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Gadoxetate-enhanced dynamic contrast-enhanced MRI for evaluation of liver function and liver fibrosis in preclinical trials

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dc.contributor.authorHuh, J-
dc.contributor.authorHam, SJ-
dc.contributor.authorCho, YC-
dc.contributor.authorPark, B-
dc.contributor.authorKim, B-
dc.contributor.authorWoo, CW-
dc.contributor.authorChoi, Y-
dc.contributor.authorWoo, DC-
dc.contributor.authorKim, KW-
dc.date.accessioned2022-01-14T05:20:39Z-
dc.date.available2022-01-14T05:20:39Z-
dc.date.issued2019-
dc.identifier.urihttp://repository.ajou.ac.kr/handle/201003/20169-
dc.description.abstractBACKGROUND: To facilitate translational drug development for liver fibrosis, preclinical trials need to be run in parallel with clinical research. Liver function estimation by gadoxetate-enhanced dynamic contrast-enhanced MRI (DCE-MRI) is being established in clinical research, but still rarely used in preclinical trials. We aimed to evaluate feasibility of DCE-MRI indices as translatable biomarkers in a liver fibrosis animal model.
METHODS: Liver fibrosis was induced in Sprague-Dawley rats by thioacetamide (200 mg, 150 mg, and saline for the high-dose, low-dose, and control groups, respectively). Subsequently, DCE-MRI was performed to measure: relative liver enhancement at 3-min (RLE-3), RLE-15, initial area-under-the-curve until 3-min (iAUC-3), iAUC-15, and maximum-enhancement (Emax). The correlation coefficients between these MRI indices and the histologic collagen area, indocyanine green retention at 15-min (ICG-R15), and shear wave elastography (SWE) were calculated. Diagnostic performance to diagnose liver fibrosis was also evaluated by receiver-operating-characteristic (ROC) analysis.
RESULTS: Animal model was successful in that the collagen area of the liver was the largest in the high-dose group, followed by the low-dose group and control group. The correlation between the DCE-MRI indices and collagen area was high for iAUC-15, Emax, iAUC-3, and RLE-3 but moderate for RLE-15 (r, - 0.81, - 0.81, - 0.78, - 0.80, and - 0.51, respectively). The DCE-MRI indices showed moderate correlation with ICG-R15: the highest for iAUC-15, followed by iAUC-3, RLE-3, Emax, and RLE-15 (r, - 0.65, - 0.63, - 0.62, - 0.58, and - 0.56, respectively). The correlation coefficients between DCE-MRI indices and SWE ranged from - 0.59 to - 0.28. The diagnostic accuracy of RLE-3, iAUC-3, iAUC-15, and Emax was 100% (AUROC 1.000), whereas those of RLE-15 and SWE were relatively low (AUROC 0.777, 0.848, respectively).
CONCLUSION: Among the gadoxetate-enhanced DCE-MRI indices, iAUC-15 and iAUC-3 might be bidirectional translatable biomarkers between preclinical and clinical research for evaluating histopathologic liver fibrosis and physiologic liver functions in a non-invasive manner.
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dc.subject.MESHAnimals-
dc.subject.MESHArea Under Curve-
dc.subject.MESHContrast Media-
dc.subject.MESHDisease Models, Animal-
dc.subject.MESHDrug Evaluation, Preclinical-
dc.subject.MESHFeasibility Studies-
dc.subject.MESHGadolinium DTPA-
dc.subject.MESHHumans-
dc.subject.MESHLiver-
dc.subject.MESHLiver Cirrhosis-
dc.subject.MESHLiver Function Tests-
dc.subject.MESHMagnetic Resonance Imaging-
dc.subject.MESHMale-
dc.subject.MESHRats-
dc.subject.MESHRats, Sprague-Dawley-
dc.subject.MESHThioacetamide-
dc.titleGadoxetate-enhanced dynamic contrast-enhanced MRI for evaluation of liver function and liver fibrosis in preclinical trials-
dc.typeArticle-
dc.identifier.pmid31729971-
dc.identifier.urlhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6858707/-
dc.subject.keywordDynamic contrast-enhanced-
dc.subject.keywordGadoxetate-
dc.subject.keywordLiver fibrosis-
dc.subject.keywordLiver function-
dc.subject.keywordMagnetic resonance imaging-
dc.contributor.affiliatedAuthorHuh, J-
dc.contributor.affiliatedAuthorKim, B-
dc.type.localJournal Papers-
dc.identifier.doi10.1186/s12880-019-0378-5-
dc.citation.titleBMC medical imaging-
dc.citation.volume19-
dc.citation.number1-
dc.citation.date2019-
dc.citation.startPage89-
dc.citation.endPage89-
dc.identifier.bibliographicCitationBMC medical imaging, 19(1). : 89-89, 2019-
dc.identifier.eissn1471-2342-
dc.relation.journalidJ014712342-
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Radiology
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