Human cerebral circulation: positron emission tomography studies

Hypercapnia induces cerebral vasodilation and increases cerebral blood volume (CBV), and hypocapnia induces cerebral vasoconstriction and decreases CBV. Cerebral blood volume measured by positron emission tomography (PET) is the sum of three components, that is, arterial, capillary, and venous blood volumes. Changes in arterial blood volume (V(a)) and CBV during hypercapnia and hypocapnia were investigated in humans using PET with H(2)(15)O and (11)CO. Arterial blood volume was determined from H(2)(15)O PET data by means of a two-compartment model that takes V(a) into account. Baseline CBV and values during hypercapnia and hypocapnia in the cerebral cortex were 0.034+/-0.003, 0.038+/-0.003, and 0.031+/-0.003 mL/mL (mean+/-s.d.), respectively. Baseline V(a) and values during hypercapnia and hypocapnia were 0.015+/-0.003, 0.025+/-0.011, and 0.007+/-0.003 mL/mL, respectively. Cerebral blood volume changed significantly owing to changes in PaCO(2), and V(a) changed significantly in the direction of CBV changes. However, no significant change was observed in venous plus capillary blood volume (=CBV-V(a)). This indicates that changes in CBV during hypercapnia and hypocapnia are caused by changes in arterial blood volume without changes in venous and capillary blood volume.

Cerebral Blood Flow and Oxygen Metabolism Measurements Using Positron Emission Tomography on the First Day after Carotid Artery Stenting

Using high-resolution positron emission tomography and the oxygen 15 continuous inhalation method, we examined the changes in cerebral metabolic rate of oxygen, blood flow, blood volume, and oxygen extraction fraction as a function of age in 25 optimally healthy, unmedicated volunteers who ranged in age from 20 to 68 years. Subjects were strictly selected for absence of cerebrovascular risk factors, dementia, or mental disorders; they had neither biological nor clinical abnormalities, and no focal anomaly on computed tomographic scan. Regions of interest were determined according to the anatomical structures defined on corresponding computed tomographic scan cuts obtained using a stereotaxic head-positioning method. This same method was also used for positron emission tomographic imaging. There was no significant effect of aging on PaCO2 values, hematocrit, arterial blood pressure, cholesterol and triglyceride levels, and blood glucose levels. In most cerebral cortex gyri, the cerebral metabolic rate of oxygen significantly decreased with age according to a linear pattern, with the same magnitude (about -6% per decade) in all four lobes and on both sides. This effect of age on cortical cerebral metabolic rate of oxygen persisted when the possible influence of cortical atrophy, gender, and head size were partialled out. In contrast, the white matter, deep gray nuclei, thalamus, and cerebellum were not significantly affected. The cerebral blood volume declined with a similar pattern to cerebral metabolic rate of oxygen, while changes in cerebral blood flow were less significant, presumably because of larger variance of data across subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

It is generally argued that variations in cerebral blood flow create concomitant changes in the cerebral blood volume (CBV). Because nitrous oxide (N(2)O) inhalation both increases cerebral blood flow and may increase intracranial pressure, it is reasonable to assume that N(2)O acts as a general vasodilatator in cerebral vessels both on the arterial and on the venous side. The aim of the current study was to evaluate the effect of N(2)O on three-dimensional regional and global CBV in humans during normocapnia and hypocapnia. Nine volunteers were studied under each of four conditions: normocapnia, hypocapnia, normocapnia + 40-50% N(2)O, and hypocapnia + 40-50% N(2)O. CBV was measured after (99m)Tc-labeling of blood with radioactive quantitative registration via single photon emission computer-aided tomography scanning. Global CBV during normocapnia and inhalation of 50% O(2) was 4.25 +/- 0.57% of the brain volume (4.17 +/- 0.56 ml/100 g, mean +/- SD) with no change during inhalation of 40-50% N(2)O in O(2). Decreasing carbon dioxide (CO(2)) by 1.5 kPa (11 mmHg) without N(2)O inhalation and by 1.4 kPa (11 mmHg) with N(2)O inhalation reduced CBV significantly (F = 57, P < 0.0001), by 0.27 +/- 0.10% of the brain volume per kilopascal (0.26 +/- 0.10 ml x 100 g(-1) x kPa(-1)) without N(2)O inhalation and by 0.35 +/- 0.22% of the brain volume per kilopascal (0.34 +/- 0.22 ml x 100 g(-1) x kPa(-1)) during N(2)O inhalation (no significant difference). The amount of carbon dioxide significantly altered the regional distribution of CBV (F = 47, P < 0.0001), corresponding to a regional difference in Delta CBV when CO(2) is changed. N(2)O inhalation did not significantly change the distribution of regional CBV (F = 2.4, P = 0.051) or Delta CBV/Delta CO(2) in these nine subjects. Nitrous oxide inhalation had no effect either on CBV or on the normal CBV-CO(2) response in humans.

[18F]-fluoroacetate ((18)F-FACE) can be used for evaluating glial cell metabolism. Experimental studies have shown an increase in (18)F-FACE uptake in rodent models of cerebral ischemia. The aim of this study was to determine whether (18)F-FACE uptake is increased in the noninfarcted cerebral cortex in patients with hemodynamic ischemia owing to atherosclerotic internal carotid artery or middle cerebral artery disease. We evaluated 9 symptomatic patients with unilateral atherosclerotic internal carotid artery or middle cerebral artery disease and no cortical infarction using positron emission tomography with (18)F-FACE and (15)O-gases. (18)F-FACE uptake during 40 to 60 minutes after injection was compared with the cerebral blood flow, cerebral metabolic rate of oxygen, oxygen extraction fraction, and cerebral blood volume in the middle cerebral artery distributions. Significant decreases of cerebral blood flow and cerebral metabolic rate of oxygen and increases of oxygen extraction fraction and cerebral blood volume were found in the hemisphere ipsilateral to the arterial lesion, and (18)F-FACE uptake in this region was greater than that in the contralateral hemisphere. The relative (18)F-FACE uptake (ipsilateral/contralateral ratio) was negatively correlated with cerebral blood flow or cerebral metabolic rate of oxygen values and was positively correlated with oxygen extraction fraction values. Multivariate analysis showed that the ipsilateral/contralateral (18)F-FACE uptake ratio was independently correlated with the cerebral blood flow (or oxygen extraction fraction) and cerebral metabolic rate of oxygen values. In patients with atherosclerotic internal carotid artery or middle cerebral artery disease, (18)F-FACE uptake is increased in the noninfarcted cerebral cortex with chronic hemodynamic ischemia characterized by misery perfusion with decreased oxygen metabolism. Increased (18)F-FACE uptake may indicate the cortical regions that are at particular risk for ischemic damage.

Cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO(2)), oxygen extraction fraction (OEF), and cerebral blood volume (CBV) are quantitatively measured with PET with (15)O gases. Kudomi et al. developed a dual tracer autoradiographic (DARG) protocol that enables the duration of a PET study to be shortened by sequentially administrating (15)O(2) and C(15)O(2) gases. In this protocol, before the sequential PET scan with (15)O(2) and C(15)O(2) gases ((15)O(2)-C(15)O(2) PET scan), a PET scan with C(15)O should be preceded to obtain CBV image. C(15)O has a high affinity for red blood cells and a very slow washout rate, and residual radioactivity from C(15)O might exist during a (15)O(2)-C(15)O(2) PET scan. As the current DARG method assumes no residual C(15)O radioactivity before scanning, we performed computer simulations to evaluate the influence of the residual C(15)O radioactivity on the accuracy of measured CBF and OEF values with DARG method and also proposed a subtraction technique to minimize the error due to the residual C(15)O radioactivity. In the simulation, normal and ischemic conditions were considered. The (15)O(2) and C(15)O(2) PET count curves with the residual C(15)O PET counts were generated by the arterial input function with the residual C(15)O radioactivity. The amounts of residual C(15)O radioactivity were varied by changing the interval between the C(15)O PET scan and (15)O(2)-C(15)O(2) PET scan, and the absolute inhaled radioactivity of the C(15)O gas. Using the simulated input functions and the PET counts, the CBF and OEF were computed by the DARG method. Furthermore, we evaluated a subtraction method that subtracts the influence of the C(15)O gas in the input function and PET counts. Our simulations revealed that the CBF and OEF values were underestimated by the residual C(15)O radioactivity. The magnitude of this underestimation depended on the amount of C(15)O radioactivity and the physiological conditions. This underestimation was corrected by the subtraction method. This study showed the influence of C(15)O radioactivity in DARG protocol, and the magnitude of the influence was affected by several factors, such as the radioactivity of C(15)O, and the physiological condition.

The relationships between cerebral blood volume (CBV), cerebral blood flow (CBF), and the cerebral vascular mean transit time (t v ) during acute changes in the Pa CO 2 over a range of 15 to 76 torr were investigated in vivo in rhesus monkeys by serially determining the mean transit time of a vascular tracer, 15 O-labeled carboxyhemoglobin, and the mean transit time of a diffusible tracer, 15 O-labeled water. Over this range of Pa CO 2 , a significant linear relationship of CBV = 0.041 Pa CO 2 + 2.0 was found. For each one torr change in Pa CO 2 , there is a change in CBV of 0.041 ml/100 gm of perfused tissue. At a normocarbic value of Pa CO 2 (37 torr), an average value of 3.5 ml/100 gm was found. A nonlinear relationship of CBV and CBF was found. This relationship is expressed in the equation, CBV = 0.80 CBF 0.38 . A significant linear relationship was found between CBF and Pa CO 2 . This was described by the equation, CBF = 1.8 Pa CO 2 - 16.75. For each one torr change in the PaCO 2 , there is a 1.8 ml/100 gm per minute change in the CBF. At a normocarbic value of Pa CO 2 (37 torr), an average value of CBF of 50 ml/100 gm per minute was found. The relationship of CBV and t v was nonlinear and was expressed in the equation, t C15O = 41 CBF -0.62 .

A recent dynamic model relates the functional near-infrared spectroscopy (fNIRS) measurements to hemodynamic and metabolic parameters. This note reports modified expressions of the new model in terms of cerebral blood volume (CBV), blood flow (CBF) and metabolic rate of oxygen (CMRO2). On the basis of these modified expressions, the new model reproduces known steady state relationships between hemoglobin concentration, CBF and CMRO2, and yields time-dependent relationships that describe transient changes. This new model allows for the translation of the fNIRS measurements into dynamic measures of ΔCBV/CBV0 and the difference ΔCBF/CBF0 – ΔCMRO2/CMRO2|0, provided that some baseline physiological parameters and a relationship between overall, arterial and venous blood volume changes are assumed.

The mechanisms underlying neurological symptoms, including epilepsy, in unruptured brain arteriovenous malformations (bAVM) remain to be elucidated. The dual-tracer basis function method (DBFM) with single-scan dual-tracer (15O2 and C15O2) approach is a novel PET imaging technique that can evaluate the hemodynamics and metabolism of brain tissue adjacent to the nidus without the influence of abundant vascular radioactivity. We aimed to clarify the relationship between neurological symptoms and hemodynamic and metabolic abnormalities using the DBFM. Cerebral blood volume (CBV), cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO2), and oxygen extraction fraction (OEF) were compared between symptomatic and asymptomatic bAVMs and before and after treatment. Among 46 patients with unruptured bAVMs who underwent DBFM, 26 cases were included. While CBV and OEF increased in the perinidus (p < 0.01), CBF and CMRO2 decreased (p < 0.01). Symptoms were significantly associated with higher OEF (symptomatic vs. asymptomatic, ratio of perinidal to contralateral, n = 13 vs. n = 13, 1.07 ± 0.030 vs. 1.01 ± 0.080, p = 0.017). All elevated OEFs in symptomatic bAVMs with therapeutic symptom resolved in post-therapeutic PET imaging. DBFM revealed a higher OEF was associated with symptomatic bAVM. The DBFM potentially aids in predicting post-therapeutic symptom improvement.

To noninvasively assess global cerebral blood flow (CBF), oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO2) in young adults with end-stage renal disease (ESRD). Thirty-six patients and 38 healthy volunteers were included and took part in MR examinations, blood and neuropsychological tests. CBF and OEF were measured by phase-contrast and T2-relaxation-under-spin-tagging MRI techniques, respectively. CMRO2 was computed from CBF, OEF and hematocrit according to Fick's principle. Correlations were performed between MR measurements, blood biochemistry measurements and neuropsychological test scores. Compared with controls, ESRD patients had elevated CBF (72.9 ± 12.5 vs. 63.8 ± 8.5mlmin(-1) 100g(-1), P < 0.001), elevated OEF (47.2 ± 10.2 vs. 35.8 ± 5.4%, P < 0.001), but unaffected CMRO2 (199.5 ± 36.4 vs. 193.8 ± 28.6μmol O2 min(-1) 100g(-1), P = 0.879). Hematocrit negatively correlated with CBF (r = -0.640, P < 0.001) and OEF (r = -0.701, P < 0.001), but not with CMRO2. Altered neuropsychological test scores of ESRD patients were associated with OEF and CBF, but not with CMRO2. There were weak relationships between eGFR and hematocrit (r = 0.308, P = 0.068) or CBF (r = 0.318, P = 0.059). Our findings suggested that anaemic young adults with ESRD may afford higher CBF and OEF to maintain a normal CMRO2. Despite this compensatory process, however, cognitive function was still impaired and its severity was correlated with their CBF and OEF abnormality. • Anaemic young adults with ESRD may afford higher CBF and OEF. • Anaemic young adults with ESRD maintain a normal CMRO 2 . • Cognitive function was still impaired in young ESRD adults. • The severity of cognitive dysfunction correlated with CBF and OEF changes.

OBJECTIVESSilent brain infarction (SBI) is of growing interest as a possible risk factor for symptomatic stroke. Although morphological characteristics of SBI have been well defined, their characteristic patterns of cerebral...

Introduction: It is reported that moyamoya disease (MMD) associated with posterior cerebral artery (PCA) stenoses or occlusions (PCS/PCO) progresses aggressively in clinical course and results in poor prognosis. In these cases, the thalamic perforating branches from PCA and the posterior choroidal arteries develop and present as moyamoya vessels. But it still remains unclear that the correlation between collateral circulations, cerebral metabolisms and PCS/PCO. Hypothesis: In the current study, we assessed hypothesis that PCS/PCO leads to misery perfusion in the anterior circulation and results in unstable MMD. Methods: A total of 79 patients, 158 hemispheres were included in this study. The average age was 42.5±15.6 years and 53 patients were women. We divided them into 2 groups (PCS/PCO positive or negative group) and cerebral blood flow (CBF), cerebral blood volume (CBV), oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO2) were examined by 15O-gas PET in following regions: anterior cerebral artery (rACA), anterior and posterior part of middle cerebral artery (rMCAa and rMCAp), and posterior cerebral artery (rPCA). Angiogram helped us to evaluate the development of the collateral vessels. Results: In PCS/PCO positive group, CBF and CMRO2 were reduced whereas CBV and OEF were elevated in rMCAp compared to negative group. These parameters were all statistically significant (p&lt;0.05). In addition, collateral circulations including anterior meningeal artery (AMA), middle meningeal artery (MMA) and posterior choroidal artery (PchoA) sufficiently developed in PCO/PCS positive group (P&lt;0.05). Conclusions: MMD associated with PCS/PCO has well developed AMA, MMA and PchoA because the stenotic or obliterative changes in the terminal portions of internal carotid artery have already progressed. In these patients, decreased CBF, increased CBV and OEF lead to misery perfusion in rMCAp despite the growth of the collateral flow. Early revascularization is recommended because PCS/PCO causes repeated stroke and unstable MMD.

Neuroradiological functional imaging techniques demonstrate the patterns of hypoperfusion and hypometabolism that are thought to be useful in the differential diagnosis of Alzheimer's disease (AD) from other dementing disorders. Besides the distribution patterns of perfusion or energy metabolism, vascular transit time (VTT), vascular reactivity (VR), and oxygen extraction fraction (OEF), which can be measured with positron emission tomography (PET), provide hemodynamic aspects of brain pathophysiology. In order to evaluate the hemodynamic features of AD, PET studies were carried out in 20 patients with probable AD and 20 patients with vascular dementia (VaD). The PET findings were not included in their diagnostic process of AD. Using oxygen-15-labeled compounds, cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO(2)), OEF, cerebral blood volume, and VTT were measured quantitatively during resting state. To evaluate VR, CBF was also measured during CO(2) inhalation. There was a significant increase in OEF in and around the parietotemporal cortices, but both VTT and VR were well preserved in patients with AD. By contrast, VR was markedly depressed and VTT was mildly prolonged in patients with VaD. Thus, from the hemodynamic point of view, the preservation of vascular reserve may be a distinct difference between AD and VaD. Furthermore, this indicates a hemodynamic integrity of the vasculature in the level of arterioles in AD.

Functional neuroimaging is most commonly performed using the blood-oxygenation-level-dependent (BOLD) approach, which is sensitive to changes in cerebral blood flow (CBF), cerebral blood volume (CBV), and the cerebral metabolic rate of oxygen (CMRO(2)). However, the precise mechanism by which neuronal activity elicits a hemodynamic response remains controversial. Here, visual stimulation (14 secs flashing checkerboard) and breath-hold (4 secs exhale+14 secs breath hold) experiments were performed in alternating sequence on healthy volunteers using BOLD, CBV-weighted, and CBF-weighted fMRI. After visual stimulation, the BOLD signal persisted for 33+/-5 secs (n=9) and was biphasic with a negative component (undershoot), whereas CBV and CBF returned to baseline without an undershoot at 20+/-5 and 20+/-3 secs, respectively. After breath hold, the BOLD signal returned to baseline (23+/-7 secs) at the same time (P>0.05) as CBV (21+/-6 secs) and CBF (18+/-3 secs), without a poststimulus undershoot. These data suggest that the BOLD undershoot after visual activation reflects a persistent increase in CMRO(2). These observations support the view that CBV and CBF responses elicited by neuronal activation are not necessarily coupled to local tissue metabolism.

Studies that have examined abnormalities in cerebral blood flow (CBF) in patients with systemic lupus erythematosus (SLE) reported CBF relative to a region assumed to be normal in the brain. We examined the absolute differences in both regional CBF and cerebral blood volume (CBV) between patients with SLE and healthy controls. CBF and CBV were measured with dynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI), a technique that provides an alternative to radionuclide perfusion studies and permits quantitative anatomic, CBF, and CBV imaging in a single scanning session. CBF and CBV were measured in lesions and in normal-appearing tissue in the major cerebral and subcortical brain regions. Unlike most perfusion studies in SLE, CBF and CBV values were not normalized to a region of the brain assumed to be healthy. CBF and CBV within MRI-visible lesions were markedly reduced relative to surrounding normal-appearing white matter. CBF and CBV in normal-appearing tissue were both higher in SLE patient groups, with or without lesions, relative to the control group. DSC MRI, without normalization to a region presumed to be healthy, revealed that CBF and CBV in normal-appearing tissue in patients with SLE was higher than CBF and CBV in controls. Since this finding was made in subgroups of patients with and without lesions, the higher CBF and CBV appear to precede lesion pathology.