Quantitative MRI of diffuse liver diseases: techniques and tissue-mimicking phantoms

Abstract

Quantitative magnetic resonance imaging (MRI) techniques are emerging as non-invasive alternatives to biopsy for assessment of diffuse liver diseases of iron overload, steatosis and fibrosis. For testing and validating the accuracy of these techniques, phantoms are often used as stand-ins to human tissue to mimic diffuse liver pathologies. However, currently, there is no standardization in the preparation of MRI-based liver phantoms for mimicking iron overload, steatosis, fibrosis or a combination of these pathologies as various sizes and types of materials are used to mimic the same liver disease. Liver phantoms that mimic specific MR features of diffuse liver diseases observed in vivo are important for testing and calibrating new MRI techniques and for evaluating signal models to accurately quantify these features. In this study, we review the liver morphology associated with these diffuse diseases, discuss the quantitative MR techniques for assessing these liver pathologies, and comprehensively examine published liver phantom studies and discuss their benefits and limitations.

Keywords: DWI; Elastography; Fat fraction; Fibrosis; Iron overload; Liver; MRI; Phantoms; R2*; Steatosis; T1.

Figure 1.

Hemosiderin deposits shown in the liver biopsy samples using hematoxylin & eosin (H&E) stain (A) and Perls Prussian blue iron stain (B) at 20x in a severely iron overloaded patient with biopsy hepatic iron content of 16.5 mg Fe/g. Iron deposits are seen as brown granules in the cytoplasm of the Kupffer cells and hepatocytes on the H&E stain and as blue pigment on Perls iron stain.

Figure 2.

Representative MRI iron phantoms mimicking liver iron overload. (A) MRI magnitude images of iron phantoms consisting of BNF iron nanoparticles of size 80 nm in 2% agar, (B) R2* maps calculated by fitting a mono-exponential model [10], and (C) linear regression plot of R2* (s⁻¹) vs iron concentrations (%) demonstrating an excellent linear correlation with R² = 0.9945.

Figure 3.

Histology images at 20x of liver biopsy samples stained with hematoxylin and eosin showing the fat droplet morphology and deposition in patients with macrovesicular steatosis. The steatosis grades of these liver biopsy samples based on the NASH CRN scoring system are (A) grade 0 (normal), (B) grade 1 (mild), (C) grade 2 (moderate) and (D) grade 3 (severe).

Figure 4.

Histology images at 20x of liver biopsy samples showing the deposition of extracellular matrix (primarily collagen) with Mason’s trichrome stain in patients with different fibrosis grades. The fibrosis grades of these histology samples based on the NASH CRN scoring system are stage 1, perisinusoidal (A), stage 2, perisinusoidal and periportal (B), stage 3, bridging fibrosis (C), and stage 4, cirrhosis (D).

Figure 5:

P-wave, stiffness maps, and shear moduli (G) obtained from four magnetic resonance elastography (MRE) phantoms made of Phytagel (1.25 – 1.875%) for emulating liver fibrosis [219]. The stiffness values obtained with MRE ranged from 1.83 – 9.84 kPa.

Figure 6.

Representative MRI iron-fat phantoms mimicking both liver iron overload and steatosis. BNF iron particles (size: 80 nm) and peanut oil are used to emulate iron overload and steatosis, respectively. MRI magnitude images (A), R2* and fat fraction (FF) maps calculated by fitting a non-linear least squares (NLSQ) multi-spectral fat-water model with R2* correction (B, C) [28], and scatter plots (with error bars) of R2* (s⁻¹) vs iron concentrations (D) and measured fat fraction (FF) vs true FF values (E) are shown for these iron-fat phantoms. Both measured R2* and FF values showed an excellent linear correlation with iron concentrations and true FFs respectively, except for the highest iron concentration.