Biomedical subjects

R E Carson

Publications and source records attributed to R E Carson.

At least 37 records · Page 2Linked to original sources

PubMed1999

Comparison of PET [15O]water studies with 6-minute and 10-minute interscan intervals: single-subject and group analyses.

The authors recently showed that [15O]water PET data obtained with a short interscan interval (6 minutes) produced similar results whether or not the residual background from the previous scan is subtracted. The purpose of the present study was to compare scans obtained during motor activation using a short (6-minute) interscan interval protocol with those obtained with a standard (10-minute) protocol in the same scanning session. Single-subject and group analyses were performed using Worsley's method, which uses a pooled variance estimate and statistical parametric mapping with a local variance estimate. High consistency in both the activation maps, i.e., the number of activated motor brain structures and the Talairach coordinates of peak intensities of the activated regions, was obtained in the 6- and 10-minute studies in both single-subject and group analyses. However, in comparison to the 6-minute studies, a larger cluster size of activated brain regions and an approximately 20% higher peak activation in these regions were observed in the 10-minute studies with the same number of replicates. Analysis of these results suggests that using a 6-minute interval with an increased number of replications, i.e., without changing the subject's total study duration, should produce comparable statistical power to that of the 10-minute interval for group analysis and increased statistical power for single-subject analyses that use a local variance estimate because of increased degrees of freedom. Alternatively, with a small increase in the number of scans and the use of a 6-minute interscan interval, a comparable level of statistical significance may be achieved for single-subject experiments that use a local variance estimate, with an overall shortening of the study duration.

Adult↗

PubMed1999

Bolus injection versus slow infusion of [15O]water for positron emission tomography activation studies.

In positron emission tomography studies using bolus injection of [15O]water, activation responses reflect underlying CBF changes during a short time (15 to 20 seconds) after arrival of the bolus in the brain. This CBF sensitivity window may be too short for complex activation paradigms, however, particularly those of longer duration. To perform such paradigms, we used a slow infusion method of tracer administration to lengthen the CBF sensitivity window. The present study was designed to determine if this slow infusion technique yields similar results to a bolus injection with a short activation task involving memory for faces. When analyzed using statistical parametric mapping, scanning durations of either 90 or 120 seconds and a 90-second slow infusion schedule produced very similar results to a standard 60-second scan collected after bolus injection, indicating that statistically similar brain activation maps can be produced with the two infusion techniques. This slow infusion approach allows for increased flexibility in designing future studies in which a short CBF sensitivity window is a limiting factor.

Adult↗

PubMed1998

Opiate receptor avidity is reduced in non-motor impaired MPTP-lesioned rhesus monkeys.

Opiate receptor avidity, roughly equivalent to the ratio of unoccupied receptor density to the receptor dissociation constant (B'max/KD), was measured in four MPTP (1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine)-lesioned rhesus monkeys and nine normal controls with positron emission tomography (PET) and 6-deoxy-6-beta-[18F]fluoronaltrexone (cyclofoxy, CF), a mu- and kappa-opiate receptor antagonist. Although the MPTP-lesioned monkeys were dopamine deficient as measured with [18F]-L-fluorodopa ([18F]-DOPA) and PET [Doudet et al., 6-[18F]-L-DOPA imaging of the dopamine neostriatal system in normal and clinically normal-MPTP-treated rhesus monkeys, Exp. Brain Res. 78 (1989) 69-80], they had clinically recovered from the acute motor effects of MPTP exposure. Opiate receptor avidity was found to be reduced by 30-35% in the opiate-receptor rich areas of caudate, anterior putamen, thalamus, and amygdala of the MPTP-lesioned animals. The results suggest that opiate pathways make a significant contribution to the adjustment of cortico-striatal-thalamic pathway activity and thereby to behavior in rhesus monkeys following dopamine loss.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed1998

Dissociated pattern of activity in visual cortices and their projections during human rapid eye movement sleep.

Positron emission tomography was used to measure cerebral activity and to evaluate regional interrelationships within visual cortices and their projections during rapid eye movement (REM) sleep in human subjects. REM sleep was associated with selective activation of extrastriate visual cortices, particularly within the ventral processing stream, and an unexpected attenuation of activity in the primary visual cortex; increases in regional cerebral blood flow in extrastriate areas were significantly correlated with decreases in the striate cortex. Extrastriate activity was also associated with concomitant activation of limbic and paralimbic regions, but with a marked reduction of activity in frontal association areas including lateral orbital and dorsolateral prefrontal cortices. This pattern suggests a model for brain mechanisms subserving REM sleep where visual association cortices and their paralimbic projections may operate as a closed system dissociated from the regions at either end of the visual hierarchy that mediate interactions with the external world.

Adult↗

PubMed1998

Axial slice width in 3D PET: characterization and potential improvement with axial interleaving.

The axial slice width for the GE Advance PET scanner has previously been reported to be worse for 3D acquisitions than for 2D. The goals of this study were to investigate the source(s) of this observed difference and to assess whether the 3D axial slice width could be significantly improved by acquisition and simultaneous reconstruction of axially interleaved data. The axial slice width was measured for the three acquisition modes of the Advance scanner ('standard' high-sensitivity 2D, high-resolution 2D and 3D), with the septa both extended and retracted. A significant degradation in the axial slice width for 3D compared with that for high-sensitivity 2D mode was seen. Near the centre, this difference can largely be attributed to septa collimation effects of the 2D data. At larger radial positions, axial mispositioning of cross-coincidences in 2D acquisitions overshadows the effects of septa collimation, while 3D reconstruction effects also become more important. The axial slice width was estimated to improve by 0.3-1.1 mm with interleaving. This modest improvement would be accompanied by an increase in image noise, since an axial filter with a higher cut-off would be required in the 3D reconstruction to achieve this resolution in the image.

Equipment Design↗

PubMed1998

Positron emission tomography [15O]water studies with short interscan interval for single-subject and group analysis: influence of background subtraction.

Use of short interscan interval [15O]water positron emission tomography (PET) studies reduces the overall study duration and may allow an increased number of scans for single-subject analysis of unique cases (e.g., stroke). The purpose of this study was to examine how subtraction of residual radioactivity from the previous injection (corrected scan) compared to nonsubtraction (uncorrected scan) in a PET short interscan interval (6 minutes) study affects single-subject and group data analysis using a motor activation task. Two currently widely used analytic strategies, Worsley's method and the SPM technique, were applied. Excellent agreement between activation maps obtained from corrected and uncorrected data sets was obtained both in single-subject analyses performed on data sets from the six normal subjects and three stroke (subcortical infarct) patients, and in group analysis (six normal subjects) within a particular statistical method. The corrected and uncorrected data were very similar in the (1) number of activated brain regions; (2) size of clusters of activated brain voxels; (3) Talairach coordinates of the activated region; and (4) t or Z value of the peak intensity for every significantly activated motor brain structure (both for large activations such as in motor cortex and small activations such as in putamen and thalamus). [15O]Water PET data obtained with a short interscan interval (6 minutes) produce similar results whether or not the background is subtracted. Thus, if injection dose and timing are constant, one can achieve the advantage of a short interscan interval without the added complexity of correcting for background radioactivity.

Adult↗

PubMed1998

Muscarinic cholinergic receptor measurements with [18F]FP-TZTP: control and competition studies.

[18F]Fluoropropyl-TZTP (FP-TZTP) is a subtype-selective muscarinic cholinergic ligand with potential suitability for studying Alzheimer's disease. Positron emission tomography studies in isofluorane-anesthetized rhesus monkeys were performed to assess the in vivo behavior of this radiotracer. First, control studies (n = 11) were performed to characterize the tracer kinetics and to choose an appropriate model using a metabolite-corrected arterial input function. Second, preblocking studies (n = 4) with unlabeled FP-TZTP were used to measure nonspecific binding. Third, the sensitivity of [18F]FP-TZTP binding to changes in brain acetylcholine (ACh) was assessed by administering physostigmine, an acetylcholinesterase (AChE) inhibitor, by intravenous infusion (100 to 200 microg x kg(-1) x h(-1)) beginning 30 minutes before tracer injection (n = 7). Tracer uptake in the brain was rapid with K1 values of 0.4 to 0.6 mL x min(-1) x mL(-1) in gray matter. A model with one tissue compartment was chosen because reliable parameter estimates could not be obtained with a more complex model. Volume of distribution (V) values, determined from functional images created by pixel-by-pixel fitting, were very similar in cortical regions, basal ganglia, and thalamus, but significantly lower (P < 0.01) in the cerebellum, consistent with the distribution of M2 cholinergic receptors. Preblocking studies with unlabeled FP-TZTP reduced V by 60% to 70% in cortical and subcortical regions. Physostigmine produced a 35% reduction in cortical specific binding (P < 0.05), consistent with increased ACh competition. The reduction in basal ganglia (12%) was significantly smaller (P < 0.05), consistent with its markedly higher AChE activity. These studies indicate that [18F]FP-TZTP should be useful for the in vivo measurement of muscarinic receptors with positron emission tomography.

Acetylcholine↗

PubMed1998

Assessment of dynamic neurotransmitter changes with bolus or infusion delivery of neuroreceptor ligands.

To describe the effect of endogenous dopamine on [11C]raclopride binding, we previously extended the conventional receptor ligand model to include dynamic changes in neurotransmitter concentration. Here, we apply the extended model in simulations of neurotransmitter competition studies using either bolus or bolus-plus-infusion (B/I) tracer delivery. The purpose of this study was (1) to develop an interpretation of the measured change in tracer binding in terms of underlying neurotransmitter changes, and (2) to determine tracer characteristics that maximize sensitivity to neurotransmitter release. A wide range of kinetic parameters was tested based on existing reversible positron emission tomography tracers. In simulations of bolus studies, the percent reduction in distribution volume (deltaV) caused by a neurotransmitter pulse was calculated. For B/I simulations, equilibrium was assumed, and the maximum percent reduction in tissue concentration (deltaC) after neurotransmitter release was calculated. Both deltaV and deltaC were strongly correlated with the integral of the neurotransmitter pulse. The values of deltaV and deltaC were highly dependent on the kinetic properties of the tracer in tissue, and deltaV could be characterized in terms of the tissue free tracer concentration. The value of deltaV was typically maximized for binding potentials of approximately 3 to 10, with deltaC being maximized at binding potentials of approximately 1 to 2. Both measures increased with faster tissue-to-blood clearance of tracer and lower nonspecific binding. These simulations provide a guideline for interpreting the results of neurotransmitter release studies and for selecting radiotracers and experimental design.

Brain↗

PubMed1998

Noise characteristics of 3-D and 2-D PET images.

We analyzed the noise characteristics of two-dimensional (2-D) and three-dimensional (3-D) images obtained from the GE Advance positron emission tomography (PET) scanner. Three phantoms were used: a uniform 20-cm phantom, a 3-D Hoffman brain phantom, and a chest phantom with heart and lung inserts. Using gated acquisition, we acquired 20 statistically equivalent scans of each phantom in 2-D and 3-D modes at several activity levels. From these data, we calculated pixel normalized standard deviations (NSD's), scaled to phantom mean, across the replicate scans, which allowed us to characterize the radial and axial distributions of pixel noise. We also performed sequential measurements of the phantoms in 2-D and 3-D modes to measure noise (from interpixel standard deviations) as a function of activity. To compensate for the difference in axial slice width between 2-D and 3-D images (due to the septa and reconstruction effects), we developed a smoothing kernel to apply to the 2-D data. After matching the resolution, the ratio of image-derived NSD values (NSD2D/NSD3D)2 averaged throughout the uniform phantom was in good agreement with the noise equivalent count (NEC) ratio (NEC3D/NEC2D). By comparing different phantoms, we showed that the attenuation and emission distributions influence the spatial noise distribution. The estimates of pixel noise for 2-D and 3-D images produced here can be applied in the weighting of PET kinetic data and may be useful in the design of optimal dose and scanning requirements for PET studies. The accuracy of these phantom-based noise formulas should be validated for any given imaging situation, particularly in 3-D, if there is significant activity outside the scanner field of view.

Artifacts↗

PubMed1997

Opiate receptor avidity and cerebral blood flow in Alzheimer's disease.

Positron emission tomography was performed on 12 Alzheimer's patients and 12 age-matched normal controls following the administration of the opiate receptor antagonist 6-deoxy-6-beta-[18F]fluoronaltrexone (cyclofoxy, CF). Tracer kinetic analysis was used to determine the volume of distribution of CF, a measure of unoccupied mu and kappa receptor density, i.e. opiate receptor avidity in 34 brain regions. Regional cerebral blood flow rates (CBF) were determined on the same day with H2[15O]. Global gray CF avidity and global gray CBF were found to be lower in the Alzheimer's patients and correlated (r=0.73, P<0.03). Regional CBF differences were superimposed on global CBF changes in the Alzheimer's patients, with the subcortex relatively spared. Multivariate statistical analyses, however, failed to demonstrate regional specificity for the CF avidity changes. Furthermore, percent changes in regional CF avidity were not correlated with percent changes in regional CBF (r=0.12, P=NS). These findings demonstrate involvement of the opiate system in Alzheimer's disease. Although, neurodegeneration is the likely underlying process responsible for both the changes in CF avidity and CBF in Alzheimer's disease, the differences with respect to the patterns of these losses suggest that the intermediate mechanisms leading from neurodegeneration to loss are distinct.

Aged↗

PubMed1997

Schizophrenia is associated with elevated amphetamine-induced synaptic dopamine concentrations: evidence from a novel positron emission tomography method.

A major line of evidence that supports the hypothesis of dopamine overactivity in schizophrenia is the psychomimetic potential of agents such as amphetamine that stimulate dopamine outflow. A novel brain imaging method provides an indirect measure of in vivo synaptic dopamine concentration by quantifying the change in dopamine receptor radiotracer binding produced by agents that alter dopamine release but do not themselves bind to dopamine receptors. The purpose of this investigation is (i) to determine the sensitivity (i.e., amount of dopamine reflected in radiotracer binding changes) of this method by examining the relationship between amphetamine-induced changes in simultaneously derived striatal extracellular dopamine levels with in vivo microdialysis and striatal binding levels with the dopamine D2/D3 positron-emission tomography radioligand [11C]raclopride in nonhuman primates, and (ii) to test the hypothesis of elevated amphetamine-induced synaptic dopamine levels in schizophrenia. In the nonhuman primate study (n = 4), doubling the amphetamine dose produced a doubling in [11C]raclopride specific binding reductions. In addition, the ratio of percent mean dopamine increase to percent mean striatal binding reduction for amphetamine (0.2 mg/kg) was 44:1, demonstrating that relatively small binding changes reflect large changes in dopamine outflow. In the clinical study, patients with schizophrenia (n = 11) compared with healthy volunteers (n = 12) had significantly greater amphetamine-related reductions in [11C]raclopride specific binding (mean +/- SEM): -22.3% (+/-2.7) vs. -15.5% (+/-1.8),P = 0.04, respectively. Inferences from the preclinical study suggest that the patients' elevation in synaptic dopamine concentrations was substantially greater than controls. These data provide direct evidence for the hypothesis of elevated amphetamine-induced synaptic dopamine concentrations in schizophrenia.

Amphetamine↗

PubMed1997

Measurement of transferrin receptor kinetics in the baboon liver using dynamic positron emission tomography imaging and [18F]holo-transferrin.

We have evaluated the use of [18F]holo-transferrin ([18F]Tf) and positron emission tomography (PET) to measure in vivo Tf receptor expression and recycling using the baboon liver as a model. [18F]Tf was intravenously injected in three baboons and dynamic PET was performed over the region containing liver and spleen. In two of the three baboons, [18F]albumin ([18F]Alb), labeled with the same technique, was administered 3 hours later. Time activity curves (TACs) were obtained from liver and spleen for both tracers. TACs for [18F]Tf over the liver were fit to a pharmacokinetic model including vascular radioactivity and an extravascular tissue compartment corresponding to transferrin uptake and release. [18F]Alb data provided an independent estimate of plasma volume. Kinetic analysis showed the presence of a tissue compartment for [18F]Tf that rapidly reaches equilibrium (half time 7-10 minutes). In this organ, the measured rates for Tf turnover obtained with quantitative PET are similar to previously published data using cell culture systems. A model for [18F]Tf in the spleen was not statistically improved by adding a tissue compartment. These data and the pharmacokinetic modeling provide in vivo evidence of a high flux equilibrium binding compartment in the liver, consistent with Tf internalization and recycling.

Albumins↗

PubMed1997

In vivo muscarinic binding selectivity of (R,S)- and (R,R)-[18F]-fluoromethyl QNB.

We have developed a multistep radiochemical synthesis of two diastereomers of quinuclidinyl-4-[18F]-fluoromethyl-benzilate ([18F]-FMeQNB), a high-affinity ligand for muscarinic acetylcholine receptors. Previously, we have shown that the nonradioactive (R,R)-diastereomer displays an eightfold selectivity for M1 over M2 while the nonradioactive (R,S)-diastereomer displays a sevenfold selectivity for M2 over M1 in vitro. This paper reports the results of in vivo comparison studies. In the rat, uptake of (R,S)-[18F]-FMeQNB was nearly uniform in all brain regions following the concentration of M2 subtype. The uptake was reduced by 36-54% in all brain regions on coinjection with 50 nmol of unlabeled ligand. An injection of (R,S)-[18F]-FMeQNB followed at 60 min by injection of unlabeled ligand and subsequent sacrifice at 120 min displaced 30-50% of radioactivity in the pons, medulla, and cerebellum, which contain a high proportion of M2 subtype. The most dramatic displacement and inhibition of uptake on coinjection of (R,S)-[18F]-FMeQNB was observed in the heart. In rhesus monkey, the compound showed prolonged uptake and retention in the brain. In the blood, the parent compound degraded rapidly to a single radiolabeled polar metabolite believed to be fluoride. Within 30 min the parent compound represented less than 5% of the plasma activity. Displacement with (R)-QNB was generally slow, but was more rapid from those tissues which contain a higher proportion of M2 subtype. The results are consistent with the hypothesis that (R,S)-[18F]-FMeQNB is M2 selective in vivo. On the other hand, (R,R)-[18F]-FMeQNB showed higher uptake in those brain regions containing a higher concentration of M1 subtype. Uptake in the heart at 60 min was much lower than that observed with the (R,S)-diastereomer. Inhibition of uptake on coinjection with unlabeled (R,S)-FMeQNB is only significant in the heart, thalamus, and pons. Inhibition of uptake on coinjection with unlabeled (R,R)-FMeQNB is quite uniform in all brain regions. Displacement with (R)-QNB shows a more varying amount displaced. These results are consistent with (R,R)-[18F]-FMeQNB being M1 selective in vivo.

Anesthetics, Dissociative↗

PubMed1997

Altered patterns of cerebral activity during speech and language production in developmental stuttering. An H2(15)O positron emission tomography study.

To assess dynamic brain function in adults who had stuttered since childhood, regional cerebral blood flow (rCBF) was measured with H2O and PET during a series of speech and language tasks designed to evoke or attenuate stuttering. Speech samples were acquired simultaneously and quantitatively compared with the PET images. Both hierarchical task contrasts and correlational analyses (rCBF versus weighted measures of dysfluency) were performed. rCBF patterns in stuttering subjects differed markedly during the formulation and expression of language, failing to demonstrate left hemispheric lateralization typically observed in controls; instead, regional responses were either absent, bilateral or lateralized to the right hemisphere. Significant differences were detected between groups when all subjects were fluent-during both language formulation and non-linguistic oral motor tasks-demonstrating that cerebral function may be fundamentally different in persons who stutter, even in the absence of stuttering. Comparison of scans acquired during fluency versus dysfluency-evoking tasks suggested that during the production of stuttered speech, anterior forebrain regions-which play an a role in the regulation of motor function-are disproportionately active in stuttering subjects, while post-rolandic regions-which play a role in perception and decoding of sensory information-are relatively silent. Comparison of scans acquired during these conditions in control subjects, which provide information about the sensorimotor or cognitive features of the language tasks themselves, suggest a mechanism by which fluency-evoking maneuvers might differentially affect activity in these anterior and posterior brain regions and may thus facilitate fluent speech production in individuals who stutter. Both correlational and contrast analyses suggest that right and left hemispheres play distinct and opposing roles in the generation of stuttering symptoms: activation of left hemispheric regions appears to be related to the production of stuttered speech, while activation of right hemispheric regions may represent compensatory processes associated with attenuation of stuttering symptoms.

Adult↗

PubMed1997

Regional cerebral blood flow throughout the sleep-wake cycle. An H2(15)O PET study.

To assess dynamic changes in brain function throughout the sleep-wake cycle, CBF was measured with H2(15)O and PET in 37 normal male volunteers: (i) while awake prior to sleep onset; (ii) during Stage 3-4 sleep, i.e. slow wave sleep (SWS); (iii) during rapid eye movement (REM) sleep; and (iv) upon waking following recovery sleep. Subjects were monitored polysomnographically and PET images were acquired throughout the course of a single night. Stage-specific contrasts were performed using statistical parametric mapping. Data were analysed in repeated measures fashion, examining within-subject differences between stages [pre-sleep wakefulness-SWS (n = 20 subjects); SWS-post-sleep wakefulness (n = 14); SWS-REM sleep (n = 7); pre-sleep wakefulness-REM sleep (n = 8); REM sleep-post-sleep wakefulness (n = 7); pre-sleep wakefulness-post-sleep wakefulness (n = 20)]. State dependent changes in the activity of centrencephalic regions, including the brainstem, thalamus and basal forebrain (profound deactivations during SWS and reactivations during REM sleep) are consistent with the idea that these areas are constituents of brain systems which mediate arousal. Shifts in the level of activity of the striatum suggested that the basal ganglia might be more integrally involved in the orchestration of the sleep-wake cycle than previously thought. State-dependent changes in the activity of limbic and paralimbic areas, including the insula, cingulate and mesial temporal cortices, paralleled those observed in centrencephalic structures during both REM sleep and SWS. A functional dissociation between activity in higher order, heteromodal association cortices in the frontal and parietal lobes and unimodal sensory areas of the occipital and temporal lobes appeared to be characteristic of both SWS and REM sleep. SWS was associated with selective deactivation of the heteromodal association areas, while activity in primary and secondary sensory cortices was preserved. SWS may not, as previously thought, represent a generalized decrease in neuronal activity. On the other hand, REM sleep was characterized by selective activation of certain post-rolandic sensory cortices, while activity in the frontoparietal association cortices remained depressed. REM sleep may be characterized by activation of widespread areas of the brain, including the centrencephalic, paralimbic and unimodal sensory regions, with the specific exclusion of areas which normally participate in the highest order analysis and integration of neural information. Deactivation of the heteromodal association areas (the orbital, dorsolateral prefrontal and inferior parietal cortices) constitutes the single feature common to both non-REM and REM sleep states, and may be a defining characteristic of sleep itself. The stages of sleep could also be distinguished by characteristic differences in the relationships between the basal ganglia, thalamic nuclei and neocortical regions of interest.

Adult↗

PubMed1997

Quantification of amphetamine-induced changes in [11C]raclopride binding with continuous infusion.

Positron emission tomography and single-photon emission computer tomography receptor-binding ligands can be used to measure changes in neurotransmitter levels. In particular, amphetamine-induced dopamine release has been assessed with [11C]raclopride by paired bolus injections and with [123I]iodobenzamide by using a single bolus plus infusion (B/I) study. Here, we measured the change in [11C]raclopride-specific binding in rhesus monkeys after i.v. administration of 0.4 mg/kg amphetamine by using both the bolus and B/I paradigms. Paired bolus studies (control and postamphetamine) were analyzed using compartment modeling and graphical analysis with a new plasma metabolite model to measure the total distribution volume (VT). Specific binding, calculated with three measures linearly proportional to the binding potential, demonstrated a 22-42% reduction in the postamphetamine study. VT values from B/I studies were determined by the tissue-to-plasma ratio at equilibrium, in addition to the bolus methods. There was good agreement between the control VT values between bolus and B/I studies. The amphetamine-induced change in specific binding in B/I studies was 19 +/- 16%, measured directly from tissue radioactivity levels. This study demonstrates that stimulus-induced changes in specific binding can be measured with a single [11C]raclopride study using the B/I method.

Amphetamine↗

PubMed1997

Optimization of noninvasive activation studies with 15O-water and three-dimensional positron emission tomography.

We investigated the effects of varying the injected dose, speed of injection, and scan duration to maximize the sensitivity of noninvasive activation studies with 15O-water and three-dimensional positron emission tomography. A covert word generation task was used in four subjects with bolus injections of 2.5 to 3D mCi of 15O-water. The noise equivalent counts (NEC) for the whole brain peaked at an injected dose of 12 to 15 mCi. This was lower than expected from phantom studies, presumably because of the effect of radioactivity outside of the brain. A 10 mCi injection gave an NEC of 92.4 +/- 2.2% of the peak value. As the scan duration increased from 60 to 90 to 120 seconds, the areas of activation decreased in size or were no longer detected. Therefore, we selected a 1 minute scan using 10 mCi for bolus injections. We then performed simulation studies to evaluate, for a given CBF change, the effect on signal-to-noise ratio (S/N) of longer scan duration with slow tracer infusions. Using a measured arterial input function from a bolus injection, new input functions for longer duration injections and the corresponding tissue data were simulated. Combining information about image noise derived from Hoffman brain phantom studies with the simulated tissue data allowed calculation of the S/N for a given CBF change. The simulation shows that a slow infusion permits longer scan acquisitions with only a small loss in S/N. This allows the investigator to choose the injection duration, and thus the time period during which scan values are sensitive to regional CBF.

Adult↗

PubMed1997

Kinetic modeling of [11C]raclopride: combined PET-microdialysis studies.

The in vivo binding of D2 receptor ligands can be affected by agents that alter the concentration of endogenous dopamine. To define a more explicit relation between dopamine and D2 receptor binding, the conventional compartment model for reversible ligands has been extended to account for a time-varying dopamine pulse. This model was tested with [11C]raclopride positron emission tomography and dopamine microdialysis data that were acquired simultaneously in rhesus monkeys. The microdialysis data were incorporated into the model assuming a proportional relation to synaptic dopamine. Positron emission tomography studies used a bolus-plus-infusion tracer delivery with amphetamine given at 40 minutes to induce dopamine release. The extended model described the entire striatal time-activity curve, including the decrease in radioactivity concentration after an amphetamine-induced dopamine pulse. Based on these results, simulation studies were performed using the extended model. The simulation studies showed that the percent decrease in specific binding after amphetamine measured with the bolus-plus-infusion protocol correlates well with the integral of the postamphetamine dopamine pulse. This suggests that changes in specific binding observed in studies in humans can be interpreted as being linearly proportional to the integral of the amphetamine-induced dopamine pulse.

Animals↗