Evaluation of a potential generator-produced PET tracer for cerebral perfusion imaging: single-pass cerebral extraction measurements and imaging with radiolabeled Cu-PTSM.

Copper(II) pyruvaldehyde bis(N4-methylthiosemicarbazone) (Cu-PTSM), copper(II) pyruvaldehyde bis(N4-dimethylthiosemicarbazone) (Cu-PTSM2), and copper(II) ethylglyoxal bis(N4-methylthiosemicarbazone) (Cu-ETSM), have been proposed as PET tracers for cerebral blood flow (CBF) when labeled with generator-produced 62Cu (t1/2 = 9.7 min). To evaluate the potential of Cu-PTSM for CBF PET studies, baboon single-pass cerebral extraction measurements and PET imaging were carried out with the use of 67Cu (t1/2 = 2.

The anterior cingulate cortex mediates processing selection in the Stroop attentional conflict paradigm.

Regional cerebral blood flow, an index of local neuronal activity, was measured using positron emission tomography (PET) during the performance of the classic Stroop color/word task in eight healthy right-handed subjects. In the first condition of this paradigm, subjects name the color of the words presented on a video monitor. All the words are the color names congruent to the color presented (e.

Non-steady-state measurement of in vivo receptor binding with positron emission tomography: "dose-response" analysis.

We previously developed a non-steady-state technique using positron emission tomography (PET) and the radioligand 18F-spiperone (18F-SP) for the measurement of in vivo radioligand-receptor binding in brain. The purpose of this investigation is to determine the sensitivity of this method to alterations in the apparent number of available specific binding sites. Nine studies were performed on the same baboon.

Neuroanatomical correlates of a lactate-induced anxiety attack.

Positron emission tomographic measurements of regional blood flow were used to assess local neuronal activity in patients with panic disorder and in normal control subjects before and during the infusion of sodium lactate. A new technique for the analysis of positron emission tomographic data was employed to identify significant changes in regional blood flow associated with lactate infusion in the panicking patients, nonpanicking patients, and controls. Lactate-induced panic was associated with significant blood flow increases bilaterally in the temporal poles; bilaterally in insular cortex, claustrum, or lateral putamen; bilaterally in or near the superior colliculus; and in or near the left anterior cerebellar vermis.

Positron emission tomographic studies of the processing of singe words.

PET images of blood flow change that were averaged across individuals were used to identify brain areas related to lexical (single-word) processing, A small number of discrete areas were activated during several task conditions including: modality-specific (auditory or visual) areas activated by passive word input, primary motor and premotor areas during speech output, and yet further areas during tasks making semantic or intentional demands.

Neuroanatomical correlates of anticipatory anxiety.

Positron emission tomographic measurements of regional blood flow, a marker of local neuronal activity, were used to investigate the neuroanatomical correlates of a normal emotion. Healthy volunteers were studied before, during, and after anticipation of a painful electric shock. During anticipatory anxiety, there were significant blood flow increases in bilateral temporal poles, the same regions recently implicated in a lactate-induced anxiety attack in patients with panic disorder.

A highly accurate method of localizing regions of neuronal activation in the human brain with positron emission tomography.

Functional mapping of the human brain with positron emission tomography (PET) can best be performed by obtaining multiple short measurements of cerebral blood flow in a single sitting. In this manner regional changes in blood flow accompanying the increased neuronal activity from a movement, sensation, or even cognition task, have been identified. However, localizing a functional region with PET has been severely limited by the poor resolving properties of PET devices.

Clinical results of extracranial-intracranial bypass surgery in patients with hemodynamic cerebrovascular disease.

The importance of hemodynamic factors in the pathogenesis and treatment of cerebrovascular disease remains uncertain. The extracranial-intracranial (EC-IC) bypass trial has been criticized for failing to identify and separately analyze those patients with chronic reduction in regional cerebral perfusion pressure (rCPP) who might be most likely to benefit from surgery. Positron emission tomography (PET) measurements of regional cerebral blood flow (rCBF) and blood volume (rCBV) were performed on 29 patients with symptomatic occlusion or intracranial stenosis of the carotid arterial system prior to undergoing EC-IC bypass surgery.

Hyperactivity of the left striato-pallidal projection. Part I: Lower level theory.

We have observed increased relative blood flow to the left globus pallidus and evidence for subtle forms of right-sided hemineglect in neuroleptic-naive schizophrenic patients. These findings occur in animals following certain lesions such as unilateral destruction of midbrain dopaminergic neurons, and are presumed to be due to left striato-pallidal hyperactivity. A survey of the literature reveals many similarities between animals with unilateral dopaminergic denervation and schizophrenic patients.

Left striato-pallidal hyperactivity in schizophrenia. Part II: Phenomenology and thought disorder.

Our previous paper summarized abundant evidence that schizophrenic patients show forms of sensory and motor hemineglect compatible with a left striato-pallidal hyperactivity model of schizophrenia. In this paper we discuss how the model may also account for some of the cognitive and phenomenological aspects of this disorder. Hemineglect can be associated with pallidal hyperactivity through its mediation of the anterior attention system of the frontal lobe.

Regional correction of positron emission tomography data for the effects of cerebral atrophy.

Given the low spatial resolution of positron emission tomography (PET), regional measurements of neural tissue are often inaccurate because of the presence of non-neural elements and to mixtures of different tissue types within the volume of space influencing the measurements. These effects are significant in scans of brains both with and without atrophy, but are particularly significant when comparing measurements of brains with atrophy with those of normals, as is typically done in studies of aging and dementia. Previous attempts to correct for cerebral atrophy have been limited to global measurements.

Enhanced detection of focal brain responses using intersubject averaging and change-distribution analysis of subtracted PET images.

Intersubject averaging and change-distribution analysis of subtracted positron emission tomographic (PET) images were developed and tested. The purpose of these techniques is to increase the sensitivity and objectivity of functional mapping of the human brain with PET. To permit image averaging, all primary tomographic images were converted to anatomically standardized three-dimensional images using stereotactic anatomical localization and interslice interpolation.

Effect of carbon dioxide in acute mountain sickness: a rediscovery.

The effect of adding CO2 to inhaled air in six subjects with acute mountain sickness was investigated during a medical expedition to 5400 m.3% CO2 in ambient air increased ventilation and resulted in a rise in PaO2 of between 24% and 40%. There was a 9-28% increase in PaCO2 and a reduction of the respiratory alkalosis normally seen at high altitude.

The effect of carotid artery disease on the cerebrovascular response to physiologic stimulation.

Eight of 16 patients with severe carotid artery disease, but no evidence of functional or structural brain damage, had abnormal regional cerebral blood flow (rCBF) responses to physiologic stimulation of sensorimotor cortex (unilateral reduction in six, abnormal diffuse increase in two). Thus, in patients with cerebrovascular disease the rCBF responses during physiologic tasks may not be reliable indicators of local neuronal activity.

Nonoxidative glucose consumption during focal physiologic neural activity.

Brain glucose uptake, oxygen metabolism, and blood flow in humans were measured with positron emission tomography, and a resting-state molar ratio of oxygen to glucose consumption of 4.1:1 was obtained. Physiological neural activity, however, increased glucose uptake and blood flow much more (51 and 50 percent, respectively) than oxygen consumption (5 percent) and produced a molar ratio for the increases of 0.

Localization of cognitive operations in the human brain.

The human brain localizes mental operations of the kind posited by cognitive theories. These local computations are integrated in the performance of cognitive tasks such as reading. To support this general hypothesis, new data from neural imaging studies of word reading are related to results of studies on normal subjects and patients with lesions.

Positron emission tomographic studies of the cortical anatomy of single-word processing.

The use of positron emission tomography to measure regional changes in average blood flow during processing of individual auditory and visual words provides support for multiple, parallel routes between localized sensory-specific, phonological, articulatory and semantic-coding areas.

N-(3-[18F]fluoropropyl)-spiperone: the preferred 18F labeled spiperone analog for positron emission tomographic studies of the dopamine receptor.

The ligands currently used for PET studies of the dopamine receptor are fluorine-18-labeled spiperone (FSp) and carbon-11 or fluorine-18-labeled N-methyl-spiperone. All three of these ligands have drawbacks in either their chemical preparation or their biological behavior. We have previously prepared a series of N-fluoroalkyl-spiperone derivatives which are simple to prepare in high radiochemical yield.

MPTP-induced up-regulation of in vivo dopaminergic radioligand-receptor binding in humans.

We measured in vivo dopaminergic receptor binding using positron emission tomography and 18F-spiperone in an untreated symptomatic subject with MPTP-induced parkinsonism. Our technique determines four variables related to entry of 18F-spiperone into brain tissue and subsequent binding to receptors: (1) the combined forward-rate constant k1' (equal to the product of the maximum number of available specific binding sites, Bmax, times the association rate constant [ka] of 18F-spiperone and receptor); (2) the binding site dissociation rate constant k-1; (3) the free fraction of radioligand not specifically bound in brain tissue, f2; and (4) the regional permeability-surface-area product (PS) of the blood-brain barrier for spiperone. PS and f2 in the patient were not different from that of 10 normal volunteers, whereas the combined forward-rate constant (left caudate: k1' = 67.

Positron emission tomographic measurement of cerebral blood flow and permeability-surface area product of water using [15O]water and [11C]butanol.

We have previously adapted Kety's tissue autoradiographic method for measuring regional CBF in laboratory animals to the measurement of CBF in humans with positron emission tomography (PET) and H2(15)O. Because this model assumes diffusion equilibrium between tissue and venous blood, the use of a diffusion-limited tracer, such as H2(15)O, may lead to an underestimation of CBF. We therefore validated the use of [11C]butanol as an alternative freely diffusible tracer for PET.

Tracer-kinetic models for measuring cerebral blood flow using externally detected radiotracers.

All tracer-kinetic models currently employed with positron-emission tomography (PET) are based on compartmental assumptions. Our first indication that a compartmental model might suffer from severe limitations in certain circumstances when used with PET occurred when we implemented the Kety tissue-autoradiography technique for measuring CBF and observed that the resulting CBF estimates, rather than remaining constant (to within predictable statistical uncertainty) as expected, fell with increasing scan duration T when T greater than 1 min. After ruling out other explanations, we concluded that a one-compartment model does not possess sufficient realism for adequately describing the movement of labeled water in brain.

Brain blood volume, flow, and oxygen utilization measured with 15O radiotracers and positron emission tomography: revised metabolic computations.

We have revised our methods for calculating regional blood volume, flow, oxygen extraction, and oxygen utilization from positron emission tomography data obtained using 15O-labeled radiotracers. These revisions include radioactive decay explicitly within the model equations instead of requiring all measured activity to be corrected for decay prior to incorporation in the equations. The revised equations yield small but significant differences in the computed values.