Anaesthetics such as those used for sedation in pediatric MRI affect cerebral blood flow and hemodynamics to varying degrees. Currently, multiple sedation regimes are used in different pediatric MRI centres worldwide. Deep propofol sedation has become a standard in paediatric sedation¹, and can be applied alone or in combination with other sedatives, e.g. ketamine². While some previous studies have reported changes in cerebral blood flow in adults treated with sub-anaesthetic^3-4 or anaesthetic⁴ doses of ketamine, the impact of anaesthetic doses of ketamine on cerebral perfusion in children is currently unknown. The purpose of the present study was to examine differences in cerebral perfusion in children undergoing elective MRI under sedation with propofol vs. a combination of propofol and ketamine.

In total 216 children undergoing elective neurological MRI under sedation were recruited into this prospective, double-blinded randomized study between 2012 and 2014. Children were randomised to undergo deep sedation with or without ketamine (1 mg/kg) at induction, followed by propofol 10 vs. 5 mg/kg/hour for maintenance. Irrespective of the sedation regime used, induction was performed either with intravenous propofol boluses or inhalational Sevoflurane until an intravenous line was established. MR imaging was performed with a 3T GE HD.xt, 1.5T GE MR450, or 3T GE MR750 MRI scanners. Arterial spin labelling (ASL) perfusion images were acquired at the beginning of the scanning session with a 3D background-suppressed, multishot, segmented pseudocontinuous arterial spin labelling (ASL) perfusion sequence, using a stack of spirals readout with TR = 5.5 s, TE = 25 ms, matrix = 64x64, slice thickness = 3 mm, and field of view = 24 cm.

Cerebral MR images were reviewed by a neuroradiologist and a subset of n=83 cerebral MRI cases were reported as normal. Two cases were subsequently excluded due to poor quality ASL. Average whole-brain perfusion values were extracted from the ASL perfusion images from the neuroradiologically normal cases, using a grey matter mask derived from the AAL atlas, registered to the ASL perfusion maps in native space. Shapiro-Wilk tests were used to test for normality of the whole brain perfusion values. Differences in whole brain perfusion between the ketamine and propofol groups were tested with a univariate general linear model with whole brain perfusion as the dependent variable, sedation regime (propofol vs. ketamine) as the fixed factor and age and scanner as covariates. Voxelwise differences in perfusion between the propofol and ketamine groups were tested with permutation testing⁵. In order to remove the confounding effects of scanner differences, the voxelwise analysis was performed for the normalised perfusion data acquired from each MRI scanner separately.

The 83 Patients with normal brain morphology ranged in age from 3 months to 10 years (mean age 3.9 years). The ketamine and propofol groups did not differ significantly in age, hematocrit, pH, or pCO2 (p > 0.23). Children induced for anaesthesia with ketamine showed a higher whole brain perfusion than those induced with propofol (p=0.003), covarying for scanner and age (corrected model significance: p<0.001, adjusted R2 = 0.226). The voxelwise analysis also revealed significantly higher perfusion in the ketamine group across a widespread network of cortical grey matter regions including frontal, parietal, occipital, and temporal cortices (figure 1).Children induced for sedation with ketamine demonstrated on average 14% higher whole brain perfusion values than those induced for sedation with propofol. This finding is in keeping with previous reports from PET and MRI studies investigating hemodynamic changes associated with subanaesthetic^3-4 and anaesthetic⁴ doses of ketamine in adults. In the context of the known neurovascular coupling between neuronal activity and microcirculation⁶, these results point towards a differential effect of ketamine and propofol on brain activity as well as hemodynamics. These results further underscore the important role that noninvasive perfusion imaging methods like ASL can play in evaluating the differences in blood flow and cerebral activity during different sedation regimes, or in response to pharmacological treatment in children.