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Mechanistic modeling of qDCE-MRI data reveals increased bile excretion of Gd-EOB-DTPA in diffuse liver disease patients with severe fibrosis
Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.ORCID iD: 0000-0001-8661-2232
Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.ORCID iD: 0000-0003-4630-6550
Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.ORCID iD: 0000-0002-4111-1693
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2016 (English)Conference paper, Published paper (Refereed)
Abstract [en]

Introduction

Over the past decades, several different non-invasive methods for staging hepatic fibrosis have been proposed. One such method is dynamic contrast enhanced MRI (DCE-MRI) using the contrast agent (CA) Gd-EOB-DTPA. Gd-EOB-DTPA is liver specific, which means that it is taken up specifically by the hepatocytes via the OATP3B1/B3 transporters and excreted into the bile via the MRP2 transporter. Several studies have shown that DCE-MRI and Gd-EOBDTPA can separate patients with advanced (F3-F4) from mild (F0-F2) hepatic fibrosis by measuring the signal intensity, where patients with advanced fibrosis have a lower signal intensity than the mild fibrosis cases.1 However, none of the studies up to date have been able to differentiate if the reduced signal intensity in the liver is because of an decreased uptake of CA or an increased excretion. Analyzing the DCE-MRI data with mechanistic mathematical modelling has the possibility of investigating such a differentiation.

Subjects and methods

88 patients with diffuse liver disease were examined using DCE-MRI (1.5 T Philips Achieva, two-point Dixon, TR=6.5 ms, TE=2.3/4.6 ms, FA=13) after a bolus injection of Gd-EOB-DTPA, followed by a liver biopsy. Regions of interest were placed within the liver, spleen and veins and a whole-body mechanistic pharmacokinetic model2 was fitted to the data. The fitted parameters in the model correspond to the rate of CA transport between different compartments, e.g. hepatocytes, blood plasma, and bile (Fig. 1).

Results

As can be seen in Fig. 2, the parameter corresponding to the transport of CA from the blood plasma to the hepatocytes, kph, is lower for patients with advanced fibrosis (p=0.01). Fig. 3 shows that the parameter corresponding to the CA excretion into the bile, khb, is higher for patients with advanced fibrosis (p<0.01).

Discussion/Conclusion

This work shows that the decreased signal intensity in DCE-MRI images in patients with advanced fibrosis depends on both a decreased uptake of CA in the hepatocytes and an increased excretion into the bile. Similar results have also been observed in a rat study3. In that study, rats with induced cirrhosis had a higher MRP2-activity than the healthy control rats.

References

1Norén et al: Eur. Radiol, 23(1), 174-181, 2013.

2Forsgren et al: PloS One, 9(4): e95700, 2014.

3Tsuda & Matsui: Radiol, 256(3): 767-773, 2010.

Place, publisher, year, edition, pages
2016.
National Category
Medical and Health Sciences Radiology, Nuclear Medicine and Medical Imaging Gastroenterology and Hepatology Pharmaceutical Sciences Anesthesiology and Intensive Care Neurology
Identifiers
URN: urn:nbn:se:liu:diva-134177OAI: oai:DiVA.org:liu-134177DiVA: diva2:1069187
Conference
ESMRMB 30 Sep - 1 Oct 2016, Vienna Austria
Available from: 2017-01-27 Created: 2017-01-27 Last updated: 2017-02-02

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Lundberg, PeterKarlsson, MarkusForsgren, MikaelDahlström, NilsLeinhard Dahlqvist, OlofNorén, BengtCedersund, GunnarEkstedt, MattiasKechagias, Stergios
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Division of Radiological SciencesCenter for Medical Image Science and Visualization (CMIV)Faculty of Medicine and Health SciencesDepartment of Radiation PhysicsDepartment of Radiology in LinköpingDepartment of Biomedical EngineeringFaculty of Science & EngineeringDivision of Cardiovascular MedicineDepartment of Gastroentorology
Medical and Health SciencesRadiology, Nuclear Medicine and Medical ImagingGastroenterology and HepatologyPharmaceutical SciencesAnesthesiology and Intensive CareNeurology

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