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Biomedical subjects

N M Alpert

Publications and source records attributed to N M Alpert.

At least 109 records · Page 6Linked to original sources
PubMed1989

Evaluation of the 11CO2 positron emission tomographic method for measuring brain pH. II. Quantitative pH mapping in patients with ischemic cerebrovascular diseases.

A practical method has been developed that, using 11CO2 and positron emission tomography (PET), computes and maps (a) "effective pH" (pHt), a weighted average of intra- and extracellular pH, and (b) "clearance" (K1), product of blood flow and 11CO2 extraction. This method, together with measurements of cerebral blood flow (CBF) and oxygen extraction fraction (OEF), was applied to 12 patients with cerebral ischemia or stroke. The regional K1 was positively correlated with CBF (n = +0.78). The k1/CBF ratio, representing the extraction fraction ratio of 11CO2 to H2 15O, was negatively correlated with CBF (r = -0.54), suggesting that 11CO2 extraction decreases as flow increases. In five acute stroke patients within 2 days of onset, the injured cortex had lower CBF (20.6 ml/min/100 g), higher OEF (78.1%), and lower pHt (6.96) than the contralateral cortex (CBF = 41.4 ml/min/100 g, OEF = 53.3%, pHt = 7.00), suggesting intracellular acidosis with intact cell membranes. In three stroke patients 5-8 days after onset, the injured cortex had higher CBF (60.9 ml/min/100 g), lower OEF (32.0%), and higher pHt (7.12) than the contralateral cortex (CBF = 45.3 ml/min/100 g, OEF = 58.0%, pHt = 7.06), which suggested an increase in extracellular volume compartment reflecting loss of cell membrane integrity. This method provides information on the regional tissue acid-base status and cell membrane integrity, which may be prognostic of tissue viability.

Adult↗
PubMed1988

Synthesis and degradation of collagens in skin of healthy and protein-malnourished rats in vivo, studied by 18O2 labelling.

To explore the effects of growth retardation, caused by restricted protein intake, on collagen turnover in the whole skin, Sprague-Dawley rats (n = 20) were labelled with 18O2 and fed on either an adequate (18%) or a low (3%) lactalbumin diet. Skin biopsies were obtained at intervals during the following 6 months. Independent groups of animals (n = 186) were used to determine the size of the 0.5 M-acetic acid-soluble and -insoluble collagen pools in the entire skin of healthy and malnourished rats. Collagen was estimated by measurement of hydroxyproline. Soluble-collagen synthesis rates were equivalent to 99 +/- 8 mumol of hydroxyproline/day in healthy animals and 11 +/- 2 mumol/day in malnourished rats. Insoluble-collagen synthesis rates were 32 and 5 mumol of hydroxyproline/day in the healthy and protein-depleted rats respectively. The degradation of soluble collagen amounted to 37 +/- 8 and 6 +/- 2 mumol of hydroxyproline/day in the healthy and malnourished groups respectively. Efflux of collagen from the soluble collagen, defined as the sum of the rate of soluble collagen that is degraded plus that which matures into insoluble collagen, was 70 +/- 8 and 11 +/- 2 mumol of hydroxyproline/day in the healthy and malnourished groups respectively. Insoluble collagen was not degraded in either group. The fraction of soluble collagen leaving the pool that was converted into insoluble collagen was 0.46 in both diet groups. It is concluded that the turnover of soluble collagen is markedly decreased with malnutrition, but degradation and conversion into insoluble collagen account for the same proportions of efflux from the soluble-collagen pool as in rapidly growing rats.

Animals↗
PubMed1988

The 15O steady-state method: correction for variation in arterial concentration.

One of the factors limiting the accuracy of the 15O steady-state method for the measurement of regional cerebral blood flow and oxygen metabolism is the requirement that a constant arterial blood concentration be maintained over long periods. A new method has been developed to correct for the variation of the arterial concentration in the C15O2 and 15O2 steady-state inhalation technique. The time course of the arterial activity is obtained by multiple sampling over the study period. The same 15O model as is used in the steady-state method is employed but is solved without assuming equilibrium. Look-up tables are generated to relate flow and oxygen extraction fraction to tissue activity, and from them the regional parameters are estimated. Theory and simulation studies suggest that substantial improvement in accuracy can be obtained with no increase in statistical error. The validity of the method was checked experimentally by making repeated measurements in the same subject after perturbing the gas delivery. The conventional steady-state method showed significantly larger deviations in repeat measurement than did the new method. Thus, it is concluded that the proposed method is superior.

Adult↗
PubMed1988

Measurement of end-capillary PO2 with positron emission tomography.

The analysis of positron emission tomography measurements of oxygen metabolism has been extended to provide a quantitative estimate of end-capillary PO2. The principle of this extension rests on the idea that the oxygen extraction fraction can be used to calculate the end-capillary oxygen saturation of the blood. The relation between oxygen saturation and PO2 is obtained through the oxygen dissociation curve. Our studies show that in addition to the local oxygen extraction fraction, arterial PO2 and pH values are needed in the calculation, whereas fairly large variations in factors such as PCO2, hematocrit, hemoglobin, and plasma protein levels have little or no effect. Rough estimates of end-capillary PO2 can be made using standard O2 dissociation nomograms. Blood gas and acid-base properties of blood have been known for decades, making it possible to account accurately for individual differences that may be encountered when studying patients. Measurements in nine normal subjects yielded a mean end-capillary PO2 value of 31.2 mm Hg. The ability to make a quantitative visualization of altered patterns of end-capillary PO2 provides an additional dimension to the investigation of stroke disease and tumor metabolism.

Blood Gas Analysis↗
PubMed1988

The effect of captopril on renal blood flow in renal artery stenosis assessed by positron tomography with rubidium-82.

The sequence and magnitude of acute changes in renal blood flow following administration of captopril were determined in a canine model of acute unilateral renal artery stenosis using rubidium-82 and positron emission tomography. Data were recorded in each of nine dogs under three conditions: 1) during a baseline control interval, 2) during renal artery stenosis, and 3) during stenosis with intravenous injection of captopril (1.2 mg/kg). Mean arterial blood pressure was 108 +/- 12 mm Hg at control, increased significantly to 125 +/- 13 mm Hg (p less than 0.01) during stenosis, and decreased to 98 +/- 13 mm/Hg (p less than 0.01) after captopril infusion. Mean renal blood flow was calculated using a steady state single compartment model from the images produced by positron emission tomography. The estimated flow to the affected kidney was 3.37 +/- 1.48 ml/min/g at control, 0.86 +/- 0.62 ml/min/g during stenosis (p less than 0.01), and 0.64 +/- 0.57 ml/min/g after captopril administration (p = NS compared with precaptopril value). The estimated flow to the contralateral kidney was minimally reduced from a baseline of 3.84 +/- 0.95 to 3.24 +/- 1.13 ml/min/g (p = NS) during stenosis and increased after captopril infusion (4.08 +/- 0.94 ml/min/g; p = 0.01). These data suggest that repetitive imaging with positron emission tomography can be used to delineate acute changes in renal perfusion following captopril administration.

Animals↗
PubMed1987

Measurement of both left ventricular function and regional myocardial perfusion with 133Xe in dogs.

A technique to measure left ventricular (LV) function and myocardial perfusion was validated in 12 dogs. 133Xe in saline was injected into the left atrium (LA) or LV and two data sets were obtained using gamma camera imaging: 1) A first pass gated scan for LV function; followed by 2) Sequential images for regional myocardial perfusion. LV ejection fraction and wall motion measurements from the 133Xe blood pool images were compared to ejection fraction (r = 0.88, P less than 0.01) and wall motion (r = 0.83, P less than 0.01) data from 99mTc labeled blood pool scans. The perfusion measurements obtained with the 133Xe method were compared to microsphere data (r = 0.79, P less than 0.01). Measurements after LV 133Xe injection were similar to data following LA injection. Thus, quantitative assessment of global LV function, regional wall motion and myocardial perfusion is possible with LA or LV 133Xe injection and gamma camera imaging.

Animals↗
PubMed1987

Evolutionary changes in left and right ventricular function in acute myocardial infarction.

To determine the evolutionary changes in right and left ventricular function in acute myocardial infarction, 3 serial gated blood pool scans were performed in 76 patients within 24 hours (24 H), at 10 days (10 D) and 3 months (3 M) following the onset of myocardial infarction. The patients were divided into 3 groups: ANT (anterior MI), INF (inferior MI without right ventricular dysfunction) and RVF (inferior MI with right ventricular dysfunction). LVEF in ANT was significantly lower than that of INF and RVF at 24 H, 10 D and 3 M. The ratio of right ventricular volume to LV volume (RVV/LVV) was compared among 3 groups. The mean values of RVV/LVV in RVF were 1.3 through 24 H and 3 M and they were significantly higher than the other two groups. The RVV/LVV in ANT and INF were around 1.0. LVEDVI in RVF was rather smaller than that of ANT and INF. LVESVI in ANT at 24 H was significantly larger than that of INF and RVF and the mean value of LVESVI in ANT were around 60 ml/M2 from 24 H to 3 M. LVEF in ANT, RVF and INF did not increase significantly during peak exercise at 3 M. However, quantitative regional wall motion analysis revealed that regional wall motion of R2 (posterolateral wall motion) in ANT and R5 (septal wall motion) in INF decreased significantly during peak exercise. These impairments in regional wall motion might be due to the exacerbation of ischemia of non-infarcted area.

Adult↗
PubMed1987

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↗
PubMed1987

Relative and absolute changes in soluble and insoluble collagen pool size in skin during normal growth and with dietary protein restriction in rats.

Absolute and relative changes in 0.5M acetic acid soluble and insoluble collagen were followed in the whole skins of young rats fed an adequate diet (18% lactalbumin) for 495 days (n = 92) and a low-protein (3% lactalbumin) diet for 210 days (n = 94). In well-nourished rats, the soluble collagen pool size reached a maximum at approximately 100-140 days of age whereas the insoluble pool tended to increase throughout the period of observation. Thus, the percent soluble collagen increased to a maximum of approximately 80% of total collagen at 40-50 days, thereafter declining progressively to about 20% by 495 days. In contrast, the size of the soluble collagen pool remained constant in protein-restricted rats, but with insoluble collagen increasing linearly throughout, although achieving only a level of about 1/6th of that reached in well-nourished rats. In the restricted rats, percent soluble collagen decreased rapidly and remained at about 25% of total between 80 and 210 days. These data were used to develop prediction equations for the size (mumoles hydroxyproline) of the soluble and insoluble collagen pools in healthy and protein-restricted rats. Hence, where A = days of age, the equations were, respectively: 0.414 X 10(-3) A - 0.390 A2 + 86.9 A - 1800; 0.262 X 10(-2) A3 + 0.793 A2 - 26.5 A + 272; 0.236 A + 155; and 5.07 A - 38.5. These findings are discussed with reference to possible mechanisms responsible for conversion of soluble to insoluble collagens in skin of well-nourished and growth-retarded rats.

Aging↗
PubMed1986

Serial analysis of renal blood flow by positron tomography with rubidium-82.

To determine whether renal blood flow can be measured by positron-emission tomography (PET) during constant infusion of rubidium-82 (82Rb) using a steady-state kinetic model, studies were performed in 10 dogs at control (n = 10), during mild flow reduction (n = 7), during severe flow reduction (n = 10), and after reperfusion of the kidney (n = 3). PET data were quantified to determine mean concentration of 82Rb (Ct) in each transverse section of the kidney. The arterial concentration (Ca) of 82Rb was measured by well counting of arterial blood samples during the equilibrium scan. 82Rb renal uptake (Ct/Ca) correlated nonlinearly with microsphere renal blood flow according to a steady-state kinetic model (r = 0.90). 82Rb estimated flow was 3.16 +/- 1.36 ml X min-1 X g-1 at control and 1.56 +/- 0.57 and 0.37 +/- 0.59 during mild and severe flow reductions, respectively. Microsphere determined flow was 2.89 +/- 0.77 ml X min-1 X g-1 at control, 1.58 +/- 0.42 at mild reduction, and 0.27 +/- 0.49 at severe reduction. In the occlusion and reperfusion model, the 82Rb estimated flow during occlusion was 0.21 +/- 0.15 ml X min-1 X g-1 and on reperfusion went up to 2.13 +/- 1.08. The contralateral kidney demonstrated reductions in the 82Rb estimated flow of 3.02 +/- 1.62 ml X min-1 X g-1 (63%) and 2.92 +/- 0.89 (61%) during mild and severe flow reductions, respectively. We conclude that PET with 82Rb permits serial quantitative assessment of renal flood flow.

Animals↗
PubMed1986

[11C]MPTP: a potential tracer for Parkinson's disease research in laboratory animals.

[11C]-1-Methyl-4-phenyl-1,2,5,6-tetrahydropyridine ([11C]MPTP), a compound producing parkinson-like symptoms in several species, has been synthesized and purified in sufficient activity to obtain tomographic images in the monkey. Biodistribution data has also been obtained in rats. Carbon-11-labeled MPTP could be used as a probe to study the pharmacokinetics of the compound under various research conditions in animals. Because of its neurotoxicity, the compound is not intended for use in humans.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1985

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↗
PubMed1985

Positron emission tomography in cardiology.

This article reviews the basis of PET imaging and current applications to cardiology. Included is a discussion of physical principles, detectors, quantitative estimation of regional radioactivity concentrations, radiopharmaceuticals, and application to flow and metabolism measurements in the myocardium.

Amino Acids↗
PubMed1984

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↗
PubMed1984

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↗
PubMed1984

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↗
PubMed1984

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↗