Collagen deposition in the liver is strongly and positively associated with T1rho elongation while fat deposition is associated with T1rho shortening: an experimental study of methionine and choline-deficient (MCD) diet rat model

Abstract

Background: A number of questions concerning the histological mechanism of elongated T1rho in liver fibrosis remain unanswered. Using a rat model of non-alcoholic fatty liver disease (NAFLD) induced with methionine and choline-deficient (MCD) diet, the primary aim of this study is to clarify whether collagen deposition per se causes liver T1rho elongation.Methods: There were 45 rats in the NAFLD model group and 8 rats in the control group. NAFLD model rats were fed MCD diet for 1, 2, 4, 6, 8, or 10 weeks, respectively. At the endpoint, the rats had in vivo MRI at 3.0 T and followed by histology. For T1rho data acquisition, a rotary echo spin-lock pulse was implemented in a three-dimensional fast field echo sequence with frequency selective fat suppression. The spin-lock frequency was set to 500 Hz, and the spin-lock times of 5, 10, 40, and 50 ms were used. Liver specimens were processed with hematoxylin-eosin staining for steatosis and inflammation evaluation, and Masson's trichrome staining for collagen visualization. The semiquantitative histopathological evaluation was based on NASH Clinical Research Network criteria. Histomorphometric analysis calculated percentages of fat and collagen accumulations in the livers.Results: A strong (r=0.82) and significant (P<0.0001) positive correlation between liver collagen content and liver T1rho was observed. Rats with no or minimal inflammation could have very long T1rho value.Among experimental rats without a positive fibrosis grading, five rats did not have an inflammation score (i.e., had minimal inflammation or no inflammation) while four had a positive inflammation score; the difference in liver T1rho between these two types of rats was minimal. Eight control rat livers and 15 stage-1 fibrosis rat livers were separated by liver T1rho completely. When four subgroups of experiment rats were selected where the liver collagen had a very narrow range within these subgroups, all these four subgroups showed a trend of negative correlation between liver fat and liver T1rho.Conclusions: Collagen deposition in the live strongly contributes to liver T1rho elongation, while fat deposition contributes to T1rho shortening. In a well-controlled experimental setting, T1rho measure alone allows separation of healthy livers and stage-1 liver fibrosis in the MCD rat liver model.

Gender-specific liver aging and magnetic resonance imaging

“…Decrease of liver T1rho measure in women with aging T1rho (T1ρ) relaxation time describes spin-lattice relaxation in the rotation frame at the presence of an external radiofrequency pulse in the transverse plane. It has been demonstrated that T1rho elongation is a sensitive biomarker for collagen deposition and thus a sensitive biomarker for liver fibrosis (62)(63)(64). To translate liver T1rho MRI into clinical practice, it is important to know the physiological liver T1rho measure in healthy subjects.…”

Water Specific MRI T1 Mapping for Evaluating Liver Inflammation Activity Grades in Rats With Methionine‐Choline‐Deficient Diet‐Induced Nonalcoholic Fatty Liver Disease

“…36,37 A previous study used a T1ρ relaxation time to detect inflammation in the same MCD diet rat model. 38 They found a weak correlation of liver inflammation with the liver T1ρ values (r = 0.25) but a strong (r = 0.82) and significant positive correlation between liver collagen content and liver T1ρ. In a study of rabbit NASH models, Xie et al reported T1ρ during the hepatobiliary phase with Gd-EOB-DTPA was associated with the inflammation grade (r = 0.79).…”

“…It is worth noting that several other quantitative MRI parameters have been shown to be correlated with the inflammation grade as well 36,37 . A previous study used a T1ρ relaxation time to detect inflammation in the same MCD diet rat model 38 . They found a weak correlation of liver inflammation with the liver T1ρ values ( r = 0.25) but a strong ( r = 0.82) and significant positive correlation between liver collagen content and liver T1ρ.…”

New methods for robust continuous wave T1ρ relaxation preparation

“…In the clinical setting, T 1ρ relaxation measurements could provide important insights into disease diagnosis and progression 33,40–42 . However, small B 0 and B 1 variations are inevitable and interfere with the T 1ρ quantification.…”