Changes in Cerebral Blood Flow and Cerebral Oxygen Metabolism during Neural Activation Measured by Positron Emission Tomography: Comparison with Blood Oxygenation Level-Dependent Contrast Measured by Functional Magnetic Resonance Imaging

Abstract

The discrepancy between the increases in cerebral blood flow (CBF) and CMRO 2 during neural activation causes an increase in venous blood oxygenation and, therefore, a decrease in paramagnetic deoxyhemoglobin concentration in venous blood. This can be detected by functional magnetic resonance imaging (fMRI) as blood oxygenation level-dependent (BOLD) contrast. In the present study, changes in the cerebral oxygen extraction fraction (OEF) that corresponds to the ratio of CMRO 2 to CBF, and in the BOLD signal during neural activation, were measured by both positron emission tomography (PET) and fMRI in the same human subjects. C 15 O, 15 O 2 , and H 2 15 O PET studies were performed in each subject at rest (baseline) and during performance of a right-hand motor task. Functional magnetic resonance imaging studies were then performed to measure the BOLD signal under the two conditions. During performance of the motor task, a significant increase in CBF and a significant decrease in OEF were observed in the left precentral gyrus, left superior frontal gyrus, right precentral gyrus, right cingulate gyrus, and right cerebellum. A significant positive correlation was observed between changes in the CBF and the BOLD signal, and a significant negative correlation was observed between changes in the OEF and the BOLD signal. This supports the assumption on which BOLD contrast studies during neural activation are based.

Are glutamate and lactate increases ubiquitous to physiological activation? A 1H functional MR spectroscopy study during motor activation in human brain at 7Tesla

“…Thus, the total increase of glucose consumption during the stimulation, ΔCMR Glc(tot) , was estimated at 0.17 μmol/g/min, which corresponds to a 40-50% increase from the basal state of CMR Glc (0.34-0.42 μmol/g/min (Alkire et al, 1999;Huisman et al, 2012)). It is of interest to note that such estimated ΔCMR Glc(tot) is close to ΔCBF reported in previous PET studies during motor stimulation (Ito et al, 2005) or somatosensory stimulation (Fox and Raichle, 1986), but ΔCMR Glc(tot) may actually exceed the estimated value due to incremental CMR O2 not accounted for by this calculation.…”

“…The original ΔCBF/ΔCMR O2~6 reported by Fox and Raichle (Fox and Raichle, 1986) is generally higher than other human brain PET studies (Hyder, 2004;Ito et al, 2005;Kuwabara et al, 1992;Marrett and Gjedde, 1997). For calibrated BOLD-measurement studies, the ratio ΔCBF/ ΔCMR O2 generally lies from 2 to 4 (Buxton, 2010).…”

“…When assuming a nearcomplete oxidation of glucose at rest (Siesjo, 1978), the oxidation of ΔCMR Glc,ox leading to glutamate increase corresponds to ΔCMR O2 of 5.5 × ΔCMR Glc,ox × 8/36 = 0.14 μmol/g/min, which amounts to a relative ΔCMR O2 increase of 10% (given a basal state of 1.5 μmol/g/min (Ito et al, 2005)). Note that this incremental ΔCMR O2 is close to the reported CMR O2 increase in motor stimulation (Ito et al, 2005) and somatosensory stimulation (Fox and Raichle, 1986). In addition, a recent study by Vafaee et al (2012) reported a ΔCMR O2~6 % after 1 min of finger tapping activation in M1 motor area.…”

“…It is thus plausible that the measured changes mainly represent the metabolic events during the first minutes of the PET studies, given the characteristics of the bolus-shaped arterial input function of PET FDG studies and the short half-life of 2 min of 15 O (Fox and Raichle, 1986;Ito et al, 2005). Therefore, these considerations offer an explanation to the apparent discrepancy between the steadystate measurements by NMR implying a near complete oxidation of glucose during activation (Lin et al, 2012;Mangia et al, 2007a;Schaller et al, 2013) and PET (Fox and Raichle, 1986;Ito et al, 2005).…”

Development of new optical imaging systems of oxygen metabolism and simultaneous measurement in hemodynamic changes using awake mice

“…Neural activation has been reported to cause an increase in the cerebral metabolic rate of oxygen (CMRO 2 ) and a larger increase in cerebral blood flow (CBF) than in cerebral blood volume (CBV) in human PET studies (Ito et al, 2005). Crossed cerebellar diaschisis, which is caused by contralateral supratentorial lesions, has shown reductions in CBF and CMRO 2 in human (Lenzi et al, 1982;Yamauchi et al, 1992aYamauchi et al, ,b, 1999aIto et al, 2002).…”