The construction and use of nomograms for cerebral blood flow calculation using a 133Xe inhalation technique

Measurement of cerebral blood flow (CBF) using a 133Xe inhalation technique requires monitoring the clearance rate of the radioisotope from the head using externally situated detectors and also from arterial blood using a detector to monitor the expired air activity. The end-tidal concentration function is assumed to be proportional to the arterial concentration function and this has to be deconvoluted from the clearance functions obtained from the head to enable CBF to be calculated. A digital computer is generally considered to be essential for this. In this paper a procedure using three-dimensional nomograms is derived and tested. It is shown that results obtained using the nomograms do not differ significantly from results obtained using a full deconvolution procedure, and so it is not essential to use a computer to calculate CBF by the inhalation technique.     

Calculation of coronary blood flow from myocardial clearance of systemically administered 133Xe

Clearance curves for arterial and coronary-venous blood were determined after systemic left-ventricle or pulmonary-artery infections of 133Xe, paired with selective left-coronary-artery injections of 133Xe in 20 dogs with closed chest. Coronary blood flows calculated from systemic and coronary-artery injections were comparable only when a correction was made for arteriol recirculation of 133Xe following the systemic injection (r = 0.962) for left ventricle and 0.932 for pulmonary artery, paired with coronary artery). Experiments in four other dogs, verified that clearance of 133Xe from the pulmonary circulation was only about 60%. The myocardium/blood 133Xe partition coefficient, determined in vivo in ten dogs, agreed within 10% with that previously determined in vitro.     

Regional cerebral blood flow during experimental phobic fear

Positron emission tomographic measurements of regional cerebral blood flow (rCBF) were used to investigate central nervous system correlates of fear and anxiety. Volunteers with symptomatic snake phobia were studied while exposed to visual phobogenic, aversive, and neutral stimuli. Anxiety ratings and the number of nonspecific electrodermal fluctuations increased as a function of phobic stimulation. Phobic, compared to neutral and aversive, stimulation elevated rCBF in the visual associative cortex. The basal ganglia were not activated more by phobic than aversive or neutral stimulation. However, cortical and thalamic rCBF were always correlated during phobic but not aversive or neutral stimulation. This indicates that the thalamus could be a relay station for phobic stimulus processing and affect.     

Regional cerebral blood flow in focal cortical epilepsy

Regional cerebral blood flow (rCBF) was studied in ten patients with focal cortical epilepsy. The blood flow was measured by the intra-arterial injection of xenon 133 (133Xe), and the isotope clearance was recorded by a multidetector scintillation camera with 254 detectors. Three patients were studied both during a seizure and (in the same setting) in the interictal period; six patients were studied only in the interictal period, and one patient was studied only during a seizure. Studies during seizures all showed marked flow increases in areas presumed to participate in the seizure activity. This finding accords with earlier studies. All nine patients studied in the interictal phase showed, either spontaneously or during activation by intermittent light, focal flow increases in areas presumed to comprise the epileptic focus. These interictal hyperemic foci probably reflect subictal neuronal hyperactivity in epileptogenic nervous tissue. Only two of the patients had distinct epileptic electroencephalographic foci. It appears that rCBF studies can be a valuable diagnostic tool in the investigation of cortical epileptogenic lesions.     

Studies on 133Xe wash-out from human skin: quantitative measurements of blood flow in normal and corticosteroid-treated skin

Blood flow was measured by the 133Xe technique in normal and corticosteroid-treated skin. Epicutaneous and intracutaneous methods of tracer application were compared in normal skin. The two labeling methods were equally suitable for measuring cutaneous blood flow provided calculations in both cases were based on a biexponential resolution of the wash-out curve in its cutaneous and subcutaneous components and provided the traumatic hyperemia phase was considered, when intracutaneous application of the tracer was used. Results were invalidated if calculations were based on initial slope of the wash-out curves.Topical application of beta-methasone valerate in a reduction in cutaneous blood flow as measured by the intracutaneous technique with curve resolution, whereas no effect could be demonstrated when calculations were based on the initial slopes of the curves. The 133Xe technique is a simple and reliable method for measuring cutaneous blood flow, which might prove useful in estimations of penetration ability and potency of topical corticosteroids.     

Regional differences of cerebral blood flow in the preterm infant

The purpose of our study was to evaluate the regional distribution of the resting cerebral blood flow (CBF) pattern in preterm neonates. Sixty-eight preterm babies with a gestational age of less than 34 weeks and a birth weight of less than 1500 g were enrolled into the study. The CBF was measured by the noninvasive intravenous 133Xenon method at three different times. Depending on the age we classified our measurements into three groups. Group 1: measurement between 2-36 h (n = 46). Group 2: measurement between 36-108 h (n = 39). Group 3: measurement between 108-240 h (n = 41). In all three groups CBF was significantly lower in the occipital region than in the frontal and parietal regions (group 1: frontal region 12.8 +/- 3.5 ml/100 g/min, parietal region 12.8 +/- 3.9 ml/100 mg/min, and occipital region 11.6 +/- 3.18 ml/100 g/min; group 2: frontal region 15.4 +/- 4.2 ml/100 g/min, parietal region 15.3 +/- 4.1 ml/100 g/min, and occipital region 13.4 +/- 3.5 ml/100 g/min; group 3: frontal region 14.6 +/- 3.6 ml/100 g/min, parietal region 14.6 +/- 3.2 ml/100 g/min, and occipital region 12.8 +/- 2.7 ml/100 g/min.). CBF did not differ between the left and the right hemispheres in either of the three measured regions. No gradient was found in infants between 108 h and 240 h of age with periventricular leukomalacia and periventricular haemorrhage. CONCLUSION. In preterm neonates the antero-posterior gradient of CBF is already present. Periventricular leukomalacia as well as periventricular haemorrhage may affect the regional regulation of CBF.     

Influence of posture on flow dependence of distribution of inhaled 133Xe boli

The second 100 ml of gas inspired at constant flow rates (V) from 0.1 to 2.5 l/s was tagged with 133Xe to determine the apicobasal bolus distribution ratio (VAlvA/VAlvB) for seven normal subjects in both the upright and supine postures. Gas was preferentially distributed to the base at low V. As V increased, redistribution to the apex occurred but was greater in the supine posture. As apicobasal time constant differences should be minimal in the supine posture, the greater flow dependence of bolus distribution suggests that the pressure swing was greater over apical zones than basal zones. Model studies indicate that the pressure differences (deltaPd) necessary to predict the measured VAlvA/VAlvB at all flow rates are less than 1.0 cmH2O. Such sensitivity of gas distribution to deltaPd at both low and high flow rates makes it appear relatively insensitive to regional compliance and resistance.     

A scintigraphic method of examining the patency of oviducts using 133Xe

Described below is the radioisotope method of examining the patency of oviducts using a solution of 133Xe. Scintigraphic pictures of the uterine cavity and oviducts were obtained with a Jumbo Toshiba gamma-camera; they were subsequently analysed by an Informatek SIMIS-3 data processing system. A total of 30 women aged between 20 and 36 with primary or secondary infertility were examined. The patency of oviducts and the shape of the uterine cavity was assessed on the basis of: the overall picture of the activity of 133Xe in the uterine cavity and oviducts, the isocontours of the overall picture, curves of increasing and decreasing activity in the fallopian tubes, and the spatial picture of activity distribution in the uterus and fallopian tubes. The results of the examinations corresponded in all cases with the diagnosis made on the basis of hysterosalpingography. An advantage of the isotope method of examining the patency of fallopian tubes and the shape of the uterine cavity is the fact that it is an examination of a dynamic nature, completely safe for the patient and exposes the patients to a considerably lower dose of irradiation than during hysterosalpingography.     

Regional cerebral blood flow and cerebrospinal fluid amino acid analysis in elderly dementia

Regional cerebral blood flow and amino acid concentration in the cerebrospinal fluid were studied in 12 cases of vascular dementia, 12 cases of Alzheimer's disease, 12 cases of chronic alcoholism, and 12 age-matched healthy controls. In vascular dementia, blood flows were decreased in the cerebral cortex, frontal white matter, thalamus, caudate nucleus, and putamen and alpha-aminobutyric acid and glutamic acid concentrations were increased in the cerebrospinal fluid. In Alzheimer's disease, blood flows were decreased in the frontal cortex, parietal cortex, temporal cortex, and frontal white matter and alanine concentration was increased in the cerebrospinal fluid. In chronic alcoholism, blood flows were decreased in the cerebral cortex, thalamus, and putamen and urea, alanine, and glycine concentrations were increased in the cerebrospinal fluid.     

Regional cerebral blood flow increases during preparation for and processing of sensory stimuli

The transferrin receptor (TFR) has been detected in tissues characterised by a high degree of proliferation. We have developed a procedure for isolating TFR from human placental tissues by affinity chromatography on transferrin-Sepharose. Using gel filtration and electrophoresis in 7% PAAG, it has been shown that the molecular mass of the protein is 180 kDa. The protein has a subunit structure and is made up of two identical subunits, 90 kDa each. The constant for the protein binding to transferrin is equal to 5 x 10(-9) M. The yield of the protein isolated by the novel procedure exceeds 5-fold that obtained by previously described methods.     

Method for the determination of cerebral blood flow in conscious rabbits

A procedure for the determination of cerebral blood flow by the local clearance method after intracarotid injection of 133Xe in the conscious rabbit is described. The inert radioactive indicator is injected into a permanent nylon catheter equipped with a two-way Gordth's needle inserted into the common carotid artery and filled with heparin, emerging behind the shoulders of the animals. All branches of the homolateral common carotid artery except the internal carotid artery were ligated. Studies of the distribution of colored tracers (dark blue ink) and radioactive tracers (99mTc albumin microspheres) show that the main localization of the injected indicator is within the homolateral hemisphere. Brain to blood partition coefficients of 133Xe are worked out for rabbit's gray matter (0.576 +/- 0.048) and white matter (0.808 +/- 0.023). The slope method for first and second component of the wash-out Xenon curve is used for CBF calculations. CBF determinations in 9 normal rabbits result in 84.27 +/- 5.59 and 16.69 +/- 2.44 ml/min x 100 g tissue, respectively, for the fast and slow component. Significant changes do not occur in serial determinations within 2 hr.     

Regional cerebral blood flow during and after 2 hours of middle cerebral artery occlusion in the rat

In this study we explored if the secondary bioenergetic failure, which occurs a few hours after recirculation, following transient middle cerebral artery occlusion (MCAO) in rats, is caused by a compromised reflow. We induced 2 hours of MCAO and measured CBF at the end of the ischemia, as well as 15 minutes, 1, 2, and 4 hours after the start of recirculation, using autoradiographic or tissue sampling 14C-iodoantipyrine techniques. After 2 hours of MCAO, the autoradiographically measured CBF in the ischemic core areas was reduced to 3 to 5% of contralateral values. The reduction in CBF was less in neighboring, penumbral areas. After recirculation, flow already normalized in core tissues after 15 minutes, and remained close to normal for the 4 hours recirculation period studied. However, in penumbral tissues, recovery CBF values were usually below normal. The results show that tissues that are heavily compromised by the 2-hour period of ischemia and are destined to incur infarction, show a "relative hyperemia" during recirculation. In fact, some areas of the previously densely ischemic tissue showed overt hyperperfusion. This finding raises the question whether the relative or absolute hyperemia reflects events that are pathogenetically important. Because drugs that clearly ameliorate the final damage incurred fail to alter the relative hyperperfusion of previously ischemic tissues, it is concluded that vascular events in the reperfusion period do not play a major role in causing the final damage.     

Noninvasive quantitation of cerebral blood flow using oxygen-15-water and a dual-PET system

Measurement of the arterial input function is essential for quantitative assessment of physiological function in vivo using PET. However, frequent arterial blood sampling is invasive and labor intensive. Recently, a PET system has been developed that consists of two independent PET tomographs for simultaneously scanning the brain and heart, which should avoid the need for arterial blood sampling. The aim of this study was to validate noninvasive quantitation with this system for 15O-labeled compounds. METHODS: Twelve healthy volunteers underwent a series of PET studies after C15O inhalation and intravenous H2(15)O administration using a Headtome-V-Dual tomograph (Shimadzu Corp., Kyoto, Japan). The C15O study provided gated blood-pool images of the heart simultaneously with quantitative static blood-volume images of both the brain and heart. Weighted-integrated H2(15)O sinograms were acquired for estimating rate constant (K1) and distribution-volume (Vd) images in the brain, in addition to single-frame sinograms for estimating autoradiographic cerebral blood flow images. Noninvasive arterial input functions were determined from the heart scanner (left ventricular chamber) according to a previously developed model and compared directly to invasive input functions measured with an on-line beta probe in six subjects. RESULTS: The noninvasive input functions derived from this PET system were in good agreement with those obtained by continuous arterial blood sampling in all six subjects. There was good agreement between quantitative values obtained noninvasively and those using the invasive input function: average autoradiographic regional cerebral blood flow was 0.412 +/- 0.058 and 0.426 +/- 0.062 ml/min/g, K1 of H2(15)O was 0.416 +/- 0.073 and 0.420 +/- 0.067 ml/min/ml and Vd of H2(15)O was 0.800 +/- 0.080 and 0.830 +/- 0.070 ml/ml for the noninvasive and invasive input functions, respectively. In addition to the brain functional parameters, the system also simultaneously provided cardiac function such as regional myocardial blood flow (0.84 +/- 0.19 ml/min/g), left ventricular volume (132 +/- 22 mm at end diastole and 45 +/- 14 ml at end systole) and ejection fraction (66% +/- 5%). CONCLUSION: This PET system allows noninvasive quantitation in both the brain and heart simultaneously without arterial cannulation, and may prove useful in clinical research.     

Evaluation of cerebral blood flow and hemodynamic reserve in symptomatic moyamoya disease using stable Xenon-CT blood flow

Moyamoya disease is a vascular abnormality seen in children and adults characterized by progressive narrowing of the internal carotid, middle, anterior, and posterior cerebral arteries and the development of leptomeningeal and proximal internal carotid artery collaterals, which appear diaphanous on angiogram. Although adults tend to present with subarachnoid hemorrhage and children with ischemic events, the clinical sequelae in these two populations overlap. Expanding upon work done at this institution using stable xenon computer tomographic blood flow determinations with acetazolamide and carbon dioxide challenge to predict which population of patients with severe carotid disease and hemodynamic compromise would benefit from surgical intervention, we used similar rationale to determine which patients with moyamoya disease would likely benefit from revascularization. Data and outcome concerning four such patients make up the body of this report.     

Ceranapril and cerebral blood flow autoregulation

In order to investigate the levels of the polycyclic aromatic hydrocarbons, mainly benzo[a]pyrene because of its carcinogenicity, 55 samples of smoke flavour and smoked foods were analysed. The samples tested included 11 samples of liquid smoke flavour and 44 samples of smoked foods like bacon, loin, turkey, sausage, ox rib, etc. from different brands. A liquid chromatographic method was developed using a fluorescence detector. Benzo[a]pyrene was found in 73% of the liquid smoke flavour samples analysed. The levels varied from 0.1 to 336.6 micrograms/kg. Three liquid smoke flavour samples showed levels of benzo[a]pyrene above the maximum level recommended by FAO/WHO (10 micrograms/kg). From the total of 44 smoked food samples analysed, benzo(a)pyrene was detected in 23 samples (52%). The levels varied from 0.1 to 5.9 micrograms/kg. Anthracene and fluoranthene, non-carcinogenic polycyclic aromatic hydrocarbons, were found in almost all the samples analysed. Benzo[ghi]perylene, 3,4-benzofluoranthene and 1,2,3,4-dibenzopyrene were not found in any of the 55 samples analysed.     

Quantification of cerebral blood flow and partition coefficient using iodine-123-iodoamphetamine

The aim of this study was to develop a simple, noninvasive method for quantifying both regional cerebral blood flow (rCBF) and the partition coefficient (lambda) using N-isopropyl-p[123I]iodoamphetamine and SPECT. METHODS: By employing a two-compartment model (influx, K1: outflux, k2), a new method was introduced that requires two serial SPECT scans at 30 min and 60 min, and a single arterial sample 5 min after tracer injection. The integral of the arterial input function is inferred from the sample by using the correlation obtained from 25 subjects. Two original mathematical functions, phi for K1 and gamma for lambda (= K1/k2), were obtained from the input functions of 12 subjects. The values of K1 and lambda are determined from the two scans and the single arterial sample by using these functions. The values obtained for K1 (= rCBF) and lambda were compared with those obtained by nonlinear least-squares fitting analysis and the 133Xe inhalation SPECT method. RESULTS: K1 and lambda were in good agreement with the values obtained by nonlinear least-squares fitting analysis (r = 0.873 in K1 and r = 0.825 in lambda), and rCBF values were closely correlated with those obtained by the 133Xe method (r = 0.843). CONCLUSION: The proposed method has three advantages: (a) accurate, simultaneous quantification of both rCBF and the partition coefficient; (b) simplicity and noninvasiveness; and (c) a relatively short period (approximately 70 min) for the study.