Dynamic TSPO-PET for assessing early effects of cerebral hypoxia and resuscitation in new born pigs

Abstract

IntroductionInflammation associated with microglial activation may be an early prognostic indicator of perinatal hypoxic ischemic injury, where translocator protein (TSPO) is a known inflammatory biomarker. This piglet study used dynamic TSPO-PET with [18F]GE180 to evaluate if microglial activation after global perinatal hypoxic injury could be detected. MethodsNew born anesthetized pigs (n = 14) underwent hypoxia with fraction of inspired oxygen (FiO2)0.08 until base excess −20 mmol/L and/or a mean arterial blood pressure decrease to 20 mm Hg, followed by resuscitation with FiO2 0.21 or 1.0. Three piglets served as controls and one had intracranial injection of lipopolysaccharide (LPS). Whole body [18F]GE180 Positron emission tomography-computed tomography (PET-CT) was performed repeatedly up to 32 h after hypoxia and resuscitation. Volumes of interest were traced in the basal ganglia, cerebellum and liver using MRI as anatomic correlation. Standardized uptake values (SUVs) were measured at baseline and four time-points, quantifying microglial activity over time. Statistical analysis used Mann Whitney- and Wilcoxon rank test with significance value set to p < 0.05. ResultsAt baseline (n = 5), mean SUVs ±1 standard deviation were 0.43 ± 0.10 and 1.71 ± 0.62 in brain and liver respectively without significant increase after hypoxia at the four time-points (n = 5–13/time point). Succeeding LPS injection, SUV increased 80% from baseline values. ConclusionsCerebral inflammatory response caused by severe asphyxia was not possible to detect with [18F]GE180 PET CT the first 32 h after hypoxia and only sparse hepatic uptake was revealed. Advances in knowledgeEarly microglial activation as indicator of perinatal hypoxic ischemic injury was not detectable by TSPO-PET with [18F]GE180. Implications for patient careTSPO-PET with [18F]GE180 might not be suitable for early detection of perinatal hypoxic ischemic brain injury.