# Non-invasive identification of brain signatures of acute liver injury

## TL;DR

This study identifies brain changes caused by acute liver injury using non-invasive imaging, offering a new way to detect early signs of brain dysfunction in liver disease.

## Contribution

The study introduces a novel non-invasive method using dual radiotracer PET imaging to detect brain neuroinflammation and metabolic changes in acute liver injury.

## Key findings

- ALI causes brain region-specific neuroinflammation and altered energy metabolism.
- Dual PET imaging reveals brain 'neuroinflammetabolic' signatures linked to ALI.
- Neuroinflammation in ALI shows both gains and losses in brain connectivity.

## Abstract

Background: In many disorders, metabolic and inflammatory derangements that originate in peripheral organs have a deleterious impact on the brain. Brain functional impairment, defined as hepatic encephalopathy, is one of the main diagnostic criteria for acute liver failure (ALF), a severe complication of acute liver injury (ALI). While brain inflammation (neuroinflammation) and metabolic alterations significantly contribute to hepatic encephalopathy, their non-invasive evaluation remains challenging.

Methods: To address this limitation, we utilized dual radiotracer [18F]-fluoro-2-deoxy-2-D-glucose ([18F]FDG) and [11C]-peripheral benzodiazepine receptor ([11C]PBR28) microPET imaging followed by conjunction analysis and metabolic connectivity mapping. We applied this advanced methodology in mice with high dose acetaminophen (N-acetyl-p-aminophenol, APAP)-induced ALI, which can progress into ALF.

Results: We observed hepatocellular damage, liver and systemic inflammation, and increased density of hippocampal microglia in mice with ALI. MicroPET imaging analysis characterized the presence of brain region-specific neuroinflammation and altered brain energy metabolism in mice with ALI. We also identified both gains and losses in connectivity, as well as a dual role of neuroinflammation. These results revealed brain “neuroinflammetabolic” signatures of ALI.

Conclusion: These findings provide a platform for non-invasively diagnosing early signs of hepatic encephalopathy with the goal of informing timely diagnoses and targeted therapies. Our approach can be further utilized in non-invasive brain assessments in liver diseases and other disorders classically characterized by peripheral immune and metabolic dysregulation.