Distinguishing between Hepatic Inflammation and Fibrosis with MR Elastography

Abstract

Purpose To investigate the utility of Magnetic Resonance Elastography (MRE)-derived mechanical properties in discriminating hepatic inflammation and fibrosis in the early stages of chronic liver diseases. Material and Methods All studies were approved by our institutional animal care and use committee. A total of 187 animals were studied, including 182 mice and 5 pigs that represent five different liver diseases with a varying combination and extent of hepatic inflammation, fibrosis, congestion and portal hypertension. We performed multifrequency 3-D MRE with shear stiffness, storage and loss modulus, and damping ratio calculated in all animal subjects. Necroinflammation, fibrosis, and portal pressure were either histologically scored or bio-chemically/physically quantified in all studied animals. Two-sided Welch's t-tests were used to evaluate the mean differences between diseased and control/sham groups. Spearman's correlation analyses were used to evaluate the relationships between the mechanical parameters and the quantitative fibrosis extent (hydroxyproline concentration) and portal pressure. Results Liver shear stiffness and storage modulus increased with progressively developed fibrosis and portal hypertension (stiffness @80Hz, 48-week-feeding, steatohepatitis/controls, 0.51±0.12/0.29±0.01kPa, p=0.02). Damping ratio and loss modulus can distinguish inflammation from fibrosis at early stages, even before the development of histologically detectable necroinflammation and fibrosis (damping ratio @80Hz, 20-week-feeding, steatohepatitis/controls, 0.044±0.012 vs. 0.014±0.008, p<0.001). Damping ratio and shear stiffness vary differently with respect to etiology of portal hypertension (i.e., congestion or cirrhosis induced). These differentiation abilities have frequency-dependent variations. Conclusion Liver stiffness and damping ratio measurements can extend hepatic MRE to potentially assess necroinflammatory, congestive, and fibrotic processes of chronic liver diseases.

Magnetic resonance elastography of liver and spleen: Methods and applications

“…Interestingly, liver stiffness has been found in some cases to be correlated to mesenteric blood flow and portal venous blood flow . This dependence on hemodynamic parameters was also observed in a small‐animal study at 3.0 T …”

The Role of Three‐Dimensional Magnetic Resonance Elastography in the Diagnosis of Nonalcoholic Steatohepatitis in Obese Patients Undergoing Bariatric Surgery

“…Compared with 2D‐MRE, 3D‐MRE allows a more comprehensive analysis of the steady‐state dynamic shear wave propagation in the entire liver . In mouse models of diet‐induced NASH, the damping ratio and shear loss modulus have been shown to enable discrimination of inflammation from fibrosis at early stages of disease, even before the development of histologically detectable necroinflammation and fibrosis . These data represent a strong scientific premise that warrants investigation of MRE as an imaging biomarker for the noninvasive detection of NASH in humans.…”

Dual‐frequency MR elastography to differentiate between inflammation and fibrosis of the liver: Comparison with histopathology

“…Liver stiffness generally consists of elasticity and viscosity, and intrahepatic hemodynamic changes, such as inflammation, congestion, and portal hypertension . The utility of multifrequency MRE is emerging as an interest for the separation of fibrosis from inflammation of the liver by calculating multiple parameters including loss modulus and damping ratio . However, preliminary clinical results demonstrated no additional value of multifrequency MRE for staging liver fibrosis compared with single‐frequency MRE .…”

“…This may be because stiffness value at 80‐Hz more strongly emphasizes dispersion of elastic waves in viscous media compared with that at 60‐Hz on MRE . A previous study showed that the loss modulus at high frequency has the potential to be used to assess necroinflammation . The ΔG could emphasize the residual viscous factor in the liver parenchyma, which is associated with histological inflammation.…”