High-Resolution CMR_O2 Mapping in Rat Cortex: A Multiparametric Approach to Calibration of BOLD Image Contrast at 7 Tesla

Abstract

The blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) method, which is sensitive to vascular paramagnetic deoxyhemoglobin, is dependent on regional values of cerebral metabolic rate of oxygen utilization (CMR(O2)), blood flow (CBF), and volume (CBV). Induced changes in deoxyhemoglobin function as an endogenous contrast agent, which in turn affects the transverse relaxation rates of tissue water that can be measured by gradient-echo and spin-echo sequences in BOLD fMRI. The purpose here was to define the quantitative relation between BOLD signal change and underlying physiologic parameters. To this end, magnetic resonance imaging and spectroscopy methods were used to measure CBF, CMR(O2), CBV, and relaxation rates (with gradient-echo and spin-echo sequences) at 7 Tesla in rat sensorimotor cortex, where cerebral activity was altered pharmacologically within the autoregulatory range. The changes in tissue transverse relaxation rates were negatively and linearly correlated with changes in CBF, CMR(O2), and CBV. The multiparametric measurements revealed that CBF and CMR(O2) are the dominant physiologic parameters that modulate the BOLD fMRI signal, where the ratios of (deltaCMR(O2)/CMR(O2)/(deltaCBF/ CBF) and (deltaCBV/CBV)/(deltaCBF/CBF) were 0.86 +/- 0.02 and 0.03 +/- 0.02, respectively. The calibrated BOLD signals (spatial resolution of 48 microL) from gradient-echo and spin-echo sequences were used to predict changes in CMR(O2) using measured changes in CBF, CBV, and transverse relaxation rates. The excellent agreement between measured and predicted values for changes in CMR(O2) provides experimental support of the current theory of the BOLD phenomenon. In gradient-echo sequences, BOLD contrast is affected by reversible processes such as static inhomogeneities and slow diffusion, whereas in spin-echo sequences these effects are refocused and are mainly altered by extravascular spin diffusion. This study provides steps by which multiparametric MRI measurements can be used to obtain high-spatial resolution CMR(O2) maps.

Comprehensive correlation between neuronal activity and spin-echo blood oxygenation level-dependent signals in the rat somatosensory cortex evoked by short electrical stimulations at various frequencies and currents

“…This decrease in field-evoked potential is linearly related with the decrease in the evoked CMRO 2 as well as BOLD signal and CBF (Kida et al, 2001(Kida et al, , 2006, consistent with the result that the activation-dependent release of glutamate and the glutamate-glutamine cycles require a proportionate oxidative energy consumption (Sibson et al, 1998). Furthermore, a linear relationship between BOLD signals and oxygen consumption associated with cortical activation produced by either physiological perturbations or forepaw stimulation has been reported (Kida et al, 2000;Sanganahalli et al, 2009;Herman et al, 2009). These findings regarding cerebral oxygen consumption that correlate with both SEP and the BOLD signal support the correlation between BOLD signal and SEP amplitude obtained in the present study.…”

“…Since the T 2 -dependent signal changes are the most sensitive mathematically when the TE is set to the resting T 2 value and the value in the rat somatosensory cortex under deep anesthetic condition like this experiment is 40 ms (Kida et al, 2000), we employed 40 ms for the TE.…”

Stimulus frequency dependence of blood oxygenation level-dependent functional magnetic resonance imaging signals in the somatosensory cortex of rats

“…These results and ours using the spin-echo sequence contradict those using the gradient-echo sequence (Gyngell et al, 1996;Brinker et al, 1999). Several studies have reported that spin-echo sequences with high magnetic field strengths have an advantage over gradient-echo sequences, that is, they allow the observation of local activation Kida et al, 2000;Lee et al, 2002). The BOLD signals obtained using spin-echo sequences represent the following 3 components: (1) extravascular effect of the capillary bed, (2) intravascular effect of both the large and small blood vessels, and (3) absence of the transverse relaxation time (T 2 ) effect such as the inflow effect Lee et al, 2002).…”

“…Since BOLD signals correlate with the deoxygenated hemoglobin content (Ogawa et al, 1990), the stimulus frequency dependence of BOLD signals should correspond to the deoxygenated hemoglobin content assessed by optical imaging, and a similar dependence is expected with regard to changes in the cerebral blood flow (CBF) (Hoge et al, 1999;Kida et al, 2000;Silva et al, 2000). However, conflicting results were obtained with regard to the stimulus frequency dependence of the BOLD signals measured by MRI and the changes in CBF measured using LDF.…”

Simultaneous Detection of Blood Volume, Oxygenation, and Intracellular Calcium Changes during Cerebral Ischemia and Reperfusionin vivoUsing Diffuse Reflectance and Fluorescence

“…Several studies have examined the relationship between the cerebral metabolic rate for oxygen consumption (CMRO 2 ), cerebral blood flow (CBF) and blood volume (CBV) using MRI techniques and showed a tight proportionality between fractional changes in CMRO 2 and CBF measured at rest in humans (Hyder et al, 1998) and during graded anesthesia in the rats (Kida et al, 2000). For example, the ratio defined as DCMRO 2 / DCBF (measured during pharmacologic perturbations) in anesthetized rats is approximately 0.8 to 0.9 and can be increased or decreased slightly by assuming alterations of the oxygen diffusivity properties of the capillary bed (Kida et al, 2000).…”