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Biomedical subjects

T F Budinger

Publications and source records attributed to T F Budinger.

At least 55 records · Page 3Linked to original sources

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↗

Clinical-physiologic correlates of Alzheimer's disease and frontal lobe dementia.

Thirty patients with degenerative dementia underwent clinical evaluation, neuropsychological testing, and single photon emission computed tomography (SPECT) with the blood flow tracer [123I]-N-isopropyl-p-iodoamphetamine. Five of these patients were clinically and psychologically different from the others, demonstrating predominant behavioral disturbances with relative preservation of memory function. These five patients, who were felt to have a frontal lobe dementia (FLD), showed SPECT perfusion patterns which differed from the remaining 25 patients, who were diagnosed as having Alzheimer's disease (AD), and from 16 healthy control subjects. The FLD patients showed diminished perfusion in orbitofrontal, dorsolateral frontal, and temporal cortex relative to controls, while the AD patients showed lower perfusion in temporal and parietal cortex than controls. The FLD patients also showed hypoperfusion in both frontal cortical regions relative to AD patients. The pattern of performance on neuropsychological testing paralleled these differences in regional perfusion. These results suggest that clinical evaluation and physiological imaging may enable the differentiation of groups of degenerative dementia patients during life.

Aged↗

Quantitative NMR measurements of hippocampal atrophy in Alzheimer's disease.

Nuclear magnetic resonance (NMR) imaging was employed to study 10 patients with Alzheimer's disease (AD) and seven healthy elderly control subjects. Coronal sections were used to make volumetric measurements of the hippocampus, ventricles, subarachnoid space, and brain parenchyma. The hippocampal volume (normalized relative to the size of the lenticular nucleus) was reduced by 40% in the AD group compared to the controls, with no overlap between the two groups. Overall measures of brain atrophy and ventricular and sulcal enlargement also showed significantly different group means, although with overlap between the two groups. Hippocampal atrophy did not correlate with either overall brain atrophy or dementia severity, although the degree of brain atrophy was correlated with dementia severity. These results show that NMR is capable of providing in vivo quantification of diminished hippocampal size in AD which is not correlated with overall brain atrophy and which may differentiate AD from normal aging.

Aged↗

Residualizing and non-residualizing analogues of low-density lipoprotein as iodine-123 radiopharmaceuticals for imaging LDL catabolism.

Low-density lipoprotein (LDL) labeled via direct iodination or via the radioiodinated residualizing moiety tyramine-cellobiose (TC) were compared in rabbits as potential 123I radiopharmaceuticals for imaging sites of LDL catabolism. The tissue deposition of 131I-TC-LDL after 24 h as determined by dissection was in the major catabolic organs (liver, adrenals, spleen), and its plasma clearance was slower in rabbits with dietary hypercholesterolemia than in normals. 131I-LDL was unsuitable as a metabolic tracer due to redistribution of catabolites and/or loss of the label before protein degradation, which resulted in little accumulation of radioactivity in catabolic organs and high thyroid uptake. The plasma clearance half-time was similar (ca 22 h) for the two compounds in normal rabbits, but was increased to about 36 h for 131I-TC-LDL and decreased to approximately 9 h for 131I-LDL in hypercholesterolemic animals. The were similar with dynamic imaging of control and hypercholesterolemic rabbits using 123I-labeled analogues. 123I-TC-LDL rapidly localized in the liver, with low thyroid accumulation of radioactivity. The hepatic uptake of 123I-LDL was about half that of 123I-TC-LDL, and thyroid sequestration of radioactivity was significant for 123I-LDL but not 123I-TC-LDL. These data suggest that whereas the residualizing 123I-TC-LDL has a pharmacokinetic profile representative of lipoprotein metabolism, the biodistribution of the activity from injected 123I-LDL is complicated by processes other than protein degradation. The results are discussed with regard to nuclear medicine applications in evaluating lipoprotein catabolism in man.

Animals↗

Longitudinal studies of regional cerebral metabolism in Alzheimer's disease.

Measurement of cerebral glucose metabolism in six patients with Alzheimer's disease using positron emission tomography demonstrated that hypometabolism remained relatively more severe in parietal cortex than in frontal cortex over time. Lateral metabolic asymmetries were preserved in less severely involved brain regions, but were less stable in parietal cortex.

Aged↗

PET of malignant cerebral tumors after interstitial brachytherapy. Demonstration of metabolic activity and correlation with clinical outcome.

Positron emission tomography (PET) with rubidium-82 (82Rb) and fluorine-18-fluorodeoxyglucose (18F-FDG) was used to diagnose active tumor recurrence and to differentiate this from radiation injury after interstitial irradiation of malignant gliomas. Patients were studied when they presented with radiological or clinical deterioration after an initial period of posttreatment stabilization. Forty studies were performed in 34 patients. The 82Rb was used as a blood-brain barrier tracer to localize the lesion. Uptake of 18F-FDG by the lesion was then compared to uptake by adjacent brain in order to make a diagnosis of active tumor recurrence (higher or equal lesion uptake) or no active tumor (lower uptake). Radiation injury was diagnosed by the exclusion of active tumor. A retrospective clinical diagnosis was established in 38 cases by following the patients' progress for 8 to 142 weeks after the PET study. In two cases, no follow-up diagnosis could be determined. The PET results agreed with the follow-up diagnosis in 15 of 17 cases of active tumor and 17 of 21 cases of radiation injury. Histological examination of surgically resected tissue obtained after the PET study was performed in 18 patients (nine with tumor regrowth and nine with radiation injury). This showed apparently viable tumor as well as necrosis in all cases, regardless of eventual clinical outcome. Some cells from the irradiated volume may appear morphologically intact, but have little or no metabolic or clinical activity. The functional nature of the PET-FDG technique allows diagnosis of tumor activity, which cannot be demonstrated by anatomic imaging studies or by histological examination. The addition of a blood-brain barrier tracer to the 18F-FDG study aids in differentiating normal brain uptake from tumor activity and improves the accuracy of the technique.

Astrocytoma↗

NMR imaging and spectroscopy of the mammalian central nervous system after heavy ion radiation.

NMR imaging, NMR spectroscopy, and histopathologic techniques were used to study the proton relaxation time and related biochemical changes in the rodent brain after in vivo helium beam irradiation with single doses of 10, 20, 30, and 50 Gy. Two-dimensional Fourier transform spin-echo imaging and saturation recovery with projection reconstruction were used to measure the NMR relaxation parameters. These parameters were correlated with proton spectroscopy and histopathology. Additional high resolution in vitro proton spectroscopy was performed on brain extracts to observe chemical changes that could not be seen in vivo. The major findings from these experiments were that at 4-14 days postirradiation, image intensity and T1 relaxation time decreased on the irradiated side and increased on the nonirradiated side relative to nonirradiated control animals. In vivo surface coil proton spectroscopy methods demonstrated changes in lipid and phosphatidylcholine (p-choline) peaks. In vitro studies of the aqueous fraction of brain extracts showed radiation-induced changes in lactate, 4-aminobutyric acid, and p-choline peak areas. In the organic fraction, radiation-induced changes were observed in phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine. With histology and Evans blue injections, blood-brain barrier alterations were seen as early as 4 days after a dose of 50 Gy.

Animals↗