Introduction
Functional MR imaging (fMRI) detects neural activation through BOLD MR contrast as a result of alterations in cerebral hemodynamics accompanying a local change in brain function. However, in the case of stroke where autoregulation of cerebral blood flow to blood pressure (BP) changes may be impaired, a transient hypertension producing hyperemia that is not related to cerebral activation could also affect BOLD contrast. We hypothesized that a transient hypertension would produce an increase in the number of active voxels within T2* images that is dependent on blood pressure and greater in infarcted tissues, thereby enhancing the cerebral activation response to simultaneous stimulation of the sensory-motor cortex. We investigated the effect of transient BP increases on the electrical stimulation induced activation in sensory-motor cortex (SMC) following stroke using functional MRI.
Method and Materials
A sham procedure (n=5) or transient middle cerebral artery occlusion (MCAO, n=10) of 60 minutes duration was produced in anesthetized rats. Ischemic damage within the right SMC was confirmed using T2 imaging 2 days later. Seven days post MCAO, rats were prepared for functional MRI under alpha-chloralose anesthesia. For each scan a set of 32 gradient echo T2* images were acquired under 3 different conditions: 1. two periods of electrical stimulation of the left or right forepaw, 2. arterial BP increases (norepinephrine, 0.15–1.2 ug/kg, I.V.), or 3. electrical stimulation with simultaneous BP increases. A regional ‘activation response’ was represented by the number of voxels with intensity changes identified using a cross correlation analysis (P<0.001) to either the stimulation time course or the BP time course.
Results
One week after transient MCAO, the T2* signal intensity within ischemic tissue was affected markedly by blood pressure changes. With BP increases alone, an ‘activation response’ correlating to the BP time course was detected in the injured but not the non-ischemic contralateral SMC. The number of active voxels correlating to the BP time course in the SMC increased from 0 with no pressure change to 45 at 31–45 mm Hg and 108 voxels at pressures >60 mmHg (P<0.001). In contrast, few voxels demonstrated an activation response to BP changes contralaterally. Despite no stimulation being applied, there was also an apparent ‘activation response’ of voxels correlating with the stimulation time course in the ischemically injured right SMC at BP >45 mm Hg (P<0.001). If stimulation was combined with BP increases, the number of active voxels in the right SMC increased from 10 to 84 for BP of 0 or >60 mmHg, respectively. In contrast, the number of active voxels in the uninjured cortex increased by only 19 voxels when right forepaw stimulation was accompanied by BP increases.
Conclusion
Transient hypertension produces an increase in the number of active voxels detected by fMRI resulting in an enhanced detection of cerebral activation to simultaneous electrical stimulation of the SMC. This BP-dependent ‘activation response’ is greater in tissue injured by ischemia than in healthy tissue so that fMRI studies of diseased or damaged brain are more likely to be affected by arterial BP increases.