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Disturbances of Water Concentration and Osmolyte Homoeostasis in Hepatic Encephalopathy

Hepatic encephalopathy (HE) is understood as the clinical manifestation of a chronological low grade cerebral oedema, indicating a disturbance of water and osmolyte homeostasis. A better understanding of the mechanisms involved in this disease is of highest interest to improve patient treatments. In this regard, MR techniques helped considerably in verifying hypotheses and answering important questions of clinical relevance: the correlation between MR findings and severity of the disease, the reversibility of brain damage after successful treatment of the disease and finally interpretation of MR changes in terms of cellular processes.

This project aims to quantitatively show brain alteration in HE patients by combining 3 novel MR modalities:

  • a high field MRS protocol enabling in vivo quantification of the metabolites specifically involved in HE (mio-inositol, glutamine, glutamate, taurine)
  • sodium MRI
  • mapping of brain tissue hydration.

From these data, a rigorous analysis is envisaged in order to provide a better description of the alteration as the function of the etiology and grade of the disease. As a perspective, it is planned to use this analysis to describe the dynamics of the disease during treatment. The second part of the project addresses the verification of putative HE mechanisms in animal models of hepatic encephalopathy. The first hypothesis concerns the involvement of taurine signaling on hypothalamic structure, which could potentially explain water retention, a complication often observed in HE. The second hypothesis concerns the protective role of myo-inositol after ammonia intoxication. The last hypothesis is the enzymatic activity of the glutamine synthetase in the ammonia detoxification in astrocytes. These hypotheses can be tested in animal models (mice) since the genes responsible for the synthesis of the taurine transporter, the myo-inositol and glutamine synthetase have been isolated and can be deactivated by means of gene manipulation. It is planned to observe over time MRS data and tissue hydration maps using an animal scanner and to perform histo-pathologic analyses following the MR protocol.

This project is part (C5) of the SFB 575 initiated by D. Hauessinger from the University Heinrich-Heine Duesseldorf. For further information, please visit the web page : University Heinrich-Heine Duesseldorf

Disturbances of Water Concentration and Osmolyte Homoeostasis in Hepatic EncephalopathyAligned (Talairach space) 1H (upper row) and 23Na (lower row) images of the brain. Coronal and transversal views intersecting the basal ganglia. 1H modality : magnetization prepared rapid gradient echo image 1H image, 23Na modality : gradient echo image image (TE = 1,5 ms)

References

N.J. Shah, H. Neeb, G. Kircheis, P. Engels, D. Häussinger, and K. Zilles; Quantitative cerebral water content mapping in hepatic encephalopathy; NeuroImage 41 (2008) 706 – 717
N. J. Shah, V. Gras, A-M. Oros-Peusquens, E. D. Pracht, S. Romanzetti, G. Kircheis, and D. Häussinger; Sodium MR imaging in the study of hepatic encephalopathy; ISMRM; 2010

Additional Information

Contact Person

Prof. Dr. N. J. Shah (Teamleader)

Dr. Vincent Gras

Dr. Ana-Maria Oros-Peusquens


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