Regional Brain Blood Flow Research Articles

Brain blood flow changes measured by positron emission tomography during an auditory cognitive task in healthy volunteers and in schizophrenic patients

Objective Cognitive deficit is an essential feature of schizophrenia. One of the generally used simple cognitive tasks to characterize specific cognitive dysfunctions is the auditory “oddball” paradigm. During this task, two different tones are presented with different repetition frequencies and the subject is asked to pay attention and to respond to the less frequent tone. The aim of the present study was to apply positron emission tomography (PET) to measure the regional brain blood flow changes induced by an auditory oddball task in healthy volunteers and in stable schizophrenic patients in order to detect activation differences between the two groups. Method Eight healthy volunteers and 11 schizophrenic patients were studied. The subjects carried out a specific auditory oddball task, while cerebral activation measured via the regional distribution of [ 15O]-butanol activity changes in the PET camera was recorded. Results and discussion Task-related activation differed significantly across the patients and controls. The healthy volunteers displayed significant activation in the anterior cingulate area (Brodman Area – BA32), while in the schizophrenic patients the area was wider, including the mediofrontal regions (BA32 and BA10). The distance between the locations of maximal activation of the two populations were 33 mm and the cluster size was about twice as large in the patient group. Conclusions The present results demonstrate that the perfusion changes induced in the schizophrenic patients by this cognitive task extends over a larger part of the mediofrontal cortex than in the healthy volunteers. The different pattern of activation observed during the auditory oddball task in the schizophrenic patients suggests that a larger cortical area – and consequently a larger variety of neuronal networks – is involved in the cognitive processes in these patients. The dispersion of stimulus processing during a cognitive task requiring sustained attention and stimulus discrimination may play an important role in the pathomechanism of the disorder.

Effects of Estrogen on Platelet Reactivity After Transient Forebrain Ischemia in Rats

Estrogen's prothrombotic effects are of increasing concern, particularly in stroke risk and recovery. Using an ischemic rodent model, the authors sought to determine (a) if estrogen replacement increases postischemic platelet reactivity, (b) if changes in estrogen status alter intraplatelet endothelial nitric oxide synthase (eNOS) synthesis, and (c) if estrogen-mediated effects on platelets alter cerebral blood flow during reperfusion. Intact (I), ovariectomized (OVX), and OVX + 17 beta-estradiol (E50) rats were subjected to 30 min of forebrain ischemia and 60 min of reperfusion. Using the platelet activation marker P-selectin, postischemic platelet reactivity was quantified by flow cytometry. In a separate cohort (I, OVX, E50), the authors quantified platelet eNOS by Western blot. Another cohort (OVX, E50) was subjected to ischemia/reperfusion, and cerebral blood flow was determined using the iodoantipyrine technique. Collagen-stimulated platelet P-selectin expression was increased in the OVX rats at 60 min of reperfusion, and this effect was reversed by estrogen treatment. No differences in platelet eNOS expression were detected among groups. Cerebral blood flow at 60 min reperfusion was comparable between the OVX and the E50 rats. The authors conclude that during reper-fusion, estrogen deficiency increases postischemic platelet sensitivity to stimuli in estrogen-deficient rats. Estrogen treatment mitigates effects of estrogen loss on platelets, but this early effect is apparently not caused by intraplatelet eNOS depression. Neither estrogen deficiency nor estrogen treatment changes early postischemic regional brain blood flow. In this rodent global cerebral ischemic model, physiologic doses of estrogen are not deleterious to platelet reactivity and may initially reduce postischemic platelet reactivity.

Blockade of haem oxygenase and nitric oxide synthetase causes cortical dysfunction in sheep exposed to carbon monoxide

Twenty adult ewes underwent common surgery and following recovery were exposed to 1% carbon monoxide (CO) for 2 h. Ten of these sheep were randomly selected for treatment with haem oxygenase (HO) and nitric oxide synthetase (NOS) blockers. All sheep were killed 5 days later. The CO exposure was narcotic and EEG frequency was suppressed. The EEG recovery was rapid in the control sheep and both slow and incomplete in the treated sheep. This difference was statistically significant ( P < 0.05). For the first time in our CO studies in sheep, one showed multiple cortical infarcts. This sheep was blocked for HO and NOS function. No significant differences were seen in peri-ventricular white matter infarction distribution and frequency. We have previously shown brain protection against CO- and inert diluent-hypoxemia by way of an increase in brain blood flow (BBF) that maintains adequate brain O 2 uptake, and by an increase in circulating red blood cells. From this study, we propose that the induction of neuronal and glial HO and NOS in sheep exposed to CO is protective, especially for the cortex. We intend to study this further by both selective and collective enzyme blockade and by measuring regional BBF changes.

VEGF overexpression induces post-ischaemic neuroprotection, but facilitates haemodynamic steal phenomena

Therapeutic angiogenesis with vascular endothelial growth factor (VEGF) is a clinically promising strategy in ischaemic disease. The pathophysiological consequences of enhanced vessel formation, however, are poorly understood. We established mice overexpressing human VEGF165 under a neuron-specific promoter, which exhibited an increased density of brain vessels under physiological conditions and enhanced angiogenesis after brain ischaemia. Following transient intraluminal middle cerebral artery (MCA) occlusions, VEGF overexpression significantly alleviated neurological deficits and infarct volume, and reduced disseminated neuronal injury and caspase-3 activity, confirming earlier observations that VEGF has neuroprotective properties. Brain swelling was not influenced in VEGF-overexpressing animals, while sodium fluorescein extravasation was moderately increased, suggesting that VEGF induces a mild blood-brain barrier leakage. To elucidate whether enhanced angiogenesis improves regional cerebral blood flow in the ischaemic brain, [14C]iodoantipyrine autoradiography was performed. Autoradiographies revealed that VEGF induces haemodynamic steal phenomena with reduced blood flow in ischaemic areas and increased flow values only outside the MCA territory. Our data demonstrate that VEGF protects neurons from ischaemic cell death by a direct action rather than by promoting angiogenesis, and suggest that strategies aiming at increasing vascular density in the whole brain, e.g. by VEGF overexpression, may worsen rather than improve cerebral haemodynamics after stroke.

Renormalization of regional brain blood flow during prolonged mild hypoxic exposure in rats

In this study, we measured regional brain blood flow (BF) in rats during hypoxic exposure. Our data show the hypoxia-induced brain blood flow increase returned to baseline within 1 week as blood hemoglobin increased. Because this return to baseline occurred before capillary angiogenesis, this result suggests that the mechanism for brain blood flow renormalization during prolonged hypoxia exposure is more likely related to the increased systemic arterial oxygen carrying capacity than to local tissue hypoxia that persists for at least 2 weeks.

Genomics and phenotypic profiles in dementia: Implications for pharmacological treatment

Constitutive genomics are probably determinant for the onset of dementia in conjunction with cerebrovascular and environmental factors. Furthermore, pharmacogenomic studies predict that the therapeutic response in Alzheimer's disease (AD) is genotype-specific, and that the expression of genes involved in the regulation of drug metabolism can influence efficacy and safety issues in pharmacotherapy. AD and dementia with a vascular component (DVC = VD + MXD) are the most prevalent forms of dementia. These clinical entities share many similarities, but they differ in major phenotypic and genotypic profiles, as revealed by structural and functional genomics studies. Comparative phenotypic studies have identified significant differences in 25% of more than 100 parametric variables, including anthropometry, cardiovascular function, aortic atherosclerosis, brain atrophy, blood pressure, blood biochemistry, hematology, thyroid function, folic acid and vitamin B(12) levels, brain hemodynamics and lymphocyte markers. The phenotypic profile of patients with DVC differs from that of AD patients in the following: (a) anthropometric values, (b) cardiovascular function, (c) blood pressure, (d) lipid metabolism, (e) uric acid levels, (f) peripheral calcium levels, (g) liver function (GOT, GPT, GGT), (h) alkaline phosphatase, (i) lactate dehydrogenase, (j) red and white blood cells, (k) regional brain atrophy (left temporal region, inter-hippocampal distance) and (l) brain blood flow velocity. Functional genomics studies incorporating APOE-related changes in biological markers extended the difference between AD and DVC up to 57%. Structural genomics studies with AD-related genes, including APP, MAPT, APOE, PS1, PS2, A2M, ACE, AGT, cFOS and PRNP genes, demonstrate different genetic profiles in AD and DVC, with an absolute genetic variation rate ranging from 30 to 80%, depending upon genes and genetic clusters. Single gene analysis identifies relative genetic variations ranging from 0 to 5%. The relative polymorphic variation in genetic clusters integrated by 2, 3 or 4 genes associated with AD ranges from 1 to 3%. The main phenotypic differences between AD and DVC are genotype-dependent, especially in AD, probably indicating that different genomic factors are essential for the expression of dementia symptoms that might be accelerated or induced by environmental and/or cerebrovascular factors.

Effect of hypertension on the integrity of blood brain and blood CSF barriers, cerebral blood flow and CSF secretion in the rat

Hypertension has been related to the development of brain damage, dementia and other CNS dysfunctions. Disruption of the blood–brain barrier (BBB) is thought to contribute to these disorders. In this study, the integrity of both blood–brain and blood–CSF barriers during chronic hypertension was investigated. For this, the entry of [ 14C]sucrose and of lanthanum into brain tissue, choroid plexus, and CSF was studied. Also brain regional blood flow and brain [ 14C]sucrose volume of distribution were measured using indicator fractionation and ventriculo-cisternal perfusion methods, respectively. The above measurements were performed in normotensive (WKY) rats and in the spontaneously hypertensive rats (SHR). Choroid plexus and CSF uptakes of [ 14C]sucrose were found to be significantly greater in SHR compared to WKY rats ( P<0.05). Intercellular entry of lanthanum was observed in choroidal tissue of SHR but not in that of WKY rats and at the BBB. Choroid plexus blood flow was significantly greater in SHR, 2.82±0.21 ml g −1 min −1, compared to 2.4±0.08 ml g −1 min −1 in WKY ( P<0.05). There were no significant differences ( P>0.05) in brain % water content and extracellular fluid [ 14C]sucrose volume of distribution between SHR and WKY rats. However, choroid plexus showed greater % water content in SHR (85.7±1.9%) compared to the WKY rats (81.5±1.7%). These results suggest that chronic hypertension in SHR may cause more pronounced defects in the integrity of the blood–CSF barrier than in the BBB.

Symposium

Symposium

Neuroimaging and Geriatric Psychiatry in the New Millennium: The Promise, the Reality, and the Need for More Integrated Approaches

Neuroimaging has been at the epicenter of two concurrent scientific revolutions for over two decades—the neurobiological and the computer revolution. The development of computerized tomography (CT) in the '70s was the first major step in integrating the principles of physics and computer sciences in the study of human biology. 1 Hounsfield G Ambrose J Computerized transverse axial scanning (tomography), part I: description of system; part II: clinical applications. Br J Radiol. 1973; 46: 1016-1047 Google Scholar The CT scan revealed anatomical details that were previously inaccessible in the living brain. Contemporaneously, positron emission tomography (PET) emerged as an important tool in neuroscience research, making it possible to examine regional cerebral glucose metabolism and blood flow in brain regions implicated in the regulation and modulation of emotions. 2 Phelps ME Hoffman EJ Huang SC et al. ECAT: a new computerized tomographic imaging system for positron-emitting radiopharmaceuticals. J Nucl Med. 1978; 19: 635-647 Google Scholar These methods were immediately applied to the study of mental disorders in elderly persons, and they contributed to our early understanding of the biology of Alzheimer disease (AD) and depression. 3 Duara R Grady C Haxby J et al. Positron emission tomography in Alzheimer's disease. Neurology. 1986; 36: 879-887 Google Scholar , 4 Kumar A Newberg A Alavi A et al. Regional cerebral glucose metabolism in late-life depression and Alzheimer disease: a preliminary positron emission tomography study. Proceedings of the National Academy of Sciences of the United States of America. 1993; 90: 7019-7023 Google Scholar , 5 Small GW Ercoli LM Silverman DH et al. Cerebral metabolic and cognitive decline in persons at genetic risk for Alzheimer's disease. Proceedings of the National Academy of Sciences of the United States of America. 2000; 97: 6037-6042 Google Scholar Technological development has rapidly evolved. Images obtained from high field magnetic resonance imaging (MRI) scanners now approach the clarity of images previously seen only in anatomy textbooks and histology atlases. MR principles have been further harnessed in the development of functional MRI (fMRI), magnetic resonance spectroscopy (MRS), and diffusion and perfusion weighted imaging. 6 Frahm J Bruhn H Gyngell ML et al. Localized high-resolution proton NMR spectroscopy using stimulated echoes: initial applications to human brain in vivo. Magn Reson Med. 1989; 9: 79-93 Google Scholar , 7 Ogawa S Tank DW Menon R et al. Intrinsic signal changes accompanying sensory stimulation: functional brain mapping with magnetic resonance imaging. Proceedings of the National Academy of Sciences of the United States of America. 1992; 89: 5951-5955 Google Scholar The relevance of these technologies to clinical and research geropsychiatrists is enormous, both from a diagnostic perspective and as probes of the central nervous system to help us better understand the diseases we help manage.

Regional brain blood flow and cerebral hemispheric oxygen consumption during acute hypoxaemia in the llama fetus.

Unlike fetal animals of lowland species, the llama fetus does not increase its cerebral blood flow during an episode of acute hypoxaemia. This study tested the hypothesis that the fetal llama brain maintains cerebral hemispheric O2 consumption by increasing cerebral O2 extraction rather than decreasing cerebral oxygen utilisation during acute hypoxaemia. Six llama fetuses were surgically instrumented under general anaesthesia at 217 days of gestation (term ca 350 days) with vascular and amniotic catheters in order to carry out cardiorespiratory studies. Following a control period of 1 h, the llama fetuses underwent 3 x 20 min episodes of progressive hypoxaemia, induced by maternal inhalational hypoxia. During basal conditions and during each of the 20 min of hypoxaemia, fetal cerebral blood flow was measured with radioactive microspheres, cerebral oxygen extraction was calculated, and fetal cerebral hemispheric O2 consumption was determined by the modified Fick principle. During hypoxaemia, fetal arterial O2 tension and fetal pH decreased progressively from 24 +/- 1 to 20 +/- 1 Torr and from 7.36 +/- 0.01 to 7.33 +/- 0.01, respectively, during the first 20 min episode, to 16 +/- 1 Torr and 7.25 +/- 0.05 during the second 20 min episode and to 14 +/- 1 Torr and 7.21 +/- 0.04 during the final 20 min episode. Fetal arterial partial pressure of CO2 (P(a,CO2), 42 +/- 2 Torr) remained unaltered from baseline throughout the experiment. Fetal cerebral hemispheric blood flow and cerebral hemispheric oxygen extraction were unaltered from baseline during progressive hypoxaemia. In contrast, a progressive fall in fetal cerebral hemispheric oxygen consumption occurred during the hypoxaemic challenge. In conclusion, these data do not support the hypothesis that the fetal llama brain maintains cerebral hemispheric O2 consumption by increasing cerebral hemispheric O2 extraction. Rather, the data show that in the llama fetus, a reduction in cerebral hemispheric metabolism occurs during acute hypoxaemia.

Brain effects of TMS delivered over prefrontal cortex in depressed adults: role of stimulation frequency and coil-cortex distance.

Relative regional brain blood flow was measured in 23 clinically depressed adults by using ECD SPECT at baseline and again during actual prefrontal transcranial magnetic stimulation (TMS) following 5 daily sessions of TMS. TMS over prefrontal cortex caused increased activity in cortex directly under the stimulation (inversely correlated with distance from scalp to cortex) and decreased activity in remote regions (anterior cingulate and anterior temporal poles). High-frequency rTMS (20 Hz) caused more relative flow immediately below the TMS coil than did low-frequency rTMS (5 Hz). Confirming the hypotheses tested, repeated daily TMS over the prefrontal cortex in medication-free depressed adults appears to change both local and remote blood flow in a manner that may also depend on the frequency of stimulation and coil to outer cortex distance.

Brain Effects of TMS Delivered Over Prefrontal Cortex in Depressed Adults: Role of Stimulation Frequency and Coil-Cortex Distance

Relative regional brain blood flow was measured in 23 clinically depressed adults by using ECD SPECT at baseline and again during actual prefrontal transcranial magnetic stimulation (TMS) following 5 daily sessions of TMS. TMS over prefrontal cortex caused increased activity in cortex directly under the stimulation (inversely correlated with distance from scalp to cortex) and decreased activity in remote regions (anterior cingulate and anterior temporal poles). High-frequency rTMS (20 Hz) caused more relative flow immediately below the TMS coil than did low-frequency rTMS (5 Hz). Confirming the hypotheses tested, repeated daily TMS over the prefrontal cortex in medication-free depressed adults appears to change both local and remote blood flow in a manner that may also depend on the frequency of stimulation and coil to outer cortex distance.

Neuroimaging evidence implicating cerebellum in the experience of hypercapnia and hunger for air.

Recent neuroimaging and neurological data implicate cerebellum in nonmotor sensory, cognitive, vegetative, and affective functions. The present study assessed cerebellar responses when the urge to breathe is stimulated by inhaled CO(2). Ventilation changes follow arterial blood partial pressure CO(2) changes sensed by the medullary ventral respiratory group (VRG) and hypothalamus, entraining changes in midbrain, pons, thalamus, limbic, paralimbic, and insular regions. Nearly all these areas are known to connect anatomically with the cerebellum. Using positron emission tomography, we measured regional brain blood flow during acute CO(2)-induced breathlessness in humans. Separable physiological and subjective effects (air hunger) were assessed by comparisons with various respiratory control conditions. The conjoint physiological effects of hypercapnia and the consequent air hunger produced strong bilateral, near-midline activations of the cerebellum in anterior quadrangular, central, and lingula lobules, and in many areas of posterior quadrangular, tonsil, biventer, declive, and inferior semilunar lobules. The primal emotion of air hunger, dissociated from hypercapnia, activated midline regions of the central lobule. The distributed activity across the cerebellum is similar to that for thirst, hunger, and their satiation. Four possible interpretations of cerebellar function(s) here are that: it subserves implicit intentions to access air; it provides predictive internal models about the consequences of CO(2) inhalation; it modulates emotional responses; and that while some cerebellar regions monitor sensory acquisition in the VRG (CO(2) concentration), others influence VRG to adjust respiratory rate to optimize partial pressure CO(2), and others still monitor and optimize the acquisition of other sensory data in service of air hunger aroused vigilance.

Bedside functional imaging of the premature infant brain during passive motor activation.

Changes in regional brain blood flow and hemoglobin oxygen saturation occur in the human cortex in response to neural activation. Traditional functional radiologic methods cannot provide continuous, portable measurements. Imaging methods, which use near-infrared light allow for non-invasive measurements by taking advantage of the fact that hemoglobin is a strong absorber at these wavelengths. To test the feasibility of a new optical functional imaging system in premature infants, and to obtain preliminary brain imaging of passive motor activation in this population. A new optical imaging system, the Diffuse Optical Tomography System (DOTS), was used to provide real-time, bedside assessments. Custom-made soft flexible fiberoptic probes were placed on two extremely ill, mechanically ventilated 24 week premature infants, and three healthier 32 week premature infants. Passive motor stimulation protocols were used during imaging. Specific movement of the arm resulted in reproducible focal, contralateral changes in cerebral absorption. The data suggest an overall increase in blood volume to the imaged area, as well as an increase in deoxyhemoglobin concentration. These findings in premature infants differ from those expected in adults. In the intensive care setting, continuous non-invasive optical functional imaging could be critically important and, with further study, may provide a bedside monitoring tool for prospectively identifying patients at high risk for brain injury.

Comparison of regional cerebral blood flow and glucose metabolism in the normal brain: effect of aging

The regional cerebral blood flow (rCBF) and metabolic rate for glucose (rCMRGlc) are associated with functional activity of the neural cells. The present work reports a comparison study between rCBF and rCMRGlc in a normal population as a function of age. 10 young (25.9±5.6 years) and 10 old (65.4±6.1 years) volunteers were similarly studied at rest. In each subject, rCBF and rCMRGlc were measured in sequence, during the same session. Both rCBF and rCMRGlc values were found to decrease from young (mean rCBF=43.7 ml/100 g per min; mean rCMRGlc=40.6 μmol/100 g per min) to old age (mean rCBF=37.3 ml/100 g per min; mean rCMRGlc=35.2 μmol/100 g per min), resulting in a drop over 40 years of 14.8% (0.37%/year) and 13.3% (0.34%/year), respectively. On a regional basis, the frontal and the visual cortices were observed to have, respectively, the highest and the lowest reduction in rCBF, while, for rCMRGlc, these extremes were observed in striatum and cerebellum. Despite these differences, the ratio of rCBF to rCMRGlc was found to have a similar behavior in all brain regions for young and old subjects as shown by a correlation coefficient of 88%. This comparative study indicates a decline in rCBF and rCMRGlc values and a coupling between CBF and CMRGlc as a function of age.

EXERCISE INCREASES BLOOD FLOW TO LOCOMOTOR, VESTIBULAR, CARDIORESPIRATORY AND VISUAL REGIONS OF THE BRAIN

876 The purpose of this study was to test the hypothesis that regional brain blood flow distribution is altered by locomotor exercise. Brain blood flow was measured (radiolabeled microsphere technique) in miniature swine (n=6) during standing and treadmill exercise at 70 and 100% VO2MAX. Average brain blood flow increased from 57 ± 6 ml/min/100 g at rest to 70 ± 8 ml/min/100 g at 70%VO2MAX and 72 ± 5 ml/min/100 g at 100%VO2MAX. Perfusion of cortical areas of the brain was not altered by exercise, but flow to subcortical locomotor regions (midbrain, pons, rostral and caudal medulla, spinal cord) and the cerebellar hemispheres was elevated. Blood flow to regions associated with the maintenance of equilibrium (ventral vermis and floccular lobe of cerebellum and vestibular apparatus), cardiorespiratory regulation (pons and medulla), vision (dorsal occipital cortex and superior colliculi), and memory (hippocampus) was increased during submaximal and maximal exercise. In contrast, perfusion of structures of the central auditory pathway (cochlear nuclei, inferior colliculi and temporal cortex) and olfactory system (olfactory bulbs and rhinencephalon) was not elevated during exercise. These data indicate that subcortical locomotor regions and the cerebellum are actively involved in the control of treadmill locomotion, and that the neural activity of regions involved in the maintenance of balance, cardiorespiratory control and vision are heightened during submaximal and maximal exercise. Supported by NIH AM-37098, HL-36088 and NASA NAGW-4842, NAG5-3754.

Correlation of Near Infrared Spectroscopy Cerebral Blood Flow Estimations and Microsphere Quantitations in Newborn Piglets

We compared cerebral blood flow (CBF) estimated using transmission mode near infrared spectroscopy (NIRS) and a modification of the Fick principle with CBF quantitations by radioactive microspheres (MSs) in newborn piglets. Thirteen piglets were studied during steady state, ischemia, and during two reflow periods. NIRS and MS flows were not significantly different during any measurement period. NIRS flows were compared to total brain blood flows and to regional brain blood flows quantitated with MSs and correlated best with temporal cortical flows. Linear regression analysis of the NIRS flows plotted against MS-quantitated temporal cortical flows showed r = 0.71. Thus, CBFs obtained with NIRS were not significantly different from, showed the same directional changes, and correlated acceptably with flows quantitated by MSs.

Demonstration of Dose-Dependent Global and Regional Cocaine-Induced Reductions in Brain Blood Flow Using a Novel Approach to Quantitative Single Photon Emission Computerized Tomography

Ischemic stroke is a common cause of morbidity and mortality in cocaine addicts. Because the previous semiquantitative single photon emission computerized tomography (SPECT) method for measuring brain blood flow does not quantify blood flow, the magnitude and specificity of cocaine’s effects during drug taking has not been well established. Here, using a novel quantitative approach to SPECT, we established that intravenous cocaine administration to nine recently abstinent cocaine-dependent subjects was associated with significant decreases in global and regional brain blood flow to dopamine-rich areas such as the prefrontal, frontal, temporal, and subcortical gray matter. Establishing the utility of this relatively new quantitative SPECT technique provides an important tool for the management of vascular disorders of the brain. Additionally, identifying the site-specific effects of cocaine provides targets for the development of putative therapeutic medications to attenuate or minimize ischemic stroke in cocaine addicts.

Application of a beta microprobe for quantification of regional cerebral blood flow with (15)O-water and PET in rhesus monkeys.

A beta microprobe was successfully applied to monitor arterial input function for quantification of regional cerebral blood flow (rCBF) in the monkey brain with (15)O-water and positron emission tomography (PET). The sensitivity of the probe was approximately 0.83 to 1.67 cps/kBq/ml depending on the studies. A preliminary study was performed to find a suitable use and to evaluate the performance of the system and data analysis procedure. The results showed that dispersion correction of measured input function was unnecessary if microprobes were connected directly to the arterial catheter. Then multiple CBF measurements were done in three monkeys under anesthesia. Identical regions of interest were placed with the aid of magnetic resonance imaging (MRI) of each monkey and rCBF values were estimated. Estimated rCBFs were reproducible for several measurements. The mean CBF value for a pentobarbital anesthetized monkey was 46.0 ml/min/100 g (PaCO2 = 46.3 mmHg). This shows that the use of the beta microprobe for quantification of rCBF with PET was validated. The lack of a need for dispersion correction of observed input function is an advantage with the beta microprobe system because the probes are small enough to be placed near the arterial sampling site.

Comparative aspects on nitric oxide in brain and its role as a cerebral vasodilator

Histological studies have detected nitric oxide (NO) synthase in the central nervous system of all vertebrates examined, from lampreys to mamals. However, there are still very few comparative physiological studies on the function of NO synthase in the brain of non-mammalian vertebrates. So far, we know that acetylcholine can cause an NO-dependent increase in brain blood flow in turtles and some fish species (crucian carp and rainbow trout), whereas some other fishes appear to lack such a mechanism. Hypercapnia can induce NO-dependent cerebral vasodilation in mammals, but such a mechanism appears to be lacking in the ectothermic vertebrates examined. The number of species studied needs to be expanded before we can draw any firm conclusions about the origin of NO-dependent brain blood flow regulation: if it has evolved more than once or if it has been occasionally lost during evolution. We conclude that NO synthase may be present in all vertebrate brains but that its functions can vary, as judged from its role in cerebral blood flow regulation. The diversity of functions that NO has proven to have within the mammalian brain is likely to be paralleled by the same degree of diversity of function between vertebrate groups.