Magnetic resonance imaging (MRI) and spectroscopy (MRS) were used at a magnetic field strength of 7 T to measure CBF and CMRO2 in the sensorimotor cortex of mature rats at different levels of cortical activity. In rats maintained on morphine anesthesia, transitions to lower activity and higher activity states were produced by administration of pentobarbital and nicotine, respectively. Under basal conditions of morphine sulfate anesthesia, CBF was 0.75 +/- 0.09 mL x g(-1) x min(-1) and CMRO2 was 3.15 +/- 0.18 micromol x g(-1) x min(-1). Administration of sodium pentobarbital reduced CBF and CMRO2 by 66% +/- 16% and 61% +/- 6%, respectively (i.e., "deactivation"). In contrast, administration of nicotine hydrogen tartrate increased CBF and CMRO2 by 41% +/- 5% and 30% +/- 3%, respectively (i.e., "activation"). The resting values of CBF and CMRO2 for alpha-chloralose anesthetized rats were 0.40 +/- 0.09 mL x g(-1) x min(-1) and 1.51 +/- 0.06 micromol x g(-1) x min(-1), respectively. Upon forepaw stimulation, CBF and CMRO2 were focally increased by 34% +/- 10% and 26% +/- 12%, respectively, above the resting nonanesthetized values (i.e., "activation"). Incremental changes in CBF and CMRO2, when expressed as a percentage change for "deactivation" and "activation" from the respective control conditions, were linear (R2 = 0.997) over the entire range examined with the global and local perturbations. This tight correlation for cerebral oxygen delivery in vivo is supported by a recent model where the consequence of a changing effective diffusivity of the capillary bed for oxygen, D, has been hypothetically shown to be linked to alterations in CMRO2 and CBF. This assumed functional characteristic of the capillary bed can be theoretically assessed by the ratio of fractional changes in D with respect to changes in CBF, signified by omega. A value 0.81 +/- 0.23 was calculated for omega with the in vivo data presented here, which in turn corresponds to a supposition that the effective oxygen diffusivity of the capillary bed is not constant but presumably varies to meet local requirements in oxygen demand in a similar manner with both "deactivation" and "activation."
"These results showed that CMR O2 changes are correlated with LFP and MUA in cerebral cortex. Overall, the calibrated fMRI studies at Yale quantitatively explained the presence of large CMR O2 changes observed during sensory stimulation in anesthetized rats with a positive BOLD signal (Hyder et al., 1996, 1997) with concomitant large changes in CBF (Hyder et al., 2000; Silva et al., 1999). Notably, both in human and animal studies, the measured ΔCBF/CBF and calculated ΔCMR O2 /CMR O2 from calibrated fMRI studies (i.e., the CMR O2 –CBF coupling) show a linear trend suggesting rapid oxygen equilibration between blood and tissue pools within the physiological range (Hyder et al., 1998). "
[Show abstract][Hide abstract] ABSTRACT: The discovery of functional magnetic resonance imaging (fMRI) has greatly impacted neuroscience. The blood oxygenation level-dependent (BOLD) signal, using deoxyhemoglobin as an endogenous paramagnetic contrast agent, exposes regions of interest in task-based and resting-state paradigms. However the BOLD contrast is at best a partial measure of neuronal activity, because the functional maps obtained by differencing or correlations ignore the total neuronal activity in the baseline state. Here we describe how studies of brain energy metabolism at Yale, especially with (13)C magnetic resonance spectroscopy and related techniques, contributed to development of quantitative functional brain imaging with fMRI by providing a reliable measurement of baseline energy. This narrative takes us on a journey, from molecules to mind, with illuminating insights about neuronal-glial activities in relation to energy demand of synaptic activity. These results, along with key contributions from laboratories worldwide, comprise the energetic basis for quantitative interpretation of fMRI data.
"α and β reflect the Table 1 Cross-laboratory comparisons of baseline CBF values CBF 0 a Anaesthesia Magnetic field strength Brain regions Reference 0.4±0.9 Morphine 7T Rat somatosensory cortex Hyder et al.  0.69±0.17 b0.41–0.95N "
[Show abstract][Hide abstract] ABSTRACT: The current study investigates a new model of barrel cortex activation using stimulation of the infraorbital branch of the trigeminal nerve. A robust and reproducible activation of the rat barrel cortex was obtained following trigeminal nerve stimulation. Blood oxygen level-dependent (BOLD) effects were obtained in the primary somatosensory barrel cortex (S1BF), the secondary somatosensory cortex (S2) and the motor cortex. These cortical areas were reached from afferent pathways from the trigeminal ganglion, the trigeminal nuclei and thalamic nuclei from which neurons project their axons upon whisker stimulation. The maximum BOLD responses were obtained for a stimulus frequency of 1 Hz, a stimulus pulse width of 100 μs and for current intensities between 1.5 and 3 mA. The BOLD response was nonlinear as a function of frequency and current intensity. Additionally, modeling BOLD responses in the rat barrel cortex from separate cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO(2)) measurements showed good agreement with the shape and amplitude of measured BOLD responses as a function of stimulus frequency and will potentially allow to identify the sources of BOLD nonlinearities. Activation of the rat barrel cortex using trigeminal nerve stimulation will contribute to the interpretation of the BOLD signals from functional magnetic resonance imaging studies.
Magnetic Resonance Imaging 10/2010; 28(8):1143-51. DOI:10.1016/j.mri.2010.02.002 · 2.09 Impact Factor
"Employing a lower value for A (e.g., 0.10–0.15, gray matter at 1.5T) with the current 11.7T data leads to a reduction in ∆CMR O 2 to a very low values, which would be in clear disagreement with steady-state 13 C MRS data for the same rat model where significant changes in CMR O 2 have been reported with forepaw stimulation (Hyder et al., 1996, 2000). Furthermore, the energetic changes measured with 13 C MRS are in agreement with neural firing at steady-state (Smith et al., 2002; Kida et al., 2006; Maandag et al., 2007). "
[Show abstract][Hide abstract] ABSTRACT: Functional magnetic resonance imaging (fMRI) with blood-oxygenation level dependent (BOLD) contrast is an important tool for mapping brain activity. Interest in quantitative fMRI has renewed awareness in importance of oxidative neuroenergetics, as reflected by cerebral metabolic rate of oxygen consumption(CMRO2), for supporting brain function. Relationships between BOLD signal and the underlying neurophysiological parameters have been elucidated to allow determination of dynamic changes inCMRO2 by "calibrated fMRI," which require multi-modal measurements of BOLD signal along with cerebral blood flow (CBF) and volume (CBV). But how doCMRO2 changes, steady-state or transient, derived from calibrated fMRI compare with neural activity recordings of local field potential (LFP) and/or multi-unit activity (MUA)? Here we discuss recent findings primarily from animal studies which allow high magnetic fields studies for superior BOLD sensitivity as well as multi-modal CBV and CBF measurements in conjunction with LFP and MUA recordings from activated sites. A key observation is that while relationships between neural activity and sensory stimulus features range from linear to non-linear, associations between hyperemic components (BOLD, CBF, CBV) and neural activity (LFP, MUA) are almost always linear. More importantly, the results demonstrate good agreement between the changes inCMRO2 and independent measures of LFP or MUA. The tight neurovascular and neurometabolic couplings, observed from steady-state conditions to events separated by <200 ms, suggest rapid oxygen equilibration between blood and tissue pools and thus calibrated fMRI at high magnetic fields can provide high spatiotemporal mapping ofCMRO2 changes.
Frontiers in Neuroenergetics 08/2010; 2. DOI:10.3389/fnene.2010.00018
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