Introduction
Blood oxygenation-level dependent (BOLD) contrast used to detect brain activation using functional magnetic resonance imaging (MRI) is primarily a result of local decreases in deoxyhemoglobin (dHb) related to elevations in cerebral blood flow (CBF) produced by the coupling between changes in neural activity and local CBF. Transient hypertension producing hyperemia independent of alterations in the cerebral metabolic rate of oxygen consumption could also affect BOLD contrast. Presently, we compare the effect of transient hypertension and electrical forepaw stimulation on changes in: 1) BOLD contrast measured using functional MRI, 2) CBF measured with laser Doppler flowmetry and 3) cerebral oxygenation measured with near-infrared (IR) spectroscopy.
Material and Methods
Functional MRI or near-IR experiments were performed in 19 chloralose anethetized rats using identical preparations except that in the near-IR studies the skull was thinned and near-IR and Doppler probes were placed over the sensory motor cortex. In each animal, experiments investigated the ‘activation’ response to: 1) electrical stimulation of the forepaw, 2) increases in blood pressure (BP) or 3) a combination of an increase in BP and forepaw stimulation. For fMRI studies, experiments consisted of acquiring sets of 32 gradient echo T2* images (TR/TE=70/10ms, flip angle=20, matrix=128×128, slice thickness=1.5 mm) using a 9.4 T MRI system. Near-IR spectra were acquired every second during each paradigm of 320 seconds duration, and subsequently curve-fit (least squares) with the component absorptivity spectra of oxyHb, dHb, and water. MR images or spectra and flow data were collected with electrical stimulation of the forepaw either off or on, or during BP increases of 0, 30–45 or >60 mm Hg produced by the intravenous injection of norepinephrine (0.15–1.2 μg/kg). For the fMRI experiments, a cross-correlation analysis (p<0.001) to either the stimulation paradigm or the time course of BP changes was used to identify voxels of activation in the sensory motor cortex from which their maximum MR signal intensity changes relative to initial baseline values was determined.
Results
With electrical stimulation of the forepaw alone, activation was detected within the sensory motor cortex and the MR signal intensity increased by approx. 6%. Corresponding to these changes, forepaw stimulation resulted in increases in CBF and oxyHb and decreases in dHb. With increases in BP alone there were increases in CBF, MR signal intensity and oxyHb and decreases in dHb where the magnitude of these changes was dependent on the change in BP (e.g. MR signal intensity increased by 7+6%, p<0.05). When both forepaw stimulation and increases in BP were produced, the BOLD changes and CBF changes were enhanced compared with stimulation alone (e.g. MR signal intensity increased 15.4+4%, p<0.05 with >60 mm Hg changes in pressure). Such enhancement was less evident for the dHb and oxyHb changes.
Conclusions
The response to either an increase in BP or electrical forepaw stimulation results in decreases in dHb and increases in flow, oxyHb and BOLD MR intensity. The BOLD and CBF changes produced by neuronal activation are enhanced by increases in BP.
Footnotes
Acknowledgements
Supported by Canadian Institutes of Health Research.