Chemical exchange saturation transfer imaging in hepatic encephalopathy

Abstract

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 (APTw) chemical exchange saturation transfer (CEST) imaging has been found to be sensitive to ammonia concentration. The aim of this work was to study APTw CEST imaging in patients with HE and to investigate the relationship between disease severity, critical flicker frequency (CFF), psychometric test scores, blood ammonia, and APTw signals in different brain regions.Whole-brain APTw 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 APTw images. All APTw images were spatially normalized into a cohort space to allow direct comparison. APTw 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 APTw intensities was found in the cerebellum and the occipital cortex of manifest HE patients. In addition, APTw 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 APTw 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 APTw 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 APTw signals. These variations are most likely a consequence of hyperammonemia or hepatocerebral degeneration processes, and develop in parallel with disease severity.

Pathological Significance and Prognostic Roles of Indirect Bilirubin/Albumin Ratio in Hepatic Encephalopathy

“…HE is also associated with regional differential alterations. The cerebellum is one of the regions that of high susceptibility in HE, which has been proved in patient imaging examinations and various animal experiments (50)(51)(52). Apoptosis is one of the major ways leading to neurologic damage (53).…”

J-difference GABA-edited MRS reveals altered cerebello-thalamo-cortical metabolism in patients with hepatic encephalopathy

“…(ii) The MRS voxel used in this study included other basal ganglia structures that may also be (differentially) affected by HE. This includes pronounced changes in T 1 relaxation (Shah et al, 2003), chemical exchange saturation transfer (Zöllner et al, 2019), magnetization transfer (Miese et al, 2006, 2009), and possibly water content (Oeltzschner et al, 2016; Shah et al, 2008). These changes may confound spectral quality and quantification accuracy leading to the overall higher variance in the GABA+ estimates that we observed in the thalamus, and therefore diminished statistical power for a constant sample size.…”

“…Other electrophysiological alterations include decreased cerebellar inhibition suggesting a gradual increase of GABAergic neurotransmission (Hassan et al, 2019) and slowed beta oscillations in the left motor cortex, which closely correlate with MRS-derived GABA+/Cr levels (Baumgarten et al, 2016). Finally, chemical exchange saturation transfer imaging in HE patients, which is sensitive to ammonia concentrations and microstructural cell alterations (Zöllner et al, 2019), as well as 13 NH 3 -PET imaging (Keiding et al, 2006; Lockwood et al, 1991), suggested altered ammonia uptake in the cerebellum and thalamus. In summary, evidence from multiple modalities and disease models suggest that ammonia-induced changes of neurotransmission systems in the cerebello-thalamo-cortical system of HE patients are likely contributing to the occurrence of motor symptoms.…”

The risk of bleeding and encephalopathy in surgical patients with liver cirrhosis

“…Besides, there are also abnormalities of fibrinolysis due to the alteration of the synthesis of fibrinolytic factors, but also their clearance, for which the reticuloendothelial system of the liver is mainly responsible. Thus, one can see an imbalance between the plasminogen tissue activator and its inhibitor PAI1, resulting in a fibrinolysis deficiency which is amplified by a decreased clearance of circulating activated coagulation factors (16).…”

“…Given the apparent hypocoagulability present in cirrhosis, which can be revealed by the usual laboratory tests, PT and APTT, it is considered that this category of patients is somewhat "protected" against the risk of thrombosis (16,18).…”