MRI Measures of Murine Liver Fibrosis

Abstract

Background An imaging method that allows quantitative fibrosis estimates is needed to facilitate the diagnosis of chronic liver disease. Amide proton transfer (APT) and tissue sodium concentration (TSC) estimates could meet this need. Hypothesis APT and TSC estimates correlate with fibrosis in a mouse model of chronic liver disease. Study Type Prospective. Phantoms/Animal Model Male C57Bl/6 mice given CCl4 or vehicle (N = 8 each) twice weekly for 16 weeks. Field Strength/Sequence Liver T1 (Look‐Locker gradient recalled echo [GRE] sequence), T2 (multiecho spin echo sequence), T1rho (fast spin echo sequence with 500 Hz spin locking pulse), and APT (GRE sequence with off‐resonance pulses) data were acquired at 7 T at 12 and 16 weeks. Liver sodium data (multiple echo GRE sequence) were acquired at 12 weeks at 9.4 T. Assessment Liver proton T1, T2, T1rho, APT, sodium T2*, and TSC were calculated. Histological measures included Sirius Red, hematoxylin and eosin, liver hydroxyproline content, and serum alanine transaminase (ALT). Statistical Tests Welch's two‐sided t‐test was used to test for differences between control and CCl4‐treated groups for serum ALT, hydroxyproline, Sirius Red staining, T1, T2, T1rho, APT, TSC, and sodium T2*. Pearson's correlations between liver T1, APT, TSC, or sodium T2* with Sirius Red staining and hydroxyproline levels were calculated. Results APT was significantly different (P < 0.05) between groups in the left liver lobe at 16 weeks (CCl4: 8.0% ± 1.2%, controls: 6.2% ± 1.0%), as were average liver TSC at 12 weeks (CCl4: 38 mM ± 5 mM, controls: 27 mM ± 2 mM), and average sodium liver T2* at 12 weeks (CCl4: 10 msec ± 1.0 msec, controls: 12 msec ± 1.9 msec). APT, TSC, and sodium T2* correlated significantly (P < 0.05) with Sirius Red staining and hydroxyproline levels. Data Conclusion Liver TSC and APT significantly correlated with histopathologic markers of fibrosis in this mouse model. Evidence Level 1 Technical Efficacy Stage 3.

Does Excess Tissue Sodium Storage Regulate Blood Pressure?

“…Whether all this reflects the extravasation of fluids typical of inflammation or a primary activation of inflammatory cells by local hypertonic niches [48••], or a combination of both, remains to be established. Of note, tissue changes with less inflammatory components but similar ECV expansion, like liver fibrosis, revealed the same increase in tissue Na + signal [90,91].…”

Quantitative Magnetization EXchange MRI Measurement of Liver Fibrosis Model in Rodents

“…The T 1 values did not change significantly across groups and also did not correlate with the percentage of collagen extracted from the histology-stained images. Although T 1 , when measured by saturation or inversion recovery, appears to be a relatively good predictive parameter for fibrosis and inflammation, 15,31 MEX fitted T 1 parameter, as detailed above, is not comparable. It is mainly sensitive to the water content of the tissue, as evident by the significant changes measured between very mild and mild inflammation scores.…”

“…T 1⍴ and diffusion‐weighted imaging (DWI) are promising approaches and show high sensitivity to motion‐restricted water 14 . Amide proton transfer (APT) contrast, based on amide bond within the collagen structure, and sodium imaging, which correlates with increased proteoglycans in the ECM, may also hold great potential but are still at early stages of research 15 . Despite the multiplicity of methods reported, none has become a standard, nor have they replaced the reference standard of liver biopsy.…”

Single-cell transcriptomic profiling of kidney fibrosis identifies a novel specific fibroblast marker and putative disease target

“…Naive mice of the same strain, age and sex were used as controls. At day 28 post-injury, both models exhibited dramatic parenchymal reduction 41 (Figure 1A). 10x Chromium scRNA-seq 31 was carried out on the control, UIR and UUO left kidney suspensions.…”