New findings on cerebral ammonia uptake in HE using functional ¹³N-ammonia PET

Abstract

PET is a functional imaging technique suitable for studies of brain ammonia metabolism. Dynamic ¹³N-ammonia PET yields time-courses of radioactivity concentrations in brain (PET camera) and blood (samples). Ahl et al. (Hepatology 40:73–79, 2004) and Keiding et al. (Hepatology 43:42–50, 2006) analysed such data in patients with HE by a kinetic model accounting for transfer of ¹³N-ammonia across the blood–brain barrier (BBB) and intracellular formation of ¹³N-glutamine. Initial unidirectional ¹³N-ammonia transfer across BBB was characterized by the permeability-surface area product PS_BBB (ml blood min⁻¹ ml⁻¹ tissue). There was a tendency to lower PS_BBB values in patients with cirrhosis and HE than in patients with cirrhosis without HE and healthy controls but the differences were not statistically significant. Keiding et al. (Hepatology 43:42–50, 2006) also calculated PS_met (ml blood min⁻¹ ml⁻¹ tissue) as a measure of the combined transfer of ¹³N-ammonia across BBB and subsequent intracellular metabolism of ¹³N-ammonia; neither did this PS-value show significant difference between the groups of subjects. Net flux of ammonia from blood into intracellular metabolites was linearly correlated to arterial ammonia. In conclusion, basic brain ammonia kinetics was not changed significantly in patients with cirrhosis +/- HE compared to healthy controls. Blood ammonia seems to be the more important factor for increased brain ammonia uptake in HE.