Chemical exchange saturation transfer imaging in hepatic encephalopathy

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 T₁ mapping and structural images. T₁ normalized magnetization transfer ratio asymmetry analysis was performed around 3 ppm after B₀ and B₁ 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.