Cerebral blood flow and metabolism in sleep

A review is presented of the electrical activity of the brain and its global and regional blood flow and metabolism in the different stages of sleep and in wakefulness in animals and humans. During slow-wave sleep (SWS), the blood flow and metabolism of the brain decrease slightly below the level of wakefulness. During rapid eye movement the activity of the brain increases above that of SWS and sometimes above that of wakefulness. Some studies suggest that both at sleep onset and at arousal the brain stem-cerebellar complex (BSC) may be activated before the cortex and the right hemisphere before the left. Variation of hemispheric dominance seems to be a phenomenon of both wakefulness and sleep.     

Cerebral blood flow and metabolism in experimental hydrocephalus

Cerebral blood flow and metabolism were studied in experimental hydrocephalus which was produced by intracisternal injection of kaolin in cats, rabbits and rats. Measurements were carried out in varied stages of hydrocephalus. Local cerebral blood flow (I-CBF) was measured by the hydrogen clearance method. Assessment of cerebral metabolism was made biochemically in the brain tissues of various regions, including water content, Na, K, lactate, pyruvate, lipids, ATP, cyclic AMP, catecholamines and monoamine metabolites. Blood flow studies were performed in the cerebral cortex, periventricular white matter, thalamus and midbrain reticular formation in hydrocephalic cats. In all of these regions, I-CBF decreased to about half of the control in both acute and chronic stages of hydrocephalus. CO₂ reactivity to CBF was impaired only in the acute stage, while autoregulation of CBF was preserved in the hydrocephalic brain. Water content of the brain tissue increased temporarily only within the periventricular white matter of hydrocephalic rabbits concomitant with increase in Na and decrease in K. Transient increase in the lactate and lactate/pyruvate ratios was also observed in the frontal lobe tissue. In hydrocephalic rats, decrease in phospholipids and cholesterol was observed parallel with the degree of ventricular dilatation. ATP and cyclic AMP decreased biphasically in both acute and chronic stages. On the other hand, increase in concentrations of norepinephrine, dopamine, homovanillic acid, and 5-hydroxyindoleacetic acid became evident in the chronic stage of hydrocephalus. From the above results, it is concluded that the hydrocephalic brain sustained considerable disturbance of metabolism in all modalities in association with decreased blood flow, which is sufficient to explain the clinical symptoms of hydrocephalus.     

Psychopathological and SPECT findings in never-treated schizophrenia

A total of 24 never-treated (i.e. drug-naive) actively psychotic schizophrenic patients, operationalized according to DSM-III-R, were examined in a pre-post-treatment design using the Positive and Negative Syndrome Scale for Schizophrenia (PANSS) and ^99mTc-HMPAO-single photon emission computed tomography (SPECT) to assess regional cerebral blood flow (rCBF). The control subjects were 20 patients free of neurological and psychiatric symptoms. Before treatment there was only a slight hypofrontality, and hypoperfusion was observed in the left temporal superior region. After treatment, hypofrontality was reduced to one region and temporal hypoperfusion disappeared. Formal thought disorders were accompanied by increased rCBF in the bilateral frontal interior and left temporal superior regions. Delusions were associated with hypoperfusion in the anterior cingulate cortex. Negative symptoms showed no linkage to hypofrontality, either before or after treatment. Factor analysis showed delusions and hallucinations loading on different dimensions. The disorganized dimension correlated positively with all regions of interest, whereas these were negatively correlated with reality distortion.     

The role of vascular resistance in BOLD responses to progressive hypercapnia

The ability of the cerebral vasculature to regulate vascular diameter, hence resistance and cerebral blood flow (CBF), in response to metabolic demands (neurovascular coupling), and perfusion pressure changes (autoregulation) may be assessed by measuring the CBF response to carbon dioxide (CO₂). In healthy individuals, the CBF response to a ramp CO₂ stimulus from hypocapnia to hypercapnia is assumed sigmoidal or linear. However, other response patterns commonly occur, especially in individuals with cerebrovascular disease, and these remain unexplained. CBF responses to CO₂ in a vascular region are determined by the combined effects of the innate vascular responses to CO₂ and the local perfusion pressure; the latter ensuing from pressure‐flow interactions within the cerebral vascular network. We modeled this situation as two vascular beds perfused in parallel from a fixed resistance source. Our premise is that all vascular beds have a sigmoidal reduction of resistance in response to a progressive rise in CO₂. Surrogate CBF data to test the model was provided by magnetic resonance imaging of blood oxygen level‐dependent (BOLD) signals. The model successfully generated all the various BOLD‐CO₂ response patterns, providing a physiological explanation of CBF distribution as relative differences in the network of vascular bed resistance responses to CO₂. Hum Brain Mapp 38:5590–5602, 2017. © 2017 Wiley Periodicals, Inc.     

Cerebral blood flow findings in moyamoya disease in adults

Three adult patients with moyamoya disease are described. They presented with intracerebral hematoma, cerebral infarction and subarachnoid hemorrhage, respectively. Subarachnoid hemorrhage is rare in moyamoya and is usually the result of aneurysm rupture. No aneurysm was found in our patient. Regional cerebral blood flow (rCBF) and the cerebral perfusion reserve assessed by the acetazolamide test, were significantly reduced in all three patients. The areas with most reduced baseline rCBF and most impaired vasoreactivity did not always correspond to the site of the vascular accident, indicating that these CBF changes were at least in part due to the moyamoya disease and/or its underlying causes, and not solely to the vascular accidents.     

精神分裂症患者脑供血情况与认知功能的研究

目的：探讨精神分裂症患者脑供血情况与认知功能之间的关系。方法：对精神分裂症患者100例进行听觉事件相关诱发电位（P300）检查，以评价其认知功能；对认知功能检查“差”和“极差”的患者进行经颅多普勒脑血流图（TCD）检查记录血流峰值及脉动指数，以了解其脑供血情况。结果：100例精神分裂症患者P300检查中有83例认知功能为“差”到“极差”，这83例患者TCD检查结果显示，大脑中动脉和大脑前动脉脉动指数均显著高于我国正常成人常模。结论：精神分裂症患者认知功能普遍较差，可能与其大脑中动脉、大脑前动脉血管舒缩调节功能下降导致大脑前额叶供血不足有关。     

Cerebral blood flow identifies responders to transcranial magnetic stimulation in auditory verbal hallucinations

Auditory hallucinations comprise a critical domain of psychopathology in schizophrenia. Repetitive transcranial magnetic stimulation (TMS) has shown promise as an intervention with both positive and negative reports. The aim of this study was to test resting-brain perfusion before treatment as a possible biological marker of response to repetitive TMS. Twenty-four medicated patients underwent resting-brain perfusion magnetic resonance imaging with arterial spin labeling (ASL) before 10 days of repetitive TMS treatment. Response was defined as a reduction in the hallucination change scale of at least 50%. Responders (n=9) were robustly differentiated from nonresponders (n=15) to repetitive TMS by the higher regional cerebral blood flow (CBF) in the left superior temporal gyrus (STG) (P<0.05, corrected) before treatment. Resting-brain perfusion in the left STG predicted the response to repetitive TMS in this study sample, suggesting this parameter as a possible bio-marker of response in patients with schizophrenia and auditory hallucinations. Being noninvasive and relatively easy to use, resting perfusion measurement before treatment might be a clinically relevant way to identify possible responders and nonresponders to repetitive TMS.     

Cerebral blood flow response to flavanol-rich cocoa in healthy elderly humans

BACKGROUND AND PURPOSE: Cerebral ischemia is a common, morbid condition accompanied by cognitive decline. Recent reports on the vascular health benefits of flavanol-containing foods signify a promising approach to the treatment of cerebral ischemia. Our study was designed to investigate the effects of flavanol-rich cocoa (FRC) consumption on cerebral blood flow in older healthy volunteers. METHODS: We used transcranial Doppler (TCD) ultrasound to measure mean blood flow velocity (MFV) in the middle cerebral artery (MCA) in thirty-four healthy elderly volunteers (72 +/- 6 years) in response to the regular intake of FRC or flavanol-poor cocoa (FPC). RESULTS: In response to two weeks of FRC intake, MFV increased by 8% +/- 4% at one week (p = 0.01) and 10% +/- 4% (p = 0.04) at two weeks. In response to one week of cocoa, significantly more subjects in the FRC as compared with the FPC group had an increase in their MFV (p < 0.05). CONCLUSIONS: In summary, we show that dietary intake of FRC is associated with a significant increase in cerebral blood flow velocity in the MCA as measured by TCD. Our data suggest a promising role for regular cocoa flavanol's consumption in the treatment of cerebrovascular ischemic syndromes, including dementias and stroke.     

Cerebral blood flow changes in normal aging: Spect measurements

Global and regional cerebral blood flow (CBF) were evaluated with single photon emission computerized tomography (SPECT) utilizing both ¹³³Xenon (¹³³Xe) (47 subjects, 47–82 years old) and ⁹⁹Tc-hexamethylpropyleneamine oxime (⁹⁹Tc-HMPAO) (27 subjects, 47–80 years old). The ¹³³Xe results showed: among total subjects, no age-related decline in global CBF, but a significant regional decline in the occipital lobe (p < 0.05); among men, significant age-related declines in global, frontal, temporal, occipital and right hemisphere CBF (all p < 0.05); among women, no age-related decline in global or regional CBF. The ⁹⁹Tc-HMPAO results showed no age-related decline in either global or regional perfusion among total subjects, men or women. These results suggest that age-related global and regional (including frontal lobe) CBF declines do not occur in healthy control subjects after the age of 45 years. However, gender differences in age-related CBF changes warrant further study.     

Regional cerebral blood flow in patients with schizophrenia

Summary Regional cerebral blood flow was evaluated using Tc99m-HMPAO SPECT in 10 medicated patients with schizophrenia and 9 healthy volunteers. There were no prefrontal regions in the patient group with lower regional indices than in the control group. However, in the left hippocampal region, relative blood flow was significantly increased in the patient group compared with the control group. Furthermore, there was a relative increase in blood flow in the left basal ganglia of the patient group. A negative correlation coefficient was calculated between the relative blood flow in the left middle prefrontal cortex and the severity of the blunted affect, as well as between the relative blood flow in the left basal ganglia and the severity of the anhedonia-asociality. These findings indicate that prefrontal hypoactivity is not invariably present in all schizophrenics and that left basal ganglial hyperactivity may be associated with the effects of antipsychotic treatment and clinical improvement. Moreover, the left hippocampal hyperactivity may correspond to left limbic dysfunction in schizophrenia.     

Correlation of regional cerebral blood flow equivalents measured by single photon emission computerized tomography with P300 latency and eye movement abnormality in schizophrenia

Single photon emission tomography with the intravenous blood flow marker ^99mTc-exametazime was carried out in 14 acutely ill drug-free schizophrenic patients from whom P300 event-related potential, smooth eye pursuit eye tracking and verbal fluency were measured within a few days of scanning. Smooth pursuit eye movement abnormality correlated significantly with abnormal tracer uptake in superior pre-frontal cortex on the right and left and inferior pre-frontal cortex on the left. Abnormal eye movement was also associated with higher tracer uptake in left anterior cingulate and left posterior cingulate. P300 latency was significantly correlated with higher tracer uptake in left superior pre-frontal and left parietal regions. Verbal fluency performance was negatively correlated with tracer uptake in left frontal region. Eye tracking abnormality in schizophrenia is associated with bilateral frontal lobe disturbance and P300 latency increase with left-sided frontal and temporoparietal dysfunction. There was, however, a significant inverse relation between eye tracking abnormalities and abnormal perfusion in the left anterior cingulate region.     

Cerebral blood flow modeling in primate cortex

We report new results on blood flow modeling over large volumes of cortical gray matter of primate brain. We propose a network method for computing the blood flow, which handles realistic boundary conditions, complex vessel shapes, and complex nonlinear blood rheology. From a detailed comparison of the available models for the blood flow rheology and the phase separation effect, we are able to derive important new results on the impact of network structure on blood pressure, hematocrit, and flow distributions. Our findings show that the network geometry (vessel shapes and diameters), the boundary conditions associated with the arterial inputs and venous outputs, and the effective viscosity of the blood are essential components in the flow distribution. In contrast, we show that the phase separation effect has a minor function in the global microvascular hemodynamic behavior. The behavior of the pressure, hematocrit, and blood flow distributions within the network are described through the depth of the primate cerebral cortex and are discussed.     

Cerebral blood flow and plasma volume during hyperglycemia in the conscious rat

Cerebral blood flow (CBF) and cerebral plasma volume (CPV) were measured under steady-state hyperglycemic conditions in the hemispheres and brainstem-cerebellum of conscious rats. There groups of hyperglycemic animals each having a different level of plasma glucose concentration, 25,33.3, 44.4 mmol/l, and a normoglycemic control group were studied. CBF was not affected at the hyperglycemic levels of 25 and 33.3 mmol/l. Mean hemispheric and brainstem-cerebellum CBF values appeared lower than in controls at the highest glycemic level althoug the differences were not statistically significant. CPV was found to be unchanged at the hyperglycemic level of 25 mmol/l, while it was found to be increased in the hemispheres of the animals whose plasma glucose concentration had been elevated to 33.3 and 44.4 mmol/l. The results of the study do not support the claim that hyperglycemia may enhance ischemic brain injury by reducing CBF.

---

Sommario Il flusso ematico cerebrale (CBF) e il volume plasmatico cerebrale (CPV) sono stati misurati in corso di iperglicemia costante negli emisferi e nel tronco-cervelletto di ratti. Sono stati studiati tre gruppi di ratti, ciascuno con un diverso livello glicemico, 25, 33.3, 44.4 mml/L e un gruppo normoglicemico di controlo (8–9 ml/L). CBF è risultato immodificato ai livelli iperglicemici di 25 e 33.3 mml/L. Al livello iperglicemico più alto, i valori medi emisferici e del tronco-cervelletto sono risultati più bassi che nel controllo, benché le differenze non fossero statisticamente significative. CPV è stato trovato immodificato alla iperglicemia di 25 mml/L, mentre era aumentato ai livelli di 33.3 e 44.4 mml/L. I risultati dello studio non sono consistenti coll'ipotesi che l'iperglicemia favorisca il danno ischemico attraverso una riduzione del CBF.

     

Regional cerebral blood flow of acute carbon monoxide poisoning in cats

Summary The mechanism of selective vulnerability of the cerebral white matter and pallidum in acute carbon monoxide (CO) poisoning was experimentally investigated by measuring regional cerebral blood flow (rCBF) with the iodo-[¹⁴C]antipyrine method. A CO group consisting of five cats was exposed to 0.2%–0.3% CO gas and the rCBF was measured when moderate systemic hypotension (70–80 mm Hg) occurred; because systemic hypotension of this level during exposing to 0.2%–0.3% CO gas induces typical cerebral lesions of acute CO poisoning in almost all cats [Okeda et al. Acta Neuropathol (Berl) 54:1–10 (1981)]. Controls were a hypotension group of three cats with moderate systemic hypotension induced for 1 h without CO exposure, and a control group of five cats which inhaled only air for 2 h. The rCBF of each structure in the CO and hypotension groups was evaluated as a percentage of that of the control group. The rCBF of the CO group exhibited a wide range (68%–127%) according to the structures examined, and the mean (94.6%) was large compared with that (range: 53%–82%, mean: 67.4%) of the hypotension group. In the CO group, the examined brain structures where divided in two group according to the rCBF values; low-value structures and high-value structures. There was significant (P<0.05) difference between rCBFs of both the structure groups. The cerebral white matter and pallidum belonged to low-value structures, and these rCBFs did not show any significant difference from those of other structures in this structure group. The rCBF of the cerebral white matter was significantly lower than that of the cerebellar white matter. From these findings and our previous observations using the hydrogen clearance and rheological methods, the mechanism of the selective vulnerability of the pallidum and cerebral white matter in acute CO poisoning is discussed.Supported in part by a Grants-in-Aid for Scientific Research from the Ministry of Education, Science and Culture of Japan     

Cerebral perfusion inhomogeneities in schizophrenia demonstrated with single photon emission computed tomography and Tc99m-hexamethylpropyleneamineoxim

Cerebral blood flow was measured in relative terms with Tc99m-hexamethylpropyleneamineoxim (HMPAO) and single photon emission computed tomography (SPECT) in 28 female schizophrenic patients (20 acute and 8 chronic) classified according to DSM-III. Eleven normals served as controls. The acute patients were classified according to positive and negative symptoms. Patients with predominantly positive symptoms showed by and large normal and homogeneous cerebral isotope uptake. Those with negative symptoms, and the chronic patients, showed inhomogeneous tracer uptake with multiple regions of hypoperfusion in slices 4-6 cm above the orbitomeatal line. The findings support in principle the notion that schizophrenia with negative or chronic symptoms does not affect the whole brain homogeneously. Brain imaging with Tc99m-HMPAO and SPECT might be used to distinguish various types of schizophrenia.     

Cerebral blood flow and cerebral hematocrit in patients with cerebral ischemia measured by single-photon emission computed tomography

Abstract– Single-photon emission computed tomography (SPECT) was used for the measurement of regional cerebral blood flow (CBF), cerebral blood volume (CBV) and cerebral hematocrit (Hct). CBF was measured using N-isopropyl-p-I-123-Iodoamphetamine. CBV was measured by both RBC tracer (Tc-99m RBC) and plasma tracer (Tc-99m human serum albumin) and cerebral hematocrit (Hct) was calculated. In normals, the cerebral-to-large vessel Hct ratio was 75.9%. Isovolemic hemodilution in patients with high Hct tended to increase the cerebral-to-large vessel Hct ratio. Low CBF, high CBV and slow cerebral blood mean transit time (MTT by dynamic CT scanning) was seen during the acute stage of completed infarction and during the symptom-free interval of TIA. Cerebral Hct was increased in the ischemic region of poor prognosis.     

Cerebral blood flow quantification using vessel-encoded arterial spin labeling

Arterial spin labeling (ASL) techniques are gaining popularity for visualizing and quantifying cerebral blood flow (CBF) in a range of patient groups. However, most ASL methods lack vessel-selective information, which is important for the assessment of collateral flow and the arterial supply to lesions. In this study, we explored the use of vessel-encoded pseudocontinuous ASL (VEPCASL) with multiple postlabeling delays to obtain individual quantitative CBF and bolus arrival time maps for each of the four main brain-feeding arteries and compared the results against those obtained with conventional pseudocontinuous ASL (PCASL) using matched scan time. Simulations showed that PCASL systematically underestimated CBF by up to 37% in voxels supplied by two arteries, whereas VEPCASL maintained CBF accuracy since each vascular component is treated separately. Experimental results in healthy volunteers showed that there is no systematic bias in the CBF estimates produced by VEPCASL and that the signal-to-noise ratio of the two techniques is comparable. Although more complex acquisition and image processing is required and the potential for motion sensitivity is increased, VEPCASL provides comparable data to PCASL but with the added benefit of vessel-selective information. This could lead to more accurate CBF estimates in patients with a significant collateral flow.     

Hypofrontality in schizophrenia: Influence of normalization methods

1. 1. Studies with Single Photon Emission Computed Tomography (SPECT) in schizophrenia research have utilized different approaches to normalization of data, such as cerebellar ratio and whole brain ratio methods, leading to conflicting findings.

2. 2. The authors compared these two methods to test the hypofrontality hypothesis of schizophrenia.

3. 3. Eighteen chronic and medicated DSM-IV schizophrenic patients and 10 healthy controls underwent two SPECT examinations using ^99mTc-HMPAO as a tracer at baseline and during frontal activation while applying the Wisconsin Card Sorting Test.

4. 4. The hypofrontality hypothesis was supported with both indexes of relative perfusion, although the whole brain ratio method appeared to be more reliable and specific than the cerebellar ratio method.

5. 5. Further studies are required to confirm these preliminary results on the specificity and sensitivity of both methods.

     

Cerebral blood flow response to functional activation

Cerebral blood flow (CBF) and cerebral metabolic rate are normally coupled, that is an increase in metabolic demand will lead to an increase in flow. However, during functional activation, CBF and glucose metabolism remain coupled as they increase in proportion, whereas oxygen metabolism only increases to a minor degree—the so-called uncoupling of CBF and oxidative metabolism. Several studies have dealt with these issues, and theories have been forwarded regarding the underlying mechanisms. Some reports have speculated about the existence of a potentially deficient oxygen supply to the tissue most distant from the capillaries, whereas other studies point to a shift toward a higher degree of non-oxidative glucose consumption during activation. In this review, we argue that the key mechanism responsible for the regional CBF (rCBF) increase during functional activation is a tight coupling between rCBF and glucose metabolism. We assert that uncoupling of rCBF and oxidative metabolism is a consequence of a less pronounced increase in oxygen consumption. On the basis of earlier studies, we take into consideration the functional recruitment of capillaries and attempt to accommodate the cerebral tissue''s increased demand for glucose supply during neural activation with recent evidence supporting a key function for astrocytes in rCBF regulation.