Interindividual and regional relationship between cerebral blood flow and glucose metabolism in the resting brain

Abstract

Studies of the resting brain measurements of cerebral blood flow (CBF) show large interindividual and regional variability, but the metabolic basis of this variability is not fully established. The aim of the present study was to reassess regional and interindividual relationships between cerebral perfusion and glucose metabolism in the resting brain. Regional quantitative measurements of CBF and cerebral metabolic rate of glucose (CMR) were obtained in 24 healthy young men using dynamic [O]HO and [F]fluorodeoxyglucose positron emission tomography (PET). Magnetic resonance imaging measurements of global oxygen extraction fraction (gOEF) and metabolic rate of oxygen ([Formula: see text]) were obtained by combined susceptometry-based sagittal sinus oximetry and phase contrast mapping. No significant interindividual associations between global CBF, global CMR, and [Formula: see text] were observed. Linear mixed-model analysis showed a highly significant association of CBF with CMR regionally. Compared with neocortex significantly higher CBF values than explained by CMR were demonstrated in infratentorial structures, thalami, and mesial temporal cortex, and lower values were found in the striatum and cerebral white matter. The present study shows that absolute quantitative global CBF measurements appear not to be a valid surrogate measure of global cerebral glucose or oxygen consumption, and further demonstrates regionally variable relationship between perfusion and glucose metabolism in the resting brain that could suggest regional differences in energy substrate metabolism. NEW & NOTEWORTHY Using method-independent techniques the study cannot confirm direct interindividual correlations of absolute global values of perfusion with oxygen or glucose metabolism in the resting brain, and absolute global perfusion measurements appear not to be valid surrogate measures of cerebral metabolism. The ratio of both perfusion and oxygen delivery to glucose metabolism varies regionally, also when accounting for known methodological regional bias in quantification of glucose metabolism.

Characterizing a perfusion-based periventricular small vessel region of interest

“…The observed WM CBF distribution was found to be highly non-uniform in both cohorts, showing morphologically comparable extended region of reduced perfusion in the periventricular regions. Similar CBF gradients have previously been observed in group averaged CBF maps obtained with Positron Emission Tomography (PET) and SPECT data (Henriksen et al, 2018; Holland et al, 2008; Ito et al, 2006), albeit with lower resolution. In both cohorts, FLAIR WMLs were also found to coincide with the most poorly perfused regions and the observed spatial distribution of the lowest CBF values also matches WML frequency maps derived from other cohorts (DeCarli et al, 2005; Habes et al, 2016; Holland et al, 2008; Rostrup et al, 2012; Yoshita et al, 2006).…”

Brain SPECT perfusion and PET metabolism as discordant biomarkers in major depressive disorder

“…However, their consistent correlations are presently questioned and in part justified by other mechanisms of blood flow regulation, which could produce a different cartography of cerebral perfusion from the metabolic one. This has already been highlighted in healthy subjects [27]. Furthermore, uncoupling between glucose and oxygen metabolism, via oxygen depletion and induction of downstream hypoxia response pathways, could play a key role in neurodegenerative diseases [28].…”

Regional and interindividual relationships between cerebral perfusion and oxygen metabolism

“…(26; 48) A recent analysis of same-day measurements of rCBF (and rDO 2 ), gCMRO 2 and rCMR glc using independent techniques (in the sense that each quantity is derived from a separate measurement) failed to confirm direct between-subject associations of these measures, also with attention to arterial P CO2 and caffeine levels. (24) The analysis applied MRIbased measurements of gOEF and gCMRO 2 that have not been validated against accepted reference techniques in humans. MRI-based measurements of gOEF provide much simpler non-invasive access to quantification of oxygen metabolism than classically more invasive techniques, but provide no information on regional differences of OEF.…”