Relationship between changes in brain MRI and (1)H-MRS, severity of chronic liver damage, and recovery after liver transplantation

Abstract

Magnetic resonance imaging (MRI) and (1)H magnetic resonance spectroscopy ((1)H-MRS) have been used in clinics for diagnosis of chronic liver diseases. This study was designed to investigate the relationship between MRI/MRS outcomes and the severity of liver damage. Of 50 patients examined, the MRI signal intensity in the globus pallidus as determined by pallidus index (PI) increased as the disease severity (scored by Child Pugh ranking) worsened (r = 0.353, P < 0.05). The changes in PI values were also linearly associated with Mn concentrations in whole blood (MnB) (r = 0.814, P < 0.01). MRS analysis of four major brain metabolites (i.e., Cho, mI, Glx, and NAA) revealed that the ratios of Cho/Cr and mI/Cr in cirrhosis and CHE patients were significantly decreased in comparison to controls (P < 0.05), whereas the ratio of Glx/Cr was significantly increased (P < 0.05). The Child Pugh scores significantly correlated with mI/Cr (-0.484, P < 0.01) and Glx (0.369, P < 0.05), as well as MnB (0.368, P < 0.05), but not with other brain metabolites. Three patients who received a liver transplant experienced normalization of brain metabolites within 3 months of post-transplantation; the MR imaging of Mn in the globus pallidus completely disappeared 5 months after the surgery. Taken together, this clinical study, which combined MRI/MRS analysis, autopsy exam and liver transplant, clearly demonstrates that liver injury-induced brain Mn accumulation can reversibly alter the homeostasis of brain metabolites Cho, mI and Glx. Our data further suggest that liver transplantation can restore normal brain Mn levels.

Figures

Figure 1

Pathology of representative liver biopsy tissues. Tissues were obtained via a biopsy needle. H&E staining was conducted. (A): An autopsy liver tissue from a 45-year-old control subject who died from motor vehicle accident; (B): a biopsy tissue from a 48-year-old male patient with chronic viral hepatitis type B with HBsAg (+), HBcAg (−), HCV (−); (C): a biopsy tissue from a 46-year-old male patient with micronodular cirrhosis in active stage; (D) a biopsy tissue from a 48-year-old male patient with chronic hepatic encephalopathy, nodular cirrhosis evident in active stage. (×100). A color version of the figure is available in the online journal.

Figure 2

Representative MRI of liver disease patients and control subjects. (A): Axial T1-WI MRI from a 37-year-old male control subject; (B): axial T1-WI MRI of patient B in Figure 1B, very weak signal intensity in globus pallidus; (C): axial T1-WI MRI of patient C in Figure 1C, the signal intensity in globus pallidus visible; (D): axial T1-WI MRI of patient D in Figure 1D, strong signal intensity in globus pallidus.

Figure 3

Changes in PI values as a function of MnB levels. Data (n =31) were analyzed by correlation and linear regression analyses. Correlation coefficient (r) = 0.814, P < 0.01.

Figure 4

Representative 1H-MRS of liver disease patients and control subjects. (A): MRS from a 55-year-old female control subject; (B): MRS of patient B in Figure 1B; (C): MRS of patient C in Figure 1C, decreased Cho and mI and increased Glx can be seen; (D): MRS of patient D in Figure 1D, apparently decreased Cho and mI and increased Glx. NAA, N-acetyl aminosuccinic acid; Cho, choline compounds; Cr, total creatine; mI, myo-inositol; ppm, part per million.

Figure 5

Representative MRIs of a liver disease patient in Figure 1D, Figure 2D and Figure 4D, 1-month and 5-month post-liver transplant surgery. (A) T1-WI MRI 1 month after surgery; (B): MRS 1 month after surgery, lower Cho and mI peaks and higher Glx peak; (C): Ti-MRI 5 months after surgery; (D) MRS 5 months after surgery.