Figure 1.
Quantitative method for the estimation of regional cerebral blood oxygenation.
T2* magnetic resonance images are acquired at 17.2T in anesthetized rats. Manual segmentation is performed on coronal sections to delineate each region of interest (ROI), here the cortex. For each anesthetic molecule (termed ‘agent’), and for each extracted ROI, the magnetic resonance contrast (Cagent) between the vessels (hypointense) and brain is automatically computed, reflecting the quantity of deoxyHb of the blood [6]. The number of voxels of the ROI is also calculated. The index we computed, T2*-oxygenation-ratio, is normalized to the number of voxels of the ROI, and reflects the cerebral blood oxygenation for the ROI and the anesthetic agent [6].
Figure 2.
Magnetic resonance images of the rat brain at 17.2T.
Coronal sections from images that were acquired under different anesthetic agents. T2* magnitude, left panel; T2* phase, middle panel; susceptibility weighted images (SWI), right panel. Red arrowheads refer to hypointense signal corresponding to brain vessels. Images acquired under volatile anesthetic agents (isoflurane A,B,C; sevoflurane D,E,F) display more homogenous MR signal and less contrast between the brain vessels and the brain parenchyma, than intravenous anesthetics (propofol G,H,I; midazolam J,K,L; medetomidine M,N,O; ketamine-xylazine P,Q,R). Green arrowheads refer to hyperintense signal of the sagittal sinus reflecting increased blood oxygenation with isoflurane and sevoflurane as compared to the other anesthetics.
Figure 3.
Comparison of T2*-oxygenation-ratio of volatile anesthetics among brain regions.
Images are coronal T2* MRI sections acquired in vivo under general anesthesia using isoflurane (A: cortex, B: hippocampus, C: striatum, D: thalamus) or sevoflurane (F: cortex, G: hippocampus, H: striatum, I: thalamus). Box plots represent median, 25th and 75th percentile, minimum and maximum values, outliers (°) and extremes (*). Y-axis: regional T2*-oxygenation-ratio. X-axis: Cx, cortex; Hc, hippocampus; Str, stiatum; Th, thalamus. E: T2*-oxygenation-ratio for isoflurane. The thalamus had a lower oxygenation level than the other studied brain regions. J: T2*-oxygenation-ratio for sevoflurane. No significant difference was observed between the studied brain regions. *** p<0.001.
Figure 4.
Comparison of T2*-oxygenation-ratio of intravenous anesthetics among brain regions.
Images are coronal T2* MRI sections acquired in vivo under general anesthesia using propofol (A: cortex, B: hippocampus, C: striatum, D: thalamus), midazolam (F: cortex, G: hippocampus, H: striatum, I: thalamus), medetomidine (K: cortex, L: hippocampus, M: striatum, N: thalamus) or ketamine-xylazine (P: cortex, Q: hippocampus, R: striatum, S: thalamus). Box plots represents median, 25th and 75th percentile, minimum and maximum values, outliers (°) and extremes (*). Y-axis: regional T2*-oxygenation-ratio. X-axis: Cx, cortex; Hc, hippocampus; Str, stiatum; Th, thalamus. E: T2*-oxygenation-ratio for propofol. J: T2*-oxygenation-ratio for midazolam, O: T2*-oxygenation-ratio for medetomidine, T: T2*-oxygenation-ratio for ketamine-xylazine. * p<0.05, ** p<0.01.
Figure 5.
Differences of T2*-oxygenation-ratio between anesthetic agents.
A, cortex; B, thalamus; C, hippocampus; D, striatum. Diagrams are box plots made with IBM SPSS software. Each box plot represents median, 25th and 75th percentile, minimum and maximum values, outliers (°) and extremes (*). Y-axis: regional T2*-oxygenation-ratio. Compared to isoflurane: # p<0.05, ## p<0.01, ### p<0.001. Compared to sevoflurane: + p<0.05, ++ p<0.01, +++ p<0.001. Compared to midazolam: $ p<0.05, ($) p = 0.053. iso, isoflurane; sevo, sevoflurane; prop, propofol; mdz, midazolam; medet, medetomidine; ket-xyl, ketamine-xylazine. The dotted line at 50000 shows a separation between high and low T2*-oxygenation-ratio.
Figure 6.
Classification of sedative agents based on their effects on the blood oxygenation level assessed by MRI at 17.2 T.
A: The relative oxygenation ratio of isoflurane, sevoflurane, propofol, midazolam, medetomidine and ketamine-xylazine is displayed using a colored disk with variable intensity. Lower color saturation intensity corresponds to lower CBO level, and vice a versa. B: Proposed algorithm to identify anesthetic agents based on relative CBO in the cortex and thalamus as assessed by T2*-oxygenation-ratio. Low signal, T2*-oxygenation-ratio<50000; High signal, T2*-oxygenation-ratio>50000.