Detecting the Stage of Fibrosis in Non-alcoholic Fatty Liver Disease by 9.4T Phosphorus Magnetic Resonance Spectroscopy.

Purpose: To study the potential advantages of phosphorus magnetic resonance spectroscopy (³¹P-MRS) in differentiating advanced from mild fibrosis in non-alcoholic fatty liver disease (NAFLD) and early diagnosis at high field strength MR (9.4 Tesla).

Methods: Fibrosis of normal and carbon tetrachloride (CCl₄)-treated male rats was staged into: none (F0), perisinusoidal or periportal (F1), perisinusoidal and portal/periportal (F2), bridging fibrosis (F3) and cirrhosis (F4) by Sirius Red staining. The degree of steatosis and inflammatory activity were also graded based on Hematoxylin and Eosin staining. Rats were divided into different groups by different stages of fibrosis (F0, F1-2, F3-4) and laboratory blood tests were performed to verify the degree of liver injury. ³¹P-MRS was performed at 9.4T MR to obtain signal peaks of different phosphorus metabolites and the changes of the ratios between the peaks were observed.

Results: At 9.4 T, phosphoethanolamine (PE), phosphocholine (PC) and glycerophosphorylethanolamine (GPE), glycerophosphorylcholine (GPC) could be separated respectively from the peaks of phosphomonoesters (PME) and phosphodiesters (PDE), meanwhile nicotinamide adenine dinucleotide phosphate (NADPH) and uridine diphosphate glucose (UDPG) showed up as well. The marker of cell membrane metabolism, in F1-2, PME/PDE (P < 0.001), PC/GPE (P < 0.01), PC/GPC (P < 0.05) and PC/(PME + PDE) (P < 0.05) decreased while GPE/(PME + PDE) (P < 0.05) and GPC/(PME + PDE) (P < 0.05) increased significantly. In F3-4, there was a recovery trend of most ratios, especially for PC/(PME + PDE) (P < 0.05). As for the main ratio related to energy metabolism, β-ATP/P_total (P < 0.05) decreased in the early stage of the disease (F1-2) and this decline was maintained in advanced stage (F3-4). NADPH/P_total (P < 0.01) and β-ATP/Pi (inorganic phosphate) (P < 0.05) ratio was lower in F3-4 comparing with F0.

Conclusion: ³¹P-MRS can generally stage the liver fibrosis by comparing the ratios of the phosphorus metabolites resonance peaks at 9.4 T and more importantly it can be used for early diagnosis.