Evaluation of default mode network by quantitative ¹⁵O-labeled gases and water PET: comparison study between cerebral blood flow and oxygen consumption.

Objectives: Resting State functional MRI (fMRI) revealed existence of default mode network (DMN) by estimating functional connectivity among brain regions based on spontaneous oscillation of blood oxygenation level dependent (BOLD) signal. The BOLD signal reflects the deoxyhemoglobin concentration which depends on the relationship between regional cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO₂). However, these two factors cannot be separated in the BOLD fMRI. In this study, we aimed to estimate the functional connectivity in DMN by means of quantitative ¹⁵O-labeled gases and water PET and compare the contribution of CBF and CMRO₂ for DMN.

Methods: Nine healthy volunteers (5 men and 4 women; mean age, 47.0 ± 1.2 years) were studied by means of ¹⁵O-O₂, ¹⁵O-CO gases and ¹⁵O-water PET with arterial blood sampling. Quantitative CBF and CMRO₂ images were generated by an autoradiographic method and transformed into MNI standardized brain template for anatomical normalization by SPM8. Regions of interest (12 brain regions) were placed on normalized PET images to according to the previous fMRI study, such as anterior medial prefrontal cortex, superior frontal cortex, inferior temporal cortex, parahippocampal gyrus, posterior cingulate cortex, lateral parietal cortex, and cerebellar tonsils. For the functional connectivity analysis, Pearson's correlation coefficients (r) were calculated for all pairs in the 12 brain regions and correlation matrices were obtained for CBF and CMRO₂, respectively. We defined r>0.7 as a significant positive correlation and compared the correlation matrices of CBF and CMRO₂ focusing on the number of positive brain networks.

Results: CBF and CMRO₂ values were 37.7 ± 6.9 (ml/100mL/min) and 2.79 ± 0.43 (ml/100mL/min) in the anterior medial prefrontal cortex and 51.5 ± 8.3 and 3.90 ± 0.69 in the posterior cingulate cortex, respectively. Significant positive correlations were observed in 23 pairs of brain region for CBF and 17 pairs for CMRO₂. Among them, common networks were observed between CBF and CMRO₂ (7 pairs in the inferior temporal cortex, 4 pairs in the posterior cingulate cortex, and 7 pairs in the lateral parietal cortex). Correlation analysis of CBF detected more brain networks compared to that of CMRO₂. It was suggested that CBF could capture the state of the spontaneous activity with higher sensitivity compared to oxygen consumption in the local brain region. It was also consistent with the previous study which reported that cerebral oxygen consumption only increases to a minor degree compared to CBF during functional activation.

Conclusion: We estimated the functional connectivity in DMN by means of quantitative ¹⁵O-labeled gases and water PET. Correlation of CBF revealed more brain networks compared to that of CMRO₂, indicating that spontaneous activity of the local brain region influenced the change in blood flow more than that in oxygen consumption. Further multi-modality study should be performed to evaluate the relationship among CBF, CMRO₂ and fMRI BOLD signal and establish the integrated detection of brain networks. References: 1. Liu X, Li H, Luo F, Zhang L, Han R, Wang B. Variation of the default mode network with altered alertness levels induced by propofol. Neuropsychiatr Dis Treat. 2015;11:2573-2581. 2. Paulson OB, Hasselbalch SG, Rostrup E, Knudsen GM, Pelligrino D. Cerebral blood flow response to functional activation. J Cereb Blood Flow Metab. Jan 2010;30(1):2-14.

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