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Biomedical subjects

T F Budinger

Publications and source records attributed to T F Budinger.

At least 73 records · Page 4Linked to original sources

The diagnosis of dementia with single photon emission computed tomography.

Single photon emission computed tomography is a practical modality for the study of physiologic cerebral activity in vivo. We utilized single photon emission computed tomography and N-isopropyl-p-iodoamphetamine iodine 123 to evaluate regional cerebral blood flow in nine patients with Alzheimer's disease (AD), five healthy elderly control subjects, and two patients with multi-infarct dementia. We found that all subjects with AD demonstrated flow deficits in temporoparietal cortex bilaterally, and that the ratio of activity in bilateral temporoparietal cortex to activity in the whole slice allowed the differentiation of all patients with AD from both the controls and from the patients with multi-infarct dementia. Furthermore, this ratio showed a strong correlation with disease severity in the AD group. Single photon emission computed tomography appears to be useful in the differential diagnosis of dementia and reflects clinical features of the disease.

Aged↗

Synthesis and in vivo evaluation of 122I- and 131I-labelled iodoperidol, a potential agent for the tomographic assessment of cerebral perfusion.

Iodoperidol (IP), an iodinated analogue of the antipsychotic drug haloperiodol, was evaluated as a cerebral blood flow radiopharmaceutical for PET or SPECT. IP was labelled with 131I or 122I (76% beta +, t1/2 = 3.6 min) in greater than 75% radiochemical yield via electrophilic aromatic iododestannylation. [131I]IP showed high cerebral uptake (1.9% of injected dose after 5 min) and good brain retention for the rat, with very low blood levels (brain/blood ratio = 35 at 2 h post injection). PET imaging of a dog demonstrated that [122I]IP has high selectivity for brain localization and good retention, and indicates that this class of compounds holds promise for development as perfusion radiopharmaceuticals.

Animals↗

Disposal of blood [1-13C]lactate in humans during rest and exercise.

Lactate irreversible disposal (RiLa) and oxidation (RoxLa) rates were studied in six male subjects during rest (Re), easy exercise [EE, 140 min of cycling at 50% of maximum O2 consumption (VO2max)] and hard exercise (HE, 65 min at 75% VO2max). Twenty minutes into each condition, subjects received a Na+-L(+)-[1-13C]lactate intravenous bolus injection. Blood was sampled intermittently from the contralateral arm for metabolite levels, acid-base status, and enrichment of 13C in lactate. Expired air was monitored continuously for determination of respiratory parameters, and aliquots were collected for determination of 13C enrichment in CO2. Steady-rate values for O2 consumption (VO2) were 0.33 +/- 0.01, 2.11 +/- 0.03, and 3.10 +/- 0.03 l/min for Re, EE, and HE, respectively. Corresponding values of blood lactate levels were 0.84 +/- 0.01, 1.33 +/- 0.05, and 4.75 +/- 0.28 mM in the three conditions. Blood lactate disposal rates were significantly correlated to VO2 (r = 0.78), averaging 123.4 +/- 20.7, 245.5 +/- 40.3, and 316.2 +/- 53.7 mg X kg-1 X h-1 during Re, EE, and HE, respectively. Lactate oxidation rate was also linearly related to VO2 (r = 0.81), and the percentage of RiLa oxidized increased from 49.3% at rest to 87.0% during exercise. A curvilinear relationship was found between RiLa and blood lactate concentration. It was concluded that, in humans, 1) lactate disposal (turnover) rate is directly related to the metabolic rate, 2) oxidation is the major fate of lactate removal during exercise, and 3) blood lactate concentration is not an accurate indicator of lactate disposal and oxidation.

Adult↗

Methodologic factors affecting PET measurements of cerebral glucose metabolism.

Measurements of cerebral glucose utilization rates in similar populations of human subjects under similar conditions vary considerably because of methods used in data collection and analysis. Using data acquired in two patients, we evaluated the effects of time schedule of data collection, region of interest size, method of attenuation correction, and input function shape on LCMRglu determined by dynamic positron emission tomographic scanning and calculation of rate constants. These different strategies of data acquisition and analysis produced variations of 3 to 14% in calculated LCMRglu. These factors, in conjunction with the well described effects of instrument resolution and sensitivity may account for data discrepancies in the literature.

Brain↗

Alzheimer's disease: anterior-posterior and lateral hemispheric alterations in cortical glucose utilization.

We performed dynamic positron emission tomographic studies with [18F]fluorodeoxyglucose in 17 subjects with presumed Alzheimer's disease (AD) and 7 healthy aged subjects. Glucose metabolism was depressed by 27% in temporal-parietal cortex of the AD group, as compared to healthy aged controls. This focal impairment in temporal-parietal glucose use was found in all AD subjects. In addition, the AD group showed a striking lateral asymmetry of cortical metabolism not favoring either hemisphere, which has not been previously reported. Relationships between these focal changes and behavioral features of the illness were demonstrated. These results have important implications for the diagnosis and perhaps the etiology of Alzheimer's disease.

Alzheimer Disease↗

An attenuated projector-backprojector for iterative SPECT reconstruction.

A new ray-driven projector-backprojector which can easily be adapted for hardware implementation is described and simulated in software. The projector-backprojector discretely models the attenuated Radon transform of a source distributed within an attenuating medium as line integrals of discrete pixels, obtained using the standard sampling technique of averaging the emission source or attenuation distribution over small square regions. Attenuation factors are calculated for each pixel during the projection and backprojection operations instead of using precalculated values. The calculation of the factors requires a specification of the attenuation distribution, estimated either from an assumed constant distribution and an approximate body outline or from transmission measurements. The distribution of attenuation coefficients is stored in memory for efficient access during the projection and backprojection operations. The reconstruction of the source distribution is obtained by using a conjugate gradient or SIRT type iterative algorithm which requires one projection and one backprojection operation for each iteration.

Heart↗

Positron emission tomography with [18F]fluorodeoxyglucose differentiates normal pressure hydrocephalus from Alzheimer-type dementia.

Because diagnostic criteria for normal pressure hydrocephalus have not been clearly determined, it is often difficult to differentiate patients with this potentially treatable condition from those with Alzheimer-type dementia. We have studied three patients with normal pressure hydrocephalus, 17 patients with Alzheimer-type dementia, and seven healthy elderly controls using positron emission tomography and [18F]Fluorodeoxyglucose (FDG). Both Alzheimer-type dementia and normal pressure hydrocephalus groups showed lower cortical rates of FDG utilisation than controls. However, the patterns of metabolic abnormality were distinctly different in the two dementia groups, with Alzheimer-type dementia subjects demonstrating bilateral temporoparietal hypometabolism while normal pressure hydrocephalus subjects showed globally diminished glucose use.

Aged↗

Magnetic resonance imaging of prosthetic heart valves.

To evaluate the safety of magnetic resonance (MR) imaging of prosthetic heart valves, nine different synthetic and tissue valves were studied ex vivo. Deflection was measured in 0.35-tesla (T) and 1.5-T superconducting magnets and at the edge of the bore of a 2.35-T electromagnet in field gradients of 5, 1.1, and 6.3 mT/cm, respectively. No valve deflected in the 0.35-T magnet; six synthetic valves deflected 0.25 degrees-3 degrees in the 1.5-T magnet; all valves deflected 1 degree-27 degrees at the edge of the 2.35-T magnet. Each valve was then submerged in a vial of water and the temperature was measured immediately before and after each of two spin-echo imaging sequences in the two superconducting magnets. No significant temperature rise followed exposure in either magnet. Image distortion varied from negligible to severe in both imagers; magnitude of distortion paralleled magnitude of deflection. These data suggest that patients with present-day prosthetic heart valves can be safely imaged in present-day MR imagers and that prosthesis-induced artifacts will not interfere with interpretation in most instances.

Bioprosthesis↗

Carbon-11 choline: synthesis, purification, and brain uptake inhibition by 2-dimethylaminoethanol.

We report an improved method for the synthesis and purification of [11C]methylcholine from the precursors [11C]methyliodide and 2-dimethylaminoethanol (deanol). Preparation time, including purification, is 35 min postbombardment. Forty millicuries of purified injectable [11C]choline were produced with a measured specific activity of greater than 300 Ci/mmol and a radiochemical purity greater than 98%. The decay corrected radiochemical yield for the synthesis and purification was approximately 50%. Residual precursor deanol, which inhibits brain uptake of choline, is removed by a rapid preparative high performance liquid chromatography (HPLC) method using a reverse phase cyano column with a biologically compatible 100% water eluent. Evaporation alone did not completely remove the deanol precursor. Brain uptake of the [11C]choline product was six times greater after HPLC removal of deanol because doses of less than 1 microgram/kg significantly inhibit [14C]choline brain uptake.

Animals↗

Gallium-68 lipophilic complexes for labeling platelets.

Generator produced 68Ga-labeled platelets could be useful for positron emission tomographic (PET) studies of thrombosis or atherosclerosis. To label platelets with 68Ga, we have studied the effects of trace metals in elutions of 68Ga from 68Ge. Studies were conducted on the formation of lipophilic 68Ga complexes 8-hydroxyquinoline, tropolone, and mercaptopyridine-N-oxide (MPO). Parameters such as pH, buffers, concentration of ligand, and stability with time were investigated. High performance liquid chromatography and instant thin layer chromatography were used to quantitate formation of the 68Ga complex. Platelets from human, dog, and rabbit plasma were incubated with the 68Ga complexes and the percent labeling determined. Accumulation of platelets in the catheter scraped aorta of the rabbit was determined by PET imaging, tissue counting, and autoradiography. Gallium-68 MPO gave 40-60% labeling of rabbit platelets with higher accumulation in the scraped aorta compared to the normal.

Animals↗

Nuclear magnetic resonance technology for medical studies.

Nuclear magnetic resonance proton imaging provides anatomical definition of normal and abnormal tissues with a contrast and detection sensitivity superior to those of x-ray computed tomography in the human head and pelvis and parts of the cardiovascular and musculoskeletal systems. Recent improvements in technology should lead to advances in diagnostic imaging of the breast and regions of the abdomen. Selected-region nuclear magnetic resonance spectroscopy of protons, carbon-13, and phosphorus-31 has developed into a basic science tool for in vivo studies on man and a unique tool for clinical diagnoses of metabolic disorders. At present, nuclear magnetic resonance is considered safe if access to the magnet environment is controlled. Technological advances employing field strengths over 2 teslas will require biophysical studies of heating and static field effects.

Blood Circulation↗

Instrumentation for positron emission tomography.

Positron emission tomography with a spatial resolution of 2 mm full width at half maximum for quantitation in regions of interest 4 mm in diameter will become possible with the development of detectors that achieve ultrahigh resolution. Improved resolution will be possible using solid-state photodetectors for crystal identification or photomultiplier tubes with many small electron multipliers . Temporal resolution of 2 seconds and gating of cyclic events can be accomplished if statistical requirements are met. The major physical considerations in achieving high-resolution positron emission tomography are the degradation in resolution resulting from positron range, emission angle, parallax error, detector sampling density, the sensitivity of various detector materials and packing schemes, and the trade off between temporal resolution and statistical accuracy. The accuracy of data required for physiological models depends primarily on the fidelity of spatial sampling independent of statistical constraints.

Humans↗

Influence of metabolic fuel on the 13C/12C ratio of breath CO2.

Natural differences in 13C/12C ratios of various metabolic fuels can produce systematic changes in the 13C/12C ratio of breath CO2, and therefore introduce errors into 13CO2 breath tests. To gain insight into the potential problem, we compared 13C/12C ratios of plasma macronutrients to those of breath CO2 under conditions that should alter the percentages of carbohydrate and lipid being oxidized. In rats, 48 h of starvation decreased the 13C/12C ratio of breath CO2 by 3.5%. At this time the 13C/12C ratio of breath CO2 was very similar to that of plasma lipids. In humans, 30 min of heavy exercise increased the breath 13CO2/12CO2 ratio by 1.3%. These changes in breath 13C/12C ratios could be predicted from 13C/12C ratios of plasma macronutrients and the percentage of carbon dioxide derived from each macronutrient, but only when compared within the same populations. For example, the 13C/12C ratios of plasma macronutrients of residents of Chicago, Illinois (USA) and Tokyo (Japan) differed by 1-3%. An empirical correction of 13CO2 breath test data is recommended when breath tests are run under conditions that will change metabolic fuel utilization.

Adult↗

Bitemporal hypometabolism in Creutzfeldt-Jakob disease measured by positron emission tomography with [18F]-2-fluorodeoxyglucose.

It is well established that Creutzfeldt-Jakob disease (CJD) is caused by a slow infectious agent similar to the scrapie prion. However, the pathogenesis of this infection is poorly understood. Positron emission tomography (PET) was performed on a 54-year-old man with autopsy confirmed CJD using [18F]-2-fluorodeoxyglucose (FDG) and the Donner 280-crystal tomograph. Temporal lobe hypometabolism with hemispheric asymmetry was observed. These findings are similar to those previously obtained in PET-FDG studies of patients with clinically defined Alzheimer disease (AD). The similarities in the regional metabolic alterations between CJD and AD provide additional evidence for the possibility that AD may be caused by a slow infectious prion.

Autopsy↗