Effect of isoflurane on rat brain metabolism assessed by 18F-FDG small animal PET with voxel-based approach

Objectives Small animal PET has been frequently used for preclinical studies, but there are still some issues regarding animal handling and anesthesia may affect the result of PET images. Especially, anesthetics are known to reduce brain metabolism in small animals. In this study, we quantitatively assessed the effect of anesthesia on each rat brain regions by 18F-FDG PET.

Methods 37 Wistar rats were divided into two subgroups depending on existence of exposure to anesthesia with inhaled 1.5-2.0% isoflurane during PET imaging; anesthesia (AN, n=13) and awake (AW, n=24). All PET images were coregistered and spatially normalized to T2 MRI and FDG PET templates. Standardized uptake values (SUVs) were calculated in each rat brain regions by using predefined automated volume of interest (VOI) and were compared among brain regions and between two groups. Voxel-based t-test was also performed by using statistical parametric mapping (SPM) 5 to compare significance of the difference.

Results Grossly, AW group showed more discrete FDG uptake between cerebral white and gray matters than AN group. In quantitative analysis, there was significant decrease of SUVmean in many brain regions of AN group, including cerebral cortices (31.8-45.8%), striatum, right insula, entorhinal cortex, olfactory bulb, inferior colliculus (21.2-27.4%) and nucleus accumbens, right amygdala, and superior colliculus (18.4-22.4%). However, there was no significant difference of SUVmean in amygdala, hippocampus, cerebellum and brain stem.

Conclusions Inhaled general anesthesia with isoflurane can result in underestimation of metabolic activity in most rat brain regions. Therefore, exhaustive research planning and careful interpretation are crucial when small animal 18F-FDG PET is used.

Research Support This research was supported by grant No. R31-2008-000-10103-0 from the WCU project of the MEST and the NRF and a grant (seed-10-4) from the Inter-Institutional Collaboration Research Program under the Korea Research Council of Fundamental Science & Technology (KRCF).