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Biomedical subjects

T F Budinger

Publications and source records attributed to T F Budinger.

At least 19 recordsLinked to original sources

Pulsed magnetic field effects on calcium signaling in lymphocytes: dependence on cell status and field intensity.

The effect of 3-Hz, monopolar, quasi-rectangular magnetic field pulses on 45Ca2+ uptake in resting and mitogen-treated rat thymic lymphocytes was evaluated. A 30-min, non-thermal exposure to the pulsed magnetic field (Bpeak = 6.5 mT, Emax = 0.69 mV/cm, Jmax = 2.6 microA/cm2) reduced Concanavalin A-induced 45Ca2+ uptake by 45%. It was observed that (i) the induction of the 3-Hz field response depended on Ca2+ signal transduction activation; (ii) the response direction (stimulation or inhibition) depended on the level of lymphocyte mitogen responsiveness, and (iii) the field response magnitude increased with increasing magnetic field flux densities (Bpeak = 0, 1.6, 6.5 and 28 mT). Our results demonstrate field effects at Bmax nearly 10(4) greater than that of the average human environment for low-frequency magnetic fields and they are consistent with the independent results from other 3-Hz pulsed magnetic field studies with lymphocytes.

Animals

Tracer kinetic evidence for abnormal methyl metabolism in schizophrenia.

The original transmethylation hypothesis of schizophrenia has evolved with time and experiment to the present concept that a defect in the methyl-carbon metabolic pathway may be causative in this illness. Various researchers have proposed that specific steps in the methyl-carbon pathway may be defective, and have presented evidence to support these possibilities. We have tested the general concept of the hypothesis by administering methionine labeled with 11C or 14C in the S-methyl carbon to patients with schizophrenia and to controls and measured the expiration of 11CO2 and 14CO2. We found that the rate and total expiration of labeled CO2 were three times less in the patients than in the controls, with no overlap of data points in the two groups. Specific steps in the methylcarbon pathway that might be defective and produce the results seen here are discussed in light of this and other researchers' findings.

Adult

Quantitative in vitro and ex vivo autoradiography of the alpha 2-adrenoceptor antagonist [3H]atipamezole.

Atipamezole is an alpha-adrenoceptor antagonist with high affinity and selectivity for the alpha 2-receptor. In vitro autoradiography of [3H]atipamezole on rat and human brain sections revealed a pattern virtually identical to the one observed using 3H-labeled antagonists such as idazoxan or methoxyidazoxan or agonists such as p-aminoclonidine and 5-bromo-6-(2-imidazolin-2-yl-amino-quinoxaline (UK-14304). In vivo studies of [3H]atipamezole demonstrated good penetration into the brain (0.3-1.8% injected dose/g at 5 min, depending upon brain region). In addition, [3H]atipamezole displayed rapid in vivo clearance of nonspecific binding such that at 1 h following an i.v. injection of the drug (100 microCi/animal, rat tail vein administration) the pattern of radioactivity in the brain correlated very well with the receptor distribution as seen by in vitro autoradiography. Atipamezole binding in vivo was displaceable by idazoxan. These results demonstrate the potential of suitably labeled atipamezole for regional studies of brain alpha 2-adrenoceptors in vitro and in vivo, in experimental animals as well as in human positron emission tomography (PET) studies.

Adolescent

Emerging nuclear magnetic resonance technologies. Health and safety.

NMR imaging (MRI) and spectroscopy have been applied to an increasing number of patients and volunteers for 10 years. The field strength has increased by a factor of 10 since 1979 and the switched gradients have increased by over a factor of 10 since 1980. RF absorbed power has increased by almost a factor of 10 in many studies due to both the increase in frequency and the increase in duty cycle associated with new RF pulse protocols. Even with these increases, all available evidence argues that the clinical procedures offer no hazards to human subjects. Known hazards associated with flying ferromagnetic objects, internal prostheses, and wires or metal objects in contact with the skin of patients can be avoided. Although hazards are not expected for the present procedures, emerging methods using fast scan strategies and higher frequency RF of the higher fields will require a closer vigilance and will demand continuing experimental and theoretical work such as detailed in this symposium.

Electrocardiography

Critical review of PET, SPECT and neuroreceptor studies in schizophrenia.

Hypotheses having to do with the neurochemical basis for mental disease can be tested by noninvasive measurement of flow, metabolism and neuroreceptor concentrations in various parts of the brain. The capabilities of these technologies for accurate absolute quantitation are limited by the instrument resolution and the limited statistics associated with allowable radiation doses. Nevertheless, very important new information regarding the brain function in normal and diseased states can be gleaned from the techniques of positron emission tomography (PET) and single photon emission tomography (SPECT). This chapter presents the critical problems which face the clinical researcher who endeavors to test hypotheses regarding mental illnesses using PET or SPECT. First, the quantitative capabilities of emission tomography will be discussed; then the special requirements of SPECT for attenuation correction will be reviewed. Next, the physiological principles required for inter-institutional comparisons are presented.

Activation Analysis

Hypoxia in human gliomas: demonstration by PET with fluorine-18-fluoromisonidazole.

Positron emission tomography (PET) with the hypoxic-cell tracer [18F]fluoromisonidazole presents a possible means of noninvasively demonstrating tumor hypoxia. PET studies using this tracer were performed in three patients with malignant glioma, and in all patients the tumor was clearly seen at 5 min postinjection and initial tumor activity exceeded cortical activity. In one patient, there was no tumor retention of [18F] fluoromisonidazole and tumor activity fell while cortical activity increased, with the two tissues reaching equality at 40-50 min. The tumor-to-plasma ratio was 0.71 at 3 hr. The other two patients showed variable tumor retention of [18F]fluoromisonidazole, with tumor-to-plasma ratios of 1.10 and 1.49 at 2 and 3 hr. These results demonstrate the feasibility of using [18F]fluoromisonidazole PET to detect hypoxia in human gliomas in vivo. Clinical trials are needed to determine whether a relationship exists between [18F]fluoromisonidazole uptake and tumor radiation response.

Adult

Generalized approach to inverse problems in tomography: image reconstruction for spatially variant systems using natural pixels.

A major limitation in tomographic inverse problems is inadequate computation speed, which frequently impedes the application of engineering ideas and principles in medical science more than in the physical and engineering sciences. Medical problems are computationally taxing because a minimum description of the system often involves 5 dimensions (3 space, 1 energy, 1 time), with the range of each space coordinate requiring up to 512 samples. The computational tasks for this problem can be simply expressed by posing the problem as one in which the tomograph system response function is spatially invariant, and the noise is additive and Gaussian. Under these assumptions, a number of reconstruction methods have been implemented with generally satisfactory results for general medical imaging purposes. However, if the system response function of the tomograph is assumed more realistically to be spatially variant and the noise to be Poisson, the computational problem becomes much more difficult. Some of the algorithms being studied to compensate for position-dependent resolution and statistical fluctuations in the data acquisition process, when expressed in canonical form, are not practical for clinical applications because the number of computations necessary exceeds the capabilities of high-performance computer systems currently available. Reconstruction methods based on natural pixels, specifically orthonormal natural pixels, preserve symmetries in the data acquisition process. Fast implementations of orthonormal natural pixel algorithms can achieve orders of magnitude speedup relative to general implementations. Thus, specialized thought in algorithm development can lead to more significant increases in performance than can be achieved through hardware improvements alone.

Algorithms

Electromagnetic fields of surface coil in vivo NMR at high frequencies.

A high frequency solution of the electromagnetic field produced by a circular surface coil adjacent to a homogeneous conducting, dielectric sphere is used to predict the attainable signal to noise ratio (S/N) and specific absorption rate (SAR) for in vivo 1H NMR spectroscopy experiments from 200 to 430 MHz (4.7-10 T). Above 200 MHz the S/N increases more rapidly with frequency and the SAR increases less rapidly compared with the respective S/N and SAR frequency dependence below 200 MHz. The difference in frequency dependence is due to dielectric resonances of the magnetic field inside the sphere at frequencies above 200 MHz. It is predicted that surface coil 1H NMR experiments may be performed on a head-sized sphere, having conductivity and relative dielectric constant of brain, at frequencies up to 430 MHz without exceeding 8 W/kg local SAR and 3.2 W/kg SAR. The calculations of the S/N and SAR are used to determine optimum surface coil geometries for NMR experiments. The power radiated by the surface coil in the absence of shielding and asymmetries in the received signal with respect to the plane defined by the surface coil axis and the direction of the static magnetic field are significant at high frequency. Experimental measurements of the magnetic field inside a head-sized sphere verify the presence of dielectric resonances at frequencies above 200 MHz.

Brain

Diminished glucose transport in Alzheimer's disease: dynamic PET studies.

Dynamic positron emission tomography with [18F]fluorodeoxyglucose was used in six patients with Alzheimer's disease (AD) and seven healthy age-matched control subjects to estimate the kinetic parameters K1*, k2*, and k3* that describe glucose transport and phosphorylation. A high-resolution tomograph was used to acquire brain uptake data in one tomographic plane, and a radial artery catheter connected to a plastic scintillator was used to acquire arterial input data. A nonlinear iterative least-squares fitting procedure that included terms for the vascular fraction and time delay to the peripheral sampling site was used to fit a three-compartment model to the brain data. Regions studied included frontal, temporal, occipital, and the entire cortex and subcortical white matter. The values obtained for the individual rate constants and regional CMRglc (rCMRglc; calculated using regional values of the rate constants) were higher than those reported previously. A significant (p less than 0.05) decrease was found in K1* in frontal and temporal cortex in the AD patients compared with the controls, with values of 0.157 and 0.161 ml/g/min in frontal and temporal cortex, respectively, of controls and 0.127 and 0.126 ml/g/min in frontal and temporal cortex of the AD patients. rCMRglc was also significantly (p less than 0.02) lower in the AD patients than controls in all cortical brain regions. Lower values of k3* were found in all brain regions in the AD patients, although these were not statistically significant. These findings provide evidence of an in vivo abnormality of forward glucose transport in AD.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

Alzheimer's disease. Age at onset and single-photon emission computed tomographic patterns of regional cerebral blood flow.

We performed this study to determine whether early- and late-onset Alzheimer's disease differ physiologically. Ten patients with a presenile (before 65 years old) onset of the disease and 16 with senile onset of the disease were evaluated clinically and neuropsychologically and studied with single photon emission computed tomography using the blood flow tracer [123I]N-isopropyl-p-iodoamphetamine. Although the presenile subjects had more severe neuropsychological abnormalities in all realms of cognitive function, including language, and showed greater reductions in regional blood flow than the older patients, they were also more severely demented, thus complicating interpretation of the results. Two indexes of cerebral perfusion, a ratio of regional flow compared with occipital flow and a left-right asymmetry index, demonstrated relative left frontal hypoperfusion in presenile- but not senile-onset patients and did not appear to be an artifact of the severity differences. Although no asymmetry of cognitive function was noted, the perfusion asymmetry provides biological evidence for an alteration in left-hemisphere function in patients with the early onset of Alzheimer's disease.

Age Factors

Magnetohydrodynamics of blood flow.

The changes in hydrostatic pressure and electrical potentials across vessels in the human vasculature in the presence of a large static magnetic field are estimated to determine the feasibility of in vivo NMR spectroscopy at fields as high as 10 T.A 10-T magnetic field changes the vascular pressure in a model of the human vasculature by less than 0.2%. An exact solution to the magnetohydrodynamic equations describing a conducting fluid flowing transverse to a static magnetic field in a nonconducting, straight, circular tube is used. This solution is compared to an approximate solution that assumes that no magnetic fields are induced in the fluid and that has led previous investigators to predict significant biological effects from static magnetic fields. Experimental results show that the exact solution accurately predicts the magnetohydrodynamic slowing of 15% NaCl flowing transverse to 2.3- and 4.7-T magnetic fields for fluxes below 0.5 liter/min while the approximate solution predicts a much more retarded flow.

Blood Circulation

Rapid detection of spatial pattern by Fourier analysis.

Fast Fourier transform analysis can be used to accurately and rapidly detect pattern in large two-dimensional arrangements of points, such as the locations of cells in culture or plants in a unit square. We present here a sample study of pattern in spatial random point processes. This is evidently the first time that Fourier transform-based cross-correlation techniques have been applied to the analysis of point processes of biological origin. Radial profiles of the power spectra and autocorrelation estimates revealed a nearly constant interpore distance of 0.49 +/- 0.04 mm in the locations of eccrine gland pores on the surface of human skin. Additionally, gland-free areas may exist near hair follicles.

Algorithms

Clinical evaluation of a high-resolution (2.6-mm) positron emission tomography.

The intrinsic resolution of the Donner 600-crystal positron emission tomograph (PET 600) is 2.6 mm full width at half maximum (FWHM) in-plane and 6 mm FWHM axially. More than 100 patients with glioma, radiation necrosis, Alzheimer disease, or epilepsy have been studied with this system. Approximately 1 million events are acquired in 15 minutes, starting 1 hour after injection of 10 mCi (370 MBq) of fluorine-18-fluorodeoxyglucose. Normal structures as small as the superior colliculi and the external capsule have been resolved. Improved separation of the cortical ribbon from adjacent white matter has allowed more accurate determination of cortical metabolic rate. In two of 15 patients undergoing evaluation for recurrent glioma, the PET 600 images showed tumor uptake that was not apparent on a lower-resolution study. A high-activity orbiting transmission source with electronic collimation allows accurate, short-duration transmission measurements to be made after radiopharmaceutical administration. The anatomic detail seen on the transmission images can be used for reproducible patient positioning with an accuracy of 1-2 mm perpendicular to the image plane. These findings demonstrate the practicality and clinical effectiveness of high-resolution positron emission tomography.

Alzheimer Disease

Acute anemia increases lactate production and decreases clearance during exercise.

We evaluated whether elevated blood lactate concentration during exercise in anemia is the result of elevated production or reduced clearance. Female Sprague-Dawley rats were made acutely anemic by exchange transfusion of plasma for whole blood. Hemoglobin and hematocrit were reduced 33%, to 8.6 +/- 0.4 mg/dl and 26.5 +/- 1.1%, respectively. Blood lactate kinetics were studied by primed continuous infusion of [U-14C]lactate. Blood flow distribution during rest and exercise was determined from injection of 153Gd- and 113Sn-labeled microspheres. Resting blood glucose (5.1 +/- 0.2 mM) and lactate (1.9 +/- 0.02 mM) concentrations were not different in anemic animals. However, during exercise blood glucose was lower in anemic animals (4.0 +/- 0.2 vs. 4.6 +/- 0.1 mM) and lactate was higher (6.1 +/- 0.4 vs. 2.3 +/- 0.5 mM). Blood lactate disposal rates (turnover measured with recyclable tracer, Ri) were not different at rest and averaged 136 +/- 5.8 mumol.kg-1.min-1. Ri was significantly elevated in both control (260.9 +/- 7.1 mumol.kg-1.min-1) and anemic animals (372.6 +/- 8.6) during exercise. Metabolic clearance rate (MCR = Ri/[lactate]) did not differ during rest (151 +/- 8.2 ml.kg-1.min-1); MCR was reduced more by exercise in anemic animals (64.3 +/- 3.8) than in controls (129.2 +/- 4.1). Plasma catecholamine levels were not different in resting rats, with pooled mean values of 0.45 +/- 0.1 and 0.48 +/- 0.1 ng/ml for epinephrine (E) and norepinephrine (NE), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Anemia

Regional cerebral glucose transport and utilization in Alzheimer's disease.

We performed dynamic positron emission tomographic (PET) studies of glucose utilization, using (18F) 2-fluoro-2-deoxy-D-glucose (FDG), in patients with probable Alzheimer's disease (AD) and healthy age-matched controls, to evaluate blood-brain-barrier glucose transport and glucose utilization rates in the disease. We found no significant differences in rate constants for glucose transport (k1 and k2) and phosphorylation (k3), nor for the vascular fraction (fv), between the 2 groups, although k3 and fv were relatively depressed in temporal cortex in AD. Absolute rates of glucose use were depressed in temporal and parietal cortex, and relative rCMRglc rates were lower in frontal, temporal, parietal, and occipital cortices. These data suggest that in AD bidirectional glucose transport is intact, and that temporal-parietal hypometabolism is present upon a background of widespread cortical metabolic impairment.

Aged