Molecular MRI of collagen to diagnose and stage liver fibrosis.

TitleMolecular MRI of collagen to diagnose and stage liver fibrosis.
Publication TypeJournal Article
Year of Publication2013
AuthorsFuchs, BC, Wang, H, Yang, Y, Wei, L, Polasek, M, Schühle, DT, Lauwers, GY, Parkar, A, Sinskey, AJ, Tanabe, KK, Caravan, P
JournalJ Hepatol
Date Published2013 Nov
KeywordsAnimals, Carbon Tetrachloride, Collagen Type I, Disease Models, Animal, Disease Progression, Gadolinium, Liver, Liver Cirrhosis, Magnetic Resonance Imaging, Male, Mice, Mice, Inbred Strains, Molecular Probes, ROC Curve, Severity of Illness Index

BACKGROUND & AIMS: The gold standard in assessing liver fibrosis is biopsy despite limitations like invasiveness and sampling error and complications including morbidity and mortality. Therefore, there is a major unmet medical need to quantify fibrosis non-invasively to facilitate early diagnosis of chronic liver disease and provide a means to monitor disease progression. The goal of this study was to evaluate the ability of several magnetic resonance imaging (MRI) techniques to stage liver fibrosis.METHODS: A gadolinium (Gd)-based MRI probe targeted to type I collagen (termed EP-3533) was utilized to non-invasively stage liver fibrosis in a carbon tetrachloride (CCl4) mouse model and the results were compared to other MRI techniques including relaxation times, diffusion, and magnetization transfer measurements.RESULTS: The most sensitive MR biomarker was the change in liver:muscle contrast to noise ratio (ΔCNR) after EP-3533 injection. We observed a strong positive linear correlation between ΔCNR and liver hydroxyproline (i.e. collagen) levels (r=0.89) as well as ΔCNR and conventional Ishak fibrosis scoring. In addition, the area under the receiver operating curve (AUR0C) for distinguishing early (Ishak ≤ 3) from late (Ishak ≥ 4) fibrosis was 0.942 ± 0.052 (p<0.001). By comparison, other MRI techniques were not as sensitive to changes in fibrosis in this model.CONCLUSIONS: We have developed an MRI technique using a collagen-specific probe for diagnosing and staging liver fibrosis, and validated it in the CCl4 mouse model. This approach should provide a better means to monitor disease progression in patients.

Alternate JournalJ Hepatol
Citation Key260
PubMed ID23838178
PubMed Central IDPMC3805694
Grant ListK01 CA140861 / CA / NCI NIH HHS / United States
R01 EB009062 / EB / NIBIB NIH HHS / United States
EB009062 / EB / NIBIB NIH HHS / United States
CA140861 / CA / NCI NIH HHS / United States