Neurovascular coupling varies with level of global cerebral ischemia in a rat model.

In this study, cerebral blood flow, oxygenation, metabolic, and electrical functional responses to forepaw stimulation were monitored in rats at different levels of global cerebral ischemia from mild to severe. Laser speckle contrast imaging and optical imaging of intrinsic signals were used to measure changes in blood flow and oxygenation, respectively, along with a compartmental model to calculate changes in oxygen metabolism from these measured changes. To characterize the electrical response to functional stimulation, we measured somatosensory evoked potentials (SEPs). Global graded ischemia was induced through unilateral carotid artery occlusion, bilateral carotid artery occlusion, bilateral carotid and right subclavian artery (SCA) occlusion, or carotid and SCA occlusion with negative lower body pressure. We found that the amplitude of the functional metabolic response remained tightly coupled to the amplitude of the SEP at all levels of ischemia observed. However, as the level of ischemia became more severe, the flow response was more strongly attenuated than the electrical response, suggesting that global ischemia was associated with an uncoupling between the functional flow and electrical responses.

History of International Society for Cerebral Blood Flow and Metabolism.

Interest in the brain's circulation dates back more than a century and has been steadily growing. Quantitative methods for measurements of cerebral blood flow (CBF) and energy metabolism became available in the middle of the 20th century and gave a new boost to the research. Scientific meetings dealing with CBF and metabolism were arranged, and the fast growing research led to a demand for a specialized journal. In this scientific environment, the International Society for Cerebral Blood Flow and Metabolism (ISCBFM) and its official Journal of Cerebral Metabolism were established in 1981 and has since then been a major success. The development of new brain imaging methods has had a major impact. Regulation of CBF and ischemia has been the main topics at the meetings. A new field of brain mapping research emerged and has now its own society and meetings. Brain emission tomography research has grown within the society and is now an integrated part. The ISCBFM is a sound society, and support of young scientists is among its goals. Several awards have been established. Other activities including summer schools, courses, satellite meetings, and Gordon conferences have contributed to the success of the society and strengthened the research.

Regional differences in the coupling between resting cerebral blood flow and metabolism may indicate action preparedness as a default state.

Although most functional neuroimaging studies examine task effects, interest intensifies in the "default" resting brain. Resting conditions show consistent regional activity, yet oxygen extraction fraction constancy across regions. We compared resting cerebral metabolic rates of glucose (CMRgl) measured with 18F-labeled 2-fluoro-2-deoxy-D-glucose to cerebral blood flow (CBF) 15O-H2O measures, using the same positron emission tomography scanner in 2 samples (n = 60 and 30) of healthy right-handed adults. Region to whole-brain ratios were calculated for 35 standard regions of interest, and compared between CBF and CMRgl to determine perfusion relative to metabolism. Primary visual and auditory areas showed coupling between CBF and CMRgl, limbic and subcortical regions--basal ganglia, thalamus and posterior fossa structures--were hyperperfused, whereas association cortices were hypoperfused. Hyperperfusion was higher in left than right hemisphere for most cortical and subcallosal limbic regions, but symmetric in cingulate, basal ganglia and somatomotor regions. Hyperperfused regions are perhaps those where activation is anticipated at short notice, whereas downstream cortical modulatory regions have longer "lead times" for deployment. The novel observation of systematic uncoupling of CBF and CMRgl may help elucidate the potential biological significance of the "default" resting state. Whether greater left hemispheric hyperperfusion reflects lateral dominance needs further examination.

Imaging triiodothyronine binding kinetics in rat brain: a model for studies in human subjects.

Many lines of evidence indicate a role for thyroid hormones in the expression of cognitive and affective disorders. These conditions constitute a large proportion of the illness burden in the general population. Unfortunately, presently available diagnostic procedures cannot adequately identify these problems. To determine whether imaging studies of thyroid hormone kinetics in brain might be feasible in patients with these disorders, an autoradiographic method for measuring thyroid hormone kinetics was developed. Twenty-five awake adult rats received high specific activity [(125)I]-triiodothyronine (T(3)*). Brains were obtained at intervals from 5 through 300 min after i.v. hormone administration. Every 5th frozen section was thaw mounted and exposed to film. To determine whether T(3) was responsible for the autoradiographic images, the intervening sections were assembled while frozen in regional tissue pools and were extracted and then analyzed by high-performance liquid chromatography. The results demonstrated that radioactivity was almost entirely due to T(3)*( approximately 90%) while small amounts of hormone metabolites, including [(125)I]iodine accounted for the remainder. Regional concentrations of label in autoradiograms were measured by densitometry in hippocampus (CA1, CA2, CA3, and dentate gyrus), cerebellum (molecular and granular cell layers), caudate nucleus, and amygdala. Unexpectedly and interestingly, the results demonstrated that binding through 5 h was mainly irreversible. Regional values of the net uptake rate constant of T(3)* or influx constant, K(i), were determined from the time course of the T(3)* data, showing significant differences among regions. These results suggest that imaging of labeled thyroid hormone ligands by positron emission tomography or single photon emission computed tomography may be feasible and would potentially provide useful information relevant to T(3) processing in the brain during a variety of drug and disease-induced conditions.

Neuroimaging in hepatic encephalopathy.

Hepatic encephalopathy (HE) is a poorly defined, complex neuropsychological disorder that often accompanies portal hypertension. Although the mechanisms underlining HE and the characterization of HE are still under investigation, the information derived from functional neuroimaging of patients with HE complemented by laboratory investigation and neuropsychological and neurophysiological studies have clarified much of the neuroanatomical defects. In this review, we have provided an outline of the understood mechanisms of HE and the associated findings on neuroimaging.

PET brain imaging with [11C](+)McN5652 shows increased serotonin transporter availability in major depression.

BACKGROUND: Alterations in the brain serotonin (5-HT) system have been found in patients with depression. We used the selective 5-HT transporter site ligand [11C](+)McN5652 and positron emission tomography (PET) to examine the hypothesis that alterations in 5-HT transporter levels may be present in selected regions of the brain in depressed patients. METHODS: Four drug free depressed patients and four healthy control subjects were studied using [11C](+)McN5652 and PET. The distribution volume (DV) ratio of the PET ligand in selected regions of interest (ROIs) compared to cerebellum were calculated for the ROIs. RESULTS: Patients showed significantly larger DV ratios in the left frontal cortex (P=0.013) and right cingulate cortex (P=0.043) compared to control subjects. LIMITATION: The sample size was modest with gender differences between the subject groups. The PET agent, [11C](+)McN5652, may have a lower binding affinity for the 5-HT transporter in the cortical regions compared to other brain regions. CONCLUSION: These findings suggest that 5-HT transporter sites may be increased in the frontal and cingulate cortices of depressed patients. These alterations in 5-HT transporter sites may be of pathophysiologic significance in the etiology of depression and its treatment.

Significance of endogenous opioids in the maintenance of cerebral and spinal vascular CO2-sensitivity in deep hemorrhagic hypotension.

High CO(2)-sensitivity, one of the major characteristics of the cerebrovascular bed, has been shown to be influenced by a variety of factors. There are no reports, however, on the involvement of the endogenous opioid peptides in the modulation of the CO(2)-sensitivity of the cerebral and spinal cord vessels, either in normotensive or, in hypotensive conditions. The effect of general opiate receptor blockade (1.0mg/kg naloxone, i.v.) on regional cerebrovascular CO(2)-sensitivity was studied with radiolabeled microspheres in 10 distinct brain and spinal cord regions of the anesthetized cat. The CO(2)-induced flow changes were investigated in normotensive, in moderately hypotensive (MAP=80 mmHg) and in deep hypotensive cats (MAP=40 mmHg). The systemic arterial pressure was lowered by hemorrhage. In the normotensive cats, opiate receptor blockade caused no changes in the vascular CO(2)-sensitivity in the investigated cerebral and spinal cord regions. In moderate hypotension, cerebral and spinal CO(2)-sensitivity was significantly reduced by the hemorrhage itself, but remained unaffected by the naloxone administration. In deep hemorrhagic hypotension, however, general opiate receptor blockade resulted not only in a further reduction of the already impaired CO(2)-sensitivity, but even in a reversal of the effect of CO(2) from flow increase to flow decrease. These results indicate that endogenous opioid peptides, which do not seem to influence cerebrovascular reactions in steady-state, normotensive conditions, may contribute significantly to the maintenance of the normal vasodilatory response of the cerebral and spinal cord vessels to CO(2) during hemorrhage-induced deep arterial hypotension.

Rats recovering from unilateral barrel-cortex ischemia are capable of completing a whisker-dependent task using only their affected whiskers.

Rats use their vibrissae for a variety of exploratory tasks including location of objects and discrimination of texture. This study examines recovery in vibrissal function following a unilateral ischemic injury to the somatosensory cortex. Vibrissal function was examined in adult food-restricted rats performing on a two-texture discrimination device. Animals were trained and tested until the criteria of >80% correct choices was demonstrated on three consecutive days. Ischemic rats were constrained to use the affected whiskers by clipping the ipsilateral vibrissae. One group was tested after ischemia, a second group was trained before ischemia and then tested, and a third group was pre-trained and received whisker stimulation and tested post-ischemia. Nai;ve animals recovering from ischemia took longer to reach criteria than intact or unilateral trimmed control animals. Pre-trained animals with compression ischemia receiving whisker stimulation with sucrose water completed the task to criteria in the fewest number of trials. The results indicate that recovery of vibrissal function occurs following a unilateral ischemic injury. Histological analysis in animals without whisker stimulation indicates that the number of normal appearing cortical barrels following ischemia was inversely correlated to the number of trials needed to complete the behavioral task. This suggests that the natural recovery of the ability to discriminate textures is related to the degree of damage to the barrel cortex. The relationship between cortical barrels and behavioral recovery did not hold for the ischemic animals receiving whisker stimulation. This latter group demonstrated recovery despite marked anatomical lesions suggesting that the intervention influenced reorganization.

Determination of regional cerebral function with FDG-PET imaging in neuropsychiatric disorders.

Functional brain imaging using 18F fluorodeoxyglucose (FDG) and positron emission tomography (PET) has greatly enhanced our understanding of brain function both in normal conditions as well as in a wide variety of neuropsychiatric disorders. We review the uses of FDG PET in the diagnosis, management, and follow-up of patients with neuropsychiatric disorders. This article will also explore what FDG-PET imaging has revealed in these neuropsychiatric disorders and how these findings relate to both research and clinical applications.