Combined magnetic resonance elastography and collagen molecular magnetic resonance imaging accurately stage liver fibrosis in a rat model

Abstract

Background & Aims Hepatic fibrosis is associated with an overproduction of matrix proteins and a pathological increase of liver stiffness. Non-invasive magnetic resonance (MR) quantification of matrix can be assessed with a collagen-binding molecular MR probe and stiffness by MR elastography, complementary techniques. This study utilizes both imaging techniques to more accurately stage hepatic fibrosis in a rat model. Methods Thirty rats with varying levels of diethylnitrosamine-induced liver fibrosis were imaged before and 45 minutes after injection of collagen-specific probe EP-3533. MR elastography was performed in the same imaging session. The change in liver relaxation rate ΔR1 post EP-3533 and liver stiffness were compared to the collagen proportional area (CPA) determined by histology and to Ishak scoring using receiver operating characteristic (ROC) analysis. Results Collagen imaging was most sensitive to early fibrosis, while elastography was more sensitive to advanced fibrosis. This complementary feature enabled the formulation of a composite model using multivariate analysis of variance. This model incorporated the discriminating advantages of both MR techniques, resulting in more accurate staging throughout fibrotic progression. Conclusions Collagen molecular MR imaging is complementary to MR elastography and combining both techniques in a single exam leads to increased diagnostic accuracy for all stages of fibrosis.

Molecular magnetic resonance imaging accurately measures the antifibrotic effect of EDP‐305, a novel farnesoid X receptor agonist

“…Ultrasound and MR‐based elastography are two promising modalities that are currently used in the clinical setting 46, 47. Our group previously compared MR elastography and EP‐3533 in a diethylnitrosamine‐induced model of rat fibrosis and found that collagen imaging was more sensitive at earlier stages of fibrosis and may provide value in this regard 22. Further comparison between MR elastography and collagen molecular imaging is thus needed.…”

“…Collagen proportional area (CPA) and hepatic lipid vacuolization were calculated from whole‐slide scanned sections using ImageJ (National Institutes of Health). Hydroxyproline was quantified by high‐performance liquid chromatography analysis 19, 20, 21, 22…”

Molecular imaging of oxidized collagen quantifies pulmonary and hepatic fibrogenesis

“…While CT can stage pulmonary fibrosis, Gd-Hyd-enhanced MRI can report locally on regions of active fibrogenesis. In the liver, Gd-Hyd-enhanced MRI can be performed in the same study as MR elastography to provide complementary measures of fibrosis and fibrogenesis, as has been shown for other molecular imaging approaches (32).…”

Evaluation of hepatic fibrosis: a review from the society of abdominal radiology disease focus panel

“…For example, a gadolinium-based probe, EP-3533, has been explored in two different rodent models of liver fibrosis [185,186]. Recent studies suggest that EP-3533 may be synergistic with MR elastography, with changes in EP-3533 signal dominant in early fibrosis and MR elastography changes dominant in late fibrosis [187]. An alternative molecular imaging approach has been to develop molecular markers that specifically target hepatic stellate cells [188,189].…”