Abstract
Hypoxic-ischemic encephalopathy due to insufficient oxygen delivery to brain tissue is a leading cause of death or severe morbidity in neonates. The early recognition of the most severely affected individuals remains a clinical challenge. We hypothesized that hypoxic-ischemic injury can be detected using PET radiotracers for hypoxia ([ 18F]EF5), glucose metabolism ([ 18F]FDG), and inflammation ([ 18F]F-DPA). Methods: A preclinical model of neonatal hypoxic-ischemic brain injury was made in 9-d-old rat pups by permanent ligation of the left common carotid artery followed by hypoxia (8% oxygen and 92% nitrogen) for 120 min. In vivo PET imaging was performed immediately after injury induction or at different timepoints up to 21 d later. After imaging, ex vivo brain autoradiography was performed. Brain sections were stained with cresyl violet to evaluate the extent of the brain injury and to correlate it with [ 18F]FDG uptake. Results: PET imaging revealed that all three of the radiotracers tested had significant uptake in the injured brain hemisphere. Ex vivo autoradiography revealed high [ 18F]EF5 uptake in the hypoxic hemisphere immediately after the injury (P < 0.0001), decreasing to baseline even 1 d postinjury. [ 18F]FDG uptake was highest in the injured hemisphere on the day of injury (P < 0.0001), whereas [ 18F]F-DPA uptake was evident after 4 d (P = 0.029), peaking 7 d postinjury (P < 0.0001), and remained significant 21 d after the injury. Targeted evaluation demonstrated that [ 18F]FDG uptake measured by in vivo imaging 1 d postinjury correlated positively with the brain volume loss detected 21 d later (r = 0.72, P = 0.028). Conclusion: Neonatal hypoxic-ischemic brain injury can be detected using PET imaging. Different types of radiotracers illustrate distinct phases of hypoxic brain damage. PET may be a new useful technique, worthy of being explored for clinical use, to predict and evaluate the course of the injury.
| Original language | English |
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| Article number | 114673 |
| Number of pages | 9 |
| Journal | Experimental Neurology |
| Volume | 373 |
| DOIs | |
| Publication status | Published - Mar 2024 |
| MoE publication type | A1 Journal article-refereed |
Funding
This research was supported by the InFLAMES Flagship Programme of the Academy of Finland [337530]; Foundation for Pediatric Research, Finland [190154, 210225, and 210186]; The South-Western Finnish Foundation of Neonatal Research; The Finnish Cultural Foundation (Varsinais-Suomi Regional Fund); Päivikki and Sakari Sohlberg Foundation; The State Funding for University Level Health Research in Finland (Turku University Hospital); and The Finnish Medical Foundation [5159]. The authors declare no conflict of interest. This research was supported by the InFLAMES Flagship Programme of the Academy of Finland [ 337530 ]; Foundation for Pediatric Research , Finland [ 190154 , 210225 , and 210186 ]; The South-Western Finnish Foundation of Neonatal Research ; The Finnish Cultural Foundation (Varsinais-Suomi Regional Fund) ; Päivikki and Sakari Sohlberg Foundation ; The State Funding for University Level Health Research in Finland (Turku University Hospital) ; and The Finnish Medical Foundation [ 5159 ]. The authors declare no conflict of interest.