Positron emission tomography of radioligand binding in porcine striatum in vivo: haloperidol inhibition linked to endogenous ligand release.

The ligands N-methylspiperone and haloperidol both bind to D(2)-like dopamine receptors. The competitive nature of the binding over a wide range of haloperidol concentrations and the effect on dopamine release have never been tested in vivo. We determined the competitive interaction between 3-N-[(11)C]methylspiperone ([(11)C]NMSP) and haloperidol binding to striatal dopamine D(2)-like receptors with positron emission tomography (PET) of pig brain.

Cerebral blood flow and blood volume measured by magnetic resonance imaging bolus tracking after acute stroke in pigs: comparison with [(15)O]H(2)O positron emission tomography.

Background And Purpose: Early and accurate assessments of cerebral ischemia allow therapy to be tailored to individual stroke patients. We examined the feasibility of using a novel method for measuring cerebral blood flow (CBF) of ischemic tissue based on MRI after middle cerebral artery occlusion (MCAO). Moreover, the regional correlations between CBF and cerebral blood volume (CBV) were investigated in the regions with acute ischemic stroke.

Cortical networks subserving the perception of tinnitus--a PET study.

Subjective tinnitus is an auditory phantom perception that may arise from any aberrant signal within the auditory system. Further processing of this signal and the conscious perception of tinnitus takes place in the cerebral cortex. A few functional brain-imaging studies have been performed to elucidate the underlying cerebral mechanisms of this perception.

Effect of partial volume correction on estimates of the influx and cerebral metabolism of 6-[(18)F]fluoro-L-dopa studied with PET in normal control and Parkinson's disease subjects.

The poor spatial resolution of positron emission tomography (PET) is a limiting factor in the accurate assay of physiological processes investigated by compartmental modeling of tracer uptake and metabolism in living human brain. The radioactivity concentration in a region-of-interest is consequently altered by loss of signal from that structure and contamination from adjacent brain regions, phenomena known as partial volume effects. We now apply an MRI-based algorithm to compensate for partial volume effects in the special case of compartmental modeling of the cerebral uptake of 6-[(18)F]fluoro-L-dopa (FDOPA), an exogenous substrate of dopa decarboxylase.

Short-term effects of growth hormone on myocardial glucose uptake in healthy humans.

Cardiac muscle is characterized by insulin resistance in specific heart diseases such as coronary artery disease and congestive heart failure, but not in generalized disorders like diabetes mellitus and essential hypertension when cardiac manifestations are absent. To examine whether the insulin antagonistic effect of growth hormone (GH) acts upon the heart, we compared insulin-stimulated whole body and myocardial glucose uptake with and without GH administration during a 3.5-h euglycemic-hyperinsulinemic clamp in eight healthy males.

The DaNeX study of embryonic mesencephalic, dopaminergic tissue grafted to a minipig model of Parkinson's disease: preliminary findings of effect of MPTP poisoning on striatal dopaminergic markers.

A multicenter study is under way to investigate the efficacy of allografting of embryonic mesencephalic neurons in a pig model of Parkinson's disease. We have first established that a stable parkinsonian syndrome can be established by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxication of adult male Göttingen minipigs. We are now using positron emission tomography (PET) methods for testing the physiological responses to MPTP intoxication and the time course of the response to several treatment strategies.

Model of blood-brain transfer of oxygen explains nonlinear flow-metabolism coupling during stimulation of visual cortex.

The coupling between cerebral metabolic rate of oxygen (CMRO2) and blood flow (CBF) in response to visual stimulation was evaluated by means of a model of oxygen delivery. The model predicted a nonlinear relationship between stimulus-evoked changes of oxygen consumption and blood flow. The magnitude of the CMRO2/CBF ratio index (IO2) was used to indicate the degree of flow-metabolism coupling prevailing in specific areas of the brain during physiological stimulation.

Cerebral blood flow in volunteers measured by PET and Xe CT/CBF. A comparison.

Aim of this study was to compare two quantitative CBF methods. Seven young, healthy volunteers were studied with PET (15-0 labelled water) and afterwards with Xe CT/CBF (30% xenon in oxygen, 3 minutes wash-in, 5 minutes washout protocol). Xe CT/CBF showed greater differences between high and low flow areas than PET CBF.

Cortical centres underlying auditory temporal processing in humans: a PET study.

We have used positron emission tomography (PET) to test a specific hypothesis of a neural system subserving auditory temporal processing (acoustical stimulus duration discrimination). Maps of the cerebral blood flow distribution during specific stimulations were obtained from five normally-hearing and otherwise healthy subjects. The auditory stimuli consisted of sounds of varying duration and of auditorily presented words in which the duration of the initial phoneme was manipulated.

Functional brain imaging of tinnitus-like perception induced by aversive auditory stimuli.

Tinnitus is an aversive auditory percept of unknown origin. We tested the speculation that tinnitus may share neuronal processing mechanisms with aversive auditory percepts of known origin. This study revealed the functional neuroanatomy of the perception of aversive auditory stimuli.

Cerebral blood-flow changes evoked by two levels of painful heat stimulation: a positron emission tomography study in humans.

Positron emission tomography (PET) and accumulation of H(2)(15)O as a marker of neuronal activity were used to create maps of cerebral blood-flow changes evoked by painful heat stimulation in 10 subjects. Two levels of painful tonic and phasic heat stimuli were applied with use of a newly developed contact heat thermode on the volar surface of the dominant (right) arm. The subjects participated in two separate PET sessions.

On the oxygenation of hemoglobin in the human brain.

We test three hypotheses arising from a model of oxygen delivery to brain tissue. The hypotheses claim that mitochondrial oxygen is negligible in brain tissue such that oxygen consumption depends solely on the mean capillary oxygen tension for a given capillary density; that capillary density is adjusted to satisfy the average steady-state oxygen requirement; and that sudden changes of brain function are subserved by changes of blood flow which adjust the mean capillary oxygen tension in the required direction. The results of the tests did not reject the two former hypotheses and only partly rejected the latter: Sudden changes of blood flow are not always accompanied by increases of oxygen consumption.

Stimulation of dopa decarboxylase activity in striatum of healthy human brain secondary to NMDA receptor antagonism with a low dose of amantadine.

The efficacy of amantadine in alleviating motor symptoms of Parkinson's disease may be mediated in part by stimulation of cerebral dopa decarboxylase (DDC) activity, secondary to antagonism of N-methyl-D-aspartate (NMDA) type glutamate receptors. We tested the specific hypothesis that amantadine increases the decarboxylation rate of 6-[(18)F]fluoro-L-DOPA (FDOPA), an exogenous substrate for DDC, in healthy human brain. Radioactivity concentrations in brain tissue of neurologically normal volunteers (n = 5) injected intravenously with FDOPA ( approximately 4.

Pharmacokinetics of radiotracers in human plasma during positron emission tomography.

Many radiopharmaceuticals for positron emission tomography (PET) are substantially metabolized in peripheral organs. Pharmacological treatments intended to alter cerebral metabolism might also alter radiotracer metabolism, consequently altering the cerebral uptake. First-order rate constants for the metabolism of PET tracers can be calculated by a linear graphical method from the precursor and metabolite concentrations measured in plasma extracts fractionated by HPLC.

Stimulus-dependent central processing of auditory stimuli: a PET study.

Positron emission tomography (PET) was used to investigate the neural systems involved in the central processing of different auditory stimuli. Noise, pure tone and pure-tone pulses, music and speech were presented monaurally. O-15-water PET scans were obtained in relation to these stimulations presented to five normal hearing and healthy subjects.

Cortical responses to sustained and divided attention in Alzheimer's disease.

Neuropsychological data suggests that divided attention is more impaired than sustained attention during the early phases of Alzheimer's disease. The purpose of the present study was to compare cerebral activation patterns during sustained and divided attention between Alzheimer patients and healthy elderly. The O-15-water PET activation method was used to map sustained and divided attention in 16 patients with Alzheimer's disease (mean age +/- SD: 68 +/- 5 years; MMSE: 11-25, mean +/- SD = 19.

Positron emission tomography of cortical centers of tinnitus.

Tinnitus is associated with a wide variety of disorders in the auditory system. Whether generated peripherally or centrally, tinnitus is believed to be associated with activity in specific cortical regions. The present study tested the hypothesis that these cortical centers subserve the generation, perception and processing of the tinnitus stimulus and that these processes are suppressed by lidocaine and masking.

Measurement of myocardial glucose uptake in patients with ischemic cardiomyopathy: application of a new quantitative method using regional tracer kinetic information.

Unlabelled: Quantification of myocardial glucose uptake (MGU) by 18F-fluoro-2-deoxyglucose (FDG) using PET may be inaccurate, because the correction factor that relates myocardial FDG uptake to MGU, the lumped constant (LC), is not a true constant. Recent studies have shown that analysis of FDG time-activity curves allows determination of individual LCs and that variable LCs yield accurate determination of MGU. We compared the magnitude of the LC in different regions of the heart in patients with ischemic cardiomyopathy.

Uptake and distribution of a new SSRI, NS2381, studied by PET in living porcine brain.

This study tests the utility of a new selective serotonin reuptake inhibitor (SSRI), [11C]NS2381 {(+/-)-(8-[11C]methyl-3-(4-trifluoromethyl-phenyl)-8-azabicyclo[3.2.1]oc t-2-ene)}, as positron-emitting radioligand for labelling serotonin (5-HT) reuptake sites in living brain.

Cerebral 6-[(18)F]fluoro-L-DOPA (FDOPA) metabolism in pig studied by positron emission tomography.

We measured 6-[(18)F]fluoro-L-DOPA (FDOPA) uptake and metabolism in the brain of 4-month-old female pigs (n = 8) using a high-resolution positron emission tomograph (PET) in 3D mode. The mean net blood-brain clearance of FDOPA (K(i)(D)) to striatum was 0.011 ml g(-1) min(-1).

NMSP binding to dopamine and serotonin receptors in MPTP-induced parkinsonism: relation to dopa therapy.

We tested the hypothesis that N-methylspiperone binding to dopamine D2 receptors must be reduced when L-dopa therapy of parkinsonism augments the binding of dopamine to the receptors and improves the clinical state expressed by the Hoehn & Yahr stage. A patient with MPTP-induced parkinsonism underwent two positron emission tomographic studies of the D2-like dopamine receptors with N-[11C]methylspiperone (NMSP). The first study took place 3 days after cessation of the L-dopa medication, the second 5 days after its resumption.

Myocardial glucose uptake measured with fluorodeoxyglucose: a proposed method to account for variable lumped constants.

Unlabelled: Quantitative assessment of myocardial glucose uptake by the glucose tracer analog 2-deoxy-2-[18F]fluoro-D-glucose (FDG) depends on a correction factor (lumped constant [LC]), which may vary. We propose that this variability is caused by different affinities of FDG and glucose for membrane transport and phosphorylation and can be predicted from the time course of FDG retention. We therefore measured the LC under steady-state metabolic conditions and compared the results with values predicted from the tracer retention alone.