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T F Budinger

Publications and source records attributed to T F Budinger.

At least 37 records · Page 2Linked to original sources

Advances in positron tomography for oncology.

Development of PET instrumentation over the past 42 years has moved from simple dual-detector coincidence scanners, to proposed systems having 60,000 detectors and simultaneous coverage of 15-cm regions of the body with spatial resolutions better than 4 mm. The principal determinants of positron emission tomography (PET) instrumentation advances are positron range, noncollinearity of the annihilation photons, scattering, random event rates, detector size, efficiency, speed and light output; capability to correct for depth of crystal interaction, attenuation compensation, axial coverage, and rapid data analysis and presentation. While general-purpose systems with 2-mm resolution are expected, special-purpose PET devices are being built for breast and brain tumor studies with resolutions from 1.7 to 5 mm.

Humans↗

Temporal lobe metabolic differences in medication-free outpatients with schizophrenia via the PET-600.

Regional cerebral glucose metabolic rates (rCMRglc) were compared in 18 unmedicated outpatients with schizophrenia and 11 normal controls using high resolution positron emission tomography (PET) and the tracer [F-18]-2-fluoro-2D-deoxyglucose (FDG). From previous work we expected to see abnormal hippocampal rCMRglc in the patients, but no striatal abnormalities. Trial-by-trial Stroop cognitive task, which has been shown to activate the anterior cingulate, was performed within a day of the PET study. As our patients performed abnormally on the Stroop we tested for a correlation between the anterior cingulate rCMRglc and Stroop performance. We found no whole slice cortical average glucose metabolic abnormalities. As, predicted we found abnormally decreased left hippocampal rCMRglc in the patients. No striatal or cingulate rCMRglc abnormalities were noted in patients, but they demonstrated a highly positive correlation between anterior and cingulate rCMRglc and Stroop facilitation. Patients with higher Stroop interference had more prominent hippocampal metabolic decreases. These localized temporal lobe abnormalities could account for some of the patient's positive symptoms and are consistent with recent findings in the literature.

Adult↗

Sodium alterations in isolated rat heart during cardioplegic arrest.

Triple-quantum-filtered (TQF) Na nuclear magnetic resonance (NMR) without chemical shift reagent is used to investigate Na derangement in isolated crystalloid perfused rat hearts during St. Thomas cardioplegic (CP) arrest. The extracellular Na contribution to the NMR TQF signal of a rat heart is found to be 73 +/- 5%, as determined by wash-out experiments at different moments of ischemia and reperfusion. With the use of this contribution factor, the estimated intracellular Na ([Na+]i) TQF signal is 222 +/- 13% of preischemic level after 40 min of CP arrest and 30 min of reperfusion, and the heart rate pressure product recovery is 71 +/- 8%. These parameters are significantly better than for stop-flow ischemia: 340 +/- 20% and 6 +/- 3%, respectively. At 37 degrees C, the initial delay of 15 min in [Na+]i growth occurs during CP arrest along with reduced growth later (approximately 4.0%/min) in comparison with stop-flow ischemia (approximately 6.7%/min). The hypothermia (21 degrees C, 40 min) for the stop-flow ischemia and CP dramatically decreases the [Na+]i gain with the highest heart recovery for CP (approximately 100%). These studies confirm the enhanced sensitivity of TQF NMR to [Na+]i and demonstrate the potential of NMR without chemical shift reagent to monitor [Na+]i derangements.

Animals↗

Reduced temporal lobe glucose metabolism in aging.

The results of a positron emission tomography study of regional cerebral metabolic rates of glucose are reported for 8 healthy old subjects (mean age, 66 yr; standard deviation [SD], 5) and 9 young subjects (mean age, 27 yr; SD, 4.6) using a high-resolution positron emission tomograph and the glucose metabolic tracer 18F-fluorodeoxyglucose. Older subjects showed significantly lower cerebral metabolic rates than did the young subjects, in anterior, middle, and posterior temporal neocortex and in mesial temporal cortex, with the largest differences occurring in anterior temporal cortex (temporal pole). The current findings may reflect either decreases in regional cerebral metabolic rates for glucose that occur with normal aging, or early indications of cognitive dysfunction that is associated with age-related disorders.

Adult↗

New approaches to targeting arthritis with radiopharmaceuticals.

Though emission imaging techniques have been a major clinical tool for imaging osteoblastic activity and tumor involvement of the bony skeleton for over 20 years, radiolabelled probes specific for pathophysiology of synovium and articular cartilage are just beginning to be explored. Recent success with 99mTc labelled IgG, 18F-fluorodeoxyglucose, and antibodies to E-secretin encourage development of specific probes. The technology for radiolabelling peptide probes such as Mab and Fab with both positron emitters and conventional single photon emitters, the most recent concepts of labelling ssDNA aptamers specific for targeted proteins associated with diseases of the synovium and cartilage, and the availability of probes for substance P and porphyrin avid tissues has opened new horizons for studying the early onset of arthritis and therapeutic response to new forms of therapy.

Arthritis↗

Variability and reproducibility of rubidium-82 kinetic parameters in the myocardium of the anesthetized canine.

UNLABELLED: Kinetic analysis of 82Rb dynamic PET data produces quantitative measures which could be used to evaluate ischemic heart disease. These measures have the potential to generate objective comparisons of different patients or the same patient at different times. To achieve this potential, it is essential to determine the variability and reproducibility of the kinetic parameters. METHODS: A total of 48 82Rb dynamic PET datasets were acquired from two pure bred beagles. Each animal underwent eight 82Rb PET studies with essentially the same protocol for three successive weeks. Data were acquired with the Donner 600-Crystal Positron Tomograph (PET600). In each week, single-slice dynamic 82Rb PET datasets were collected with the animal at rest at three different gantry positions separated by 5 mm. Additional dataset were collected after dipyridamole infusion and after administration of aminophylline to induce a return to rest. A two-compartment kinetic model with correction for myocardial vasculature and spillover from the left ventricular blood pool was used to analyze the dynamic datasets. Model parameters for uptake (k1), washout (k2) and vascular fraction (fv) were estimated in 11-14 myocardial regions of interest (ROIs) using a weighted least-squares criterion. Statistical fluctuation due to the PET acquisition process was minimized by using a relatively high 82Rb dose (about 30 mCi) to take advantage of the high count rate capacity of the PET600. RESULTS: The variation in mean k1, where the mean is taken over the myocardial ROIs was 10%-20% (Dog 1) and 15%-50% (Dog 2) among the rest studies conducted on the same date. Similar variation was evident in comparing studies in the same animal for different weeks. CONCLUSION: Spatial and temporal variation in estimates of the uptake rate (k1) of 82Rb in the resting myocardium of the anesthetized canine are small in relation to the functional increase in k1 following dipyridamole infusion.

Aminophylline↗

Brain N-acetyl-L-aspartic acid in Alzheimer's disease: a proton magnetic resonance spectroscopy study.

This study was performed in order to measure changes in brain N-acetyl-L-aspartic acid (NAA) in post-mortem brain tissue in Alzheimer's disease (AD) in comparison to normal control subjects using the technique of magnetic resonance spectroscopy. Brain tissue was obtained at autopsy and frozen until use, from seven patients diagnosed according to current research criteria for AD and 7 control subjects. Detailed clinical evaluations were available for all the dementia cases. Representative brain samples were obtained from three neocortical regions and a limbic region (parahippocampal gyrus) in white and grey matter. NAA was quantified on perchloric acid extracts using proton nuclear magnetic resonance (NMR) spectroscopy. Regional NAA did not vary significantly with age. In AD, reductions were present in the grey matter of the neocortex but not in the white matter. Within the parahippocampal gyrus there were reductions in both tissue types; only cortical levels correlated with clinical scales of dementia severity. A pattern of increasing correlation was observed between dementia severity as measured by the mini mental state examination during life and NAA levels from brain areas of increasing pathological predilection in AD. These post-mortem studies show reductions in brain NAA in AD which correlate with dementia severity during life and which support the use of future in vivo NAA spectroscopic images in the evaluation of AD patients.

Aged↗

The cortical topography of temporal lobe hypometabolism in early Alzheimer's disease.

Alzheimer's disease (AD) is characterized by a pathological process with specific predilection for association neocortex and the mesial temporal lobes. Recently developed high-resolution positron emission tomographs (PET) are able to quantitate regional cerebral metabolic rates for glucose (rCMRglc) in these brain regions and map the distribution of the metabolic consequences of Alzheimer pathology. In order to evaluate the relative involvement of mesial and neocortical temporal lobe brain regions in AD, we studied 22 AD patients, 11 of whom were mildly demented and 11 of whom were moderately demented in comparison to 8 age-matched control subjects. We used a PET instrument with 2.6 mm in-plane resolution and quantitated rCMRglc in anterior, middle, and posterior temporal neocortex, visual association cortex, primary visual cortex, and mesial temporal cortex. Although the moderately demented AD patients showed significantly lower metabolic rates than controls in visual association cortex and all temporal lobe regions except right anterior temporal neocortex, the mildly demented patients were different from the controls in only middle temporal neocortex. Considerable variability was found in the relative involvement of mesial temporal lobes and temporal neocortex in the AD patients, however, as shown by greater variance of a ratio of mesial temporal lobe rCMRglc to temporal neocortical rCMRglc (MES/NEO ratio) in the AD patients than the controls. A series of stepwise multiple regressions showed that this ratio was related to patient cognitive symptomatology, with more severely memory-impaired patients showing lower MES/NEO ratios, while patients with visuospatial disturbances showed higher MES/NEO ratios. In addition, the only biological variable that was related to this ratio was patient age, with older patients showing lower MES/NEO ratios. These results indicate that mesial temporal lobe structures are not invariably the earliest nor the most severely metabolically involved brain regions in AD and that the relative involvement of the mesial and neocortical temporal lobe is related to the patient's cognitive symptoms and age.

Aged↗

High-resolution (2.6-mm) PET in partial complex epilepsy associated with mesial temporal sclerosis.

Eleven patients with medically refractory partial seizures underwent positron emission tomography (PET) with a 600-crystal tomograph and fluorine-18 fluorodeoxyglucose. All patients had been selected for temporal lobe resection, and the side of the epileptogenic focus had been demonstrated with electroencephalography (EEG). Only patients in whom structural lesions had been excluded with magnetic resonance (MR) imaging were studied. Ten of 11 patients were found to have temporal cortical hypometabolism on the same side as the focal abnormality that was demonstrated with EEG. In two patients, PET showed hypometabolism in the mesial temporal cortex only. There were no incorrectly lateralizing PET results. MR imaging showed an abnormality in the corresponding temporal lobe in seven patients. In one patient, both PET and MR images were normal. All patients underwent anterior temporal resection, and histologic examination of resected tissue showed mesial temporal sclerosis in all cases.

Adult↗

A study of radiation necrosis and edema in the canine brain using positron emission tomography and magnetic resonance imaging.

Radiation injury, a major hazard of central nervous system (CNS) radiotherapy, was investigated using sequential studies with positron emission tomography (PET) and magnetic resonance imaging (MRI) in beagle dogs with both helium and neon-ion hemibrain irradiation. All dogs receiving 7.5-11 Gy of neon showed no signs of radiation injury to 3 years after irradiation. Dogs receiving > or = 13 Gy neon or helium succumbed to radiation necrosis and died 21-32 weeks after irradiation. The findings of imaging studies for all dogs who succumbed to radiation necrosis were normal until 3-6 weeks before death. Sequential studies were performed using 0.5 T MRI spin-echo and inversion recovery imaging sequences, and high-resolution (2-3 mm) PET with 18F deoxyglucose and 82Rb. The same axial slices (within 1-2 mm) were imaged repeatedly (weekly) after irradiation until death. The earliest CNS changes were seen as decreased metabolic activity in the cortex of the irradiated hemisphere with PET or an increase in signal intensity in the periventricular white matter on T2-weighted spin-echo imaging on MRI. From the time this increase in signal intensity was first observed, T1 and T2 values increased steadily in both the gray and white matter until death. The changes in white matter were consistently greater than those in gray matter. The results of PET, MRI, and histopathological examinations support the theory that both cellular and vascular mechanisms are involved in radiation necrosis.

Animals↗

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↗