High field brain proton magnetic resonance spectroscopy and volumetry in children with chronic, compensated liver disease - A pilot study.

BACKGROUND: There is increasing evidence that children or young adults having acquired liver disease in childhood display neurocognitive impairment which may become more apparent as they grow older. The molecular, cellular and morphological underpinnings of this clinical problem are incompletely understood. AIM: Therefore, we used the advantages of highly-resolved proton magnetic resonance spectroscopy at ultra-high magnetic field to analyze the neurometabolic profile and brain morphometry of children with chronic, compensated liver disease, hypothesizing that with high field spectroscopy we would identify early evidence of rising brain glutamine and decreased myoinositol, such as has been described both in animals and humans with more significant liver disease. METHODS: Patients (n = 5) and age-matched controls (n = 19) underwent 7T MR scans and short echo time 1H MR spectra were acquired using the semi-adiabatic SPECIAL sequence in two voxels located in gray and white matter dominated prefrontal cortex, respectively. A 3D MP2RAGE sequence was also acquired for brain volumetry and T1 mapping. Liver disease had to have developed at least 6 months before entering the study. Subjects underwent routine blood analysis and neurocognitive testing using validated methods within 3 months of MRI and MRS. RESULTS: Five children aged 8-16 years with liver disease acquired in childhood were included. Baseline biological characteristics were similar among patients. There were no statistically significant differences between subjects and controls in brain metabolite levels or brain volumetry. Finally, there were minor neurocognitive fluctuations including attention deficit in one child, but none fell in the statistically significant range. CONCLUSION: Children with chronic, compensated liver disease did not display an abnormal neurometabolic profile, neurocognitive abnormalities, or signal intensity changes in the globus pallidus. Despite the absence of neurometabolic changes, it is an opportunity to emphasize that it is only by developing the use of 1H MRS at high field in the clinical arena that we will understand the significance and generalizability of these findings in children with CLD. Healthy children displayed neurometabolic regional differences as previously reported in adult subjects.

Neurometabolism and brain morphometry in an adolescent female with an extra-hepatic congenital portosystemic shunt.

Background: Chronic hepatic encephalopathy (CHE) has been reported both in patients with congenital porto-systemic shunts (CPSS) and chronic liver disease. CHE is difficult to recognize in children as there is no clear definition and its manifestations are highly variable. CHE is associated with variations in brain volumes and metabolites that have already been demonstrated using 1.5-3T MRI systems. However, the in-depth study of brain metabolism requires the high spectral resolution of high magnetic fields. Objectives and Methods: We analyzed the neurometabolic profile, brain volumes and T1 relaxation times of a child with a CPSS using high field proton magnetic resonance spectroscopy (1H MRS, 7T) combined with MRI and compared it to an age-matched control group. We also evaluated the impact of shunt closure on neurocognitive symptoms using adapted neuropsychological tests. Results: 7T MRS revealed a significant increase in glutamine compared to controls, a decrease in brain osmolytes, and a slight elevation in NAA concentrations. 7T MRI scans showed morphological abnormalities but no changes in the signal intensity of the globus pallidus. Neurocognitive testing revealed attention deficit disorder, language difficulties, and mild intellectual disability. Most of these areas improved after shunt closure. Conclusions: In this paediatric case of type B HE with normal fasting ammonia, neurometabolic profile was compatible with what has been previously shown in chronic liver disease, while also demonstrating an isolated glutamine peak. In addition, neurocognitive function partially improved after shunt closure, arguing strongly for shunt closure in both presymptomatic and symptomatic patients.