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Biomedical subjects

R H Ackerman

Publications and source records attributed to R H Ackerman.

At least 37 records · Page 2Linked to original sources

Evaluation of the 11CO2 positron emission tomographic method for measuring brain pH. I. pH changes measured in states of altered PCO2.

The 11CO2 method for measuring local brain pH with positron emission tomography (PET) has been experimentally evaluated, testing the adequacy of the kinetic model and the ability of the method to measure changes in brain pH. Plasma and tissue time/activity curves measured during and following continuous inhalation of 11CO2 were fit with a kinetic model that includes effects of tissue pH, blood flow, and fixation of CO2 into compounds other than dissolved gas and bicarbonate ions. For each of ten dogs, brain pH was measured with PET at two values of PaCO2 (range 21-67 mm Hg). The kinetic model fit the data well during both inhalation and washout of the label, with residual root mean square (RMS) deviations of the model from the measurements consistent with the statistical quality of the PET data. Brain pH calculated from the PET data shows a linear variation with log(PaCO2). These results were in good agreement with previously reported measurements of brain pH, both in absolute value and in variation with PCO2. The interpretation of these pH values in normal and pathological states is discussed.

Administration, Intranasal↗

N-[11C-Methyl]chlorphentermine and N,N-[11C-dimethyl]chlorphentermine as brain blood-flow agents for positron emission tomography.

N-[11C-methyl]chlorphentermine ([11C]NMCP) and N,N-[11C-dimethyl]chlorphentermine ([11C]NDMCP) were prepared from chlorphentermine and 11CH3I in DMF and evaluated in rats as brain blood-flow agents for positron emission tomography (PET). Tissue distribution of [11C]NMCP showed that brain uptake was 2.70 +/- 0.40% of injected dose per organ at 5 min with no change in radioactivity concentration up to 30 min after i.v. injection. Approximately 80% of the initial brain uptake remained at 60 min. On the other hand, initial brain uptake of [11C] NDMCP (3.66 +/- 0.31 and 3.63 +/- 0.88% injected dose per organ at 5 and 15 min, respectively) was greater than that of [11C]NMCP. The brain activity however, rapidly decreased to 2.38 +/- 0.17 and 1.82 +/- 0.32% at 30 and 60 min, respectively. Because of its longer retention in the brain compared with [11C]NDMCP, [11C]NMCP would be a potential brain blood-flow agent for quantitative PET studies.

Animals↗

Analysis of some errors in the measurement of oxygen extraction and oxygen consumption by the equilibrium inhalation method.

Some sources of error in the equilibrium inhalation method for the measurement of oxygen extraction fraction and CMRO2 by positron emission computed tomography scanning have been evaluated by computer simulation. Emphasis has been placed on errors that have not been thoroughly studied in past work. These include effects of random statistical errors, systematic errors in arterial blood radioactivity concentrations, and errors due to perturbations of the equilibrium state, to tissue inhomogeneity, and to subject motion.

Blood Volume↗

Positron imaging in ischemic stroke disease.

Positron emission tomography (PET) is well suited to the study of ischemic stroke disease. It has the potential to help elucidate pathophysiological mechanisms, differentiate viable from nonviable tissue, and provide a more rational basis for developing specific therapies for ischemic lesions. The different tracer strategies that may be applied to the study of ischemic disease, however, all have relative limitations, which may be related to the physical or biological determinants of the tracer distributions, to the tracer half-lives, or to the methods required for quantitation of the data. Determination of blood flow and oxygen metabolism are useful for characterizing stroke lesions, but other parameters, such as the oxygen extraction fraction, blood volume, and glucose metabolism, can provide important interpretative information. Correlation of the physiological PET data with the clinical presentation and course is a primary requisite for the development of the full potential of PET.

Adult↗

Comparison of 2- and 3-18F-fluoro-deoxy-D-glucose for studies of tissue metabolism.

2- and 3-18F-fluoro-deoxy-D-glucose were proposed as sugar analogs to study glucose metabolism in brain and heart tissues. To evaluate their usefulness, the in vivo behavior of 2- 28FDG and 3-18FDG was investigated in mice and rats and for 3-18FDG in dogs at various times post-injection. Positron emission tomographic (PET) imaging was performed for heart and brain of anesthetized dogs with both radiopharmaceuticals. In all species studied, a higher uptake in brain, heart and kidney was observed for 2-18FDG compared with 3-18FDG. Radioactivity also cleared blood and liver more rapidly with 2-18FDG than with 3-18FDG. Estimates of brain kinetic model parameters revealed the metabolic trapping of 2-18FDG, making this agent favorable for studies of tissue metabolism, and the relative lack of phosphorylation of 3-18FDG, which makes it a potential agent for studies of glucose transport.

Animals↗

Measurement of brain pH using 11CO2 and positron emission tomography.

We have examined the feasibility of measuring local brain pH in vivo with 11CO2 and positron emission tomography. In particular, we have addressed two objections that have been raised against this method: the assumed need to estimate local tissue PCO2 and the rapid fixation of 11C in tissue. From a reexamination of the basic theory, we argue that after administration of 11CO2 the time-dependent distribution of 11C between tissue and blood is independent of the distribution of CO2 already in the body, making it unnecessary to estimate local tissue PCO2. Assuming that the blood--brain barrier is impermeable to bicarbonate ions, there will be equal partial pressures of 11CO2 in blood and tissue at equilibrium. To overcome the problem of fixation in the tissue we have developed a kinetic model of the time-dependent distribution of 11C that accounts for regional variations in blood flow, CO2 extraction, pH, and rate of fixation. The values of the model parameters can be estimated from sequential measurements of tissue activity concentration during administration of 11CO2. Tissue pH can then be calculated from one of the parameter values, a measurement of arterial pH, and known constants. Numerical calculations based on the kinetic model with assumed values of the parameters were used to optimize the experimental design. The calculations show that problems with fixation are much less severe with continuous infusion of activity than with bolus administration. During infusion the tissue curve depends strongly on tissue pH but only weakly on the rate of fixation.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain↗

Strategy for the measurement of regional cerebral blood flow using short-lived tracers and emission tomography.

This report describes a strategy for measurement of regional CBF that rigorously accounts for differing tracer partition coefficients and recirculation, and is convenient for use with positron emission tomography. Based on the Kety model, the measured tissue concentration can be expressed in terms of the arterial concentration, the rate constant K, and the blood flow f. The local partition coefficient may be computed as p = f/K. In our approach, maps of K and f are computed from two transverse section reconstructions. The reconstructions are based on weighted sums of projection data measured frequently during the observation period. Theoretical studies of noise propagation in the estimates of K and f were carried out as a function of tomographic count rate, total measurement time, and tracer half-life for varying input functions. These calculations predict that statistical errors in f of between 5 and 10% at a resolution of 1 cm full width at half maximum can be obtained with existing tomographs following i.v. injection. To compare theory and experiment, a series of flow studies were carried out in phantoms using a positron tomograph. These measurements demonstrate close agreement between computed flow and noise estimates and those measured in a controlled situation. This close agreement between theory and experiment as well as the low statistical errors observed suggest that this approach may be a useful tool in clinical investigation.

Cerebrovascular Circulation↗

Temporary neurological deterioration after extracranial-intracranial bypass.

Five patients who experienced temporary neurological deterioration after extracranial to intracranial bypass procedures are reported in detail. These patients suffered transient ischemic attacks or more prolonged deficits usually of a different nature than the preoperative symptoms. All patients had a good outcome and the spells ceased; the neurological deficits improved within a maximum of 2 weeks. Obvious causes of deterioration such as intra- or extracerebral hematomas, occlusion of a previously stenotic vessel, or graft occlusion were ruled out by computed tomography and angiography in each case. Intraoperative causes of neurological deterioration such as anesthetic effect, hypotension, and temporary occlusion of the cortical vessel or sacrifice of its small branches were not likely to be the cause of the deficits because in each case, the patient awoke satisfactorily and deterioration occurred hours to days later. In each case, postoperative angiography showed good perfusion of at least one major division of the middle cerebral territory. Anticoagulation with heparin in three patients did not change the clinical course. In one patient who was not anticoagulated, embolism could have been responsible for a single prolonged ischemic event, but in the other patients thromboembolism does not seem likely to have been responsible for the deficits. The cause of the deterioration in these patients remains unexplained. We speculate that hyperperfusion of chronically ischemic brain tissue and shifts in the watershed region resulting from the new flow pattern after bypass grafting are two mechanisms that may have been of importance in the etiology of these deficits.

Aged↗

Brain uptake and organ distribution of 11C from 11C-labeled glucose.

The time course of the distribution of carbon-11 (11C, t1/2 = 20.4 min) in brain after the i.v. administration of 11C-labeled glucose [( 11C]glucose) was studied in an effort to understand and explore its behavior in relation to the known factors concerning the catabolic fate of glucose carbon in the brain. The biodistribution of 11C from [11C]glucose was studied in rats using organ dissection. Human radiation doses were estimated from rat biodistribution data. All the rat organs except the brain cleared with a half time of 30-60 min. The brain showed delayed uptake that plateaued from 20 to 60 min. The 11C distribution in normal, non-ischemic, brain 30 min after intravenously administered [11C]glucose is due to labeled carbon incorporation into amino acids associated with tricarboxylic acid cycle intermediates. External imaging with the Massachusetts General Hospital positron camera, PC I, was performed in dogs and humans and the time course of 11C incorporation was similar to the rat brain results. Regional uptake paralleled known metabolic differences between grey and white matter in normal human volunteers. A patient with progressive dementia had less uptake in an area of decreased perfusion as demonstrated angiographically, suggesting that the image obtained 20 min after tracer administration could be used to detect abnormalities in cerebral metabolism due to pathology.

Adult↗

Quantitation of regional cerebral glucose metabolism.

Kinetic analysis of 18F-labeled 2-fluoro-2-deoxy-D-glucose (2FDG) has been carried out in 28 studies on 25 subjects. The object of the analysis was to determine the practical problems of quantitation of glucose metabolic rate (GMR) using the Sokoloff model with 2FDG. We found that arterial and venous plasma concentration of 2FDG yielded equivalent values of the integrated plasma concentration (IPC*) and that one arterial or venous plasma sample at 30 min serves to predict IPC* to within +/- 7%. These observations suggest that quantitation is indeed possible in such subjects without using complex arterial or venous sampling procedures. The average values of K1, K2, and K3 are observed to be 0.14 +/- 0.08, 0.20 +/- 0.10, and 0.030 +/- 0.012 min-1. The data are consistent with a value of lumped constant of 0.4 and a considerable spread in global values of GMR (30%) in an unselected group of subjects.

Blood Glucose↗

Cerebral blood flow and cerebrovascular CO2 reactivity in stroke-age normal controls.

We used the noninvasive 133-xenon inhalation technique to determine cerebral hemodynamics in 55 normal volunteers aged 18 to 88. Values for cerebral blood flow and cerebrovascular CO2 reactivity in fast-clearing tissue (flow gray) and slow-clearing tissue (flow white) were examined as functions of age and in relation to hematocrit, blood pressure, and evidence of extracranial vascular disease. Flow gray declined linearly with age, but no corresponding change was found in flow white or in CO2 reactivity. The data suggest that the progressive fall in flow gray is due to a physiologic aging process.

Adolescent↗

Positron brain imaging--normal patterns and asymmetries.

Regional brain physiology was investigated in 11 normal resting right-handed subjects using positron emission tomography. Cerebral blood flow was studied in all subjects. Cerebral oxygen metabolism was studied in six subjects, and cerebral glucose metabolism was also studied in one subject. In five subjects, physiological activity was higher in left frontotemporal regions than right. These findings may be related to structural cerebral asymmetries or to activation of brain language centers.

Adult↗

Positron imaging in ischemic stroke disease using compounds labeled with oxygen 15. Initial results of clinicophysiologic correlations.

Initial results in over 50 patients with stroke suggest that positron images made during continuous inhalation of carbon dioxide labeled with oxygen 15 and molecular oxygen labeled with oxygen 15 provide data on tissue function that may be relevant to acute stroke management. Five cases illustrate the following findings: 15O-activity patterns observed in areas of ischemic injury or infarction are what one would expect if the 15O distributions represented physiologic functions, such as cerebral blood flow and metabolism. Areas of abnormal 15O activity correlate with the clinical or computed tomographic (CT) localization of the deficit. In studies performed acutely, changes in 15O distributions anticipate alterations in CT scans and may be predictive of outcome. Data related to oxygen metabolism correlate better with tissue viability than do those reflecting cerebral blood flow.

Aged↗

F-18-labeled 3-deoxy-3-fluoro-D-glucose for the study of regional metabolism in the brain and heart.

Glucose is the major physiological substrate of the brain and an important physiological substrate for the myocardium. [19F]fluoro-3-deoxy-glucose [3-FDG(F-18)] was studied to determine whether it is a suitable tracer for evaluating the metabolic function of the brain and myocardium. 3-FDG(F-18) was rapidly accumulated in the mouse myocardium (10-12% injected dose/g) and remained constant up to 120 min. Blood, liver, and lung activities exhibited a rapid accumulation of activity (4% injected dose/g) at 1 min, followed by elimination of activity up to 30 min (2% injected dose/g), and then remaining unchanged for a period of 120 min. The arterial blood curve in the dog was fit best by three exponential components (T 1/2 = 0.52 min, 2.75 min, and 142.8 min). Transverse-section images were obtained of the dog's brain and myocardium. From sequential two-dimensional images, a clearance half-time of 26.88 min was determined for the canine brain. Radiation doses for man were calculated from tissue distribution data for mice.

Animals↗