Age-related norms for the regional cerebral blood flow (rCBF) response to Diamox (acetazolamide) were based on studies of 55 normal subjects at rest and on studies of 33 of these 55 normal subjects following an intravenous injection of Diamox (22 mg/kg). After the Diamox injection, rCBF increased at all locations measured in all subjects. On average, rCBF increased 1.7 times. The following were found for rCBF in both resting and Diamox-treated subjects: 1) rCBF decreased significantly with increasing age; 2) slope and intercept for the regression of rCBF on age were largest for frontal detectors, intermediate for parietal detectors, and smallest for occipital detectors; 3) rCBF hyperfrontality was most noticeable in younger subjects; 4) in subjects of any age, 95% confidence intervals for rCBF were relatively large (expected value +/- 30%) and lower 95% confidence intervals for Diamox rCBF tended to overlap the upper 95% confidence intervals for resting rCBF; and 5) side-to-side percentage difference in rCBF did not have a significant regression on age and tended to be less than 10% to 20%. Diamox did not have an important effect on blood pressure, pulse rate, or respiratory rate. The normative data for the rCBF response to Diamox was used in evaluating 20 patients with cerebrovascular disease. Forty percent of these patients, all of whom exhibited angiographic evidence of potentially hemodynamically significant lesions, had normal rCBF at rest and after Diamox injection. Twenty percent had normal resting flows with abnormal Diamox-activated flows. Asymmetry in rCBF was the most sensitive indicator of a potential abnormality in cerebral perfusion. Thirty percent of the abnormal studies showed only significant asymmetry. It is suggested that rCBF studies at rest and after Diamox treatment, with age-related norms, may be useful in the management of patients with cerebrovascular disease.
Relative to other approaches that have been recommended, fitting all head data, solving for a time shift, and including an air passage artifact term in the model significantly improved the estimate of gray matter blood flow by the inhalation technique. A robust algorithm, which incorporates these features, has been developed. Formulas which facilitate implementation of this algorithm are reported. An artifact from large scalp arteries was not significant and does not need to be included in the model. (Stroke 1987; 18:495-502) W E report experiments designed to answer the following questions regarding calculation of regional cerebral blood flow (rCBF) by the inhalation method: 1) Does solving for the time shift (At) between the head and expired alveolar time-activity curves decrease the bias in the estimate of rCBF? 2) Do an air passage artifact (APA) and an arterial artifact (AA) exist physiologically? 3) If APA and AA exist, does including them in the model improve the estimate of rCBF? 4) If APA exists and must be accounted for in the model, does fitting all head data with a model containing an APA term improve the estimate of rCBF compared to a delayed-start fit? Studies investigating these questions have led to the development of a robust new rCBF algorithm that has been demonstrated to improve estimates of rCBF compared with approaches that have been employed in the past. Overview of the Approach for Determination of Regional Gray Matter Flow by Xenon-133 InhalationAssumptions based on the Fick principle and a model containing two tissue compartments and artifact terms lead to the equation for expected head counts, h(tj), at any time, tj, as:where A,, v (t) = time-activity curve for radionuclide in expired alveolar gas sampled from the mouth and measured at time t, At = time subtracted from head times (t,,) so that A llv (t h -At) coincides in time with the Received August 2, 1985; accepted October 14, 1986. arterial input function at t,,, k, = rate constant for jth compartment, Xj = partition coefficient for tracer in jth compartment, Wj = fractional weight of jth compartment, a = constant scaling A,, v (t) to the arterial input function for each tissue compartment, P t = WjlcjO/X-j for J = 1,2, and P, = constant determining artifact magnitude for J = 3,...x.'~7 The first artifact term is APA, multiplied by the linear scaling factor P 3 , and the second artifact is AA, multiplied by the linear scaling factor P 4 . The usual approach to finding k, for the calculation of gray matter flow is to apply least-squares criteria, where the set or a subset of the parameters Q = {k,, k 2 , P,, P 2 , ••• P,, At} is found that minimizes the sum of the squares of the residuals (S) between the measured and expected head curves.where H(t,) = measured head counts at time t,, h(t,) = expected head counts at time t,, and n = number of data points in the measured head curve. Considering both artifacts, Equation 1 contains 7 parameters (k,, k 2 , P,, P 2 , P 3 , P 4 , and At). Two-compartment analysis solving for k,, k 2 , ...
When calculating cerebral blood flow by the inhalation regional cerebral blood flow technique, radionuclide activity associated with exhaled alveolar gas is used to represent the arterial input function for each brain region. In this study, tidal CO2 data are used to identify respiratory gas samples that contain alveolar gas. Traditional methods identify alveolar gas samples by searching for maxima and minima in the raw air curve. The raw air curve is determined by sequentially counting radionuclide activity in respiratory gases sampled at the mouth. Traditional methods sometimes erroneously identify and use maxima or minima that do not represent alveolar gas. The use of CO2 data is advantageous since the range of CO2 during exhalation can identify those exhalations that approach the functional reserve capacity and hence represent alveolar gas. The arterial input function is represented by counting intervals from the raw air curve which coincide with exhalation of alveolar gas as identified by CO2 data. This approach for representing the arterial input function is fully automatic, accurate, and reproducible.
With 14C-labeled dextran as the tracer, studies of the original configuration of spinal recirculatory perfusion and the original model for data analysis demonstrated that this approach does not yield acceptable accuracy in determining cerebrospinal fluid (CSF) formation (Fcsf) and absorption (Acsf) rates. A significant component of this error was due to the fact that the method of data analysis used originally is not based on a realistic mathematical model of the system. A more realistic mathematical model resulted in two simultaneous differential equations that did not have simple analytical solutions and, therefore, could not be used easily for data analysis. By computer simulation, a comparison of the more realistic model with the original model demonstrated that, under ideal conditions, there was a 10% error inherent in the original data analysis method. In the experimental setting, the magnitude of this inherent error is probably 20%. There were three other major problems with the original system: (a) one could not tell when enough data had been collected to ensure convergence of the data analysis algorithm; (b) calibration of the syringe pump in the external circuit was not accurate for short infusion periods; and (c) the presence of the syringe in the external circuit unnecessarily lengthened the period of nonhomogeneous mixing. A new system configuration and new data analysis methods have been developed. In the new system, the syringe is removed from the external circuit and intracranial pressure is controlled by infusion from a separate reservoir where the pressure head is maintained at any desired level by feedback control. Spectrophotometry is used to measure tracer concentration in the external circuit. Data collection and analysis are fully automated under computer control so that, during an experimental run, the investigators are updated at 1- to 2-second intervals as to the convergence of the data analysis routine. Data analysis methods for the new system are superior to previous methods because the models are realistic and no extrapolation is required. In addition, all of the data during the initial period of nonhomogeneous mixing are used to calculate Fcsf and Acsf. With the new system and a simple phantom of the CSF system, the mean error in finding Acsf was 1.7 +/- 1.2% for 27 determinations covering a wide range of absorption rates. Fcsf could be determined to within 0.001 ml/minute. In up to six sequential pressure plateaus, the magnitude of error did not increase with each subsequent run.(ABSTRACT TRUNCATED AT 400 WORDS)
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