpings universitet, Linköping, 09:00 (English)
Opponent
Supervisors
Available from: 2010-10-08 Created: 2010-10-08 Last updated: 2017-01-31Bibliographically approved
2. Quantitative Magnetic Resonance in Diffuse Neurological and Liver Disease
Open this publication in new window or tab >>Quantitative Magnetic Resonance in Diffuse Neurological and Liver Disease
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Introduction: Magnetic resonance (MR) imaging is one of the most important diagnostic tools in modern medicine. Compared to other imaging modalities, it provides superior soft tissue contrast of all parts of the body and it is considered to be safe for patients. Today almost all MR is performed in a nonquantitative manner, only comparing neighboring tissue in the search for pathology. It is possible to quantify MR-signals and relate them to their physical entities, but time consuming and complicated calibration procedures have prevented this being used in a practical manner for clinical routines. The aim of this work is to develop and improve quantification methods in MRspectroscopy (MRS) and MR-imaging (MRI). The techniques are intended to be applied to diffuse diseases, where conventional imaging methods are unable to perform accurate staging or to reveal metabolic changes associated with disease development.

Methods: Proton (1H) MRS was used to characterize the white matter in the brain of multiple sclerosis (MS) patients. Phosphorus (31P) MRS was used to evaluate the energy metabolism in patients with diffuse liver disease. A new quantitative MRI (qMRI) method was invented for accurate, rapid and simultaneous quantification of B1, T1, T2, and proton density. A method for automatic assessment of visceral adipose tissue volume based on an in- and out-ofphase imaging protocol was developed. Finally, a method for quantification of the hepatobiliary uptake of liver specific T1 enhancing contrast agents was demonstrated on healthy subjects.

Results: The 1H MRS investigations of white matter in MS-patients revealed a significant correlation between tissue concentrations of Glutamate and Creatine on the one hand and the disease progression rate on the other, as measured using the MSSS. High accuracy, both in vitro and in vivo, of the measured MR-parameters from the qMRI method was observed. 31P MRS showed lower concentrations of phosphodiesters, and a higher metabolic charge in patients with cirrhosis, compared to patients with mild fibrosis and to controls. The adipose tissue quantification method agreed with estimates obtained using manual segmentation, and enabled measurements which were insensitive to partial volume effects. The hepatobiliary uptake of Gd-EOB-DTPA and Gd-BOPTA was significantly correlated in healthy subjects.

Conclusion: In this work, new methods for accurate quantification of MR parameters in diffuse diseases in the liver and the brain were demonstrated. Several applications were shown where quantitative MR improves the interpretation of observed signal changes in MRI and MRS in relation to underlying differences in physiology and pathophysiology.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2010. 127 p.
Series
Linköping Studies in Science and Technology. Dissertations, ISSN 0345-7524 ; 1184
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:liu:diva-54728 (URN)978-91-7393-390-2 (ISBN)
Public defence
2010-04-29, Elsa Brändströmsalen, Campus US, Linköpings universitet, Linköping, 13:15 (English)
Opponent
Supervisors
Available from: 2010-04-07 Created: 2010-04-07 Last updated: 2017-01-31Bibliographically approved

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Dahlqvist Leinhard, OlofDahlström, NilsKihlberg, JohanSandström, PerSmedby, ÖrjanLundberg, Peter

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