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<zdoi;10.1097/ALN.1155> Anesthesiology, V 125 • No 1 22 July 2016 I t is now undisputed that anesthetic agents with effects on N-methyl-d-aspartate and/or γ-aminobutyric acid A receptors (e.g., isoflurane, sevoflurane, ketamine, or midazolam) can induce cellular damage in the rodent or nonhuman primate (NHP) brain when administered during a window of developmental vulnerability, coinciding with high rates of synaptogenesis, maturation of neurons, and neurogenesis.1,2 For rodents, this period spans from postnatal day 7 to 14,3 while in NHPs, postnatal day 6 has been highlighted.4 Anesthesia-induced neurotoxicity in the developing animal brain is associated with learning disabilities as well as abnormal behavior including anxiety.1,5 disturbingly, the question of whether or not anesthesia neurotoxicity occurs in the young human brain remains unanswered. Retrospective, observational human studies linking anesthesia exposures in young children to cognitive and behavioral deficits later on in life have yielded conflicting and somewhat inconclusive results.6,7 This has in part been attributed to “lack of an obvious human phenotype for anesthesia neurotoxicity.”8 Prospective clinical studies are currently underway (Clinicaltrials.gov, Bethesda, Maryland), with some very recent data raising doubts as to the clinical relevance of this effect.9 Given the uncertainty, there has also been a strong effort to search for new approaches to explore and validate the possibility of neonatal anesthesia neurotoxicity in the human brain. Molecular imaging approaches can play an important role in shedding light on the mechanisms involved in neonatal anesthesia-induced neurotoxicity. Such methodology has been extremely informative in understanding neurochemical and metabolic changes in disease states such as depression,10 addiction to substances of abuse,11,12 multiple sclerosis,13 and Parkinson disease,14 leading to discovery of new diagnostic and therapeutic targets. In this issue of ANeStHeSIoloGy, Zhang et al.15 take an innovative approach to this problem with a translational tool by using positron emission tomography (Pet) in combination with a radiotracer, 18F-labeled f l u o r o e t h o x y b e n z y l N ( 4 phenoxypyridin-3-yl) acetamide (18F-FePPA), to explore the state of “inflammation” in the brain of neonatal NHP rhesus monkeys after exposure to 2.5% sevoflurane for 8 h. The authors report that 18F-FePPA binding (measured quantitatively as “standard uptake values”) is significantly increased in the frontal and temporal lobes 24 h after sevoflurane exposure compared to nonexposed neonatal controls and remains elevated up to 1 week after exposure. The authors conclude that increased 18F-FePPA uptake in the neonatal NHP brain is representative of glial cell activation (inflammation) and associated sevoflurane-induced neurotoxicity; the latter was confirmed histologically in a separate series of animals. In addition, it is reported that acetyl-l-carnitine (AlC) effectively blocks the inflammation as defined by increased 18F-FePPA standard uptake values, and it is suggested that AlC may be protective in the setting of neurotoxicity from sevoflurane exposure in the neonate. What is the evidence for the presence of neuroinflammation in the setting of an increase in 18F-FePPA binding in the brain? The 18F-FePPA ligand binds with high affinity to the translocator protein (tSPo) site of 18 kda,16,17 which in the central nervous system is expressed mainly in glial cells (microglia as well as astrocytes). Specifically, tSPo is located on the outer membrane of mitochondria in glial cells and is part of a larger complex comprising a voltage-dependent anion channel and the adenine nucleotide carrier.16 There Are We Moving Closer to Noninvasive Imaging and Monitoring of Neonatal Anesthesia–induced Neurotoxicity?