Relationship CBF, CMRO2 , CMRglu

Relationship CBF, CMRO2, CMRgl

Introduction

Relative changes in the cerebral metabolic rate of oxygen (dCMRO2) and its relation to relative changes in cerebral blood flow (dCBF) during neuronal activations have attracted intense interest in the fields of neuroscience and metabolic physiology. One hundred years ago, it was suggested in the study of Roy and Sherrington (1890) that the CBF changes may be a function of a tight coupling between cellular energy requirements and the supplies of glucose and oxygen to the brain. Since then, a consensus among neuroscientists is that the significant increase in regional CBF is necessary to meet the oxygen demand from the activated neurons in the region, and therefore, dCMRO2 and dCBF should be tightly coupled (Gjedde, 1997).

Discussion

With development of neuroimaging techniques, the understanding of the flow-metabolism relationship has evolved. For example, using positron emission tomography (PET), a mismatch in CBF and CMRO2 was found during neuronal activations by (Fox and Raichle, 1986) and Fox et al., 1988 P.T. Fox, M.E. Raichle, M.A. Mintun and C. Dence, Nonoxidative glucose consumption during focal physiologic neural activity, Science 241 (1988), pp. 462-464. View Record in Scopus | Cited By in Scopus (628)(Fox et al., 1988)). In a visual study using a frequency stimulus rate (10 Hz), Fox et al. (1988) reported a dramatic increase in CBF ( 50%), but much less increase in CMRO2 ( 5%) in activated human visual cortex. With a frequency-varying paradigm (1 to 32 Hz), rate-dependent dCMRO2 and non-linear flow-metabolism coupling were observed during visual stimulation in PET studies ([Vafaee et al., 1999] and [Vafaee and Gjedde, 2000]); such that dCBF peaks at 8 Hz while dCMRO2 reaches its maximum at 4 Hz. These findings have been recently validated using functional magnetic resonance imaging (fMRI) techniques (Lin et al., 2008).

The temporal information regarding the dynamic nature of the hemodynamic and metabolic response to prolonged brain stimulation plays an important role in understanding of the underlying mechanism of neuronal activity. With prolonged (20 min) visual stimulation at 8 Hz, cerebral metabolic rate of glucose (CMRGlu) measurements have been performed using [18F]fluorodeoxyglucose (FDG) PET (Vlassenko et al., 2006a). Their result shows that CMRGlu is dramatically increased in the early stage of stimulation and decreases with time as the stimulation continuous. Interestingly, using PET and prolonged achromatic grating visual stimulation (25 min), Mintun et al. (2002) found that the dCMRO2 is increased with time as the brain activation lasted. These PET results indicated that significant non-oxidative glycolysis is transient followed by an increase in oxygen utilization. Similar interpretations have been made in measurements of glucose and lactate levels with MR spectroscopy (MRS) ([Chen et al., 1993], [Frahm et al., 1996] and [Prichard et al., 1991]).

Using fMRI, the temporal behaviors of dCBF and relative changes in blood oxygenation level-dependent (dBOLD) signals have been reported during continuous high-frequency (= 8 Hz) visual stimulation ([Bandettini et al., 1997], [Hathout et al., 1994] and [Howseman et al., 1998]). The decreased signal intensity of dCBF and dBOLD suggested increase of dCMRO2 over time, which is in good agreement with ...