Transient relationships among BOLD, CBV, and CBF changes in rat brain as detected by functional MRI

Abstract

The transient relationship between arterial cerebral blood flow (CBF A ) and total cerebral blood volume (CBV T ) was determined in the rat brain. Five rats anesthetized with urethane (1.2 g/kg) were examined under graded hypercapnia conditions (7.5% and 10% CO 2 ventilation). The blood oxygenation level-dependent (BOLD) contrast was determined by a gradient-echo echo-planar imaging (GE-EPI) pulse sequence, and CBV T changes were determined after injection of a monocrystalline iron oxide nanocolloid (MION) contrast agent using an iron dose of 12 mg/kg. The relationship between CBV T and CBF A under transient conditions is similar to the power law under steady-state conditions. In addition, the transient relationship between CBV T and CBF A is region-specific. Voxels with ≥15% BOLD signal changes from hypercapnia (7.5% CO 2 ventilation) have a larger Cerebral blood flow (CBF), cerebral blood volume (CBV), and blood oxygenation level-dependent (BOLD) signal changes can be noninvasively quantified in human (1,2) and animal (3) brains using functional MRI (fMRI) methods, which can be employed to calculate the relative cerebral metabolic rate of oxygen consumption (CMRO 2 ). Recent studies reported that fractional changes in blood flow and oxygen uptake are linearly coupled in a consistent ratio of approximately 2:1 in the human primary visual cortex (V1) during graded stimulation. The most potent stimulus produced CBF and CMRO 2 increases of 48% and 25%, respectively (4). Task-induced neural activity, detected by fMRI, significantly increased oxygen consumption in the brain.These fMRI results conflict with previous results from a PET study that employed 18 F-deoxy-glucose, in which neural activity produced only a modest boost (5%) in a brain area's CMRO 2 (5). The PET results suggest that the energy demand required by neural activity is largely met by anaerobic glycolysis. The metabolism of glucose to lactate does not require oxygen. The more significant issue with regard to functional physiology is the extent to which regional brain activation requires an increase in CMRO 2 . This question remains controversial, because some experiments suggest that neural activation significantly increases CMRO 2 (4,6), while others suggest that neural activation is essentially decoupled with CMRO 2 changes (7).One of the potential factors contributing to the controversy over whether fMRI methods can determine CMRO 2 is the important assumption that the relationship between CBV and CBF fits the power law (8):where ␣ ϭ 2.63 and the subscript "0" is used to refer to the baseline steady-state value of a variable in this study. This quantitative relationship between CBF and CBV was obtained from an early PET study on whole monkey brain under the steady-state condition. It is questionable whether such a quantitative relationship obtained from a whole brain is necessarily applicable to a specific brain region. Rapoport et al. (9) showed that the ␣ values differ among different regions in the rat brain. Furthermore, since the temporal r...

Similarities and Differences in Arterial Responses to Hypercapnia and Visual Stimulation

“…It was found that changes in capillary red blood cell velocities occurred mainly in the larger and medium capillaries, whereas volume changes were observed mainly in the small capillaries. Spatial heterogeneity of the exponent a has been shown for hypercapnia and hypocapnia (Wu et al, 2002;Rostrup et al, 2005). The dissociations in our results go further to show that spatial dependence of the volume-flow relationship is influenced by the nature of the conditionsareas around sizeable arteries show different volume-flow relationships during neurogenic and nonneurogenic conditions, unlike areas with mainly tissue.…”

Effects of hypoxia, hyperoxia, and hypercapnia on baseline and stimulus-evoked BOLD, CBF, and CMRO2 in spontaneously breathing animals

“…All these parameters and other physiological quantities are lumped into the constant M which can be measured on a pixel-by-pixel basis. A modified CMRO 2 model has been proposed to take into account the arterial-venous blood volume contributions and includes a non-steady state determination of CMRO 2 (Wu et al, 2002). While Hoge et al (1999), Mandeville et al (1999), and others have reproduced and extended Davis' findings.…”

“…Of note, in an fMRI study performed at 4.7 T, Spenger et al (2000) also report highly variable activations outside the somatosensory pathway (with no changes in MABP and HR) during forepaw stimulation in rats under α-chloralose anesthesia previously optimized to eliminate pain response to electrical stimulation. Second, isoflurane also depresses cerebrovascular reactivity to CO 2 relative to awake conditions (Sicard et al, 2003) which may explain the stronger hypercapnic challenges required to derive M. In animal studies, 5% and 10% CO 2 challenges are commonly used with other anesthetics (Luo et al, 2003;Wu et al, 2002), and the former is frequently used in human studies (Davis et al, 1998;Hoge et al, 1999). Third, isoflurane is a cerebrovasodilator which increases basal CBF (Hendrich et al, 2001;Matta et al, 1999), thus potentially reducing the head room for forepaw stimulation-or hypercapnia-evoked CBF and/or BOLD increases.…”

BOLD‐specific cerebral blood volume and blood flow changes during neuronal activation in humans

“…This equation has since been used extensively in fMRI signal modeling, and the power-law coefficient of 0.38 has been widely assumed when estimating the oxygen metabolism change (DCMRo 2 ) using calibrated BOLD (1,4,5). The general validity of Grubb's power-law relationship has been supported by data from other imaging modalities in animal and human studies (6)(7)(8)(9), but as much as it is widely assumed, the value of a has remained a subject of investigation and debate. Using MRI at 9.4 T, Lee et al (7) found the relationship between the relative CBF (rCBF) and total relative CBV (rCBV) during hypercapnia to be rCBV(total) ¼ rCBF 0.…”