Anesthetic agents work by binding to certain proteins on neurons and interrupting their function. Disrupting the communication between distant brain regions is what is thought to result in unconsciousness. While most of the research of the effects of anesthesia on the brain is related to Postoperative Delirium (PD) and PostOperative Cognitive Dysfunction (POCD) [1, 2], little is known about anatomical effects of anesthesia. In this study we sought to analyze the effects of the anesthesia on brain white matter. The difficulties in anesthesia studies are the confounding factors such as disease and the medical procedures (e.g. surgery) that accompany these studies because the data is drawn from clinical samples. The subjects in our study are healthy elderly control volunteers that have been carefully screened.This pilot study is part of an ongoing larger study on the effects of anesthesia on cognitive function in the elderly (Trajectory of Recovery in the Elderly, NIH 1R01AG046634, NCT 2275026). All subjects signed written informed consent and received an extensive battery of neurocognitive tests. Eight healthy subjects were analyzed in this study with an average age of 73 years. Each volunteer had general anesthesia under sevoflurane for two hours. MRI scans were obtained before and during anesthesia as well as 1 day and 7 days after anesthesia. All scans were performed on the Siemens 3T Skyra using a 32 channel head coil. Sequences included Dual Echo TSE (PD-T2), GE-EPI BOLD N-Back, GE-EPI ME-BOLD Resting State, Diffusion Tensor Imaging (DTI), T1 3D MP-RAGE, T2/FLAIR, pulsed arterial spin labeling (PASL), and Susceptibility Weighted Imaging (SWI). DTI was performed axially in 70 directions with bi-directional phase encoding (b-value 1250 s/mm2) and were eddy-current corrected. For this study only the DTI images were analyzed. The fractional anisotropy (FA), mean diffusivity maps (MD) and radial diffusivity maps (RD) were calculated using FSL (www.fmrib.ox.ac.uk/fsl). FA images are spatially normalized to the ICBM template using Tract Based Spatial Statistics (TBSS). TBSS FA images of awake state were compared to the ones under anesthesia using a paired t-test.Fractional anisotropy was decreased during anesthesia throughout the brain (Fig 1). Mean diffusivity was increased during anesthesia and there were minimal difference in radial diffusivity. There were no differences detected between before anesthesia and the follow-up 1 day or 7 day post anesthesia scans.Our data showed a transient decrease in FA and increase in MD during anesthesia. RD was increased in only a limited number of voxels. These differences between on and off anesthesia state were highly significant. This is the first time that this has been reported and the underlying physiology is not well understood. This difference in FA and MD is normally observed when there are increases in the extracellular space between the axons. The source of Diffusion Weighted signal is mostly from extracellular water. A potential source of these changes might the vasodilatory effects of sevoflurane that give rise to microscopy vasogenic swelling and subsequent increase extracellular space. These results suggests that it is important to study the underlying mechanism of this change and whether there are any potential long term effects of anesthesia on white matter integrity and volume.