Immunosuppressive calcineurin inhibitors (CNI) are often used successfully for patients after liver or lung transplantation to treat graft rejection. However, the accompanied neurotoxic side effects are less studied and the mechanism behind still remains unclear. By aim to estimate the long-term influence of immunosuppressives on energy metabolism in human brain after liver transplantation we carried out this brain phosphorus magnetic resonance spectroscopy (31P-MRS) study.

Sixty patients (mean age: 58±10) with a history of at least 3 years after liver transplantation were studied. Twenty-seven patients were treated with low dose of CNI (group low dose) and twenty-nine patients with standard dose of CNI (group standard dose). Four patients were excluded due to incomplete examinations or artefacts. In addition, 30 age-matched healthy volunteers as reference group were also studied. All subjects underwent MR examinations at 3T (Verio, Siemens, Erlangen). The MR protocol included a non-localized whole brain 31P-MRS, for which a double-tuned 1H/31P volume head coil (Rapid Biomedical, Würzburg, Germany) was used, with a scan time of about 2 min. In a separate acquisition (TR 9s), 50mM potassium phosphate monobasic (KH2PO4) was used as calibration standard. The MRS data were analyzed with the adapted software LCModel [1,2] to estimate the contents of high-energy metabolites phosphocreatine (PCr) and adenosin triphosphat (ATP). After a coil loading correction based on the transmitter amplitude required for a 50˚ pulse in each spectrum, whole brain concentrations of ATP and PCr were estimated by referencing to the phantom (in mM). One-way ANOVA with post hoc tests were used to compare the data between the different groups.

The mean whole brain concentrations of the adenosin triphosphat (ATP) and the phosphocreatine (PCr) were determined as follows: ATP = 2.24±0.24 mM, PCr = 2.77±0.43 mM for the heathy group, ATP = 2.06±0.21 mM, PCr = 2.52±0.34 mM for the group low dose, and ATP = 1.99±0.37 mM, PCr = 2.24±0.58 mM for the group standard dose. Statistically significant differences of ATP as well as PCr were found between the healthy group and the both patient groups (p < 0.05), with both ATP and PCr being lower in patients. Although the differences of ATP and PCr between two patient groups were not significant (p > 0.05), both ATP and PCr in patients treated with standard dose of CNI were also lower than those in patients treated with low dose.

These preliminary results showed that long term medication with immunosuppressives affects the energy metabolism and results in lower brain contents of high energy metabolites ATP and PCr in patients.