Biomedical subjects

R E Carson

Publications and source records attributed to R E Carson.

At least 55 records · Page 3Linked to original sources

PubMed1997

Effects of time delay in cardiac blood flow measurements by bolus H2(15)O.

Myocardial blood flow (rMBF) can be measured using dynamic positron emission tomography (PET) and bolus injection of H2(15)O. Recent studies indicate that large errors in the estimates of flow (f) can be produced by time shifts between the true arterial input function and the measured input function [A(t)]. We have investigated this phenomenon further using A(t) derived from patient data, and using simulated myocardial time activity curves [M(t)]. We found that with judicious choice of scan parameters and region of interest (ROI) placement, these errors can be greatly reduced. In particular, when A(t) is measured from the left ventricular (LV) cavity, the bias in f is negligible over a wide range of circumstances. However, when A(t) is not measured from the LV cavity, the bias in flow can be large for short scans (< 2 min) or low flow values (f < 0.4 ml/g/min). We show that the bias is primarily due to the spill-over term in the model that is most commonly used to compute rMBF and suggest some correction methods. We conclude that it is possible to avoid errors in estimates of flow due to time delay.

Blood Flow Velocity↗

PubMed1997

Multimodality Bayesian algorithm for image reconstruction in positron emission tomography: a tissue composition model.

The use of anatomical information to improve the quality of reconstructed images in positron emission tomography (PET) has been extensively studied. A common strategy has been to include spatial smoothing within boundaries defined from the anatomical data. We present an alternative method for the incorporation of anatomical information into PET image reconstruction, in which we use segmented magnetic resonance (MR) images to assign tissue composition to PET image pixels. We model the image as a sum of activities for each tissue type, weighted by the assigned tissue composition. The reconstruction is performed as a maximum a posteriori (MAP) estimation of the activities of each tissue type. Two prior functions, defined for tissue-type activities, are considered. The algorithm is tested in realistic simulations employing a full physical model of the PET scanner.

Algorithms↗

PubMed1996

Nutritional status and lipid profiles of trained steroid-using bodybuilders.

Fourteen trained male anabolic steroid-using bodybuilders (SBBs) (19-41 years) were recruited for the study. Three-day diet records were obtained from SBBs and analyzed. A resting venous blood sample was drawn, and serum/plasma was subsequently analyzed for various nutritionally related factors. Results showed that mean dietary energy (4,469 +/- 1,406 kcal), protein 252 +/- 109 g), and vitamin and mineral intakes of SBBs greatly exceeded U.S. Recommended Dietary Allowances. Dietary cholesterol intake was 2.8 times the recommended levels. Mean serum/plasma nutrient concentrations of SBBs were within normal range. However, individual SBBs had a number of serum/plasma values outside of the normal or recommended range, the most notable of which was hypercalcemia, which was present in 42% of SBBs. Serum/plasma lipids were such as to increase the risk of cardiovascular disease in these subjects.

Adult↗

PubMed1996

Hyperosmolar blood-brain barrier disruption in baboons: an in vivo study using positron emission tomography and rubidium-82.

Hyperosmolar blood-brain barrier (BBB) disruption remains controversial as an adjuvant therapy to increase delivery of water-soluble compounds to extracellular space in the brain in patients with malignant brain tumors. To understand the physiological effects of BBB disruption more clearly, the authors used positron emission tomography (PET) to study the time course of BBB permeability in response to the potassium analog rubidium-82 (82Rb, halflife 75 seconds) following BBB disruption in anesthetized adult baboons. Mannitol (25%) was injected into the carotid artery and PET scans were performed before and serially at 8-to 15-minute intervals after BBB disruption. The mean influx constant (K1), a measure of permeability-surface area product, in ipsilateral, mannitol-perfused mixed gray- and white-matter brain regions was 4.9 +/-2.4 microliter/min/ml (+/- standard deviation) at baseline and increased more than 100% (delta K1=9.4 +/-5.1 microliter/min/ml, 18 baboons) in brain perfused by mannitol. The effect of BBB disruption on K1 correlated directly with the total amount of mannitol administered (p< 0.005). Vascular permeability returned to baseline with a halftime of 24.0 +/- 14.3 minutes. The mean brain plasma volume rose by 0.57 +/- 0.34 ml/100 ml in ipsilateral perfused brain following BBB disruption. This work provides a basis for the in vivo study of permeability changes induced by BBB disruption in human brain and brain tumors.

Animals↗

PubMed1996

Quantification and pharmacokinetics of blood-brain barrier disruption in humans.

Hyperosmolar blood-brain barrier disruption (HBBBD), produced by infusion of mannitol into the cerebral arteries, has been used in the treatment of brain tumors to increase drug delivery to tumor and adjacent brain. However, the efficacy of HBBBD in brain tumor therapy has been controversial. The goal of this study was to measure changes in vascular permeability after HBBBD in patients with malignant brain tumors. The permeability (K1) of tumor and normal brain blood vessels was measured using rubidium-82 and positron emission tomography before and repeatedly at 8- to 15-minute intervals after HBBBD. Eighteen studies were performed in 13 patients, eight with glioblastoma multiforme and five with anaplastic astrocytoma. The HBBBD increased K1 in all patients. Baseline K1 values were 2.1 +/- 1.4 and 34.1 +/- 22.1 microl/minute/ml (+/- standard deviation) for brain and tumor, respectively. The peak absolute increases in K1 following HBBBD were 20.8 +/- 11.7 and 19.7 +/- 10.7 microl/minute/ml for brain and tumor, corresponding to percentage increases of approximately 1000% in brain and approximately 60% in tumor. The halftimes for return of K1 to near baseline for brain and tumor were 8.1 +/- 3.8 and 4.2 +/- 1.2 minutes, respectively. Simulations of the effects of HBBBD made using a very simple model with intraarterial methotrexate, which is exemplary of drugs with low permeability, indicate that 1) total exposure of the brain and tumor to methotrexate, as measured by the methotrexate concentration-time integral (or area under the curve), would increase with decreasing infusion duration and would be enhanced by 130% to 200% and by 7% to 16%, respectively, compared to intraarterial infusion of methotrexate alone; and 2) exposure time at concentrations above 1 microM, the minimal concentration required for the effects of methotrexate, would not be enhanced in tumor and would be enhanced by only 10% in brain. Hyperosmolar blood-brain barrier disruption transiently increases delivery of water-soluble compounds to normal brain and brain tumors. Most of the enhancement of exposure results from trapping the drug within the blood-brain barrier, an effect of the very transient alteration of the blood-brain barrier by HBBBD. Delivery is most effective when a drug is administered within 5 to 10 minutes after disruption. However, the increased exposure and exposure time that occur with methotrexate, the permeability of which is among the lowest of the agents currently used clinically, are limited and the disproportionate increase in brain exposure, compared to tumor exposure, may alter the therapeutic index of many drugs.

Adult↗

PubMed1996

Effect of smoothing during transmission processing on quantitative cardiac PET scans.

UNLABELLED: The effects of attenuation in cardiac PET are large and are produced by varied and inhomogeneous attenuating media. Although a measured attenuation correction can potentially provide an exact correction for attenuation, it introduces noise into the attenuation-corrected emission scan. Transmission smoothing reduces this noise but can introduce error of its own. This study investigates these errors in absolute and relative quantitation and estimates their magnitude in a clinical setting. METHODS: Fluorodeoxyglucose cardiac PET scans of 24 subjects were processed using measured attenuation correction with different levels of transmission smoothing. Mean activity concentrations were determined in septal, anterior and lateral regions of the left ventricle at each level of transmission smoothing. A theoretical derivation of the effects of transmission smoothing is presented, so that the observed effects could be compared with theory-based predictions. RESULTS: In addition to the reduction of noise, transmission smoothing produced two further effects: (a) a previously unreported reduction in noise-induced bias, which is beneficial and (b) introduction of errors due to bad estimates of attenuation correction factors resulting from smoothing over regions where attenuation changes. The first effect was observed over all regions of the left ventricle, whereas the second reduced counts primarily in the lateral wall. Twenty-millimeter smoothing reduced noise-induced bias by an average of 4% (compared with 6-mm smoothing). This same smoothing caused an additional 9% decrease in the lateral wall as a result of the adjacent lung-lateral wall boundary. CONCLUSION: Transmission smoothing reduces both noise and noise-induced bias, but near transitions between differently attenuating media (e.g., lung-myocardial borders) may produce errors in absolute and relative quantitation. The data presented here document the magnitudes of these effects, permitting one to ensure that artifactually introduced inhomogeneities are kept small.

Artifacts↗

PubMed1996

Noise reduction in PET attenuation correction by maximum likelihood histogram sharpening of attenuation images.

UNLABELLED: A new method for PET transmission data processing was developed and found to reduce transmission noise in 18F-FDG cardiac emission images. This method is based on a model that describes the measured attenuation image histogram as some unknown true underlying histogram, blurred by noise. METHODS: Emission data from an elliptical phantom (cardiac insert) and three humans were reconstructed using transmission data of varying duration with varying levels of smoothing. Biases and noise levels (cardiac sector analysis) were evaluated for the phantom (simulated replicates) and human emission images. RESULTS: The estimated attenuation histograms typically displayed three distinct peaks corresponding to air, lung and soft tissue without a priori assumptions of the underlying mu values. This method effectively sharpened the histogram peaks and performed well for the phantom and human data. For intermediate transmission noise levels, biases in the phantom sector values were <4%. The human sector results were more variable but consistent with the phantom results. Noise reduction (approximately 30%) was demonstrated across all smooth levels for the phantom data. CONCLUSION: This histogram sharpening method introduces only small bias in the cardiac sector values while achieving an increase in effective transmission scan time of 50-100%. Alternatively, histogram sharpening permits less transmission data smoothing without increased noise.

Algorithms↗

PubMed1995

Benzodiazepine receptors mediate regional blood flow changes in the living human brain.

We studied the effects of a high-affinity gamma-aminobutyric acid (GABA)-benzodiazepine-receptor agonist (lorazepam) and an antagonist (flumazenil) in humans, using H2(15)O positron-emission tomography. Administration of lorazepam to healthy volunteers caused time- and dose-dependent reductions in regional cerebral blood flow and self-reported alterations in behavioral/mood parameters. Flumazenil administration reversed these changes. These observations indicated that benzodiazepine-induced effects on regional cerebral blood flow and mood/behavior are mediated at some level through GABA-benzodiazepine receptors, although the specific mechanism remains unclear. The approach described here provides a method for quantifying GABA-benzodiazepine-receptor-mediated neurotransmission in the living human brain and may be useful for studying the role of these receptors in a variety of neuropsychiatric disorders.

Adult↗

PubMed1995

Physiological activation of a cortical network during performance of the Wisconsin Card Sorting Test: a positron emission tomography study.

To determine the neural circuitry engaged by performance of the Wisconsin Card Sorting Test (WCST), a neuropsychological test traditionally considered to be sensitive to prefrontal lesions, regional cerebral blood flow was measured with oxygen-15 water and positron emission tomography (PET) while young normal subjects performed the test as well as while they performed a specially designed sensorimotor control task. To consider which of the various cognitive operations and other experiential phenomena involved in the WCST PET scan are critical for the pattern of physiological activation and to focus on the working memory component of the test, repeat WCST scans were also performed on nine of the subjects after instruction on the test and practice to criteria. We confirmed that performance of the WCST engages the frontal cortex and also produces activation of a complex network of regions consistently including the inferior parietal lobule but also involving the visual association and inferior temporal cortices as well as portions of the cerebellum. The WCST activation in the dorsolateral prefrontal cortex (DLPFC) remained significant even after training and practice on the test, suggesting that working memory may be largely responsible for the physiological response in DLPFC during the WCST and, conversely, that the DLPFC plays a major role in modulating working memory.

Adolescent↗

PubMed1995

The functional neuroanatomy of Tourette's syndrome: an FDG-PET Study. II: Relationships between regional cerebral metabolism and associated behavioral and cognitive features of the illness.

We analyzed F-18 fluoro-deoxyglucose PET scans carried out in 18 drug-free patients with Tourette's syndrome (TS) in order to evaluate relationships between cerebral metabolism and complex cognitive and behavioural features commonly associated with this disorder. These features (obsessions and compulsions, impulsivity, coprolalia, self-injurious behavior, echophenomena, depression, and measures of attentional and visuospatial dysfunction) were associated with significant increases in metabolic activity in the orbitofrontal cortices. Similar increases, although less robust, were observed in the putamen and, in the case of attentional and visuospatial measures, in the inferior portions of the insula. On the other hand, behavioral and cognitive features were not associated with metabolic rates in other subcortical (midbrain, ventral striatum), paralimbic (parahippocampal gyrus), or sensorimotor regions (supplementary motor area, lateral premotor or Rolandic cortices), in which metabolism had, in some cases more robustly, distinguished these TS patients from controls (Braun et al., 1993). These results suggest that a subset of regions in which metabolic activity appears to be associated with the diagnosis of TS per se, may be explicitly associated with the emergence of complex behavioral and cognitive features of the illness. This is most conspicuous in the orbitofrontal cortices, and it is consistent with the observation that these features resemble the elements of a behavioral syndrome typically seen in patients with lesions of the orbitofrontal cortex.

Adult↗

PubMed1995

Frequency of self-reported medical conditions in periodontal patients.

Assessing the medical history of patients before any treatment is provided is an essential aspect of the periodontist's responsibility. A patient's compromised medical state could alter the response to periodontal treatment or worse, contribute to a crisis situation that may prove harmful to his or her well-being. This study examines the frequency of medical conditions in periodontal patients utilizing a self-administered health questionnaire succeeded by directly interviewing the patient for validity. Health histories were taken from 590 periodontal patients in an outpatient setting; 52.5% of these patients reported a positive finding in their medical history, with drug allergies and cardiovascular disorders being by far the most frequently found conditions. The frequency of medical conditions increased with increasing age. Thorough evaluation of a patient's health history is a mandatory first step in the treatment process.

Adolescent↗

PubMed1994

A kinetic comparison of [18F]2-fluoro-2-deoxyglucose and [18F]2-fluoro-2-deoxymannose using positron emission tomography.

Rate constants and fractional metabolic rates were estimated for the stereoisomers [18F]2-fluoro-2-deoxyglucose (FDG) and [18F]2-fluoro-2-deoxymannose (FDM) in 5 male baboons using positron emission tomography. Each animal, serving as its own control, was injected with both compounds under controlled physiological conditions. Results indicate that there is a 20% reduction in apparent cerebral metabolic rates for glucose when FDM is used as the analogue. This suggests that as supplies of 18O become depleted, the presence of FDM as an impurity should warrant consideration in the choice of alternatives to no-carrier-added FDG synthesis.

Animals↗

PubMed1994

Whither water?

Explore the source record for details and available documents.

Coronary Circulation↗

PubMed1993

Comparison of bolus and infusion methods for receptor quantitation: application to [18F]cyclofoxy and positron emission tomography.

Positron emission tomography studies with the opiate antagonist [18F]cyclofoxy ([18F]CF) were performed in baboons. Bolus injection studies demonstrated initial uptake dependent on blood flow. The late uptake showed highest binding in caudate nuclei, amygdala, thalamus, and brainstem and the least accumulation in cerebellum. By 60 min postinjection, regional brain radioactivity cleared at the same rate as metabolite-corrected plasma, i.e., transient equilibrium was achieved. Compartmental modeling methods were applied to time-activity curves from brain and metabolite-corrected plasma. Individual rate constants were estimated with poor precision. The model estimate of the total volume of distribution (VT), representing the ratio of tissue radioactivity to metabolite-corrected plasma at equilibrium, was reliably determined. The apparent volume of distribution (Va), the concentration ratio of tissue to metabolite-corrected plasma during transient equilibrium, was compared with the fitted VT values to determine if single-scan methods could provide accurate receptor measurements. Va significantly overestimated VT and produced artificially high image contrast. These differences were predicted by compartment model theory and were caused by a plasma clearance rate that was close to the slowest tissue clearance rate. To develop a simple method to measure VT, an infusion protocol consisting of bolus plus continuous infusion (B/I) of CF was designed and applied in a separate set of studies. The Va values from the B/I studies agreed with the VT values from both B/I and bolus studies. This infusion approach can produce accurate receptor measurements and has the potential to shorten scan time and simplify the acquisition and processing of scan and blood data.

Algorithms↗

PubMed1993

Reproducibility of resting cerebral blood flow measurements with H2(15)O positron emission tomography in humans.

Two consecutive measurements of resting CBF were carried out in normal volunteers (n = 25) using H2(15)O positron emission tomography. Absolute whole-brain blood flow (WBBF; ml 100 g-1 min-1, mean +/- SD) for the first (40.3 +/- 6.4) and second (39.3 +/- 6.5) measurements was not significantly different (mean % difference 2.3 +/- 8.7). Analysis of regions of interest showed no significant differences in absolute regional CBF (rCBF) and normalized (rCBF/WBBF) rCBF. Left-right differences were also not significant. These data demonstrate the reproducibility of resting CBF measurements in normal humans.

Adult↗

PubMed1993

The functional neuroanatomy of Tourette's syndrome: an FDG-PET study. I. Regional changes in cerebral glucose metabolism differentiating patients and controls.

Regional metabolic rates for glucose estimated using [18F]fluorodeoxyglucose positron-emission tomography were compared in 16 drug-free patients with Tourette's syndrome (TS) and 16 age- and sex-matched normal volunteers. Tourette's syndrome patients were characterized by decreased normalized metabolic rates in paralimbic and ventral prefrontal cortices, particularly in orbitofrontal, inferior insular, and parahippocampal regions. Similar decreases were observed in subcortical regions, including the ventral striatum (nucleus accumbens/ventromedial caudate) and in the midbrain. These changes were more robust and occurred with greater frequency in the left hemisphere. They were associated with concomitant bilateral increases in metabolic activity the supplementary motor, lateral premotor, and Rolandic cortices. Effects of prior exposure to neuroactive drugs did not account for these findings. These results suggest that an altered relationship between limbic-related regions of the cortex and striatum and cortical regions involved in the initiation of movement may play a role in the pathogenesis of this illness.

Adult↗

PubMed1993

Three-dimensional registration of cardiac positron emission tomography attenuation scans.

A method is described and tested which allows three-dimensional registration of two cardiac PET attenuation scans of the same subject acquired at different times. The alignment method is based on maximizing the correlation coefficient between the stacks of slices obtained during each of the two imaging sessions. The method appears accurate to better than 1 mm in x, y and z, and better than 1.5 degrees in the three angles of rotation. The method has been tested by using it to realign deliberately misaligned attenuation scans, and also by using realigned attenuation scans to correct fluorodeoxyglucose (FDG) emission scan data. The FDG emission data reconstructed with the realigned attenuation scans do not differ appreciably from the FDG data obtained using the original attenuation data. The method should be useful in realigning emission data (using the alignment coordinates predicted by realigning the attenuation scans), correcting for subject motion between scans (especially multiple intervention scans) and may allow a subject to leave the scanning table between scans during long imaging sessions.

Deoxyglucose↗

PubMed1992

PET imaging of opiate receptor binding in human epilepsy using [18F]cyclofoxy.

We used [18F]cyclofoxy (CF), a potent opiate antagonist with affinity for mu and kappa receptors, and the Scanditronix PC1024-7B PET scanner to study 14 patients with complex partial seizures (CPS), and 14 normal controls. Epileptic foci were localized by prolonged EEG-video monitoring. EEG was recorded continuously during each scan. Immediately before CF administration, [15O]labeled water was used to measure cerebral blood flow, and showed hypoperfusion ipsilateral to the EEG focus. Blood samples (corrected for radiolabeled metabolites) and tissue time-activity data were acquired over 90 min following bolus CF injection. Anatomic regions were outlined directly on the PET images. A kinetic model was used to derive the total volume of distribution (Vt) in each brain region. Specific binding (Vs) was determined by substracting non-specific binding (Vt) measured in a receptor-poor brain region (occipital cortex). Regions with high Vs included mesial temporal lobes, thalamus, basal ganglia, and frontal cortex. Individual patients appeared to have higher binding in temporal lobe ipsilateral to the EEG focus, but there was no asymmetry for the patients as a group in mean Vt or Vs in anterior mesial, posterior mesial, anterior lateral, posterior lateral temporal cortex, thalamus, basal ganglia, or, for Vt, in regions of low specific binding: occipital lobe, parietal lobe, cerebellum.

Adolescent↗