Database of normal human cerebral blood flow, cerebral blood volume, cerebral oxygen extraction fraction and cerebral metabolic rate of oxygen measured by positron emission tomography with 15O-labelled carbon dioxide or water, carbon monoxide and oxygen: a multicentre study in Japan

Measurement of cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO₂) by positron emission tomography (PET) with oxygen-15 labelled carbon dioxide (C¹⁵O₂) or ¹⁵O-labelled water (H₂ ¹⁵O), ¹⁵O-labelled carbon monoxide (C¹⁵O) and ¹⁵O-labelled oxygen (¹⁵O₂) is useful for diagnosis and treatment planning in cases of cerebrovascular disease. The measured values theoretically depend on various factors, which may differ between PET centres. This study explored the applicability of a database of ¹⁵O-PET by examining between-centre and within-centre variation in values. Eleven PET centres participated in this multicentre study; seven used the steady-state inhalation method, one used build-up inhalation and three used bolus administration of C¹⁵O₂ (or H₂ ¹⁵O) and ¹⁵O₂. All used C¹⁵O for measurement of CBV. Subjects comprised 70 healthy volunteers (43 men and 27 women; mean age 51.8±15.1 years). Overall mean±SD values for cerebral cortical regions were: CBF=44.4±6.5 ml 100 ml^–1 min^–1; CBV=3.8±0.7 ml 100 ml^–1; OEF=0.44±0.06; CMRO₂=3.3±0.5 ml 100 ml^–1 min^–1. Significant between-centre variation was observed in CBV, OEF and CMRO₂ by one-way analysis of variance. However, the overall inter-individual variation in CBF, CBV, OEF and CMRO₂ was acceptably small. Building a database of normal cerebral haemodynamics obtained by the¹⁵O-PET methods may be practicable.     

Application of carbon-11 labelled nicotine in the measurement of human cerebral blood flow and other physiological parameters

Using positron emission tomography (PET), we measured the regional cerebral blood flow (rCBF) in five normal human subjects after intravenous injection of carbon-11 labelled (R)nicotine. The rCBF of the same subjects was measured by PET using the C¹⁵O₂ inhalation steady-state method. The distribution of¹¹C activity in the brain after injection of¹¹C-(R)nicotine was almost equivalent to the CBF image obtained with the C¹⁵O₂ inhalation stead-state method. The kinetics of¹¹C-(R)nicotine in the brain was analysed using a two-compartment model consisting of vascular and brain tissue compartments. The rCBF values obtained with¹¹C-(R)nicotine were higher than with C¹⁵O₂ gas. The relatively long fixed distribution of¹¹C-(R)nicotine with a short uptake period allows stimulation studies by measurement of CBF to be performed with better photon flux and a longer imaging time than are possible with H₂ ¹⁵O.     

Changes in cerebral oxygenation during hemodialysis before and after carotid artery stenting

A 68-year-old man received hemodialysis (HD) for the treatment of end-stage renal failure for 6 years. Five years prior to carotid artery stenting (CAS), a neck ultrasound performed to screen for carotid atherosclerosis revealed an asymptomatic right internal carotid artery stenosis. One month prior, the stenotic lesion progressed to 74% by cerebral angiography; therefore, CAS was performed. To evaluate the influence of right internal carotid artery stenosis on the intradialytic cerebral circulation and oxygenation, cerebral regional oxygen saturation (rSO₂) at bilateral forehead was measured using the INVOS 5100c oxygen saturation monitor (Covidien Japan, Japan) during HD before and after CAS. Before CAS, right cerebral rSO₂ was maintained during HD, whereas left cerebral rSO₂ gradually increased from the initiation to end of HD. However, the differences of intradialytic cerebral rSO₂ changes between bilateral sides disappeared after CAS. In the present case, before CAS, the intradialytic increase in left cerebral rSO₂ might reflect the increase in the left cerebral blood flow to compensate for the ultrafiltration-associated decreases in the right cerebral blood flow and perfusion pressure. Furthermore, the preserved right cerebral rSO₂ before CAS might reflect the mechanism maintaining the right cerebral blood flow from the collateralized circle of Willis during HD. Throughout our experience, cerebral oxygenation monitoring during HD might disclose intradialytic changes in cerebral blood flow distribution between the ipsilateral and contralateral side in HD patients with carotid artery stenosis.     

Regional cerebral blood flow and oxygen metabolism in a patient with Korsakoff syndrome

We report a functional neuroimaging study of a patient clinically diagnosed with Korsakoff syndrome. Positron emission tomography (PET) with the¹⁵O inhalation method showed decreased regional cerebral blood flow (rCBF) and decreased regional cerebral metabolic ratio for oxygen (rCMRO₂) in the bilateral fronto-temporal areas and in the left thalamus. These results suggest that dysfunction of the frontal-thalamic neural network plays a role in the disturbance of Korsakoff syndrome.     

Parametric imaging of cerebral vascular reserve

We report the reproducibility and response to change in end-tidal CO₂ of a new method of quantifying regional mean cerebral transit time (MCTT) compared with the reproducibility and CO₂ reactivity of middle cerebral artery (MCA) blood flow velocities measured using transcranial Doppler ultrasound. Within the range of end-tidal CO₂ which could be achieved in conscious subjects breathing spontaneously, hemispheric MCTT, peak MCA velocity and mean MCA velocity showed a linear relationship with end-tidal CO₂. After correction to a standardised end-tidal CO₂, the coefficients of variation were 5.7% for hemispheric MCTT, 6.3% for peak MCA velocity and 6.8% for mean MCA velocity. Under the conditions of this study, MCA blood flow velocity was proportional to the reciprocal of MCTT, which in turn represents the ratio of blood flow to blood volume. Although the two methods appear to provide similar information, measurement of MCTT is quicker to perform, is less observer-dependent, provides regional information, uses conventional equipment present in most nuclear medicine departments and is less subject to problems associated with patient movement. Offprint requests to: M.V. Merrick     

Regional cerebral blood flow,blood volume,oxygen extraction fraction,and oxygen utilization rate in normal volunteers measured by the autoradiographic technique and the single breath inhalation method

By means of a high resolution PET scanner, the regional cerebral blood flow (rCBF), cerebral blood volume (rCBV), oxygen extraction fraction (rOEF), and metabolic rate of oxygen (rCMRO₂) for major cerebral gyri and deep brain structures were studied in eleven normal volunteers during an eye-covered and ear-unplugged resting condition. Regional CBF was measured by the auto-radiographic method after intravenous administration of H₂ ¹⁵O. Regional OEF and rCMRO₂ were measured by the single inhalation of¹⁵O₂. With MR T₁-weighted images as an anatomical reference, thirteen major cerebral gyri, caudate nucleus, lentiform nucleus, thalamus, midbrain, pons, cerebellum and vermis were defined on the CMRO₂ images. Values were read by using circular regions of interest 16 mm in diameter. The posterior part of the cingulate gyri had the highest rCBF and rCMRO₂ values among brain structures, followed by the lentiform nucleus, the cerebellum, the caudate nucleus, and the thalamus. Parahippocampal gyri had the lowest rCBF and rCMRO₂ values amongthe cortical gyri.RegionalOEFforthepontinenuclei (0.34 ± 0.04), the midbrain (0.35 ± 0.05), the parahippocampal gyri (0.35 ± 0.04 for the right and 0.37 ± 0.05 for the left), and the thalami (0.37 ± 0.05 for the right and 0.36 ± 0.04 for the left) were significantly lower than the mean OEF for the cerebral cortices (0.42 ± 0.04) (p < 0.05 or less). The global CBF and CMRO₂ were consistent with those obtained by the Kety-Schmidt method. Although several limitations to the quantification derived from an inadequate spacial resolution remain unsolved, the performance of the present PET scanner and the method for the quantification employed provide regional estimates of brain circulation and oxygen metabolism more acurately than the PET system and the steady state method previously used.     

Influence of residual oxygen-15-labeled carbon monoxide radioactivity on cerebral blood flow and oxygen extraction fraction in a dual-tracer autoradiographic method

Objective  Cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO₂), oxygen extraction fraction (OEF), and cerebral blood volume (CBV) are quantitatively measured with PET with ¹⁵O 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 ¹⁵O₂ and C¹⁵O₂ gases. In this protocol, before the sequential PET scan with ¹⁵O₂ and C¹⁵O₂ gases (¹⁵O₂–C¹⁵O₂ PET scan), a PET scan with C¹⁵O should be preceded to obtain CBV image. C¹⁵O has a high affinity for red blood cells and a very slow washout rate, and residual radioactivity from C¹⁵O might exist during a ¹⁵O₂–C¹⁵O₂ PET scan. As the current DARG method assumes no residual C¹⁵O radioactivity before scanning, we performed computer simulations to evaluate the influence of the residual C¹⁵O 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 C¹⁵O radioactivity. Methods  In the simulation, normal and ischemic conditions were considered. The ¹⁵O₂ and C¹⁵O₂ PET count curves with the residual C¹⁵O PET counts were generated by the arterial input function with the residual C¹⁵O radioactivity. The amounts of residual C¹⁵O radioactivity were varied by changing the interval between the C¹⁵O PET scan and ¹⁵O₂–C¹⁵O₂ PET scan, and the absolute inhaled radioactivity of the C¹⁵O 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 C¹⁵O gas in the input function and PET counts. Results  Our simulations revealed that the CBF and OEF values were underestimated by the residual C¹⁵O radioactivity. The magnitude of this underestimation depended on the amount of C¹⁵O radioactivity and the physiological conditions. This underestimation was corrected by the subtraction method. Conclusions  This study showed the influence of C¹⁵O radioactivity in DARG protocol, and the magnitude of the influence was affected by several factors, such as the radioactivity of C¹⁵O, and the physiological condition.     

Effects of a novel tungsten-impregnated rubber neck shield on the quality of cerebral images acquired using <Superscript>15</Superscript>O-labeled gas

The present study aimed to validate the effects of a novel tungsten-impregnated rubber neck shield on the quality of phantom and clinical ¹⁵O-labeled gas positron emission tomography (PET) images. Images were acquired in the presence or absence of a neck shield from a cylindrical phantom containing [¹⁵O]H₂O (phantom study) and from three individuals using [¹⁵O]CO₂, [¹⁵O]O₂ and [¹⁵O]CO gas (clinical study). Data were acquired in three-dimensional (3D) mode using a Discovery PET/CT 710. Values for cerebral blood flow, cerebral blood volume, oxygen extraction fraction, and cerebral metabolic rate of oxygen with and without the neck shield were calculated from ¹⁵O-labeled gas images. Arterial radioactivity and count characteristics were evaluated in the phantom and clinical studies. The coefficient of variance (CV) for the phantom study and the standard deviation (SD) for functional images were also analyzed. The neck shield decreased the random count rates by 25–59% in the phantom and clinical studies. The noise equivalent count rate (NECR) increased by 44–66% in the phantom and clinical studies. Random count rates and NECR in [¹⁵O]CO₂ images significantly differed with and without the neck shield. The improvement in visual and physical image quality with the neck shield was not observed in the phantom and clinical studies. The novel neck shield reduced random count rate and improved NECR in a 3D PET study using ¹⁵O-labeled gas. The image quality with the neck shield was similar to that without the neck shield.     

Tomographic measurement of cerebral blood flow by the 68Ga-labelled-microsphere and continuous-C15O2-inhalation methods

The measurement of cerebral blood flow (CBF) by continuous C¹⁵O₂ inhalation has only been validated previously by indirect experimental protocols. In the present study using baboons, these measurements were compared directly with those obtained by injection of ⁶⁸Ga-labelled serum-albumin microspheres in the left cardiac ventricle. Using a modified labelling technique, no elution of ⁶⁸Ga occurred in vivo. Both methods provided similar regional CBF values, which could be described by a significant linear correlation ( =0.82 CBF_microspheres+5.7; P<0.001). The validity of the labelled-microsphere-injection method was verified. The feasibility of stable in vivo labelling of ⁶⁸Ga to serum-albumin microspheres provides a reference method for organ blood-flow measurements using positron-emission tomography.     

Cerebral blood flow and oxygen metabolism in senile dementia of Alzheimer's type and vascular dementia with deep white matter changes

Regional cerebral blood flow (rCBF), cerebral metabolic rate of oxygen (rCMRO₂), oxygen extraction fraction (rOEF), and cerebral blood volume (rCBV) were investigated using positron emission tomography (PET) in 16 patients with senile dementia of Alzheimer's type (SDAT), and compared with those of 6 nondemented and 3 demented patients with deep white matter high signal (DWMH) on T2-weighted MRI and 6 controls. rCBF, rCMRO₂ and rCBV were determined using C¹⁵O₂, ¹⁵O₂ and C¹⁵O, respectively. rCBF and CMRO₂ were significantly decreased in the frontal, parietal and temporal cortex (P < 0.05) in patients with SDAT, and showed a significant correlation with the severity of dementia (P < 0.05). In patients with DWMH rCBF was significantly decreased in the parietal cortex and in the frontal white matter in nondemented patients, and in the cerebral cortex and white matter of most regions studied in demented patients (P < 0.05), whereas rCMRO₂ was significantly reduced in only the frontal and temporal cortex of demented patients (P < 0.05). rOEF was significantly increased in the parietal cortex of patients with SDAT and in the white matter of patients with SDAT or DWMH (P < 0.05), and the increase in the frontal white matter significantly paralleled the progression of dementia in patients with SDAT (P < 0.05). rCBV was significantly decreased in the parietal and temporal cortex of patients with SDAT (P < 0.05), but not in any areas of those with DWMH. These results suggest that rOEF is increased in both SDAT and patients with DWMH. The increase in rOEF in patients with SDAT may be accounted for by reduction in rCBV resulting from decreased activity in the vasodilatory cholinergic system, impairment of glucose metabolism and white matter changes; the rOEF increase in patients with DWMH suggests relative preservation of oxidative metabolism compared to disturbed perfusion. Received: 24 October 1996 Accepted: 30 June 1997     

Optimal scan time of oxygen-15-labeled gas inhalation autoradiographic method for measurement of cerebral oxygen extraction fraction and cerebral oxygen metabolic rate

Objective  Regional cerebral blood flow (CBF), cerebral blood volume, oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO₂) can be estimated from C¹⁵O, H₂ ¹⁵O, and ¹⁵O₂ tracers and positron emission tomography (PET) using an autoradiographic (ARG) method. Our objective in this study was to optimize the scan time for ¹⁵O₂ gas study for accurate estimation of OEF and CMRO₂. Methods  We evaluated statistical noise in OEF by varying the scan time and error caused by the tissue heterogeneity in estimated OEF and CMRO₂ using computer simulations. The characteristics of statistical noise were investigated by signal-to-noise (S/N) ratio from repeated tissue time activity curves with noise, which were generated using measured averaged arterial input function and assuming CBF = 20, 50, and 80 (ml/100 g per minute). Error caused by tissue heterogeneity was also investigated by estimated OEF and CMRO₂ from tissue time activity curve with mixture of gray and white matter varying fraction of mixture. In the simulations, three conditions were assumed (i) CBF in gray and white matter (CBF^g and CBF^w) was 80 and 20, OEF in gray and white matter (E ^g and E ^w) was 0.4 and 0.3, (ii) CBF^g and CBF^w decreased by 50%, and E ^g and E ^w increased by 50% when compared with conditions (i) and (iii). CBF^g and CBF^w decreased by 80%, and E ^g and E ^w increased by 50% when compared with condition (i). Results  The longer scan time produced the better S/N ratio of estimated OEF value from three CBF values (20, 50, and 80). Errors of estimated OEF for three conditions owing to tissue heterogeneity decreased, as scan time took longer. Meanwhile in the case of CMRO₂, 3 min of scan time was desirable. Conclusions  The optimal scan time of ¹⁵O₂ inhalation study with the ARG method was concluded to be 3 min from taking into account for maintaining the S/N ratio and the quantification of accurate OEF and CMRO₂.     

A theoretical study of the steady-state model for measuring regional cerebral blood flow and oxygen utilisation using oxygen-15

There is a growing interest in the tomographic measurement of regional cerebral blood flow and oxygen utilisation using continuous inhalation of C15O2 and 15O2. This paper examines the influence of certain assumptions in the underlying steady-state model. Estimations are made for possible errors in the actual measurement of these quantities in grey and white matter.     

Regional perfusion,oxygen metabolism,blood volume and immunoglobulin G accumulation at focal sites of infection in rabbits

Infection causes remarkable changes in extracellular fluid volume, blood flow and oxygen consumption in the region of the lesion. To determine the sequence and magnitude of these changes, we performed serial scintigraphic measurements in 10 rabbits with experimental Escherichia coli abscesses. Positron emission tomography with C¹⁵O₂, ¹⁵O₂ and ¹¹CO was used to measure regional blood flow, oxygen extraction (OEF) and blood volume; extracellular fluid volume was evaluated by single photon scintigraphy with indium-111 immunoglobulin G (IgG). Images were recorded following tracer administration at 1 and 7–10 days after infection. At the first imaging time, blood flow to infected muscle had increased by 40% compared with control sites (7.4±0.6 to 10.8 ± 3.8 ml/min · 100 g), OEF had decreased from 55%±34% to 45%±14%, and the infected-tocontralateral (I/C) ratio of IgG had increased to 3.34±1.85. At the later imaging time, flow had increased by almost threefold compared with day 1 (29.4±9.8 ml/min · 100 g), OEF had decreased to 29%±14%, and the I/C ratio for IgG had remained constant. Although OEF fell,oxygendelivery (OEF × flow) increased from 4.07 ml/min (control value) to 4.86 ml/min on day 1 and 8.64 ml/min on days 7–9. The infected-to-contralateral (IC) ratio of ¹⁵02/C¹⁵O₂ was 0.74±0.15 on day 1 and 0.77±0.10 at 7–9 days. These studies indicate that expansion of the extracellular fluid volume increases early in the evolution of the infection and exceeds changes in regional perfusion and oxygen delivery.     

Automatic labeling method for injectable 15O-oxygen using hemoglobin-containing liposome vesicles and its application for measurement of brain oxygen consumption by PET

IntroductionThe aim of this study was to develop an injectable ¹⁵O-O₂ system using hemoglobin-containing vesicles (HbV), a type of artificial red blood cell, and to investigate the feasibility of ¹⁵O₂-labeled HbV (¹⁵O₂-HbV) to measure cerebral metabolic rate of oxygen (CMRO₂) in rats.MethodsThe direct bubbling method was combined with vortexing to enhance labeling efficiency of HbV with ¹⁵O-O₂ gas. l-Cysteine was added as a reductant to protect hemoglobin molecules in HbV from oxidation at different concentrations, and labeling efficiencies were also compared. Measurement of cerebral blood flow (CBF) and CMRO₂ in five normal rats was performed using a small animal PET scanner after the injection of H₂¹⁵O and ¹⁵O₂-HbV to evaluate the precision of hemodynamic parameters quantitatively.ResultsThe labeling efficiency of HbV was significantly increased when vortexing and bubbling were combined compared with the simple bubbling method (P<.05). The most efficient method for labeling was bubbling of ¹⁵O-O₂ combined with vortexing and the addition of 2.8 mM l-cysteine in HbV solution. The mean radioactivity of 214.4±7.8 MBq/mL HbV was obtained using this method. PET scans using ¹⁵O₂-HbV and H₂¹⁵O yielded a mean CMRO₂ value of 6.8±1.4 (mL/min per 100 g) in rats with normal CBF of 51.4±7.9 (mL/min per 100 g).ConclusionAddition of l-cysteine to HbV and simple direct bubbling of ¹⁵O-O₂ gas combined with vortexing was the most efficient method for preparation of ¹⁵O₂-HbV. The present injectable system using ¹⁵O₂-HbV was successfully utilized to measure CMRO₂ in rats, indicating that this new method could be useful for animal models to measure oxygen metabolism in the brain.     

Multislice imaging of quantitative cerebral perfusion with pulsed arterial spin labeling

A method is presented for multislice measurements of quantitative cerebral perfusion based on magnetic labeling of arterial spins. The method combines a pulsed arterial inversion, known as the FAIR (Flow-sensitive Alternating Inversion Recovery) experiment, with a fast spiral scan image acquisition. The short duration (22 ms) of the spiral data collection allows simultaneous measurement of up to 10 slices per labeling period, thus dramatically increasing efficiency compared to current single slice acquisition protocols. Investigation of labeling efficiency, suppression of unwanted signals from stationary as well as intraarterial spins, and the FAIR signal change as a function of inversion delay are presented. The assessment of quantitative cerebral blood flow (CBF) with the new technique is demonstrated and shown to require measurement of arterial transit time as well as suppression of intraarterial spin signals. CBF values measured on normal volunteers are consistent with results obtained from H₂O¹⁵ positron emission tomography (PET) studies and other radioactive tracer approaches. In addition, the new method allows detection of activation-related perfusion changes in a finger-tapping experiment, with locations of activation corresponding well to those observed with blood oxygen level dependent (BOLD) fMRI.     

Brain perfusion CT compared with 15O-H2O PET in patients with primary brain tumours

Purpose

Perfusion CT (PCT) measurements of regional cerebral blood flow (rCBF) have been proposed as a fast and easy method for identifying angiogenically active tumours. In this study, quantitative PCT rCBF measurements in patients with brain tumours were compared to the gold standard PET rCBF with ¹⁵O-labelled water (¹⁵O-H₂O).

Methods

On the same day within a few hours, rCBF was measured in ten adult patients with treatment-na?ve primary brain tumours, twice using ¹⁵O-H₂O PET and once with PCT performed over the central part of the tumour. Matching rCBF values in tumour and contralateral healthy regions of interest were compared.

Results

PCT overestimated intratumoural blood flow in all patients with volume-weighted mean rCBF values of 28.2?±?18.8?ml min^?1 100?ml^?1 for PET and 78.9?±?41.8?ml min^?1 100?ml^?1 for PCT. There was a significant method by tumour grade interaction with a significant tumour grade rCBF difference for PCT of 32.9?±?15.8?ml?min^?1 100?ml^?1 for low-grade (WHO I + II) and 81.5?±?15.4?ml?min^?1 100?ml^?1 for high-grade (WHO III + IV) tumours, but not for PET. The rCBF PCT and PET correlation was only significant within tumours in two patients.

Conclusion

Although intratumoural blood flow measured by PCT may add valuable information on tumour grade, the method cannot substitute quantitative measurements of blood flow by PET and ¹⁵O-H₂O PET in brain tumours.     

The preparation of 11C-labelled fluoromethane for the study of regional cerebral blood flow using positron emission tomography

Fluoromethane, previously labelled with ¹⁸F and used as a tracer in the measurement of regional cerebral blood flow, was ¹¹C-labelled by the reaction of ¹¹C-methyl iodide with tetraethylammonium fluoride. Sufficient quantities of radiotracer were prepared with a minimum amount of handling from 15 min target irradiations in the ¹⁴N(p, ) ¹¹C reaction. Total synthesis time was 25 min from end-of-bombardment, allowing serial blood flow measurements 30 min apart. The use of ¹¹C-fluoromethane as a cerebral blood flow tracer in positron emission tomography is discussed.     

In vivo measurement of CBF using 17O NMR signal of metabolically produced H217O as a perfusion tracer

The cerebral metabolic rate of oxygen of small animals can be reliably imaged using the in vivo ¹⁷O magnetic resonance approach at high field. However, a separate measurement is required for imaging the cerebral blood flow in the same animal. In this study, we demonstrate that the ¹⁷O NMR signal of metabolically produced H₂¹⁷O in the rat brain following an ¹⁷O₂ inhalation can serve as a perfusion tracer and its decay rate can be used to determine the absolute values of cerebral blood flow across a wide range of animal conditions. This finding suggests that the in vivo ¹⁷O magnetic resonance approach is capable of imaging both cerebral metabolic rate of oxygen and cerebral blood flow simultaneously and noninvasively; and it provides new utilities for studying the cerebral oxygen metabolism and perfusion commonly associated with brain function and diseases. Magn Reson Med 70:309–314, 2013. © 2012 Wiley Periodicals, Inc.     

Vascular risk factors,atherosclerosis, cerebral white matter lesions and cerebral perfusion in a population-based study

We studied risk factors for cerebral vascular disease (blood pressure and hypertension, factor VIIc, factor VIIIc, fibrinogen), indicators of atherosclerosis (intima-media thickness and plaques in the carotid artery) and cerebral white matter lesions in relation to regional cerebral blood flow (rCBF) in 60 persons (aged 65–85 years) recruited from a population-based study. rCBF was assessed with single-photon emission tomography using technetium-99md,l-hexamethylpropylene amine oxime (^99mTc-HMPAO). Statistical analysis was performed with multiple linear regression with adjustment for age, sex and ventricle-to-brain ratio. A significant positive association was found between systolic and diastolic blood pressure and temporo-parietal rCBF. In analysis with quartiles of the distribution, we found a threshold effect for the relation of low diastolic blood pressure (60 mmHg) and low temporo-parietal rCBF. Levels of plasma fibrinogen were inversely related to parietal rCBF, with a threshold effect of high fibrinogen levels (>3.2 g/1) and low rCBF. Increased atherosclerosis was related to low rCBF in all cortical regions, but these associations were not significant. No consistent relation was observed between severity of cerebral white matter lesions and rCBF. Our results may have implications for blood pressure control in the elderly population.