Resident University of Turku, Turku University Hospital Turku, Varsinais-Suomi, Finland
Background: Perinatal hypoxic-ischemic injury due to insufficient oxygen delivery to the brain and vital organs is one of the leading causes of death or severe morbidity in neonates. Assessing the severity of organ damage in the early stages of hypoxic-ischemic encephalopathy has remained a clinical challenge. Objective: We hypothesized that early metabolic changes associated with hypoxic-ischemic encephalopathy could be detected in multiple organs using PET radiotracers for glucose metabolism ([18F]FDG) and hypoxia ([18F]EF5). Design/Methods: Neonatal hypoxic-ischemic brain injury was induced in 9-day-old rat pups by permanent ligation of the left common carotid artery, followed by hypoxia (8% oxygen and 92% nitrogen) for 120 min. PET radiotracers were injected either immediately after the induction of the injury or at different time points up to 21 days later. After the injection, pups were imaged with a small animal PET/CT scanner and sacrificed for ex vivo analysis of organ biodistribution. Results: Both of the tested radiotracers showed significant uptake in the brain tissue. In vivo imaging demonstrated higher uptake of [18F]EF5 and [18F]FDG in the injured hemisphere immediately after the injury. The ex vivo biodistribution of [18F]EF5 (P < 0.0001) and [18F]FDG (P < 0.0001) was also the highest in the brain immediately after the injury. The increased uptake decreased to baseline levels as soon as one day after the injury.
The ex vivo biodistribution analysis revealed elevated [18F]EF5 uptake (tissue hypoxia) immediately after the hypoxic-ischemic injury in the kidneys (P < 0.001), liver (P < 0.01) and eyes (P < 0.0001). Contrastingly, [18F]EF5 uptake in the heart was lower (P < 0.0001) in injured animals than in controls immediately after the injury. There was no significant [18F]EF5 uptake in the small intestine or pancreas. [18F]FDG uptake in the heart was high immediately after the injury (P < 0.0001 compared to controls). Lower [18F]FDG uptake, indicating glucose hypometabolism, was seen in the liver (P < 0.0001), small intestine (P < 0.0001), pancreas (P < 0.001) and eyes (P < 0.01) up to 7 days later. There was no significant changes in [18F]FDG uptake in the kidneys.
Conclusion(s): Early multi-organ effects related to hypoxic-ischemic encephalopathy could be detected using PET radiotracers. As new whole-body PET/CT scanners are emerging in the nuclear imaging field for clinical use, PET could also be a useful new tool for determining whole body organ damage in hypoxic-ischemic injury.
.jpg "Emma Saha, MD (she/her/hers) photo")