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Biomedical subjects

M A Mintun

Publications and source records attributed to M A Mintun.

At least 73 records · Page 4Linked to original sources
PubMed1985

Regional lung water and hematocrit determined by positron emission tomography.

We have measured with positron emission tomography (PET) the regional distribution of extravascular lung water (EVLW) and hematocrit (HctL) in normal supine dogs. H2(15)O and C15O were used as total lung water (TLW) and intravascular water (IVW) compartment labels, respectively. An additional plasma volume label (68Ga-transferrin) was used to determine regional HctL. EVLW was calculated as the difference between TLW and IVW. In 13 dogs, EVLW was relatively constant along a gravity-dependent vertical gradient, although values in the most anterior regions were statistically less (P less than 0.05) than those in more posterior ones. The average value for EVLW (13 dogs) was 14.4 +/- 2.5 ml H2O/100 ml lung. When EVLW was compared with IVW on a regional basis, the EVLW/IVW ratio decreased significantly in a gravity-dependent direction from 1.95 +/- 0.28 to 0.88 +/- 0.18. In 7 dogs, no significant difference between HctL and systemic hematocrit (average ratio 1.01 +/- 0.08) was found nor was any significant variation of HctL within the lung detected. Thus, in contrast to gravimetric techniques, a hematocrit correction does not appear to be necessary when regional EVLW is studied by PET.

Animals↗
PubMed1985

Regional cerebral blood flow and metabolism in reversible ischemia due to vasospasm. Determination by positron emission tomography.

Regional cerebral blood flow (rCBF) and regional cerebral metabolic rate of oxygen (rCMRO2) were measured by positron emission tomography (PET) in four patients with subarachnoid hemorrhage and hemiparesis due to cerebral vasospasm. With resolution of the vasospasm, two patients recovered and two remained hemiparetic. Contralateral to the hemiparesis, rCBF was slightly higher in the two patients who eventually recovered (15.0 and 16.2 ml/100 gm/min) than in the two who remained hemiparetic (12.0 and 11.7 ml/100 gm/min). The rCMRO2 measurements showed similar differences, with values of 1.34 and 2.60 ml/100 gm/min in the patients who recovered, and 0.72 and 1.66 ml/100 gm/min in those who did not. These preliminary findings indicate that with PET studies it may be possible to prospectively differentiate patients with neurological deficits due to reversible ischemia from patients with irreversible infarction.

Adult↗
PubMed1985

Brain oxygen utilization measured with oxygen-15 radiotracers and positron emission tomography: generation of metabolic images.

We recently described a PET method for the measurement of local brain tissue oxygen extraction (E) and the local cerebral metabolic rate for oxygen (CMRO2) using 15O-labeled radiotracers. The equation for the calculation of E from measured PET data is mathematically complex and its direct application in the generation of PET images of either E or the CMRO2 on a pixel-by-pixel basis is computationally burdensome. We describe a simplification of this equation which permits the efficient generation of quantitative images.

Brain↗
PubMed1984

A quantitative model for the in vivo assessment of drug binding sites with positron emission tomography.

We propose an in vivo method for use with positron emission tomography (PET) that results in a quantitative characterization of neuroleptic binding sites using radiolabeled spiperone. The data are analyzed using a mathematical model that describes transport, nonspecific binding, and specific binding in the brain. The model demonstrates that the receptor quantities Bmax (i.e., the number of binding sites) and KD-1 (i.e., the binding affinity) are not separably ascertainable with tracer methodology in human subjects. We have, therefore, introduced a new term, the binding potential, equivalent to the product BmaxKD-1, which reflects the capacity of a given tissue, or region of a tissue, for ligand-binding site interaction. The procedure for obtaining these measurements is illustrated with data from sequential PET scans of baboons after intravenous injection of carrier-added [18F]spiperone. From these data we estimate the brain tissue nonspecific binding of spiperone to be in the range of 94.2 to 95.3%, and the regional brain spiperone permeability (measured as the permeability-surface area product) to be in the range of 0.025 to 0.036 cm3/(s X ml). The binding potential of the striatum ranged from 17.4 to 21.6; these in vivo estimates compare favorably to in vitro values in the literature. To our knowledge this represents the first direct evidence that PET can be used to characterize quantitatively, locally and in vivo, drug binding sites in brain. The ability to make such measurements with PET should permit the detailed investigation of diseases thought to result from disorders of receptor function.

Animals↗
PubMed1984

A noninvasive approach to quantitative functional brain mapping with H2 (15)O and positron emission tomography.

Positron emission tomographic (PET) measurements of regional cerebral blood flow (rCBF) with intravenously administered 15O-labeled water and an adaptation of the Kety autoradiographic model are well suited to the study of functional-anatomical correlations within the human brain. This model requires arterial blood sampling to determine rCBF from the regional tissue radiotracer concentration (Cr) recorded by the tomograph. Based upon the well-defined, nearly linear relation between Cr and rCBF inherent in the model, we have developed a method for estimating changes in rCBF from changes in Cr without calculating true rCBF and thus without arterial sampling. This study demonstrates that quantitative functional brain mapping does not require the determination of rCBF from Cr when regional neuronal activation is expressed as the change in rCBF from an initial, resting-state measurement. Patterned-flash visual stimulation was used to produce a wide range of increases in rCBF within the striate cortex. Changes in occipital rCBF were found to be accurately estimated directly from Cr over a series of 56 measurements on eight subjects. This adaptation of the PET/autoradiographic method serves to simplify its application and to make it more acceptable to the subject.

Adult↗
PubMed1984

Brain oxygen utilization measured with O-15 radiotracers and positron emission tomography.

We have developed, implemented, and validated a method for the measurement of the local cerebral metabolic rate for oxygen (CMRO2) with positron emission tomography (PET). We use data from a single inhalation of O-15-labeled CO for cerebral blood volume (CBV), an intravenous injection of [O-15]H2O for cerebral blood flow (CBF), and a single inhalation of [O-15]O2 for the final calculation of CMRO2 and the extraction of oxygen (E). The mathematical model used to analyze the data consists of two compartments and accounts for production and egress of water metabolism in the tissue, recirculating water of metabolism, and the arterial, venous, and capillary contents of [O-15]O2 in the brain. We validated our technique in baboons by comparing the PET-measured E with E measured using an intracarotid injection of [O-15]O2. The correlation between these two techniques was excellent. Mathematical simulations were done to examine the effect of errors in CBV, CBF, and recirculating water of metabolism on the measurement of E and CMRO2. The technique was implemented on five normal human subjects in whom the global CMRO2 was 2.93 +/- 0.37 (s.d.) ml/min X 100 g.

Adult↗
PubMed1983

Comparison in animal models of 18F-spiroperidol and 18F-haloperidol: potential agents for imaging the dopamine receptor.

Fluorine-18-labeled haloperidol and spiroperidol have been prepared by an exchange reaction using the corresponding non-labeled compound or the nitro analog. Studies in rats have shown that the distribution of labeled spiroperidol has a high striatum to cerebellum ratio which is not observed with haloperidol. A ratio of 10.66 +/- 1.6 is obtained two hours after administration of the 18F-spiroperidol. When 18F-spiroperidol was administered to a baboon and tomographic images obtained, the dopamine receptor rich areas were clearly visualized two hours after administration.

Animals↗
PubMed1983

Brain blood flow measured with intravenous H2(15)O. II. Implementation and validation.

We have adapted the well-known tissue autoradiographic technique for the measurement of regional cerebral blood flow (CBF), originally proposed by Kety and his colleagues, for the measurement of CBF in human subjects using positron emission tomography (PET) and intravenously administered oxygen-15-labeled water. This report describes the steps necessary for the implementation of this PET/autoradiographic technique. In order to establish the accuracy of the method, we measured CBF with intravenously administered oxygen-15-labeled water and PET in anesthetized adult baboons and compared the results with blood flow measured by a standard tracer technique that uses residue detection of a bolus of oxygen-15-labeled water injected into the internal carotid artery. The correlation between CBF measured with PET and the true CBF for the same cerebral hemisphere was excellent. Over a blood-flow range of 10-63 ml/(min X 100 g), CBF (PET) = 0.90 CBF(true) + 0.40 (n = 23, r = 0.96, p less than 0.001). When blood flow exceeds 65 ml/(min X 100 g) CBF was progressively underestimated due to the known limitation of brain permeability to water.

Adult↗
PubMed1981

Dissolution kinetics of carboxylic acids I: effect of pH under unbuffered conditions.

The dissolution behavior of benzoic acid, 2-naphthoic acid, and indomethacin from rotating compressed disks into aqueous solutions of constant ionic strength (mu = 0.5 with potassium chloride) at 25 degrees was investigated. The pH of the bulk aqueous medium was maintained during dissolution by means of a pH-stat apparatus. A model for the initial steady-state dissolution rate of a monoprotic carboxylic acid was derived from Fick's second law of diffusion. This model assumed that diffusion-controlled mass transport and simple, instantaneously established reaction equilibria existed across a postulated diffusion layer. Using previously determined intrinsic solubilities, pKa values, and diffusion coefficients, the model was found to predict the dissolution rates of these acids accurately as a function of the bulk solution pH. Hydroxide ion and water were the only reactive base species present in the bulk solution. The concentration profiles of all of the species across the diffusion layer were generated for a given bulk pH. Furthermore, the model generated values for the pH profile within the microclimate of the diffusion layer and the pH at the solid-solution boundary.

Benzoates↗
PubMed1981

Dissolution kinetics of carboxylic acids II: effect of buffers.

The dissolution behavior of 2-naphthoic acid from rotating compressed disks into aqueous buffered solutions of constant ionic strength (mu = 0.5 with potassium chloride) at 25 degrees was investigated. A model was developed for the flux of a solid monoprotic carboxylic acid in aqueous buffered solutions as a function of the solution pH and the physicochemical properties of the buffer. The model assumes a diffusion layer-controlled mass transport process and simple, instantaneously established reaction equilibrium between all reactive species (acids and bases) across the diffusion layer. Using intrinsic solubilities, pKa values, and diffusion coefficients, the model accurately predicts the dissolution of 2-naphthoic acid as a function of the bulk solution composition. The concentration profiles of all species across the diffusion layer are generated for each buffer concentration and bulk solution pH, including the pH profile within the microclimate of the diffusion layer and the pH at the solid-solution boundary.

Buffers↗
PubMed1981

Rapid computer prediction of total body water in fluid overload.

Using computer analysis of the early plasma arterial disappearance curve of tritiated water (HTO), we sought the fewest points and earliest times needed to predict the final volume of dilution, total body water (TBW). In ten anesthetized adult female dogs weighing 19.1 +/- 0.5 kg, with bilateral ureteral ligation, 500 muC HTO were given IV. Arterial blood samples were taken until equilibrium (3 hours), when the approximate equivalent of extracellular fluid (ECF), 4,000 ml of lactated Ringer's solution, was given IV within 1 hour. The next day, in the second phase of the study, 1,000 muC of HTO were given IV and arterial blood samples were taken at intervals up to equilibrium (5 hours). TBW at 3 hours after the first HTO infusion was 63.3 +/- 1.2% body weight. Using a curve-fitting Fortran program (CFIT), the arterial plasma HTO concentrations were fitted to one or two exponentials. Although initial TBW could be predicted from arterial plasma concentrations of HTO during 20 minutes after injection in normally hydrated dogs, values during 60 minutes were required for accurate prediction of TBW after infusion of 4 L of fluid. TBW in normal and fluid-loaded animals was predicted within 2.3 +/- 0.6% of the final HTO equilibrium (r = 0.987).

Animals↗
PubMedDate not supplied

Mapping human visual cortex with positron emission tomography.

Positron-emission tomography (PET) can localize functions of the human brain by imaging regional cerebral blood flow (CBF) during voluntary behaviour. Functional brain mapping with PET, however, has been hindered by PET's poor spatial resolution (typically greater than 1 cm). We have developed an image-analysis strategy that can map functional zones not resolved by conventional PET images. Brain areas selectively activated by a behavioural task can be isolated by subtracting a paired control-state image from the task-state image, thereby removing areas not recruited by the task. When imaged in isolation the centre of an activated area can be located very precisely. This allows subtle shifts in response locale due to changes in task to be detected readily despite poor spatial resolution. As an initial application of this strategy we mapped the retinal projection topography of human primary visual cortex. Functional zones separated by less than 3 mm (centre-to-centre) were differentiated using PET CBF images with a spatial resolution of 18 mm. This technique is not limited to a particular brain area or type of behaviour but does require that the increase in CBF produced by the task be both intense and focal.

Cerebrovascular Circulation↗