Multiparametric MRI Including T1ρ Mapping for Hepatic Fibrosis Assessment in Preclinical Models of Steatotic Liver Disease

Objectives: The diagnostic value of hepatic native T1, extracellular volume fraction (ECV), and T2 mapping for noninvasive assessment of liver fibrosis is limited in the complex spectrum of steatotic liver disease due to confounding factors, including hepatic fat and inflammation. Therefore, this study aimed to histologically validate T1ρ mapping and compare it with conventional mapping parameters for assessing hepatic fibrosis across different animal models of steatotic liver disease. Materials and Methods: In male Sprague-Dawley rats, different models of steatotic liver disease were induced using a high-fat diet (HFD) and carbon-tetrachloride (CCl 4 ) inhalation: (1) 12-week HFD group resulting in steatosis/steatohepatitis without fibrosis; (2) 6-week HFD + CCl 4 group resulting in steatohepatitis with fibrosis; (3) 12-week HFD + CCl 4 resulting in steatohepatitis-associated cirrhosis. Hepatic T1, ECV, T2, and T1ρ were assessed by quantitative MRI. Portal pressure was invasively measured. Hepatic fibrosis was assessed using Sirius red, alpha-smooth muscle actin (α-SMA) staining, and measurement of hydroxyproline content. Hepatic fat content was estimated in Oil red staining and triglyceride content. Results: Fifty-seven animals were analyzed (12-week HFD, n = 15; 6-week HFD + CCl 4 , n = 14; 12-week HFD + CCl 4 ; n = 16; controls, n = 12). T1ρ values were higher in the fibrosis groups, for example, 12-week HFD + CCl 4 versus HFD group (71 msec ±5 vs 60 msec ±3, P < 0.001). T1ρ values correlated with fibrosis markers (Sirius red r = 0.41; α-SMA: r = 0.67; hydroxyproline: r = 0.76; each P < 0.001) and portal pressure (r = 0.55, P < 0.001). T1ρ had the highest diagnostic performance for the detection of histologically defined fibrosis and invasively measured portal hypertension (eg, for fibrosis, T1ρ: AUC 0.96, P < 0.001; T1: AUC 0.74, P = 0.017; ECV: AUC 0.79, P = 0.043; T2: AUC 0.51, P < 0.001). T1ρ was an independent marker for the detection of histologically defined fibrosis (odds ratio: 3.81, P = 0.02). Conclusions: In preclinical models of steatotic liver disease, T1ρ mapping could most reliably detect hepatic fibrosis and portal hypertension across different mapping parameters.