4.4 Article

Relationship Between Changes in Brain MRI and 1H-MRS, Severity of Chronic Liver Damage, and Recovery After Liver Transplantation

Journal

EXPERIMENTAL BIOLOGY AND MEDICINE
Volume 234, Issue 9, Pages 1075-1085

Publisher

ROYAL SOC MEDICINE PRESS LTD
DOI: 10.3181/0903-RM-118

Keywords

hepatic encephalopathy; magnetic resonance imaging (MRI); magnetic resonance spectroscopy (MRS); Child Pugh; manganese; choline; glutamine; liver transplant

Funding

  1. National Science Foundation of China [30070663]
  2. Guangxi Science and Technology Commission [0443004-42]
  3. U.S. NIH/National Institute of Environmental Health Sciences [ES-08164]
  4. U.S. Department of Defense [USAMRMC W81XWH-05-1-0239]

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Magnetic resonance imaging (MRI) and H-1 magnetic resonance spectroscopy (H-1-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 (131) 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, ml, Glx, and NAA) revealed that the ratios of Cho/Ci and ml/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 ml/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, ml and Glx. Our data further suggest that liver transplantation can restore normal brain Mn levels. Exp Biol Med 234:1075-1085, 2009

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