Hepatic encephalopathy (HE) is a common complication in liver cirrhosis and associated with an invasion of ammonia into the brain through the blood-brain barrier. Resulting higher ammonia concentrations in the brain are suggested to lead to a dose-dependent gradual increase of HE severity and an associated impairment of brain function. Amide proton transfer-weighted (APT w ) chemical exchange saturation transfer (CEST) imaging has been found to be sensitive to ammonia concentration. The aim of this work was to study APT w CEST imaging in patients with HE and to investigate the relationship between disease severity, critical flicker frequency (CFF), psychometric test scores, blood ammonia, and APT w signals in different brain regions. Whole-brain APT w CEST images were acquired in 34 participants (14 controls, 20 patients (10 minimal HE, 10 manifest HE)) on a 3 T clinical MRI system accompanied by T 1 mapping and structural images. T 1 normalized magnetization transfer ratio asymmetry analysis was performed around 3 ppm after B 0 and B 1 correction to create APT w images. All APT w images were spatially normalized into a cohort space to allow direct comparison. APT w images in 6 brain regions (cerebellum, occipital cortex, putamen, thalamus, caudate, white matter) were tested for group differences as well as the link to CFF, psychometric test scores, and blood ammonia. A decrease in APT w intensities was found in the cerebellum and the occipital cortex of manifest HE patients. In addition, APT w intensities in the cerebellum correlated positively with several psychometric scores, such as the fine motor performance scores MLS1 for hand steadiness / tremor (r = 0.466; p =.044) and WRT2 for motor reaction time (r = 0.523; p =.022). Moreover, a negative correlation between APT w intensities and blood ammonia was found for the cerebellum (r = −0.615; p =.007) and the occipital cortex (r = −0.478; p =.045). An increase of APT w intensities was observed in the putamen of patients with minimal HE and correlated negatively with the CFF (r = −0.423; p =.013). Our findings demonstrate that HE is associated with regional differential alterations in APT w signals. These variations are most likely a consequence of hyperammonemia or hepatocerebral degeneration processes, and develop in parallel with disease severity.
Zöllner, H. J., Butz, M., Jördens, M., Füllenbach, N. D., Häussinger, D., Schmitt, B., … Schnitzler, A. (2019). Chemical exchange saturation transfer imaging in hepatic encephalopathy. NeuroImage: Clinical, 22. https://doi.org/10.1016/j.nicl.2019.101743