Dopamine D2 receptor occupancy in vivo and response to the new antipsychotic risperidone.
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Adult↗
Biomedical subjects
D C Costa
Publications and source records attributed to D C Costa.
Clozapine, single photon emission tomography, and the D2 dopamine receptor blockade hypothesis of schizophrenia.
According to the dopamine hypothesis of schizophrenia, D2 receptor blockade is essential for a drug to have antipsychotic potency, and antipsychotic potency and D2 blockade are linearly related in vitro. To test this assumption in vivo, we have compared clinical response with central D2 dopamine receptor availability measured by 123I-iodobenzamide single photon emission tomography in two groups of schizophrenic patients. 6 patients were on typical antipsychotic drugs and 10 were on the atypical antipsychotic clozapine, including 2 patients from the first group. The patients on typical antipsychotics showed poor therapeutic response despite D2 receptor blockade. Significant clinical improvement occurred in all patients on clozapine, but at a lower level of D2 blockade by the drug. These findings suggest a more complex relation between D2 blockade and clinical efficacy than was previously thought.
Adult↗
Diagnosing Alzheimer's disease.
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Alzheimer Disease↗
Physical assessment of the GE/CGR Neurocam and comparison with a single rotating gamma-camera.
The GE/CGR Neurocam is a triple-headed single photon emission tomography (SPET) system dedicated to multi-slice brain tomography. We have assessed its physical performance in terms of sensitivity and resolution, and its clinical efficacy in comparison with a modern, single rotating gamma-camera (GE 400XCT). Using a water-filled cylinder containing technetium-99m, the tomographic volume sensitivity of the Neurocam was 30.0 and 50.7 kcps/MBq.ml.cm for the high-resolution (HR) and general-purpose (GP) collimators, respectively; the corresponding values for the single rotating camera were 7.6 and 12.8 kcps/(MBq/ml)/cm. Tomographic resolution was measured in air and in water. In air, the Neurocam resolution at the cente of the field-of-view (FOV) is 9.0 and 10.7 mm full width at half-maximum (FWHM) with the HR and GP collimators, respectively, and is isotropic in the three orthogonal planes; the resolution of the GE 400XCT with 13 cm radius of rotation is 10.3 and 11.7 mm, respectively. For the Neurocam with the HR collimator, the transaxial FWHM values in water were 9.7 mm at the centre and 9.5 mm radial (6.6 mm tangential) at 8 cm from the centre. The physical characteristics of the Neurocam enable the routine acquisition of brain perfusion data with technetium-99m hexamethyl-propylene amine oxime (99mTc-HMPAO) in about 14 min, yielding better image quality than with a single rotating camera in 40 min.
Brain↗
rCBF abnormalities detected, and sequentially followed, by SPECT in neuro-Behçet's syndrome with normal CT and MRI imaging.
Conventional imaging with computed tomography (CT) and magnetic resonance imaging (MRI) may show abnormalities in central nervous system Behcet's syndrome but is normal in some cases. Recently in two cases positron emission tomography has shown abnormalities in blood flow and glucose metabolism far more extensive than the abnormalities seen on CT and MRI scans in the same patients. We report a patient with neuro-Behcet's syndrome presenting with headache and personality change in whom CT and MRI brain imaging was normal, but regional cerebral blood flow imaging using single photon emission tomography with the tracer HMPAO showed extensive perfusion deficits which partially reversed after 3 months of prednisolone therapy. This technique may aid the diagnosis of cerebral involvement in Behcet's syndrome, although the cause and incidence of the perfusion deficits need further evaluation.
Behcet Syndrome↗
Demonstration of human motor cortex activation using SPECT.
Recent advances in single photon emission computed tomography (SPECT) have allowed improved image resolution with lower doses of labelled tracer. Capitalizing on these improvements, the authors have developed a new SPECT protocol for imaging neuronal activation. We outline this technique and describe how it can demonstrate increased human motor cortex activity in normal subjects performing a motor task. The ability to accurately demonstrate neuronal activation with SPECT using this method may have important scientific and clinical implications.
Adult↗
Elevated frontal cerebral blood flow in Gilles de la Tourette syndrome: a 99Tcm-HMPAO SPECT study.
Case reports, numerous brain imaging studies, and certain disease states suggest that the orbital frontal cortex and the striatum are dysfunctional in obsessive-compulsive disorder (OCD). Interest has also grown recently concerning the genetic, neuroanatomic, and clinical links between OCD, chronic motor tics, and Gilles de la Tourette Syndrome (GTS). To test the hypothesis of possible orbito-frontal/basal ganglia dysfunction in GTS, similar to OCD, we studied 20 unmedicated GTS subjects, 10 of whom also had comorbid OCD (GTS/OCD), and 8 control subjects. The subjects were examined with high-resolution single photon emission computed tomography (SPECT) and the labeled regional cerebral blood flow (rCBF) ligand technetium-99m-d,l-hexamethyl-propylene amine oxime (99Tcm-HMPAO). As a group, GTS subjects showed significantly elevated right frontal/visual cortex activity (mean = 0.879, SD = 0.107) compared with control subjects (mean = 0.798, SD = 0.049). A subanalysis comparing simple GTS versus GTS with comorbid OCD failed to reveal significant differences in regional flow.
Adult↗
Cerebral blood flow abnormalities in adults with infantile autism.
Structural brain abnormalities have recently been discovered using magnetic resonance imaging in infantile autism, a neurodevelopmental disorder of unknown etiology. However, functional neuroimaging studies in autism using positron emission tomography have had conflicting results and have not explained how the known structural brain abnormalities in autism act in a functioning brain to produce autistic behavior. Using a new technology, high-resolution brain single photon emission tomography, we studied and scanned four young adults with infantile autism and four age-matched controls using the labeled ligand 99mTc-D,L-hexamethyl-propylene amine oxime (99mTc-HMPAO). Total brain perfusion was significantly decreased in autism subjects (range, 58% to 72% of controls, p less than or equal to .02). In addition to the globally decreased perfusion, the autism group also had regionally decreased flow in the right lateral temporal and right, left, and midfrontal lobes compared with controls (p less than or equal to .02, Mann-Whitney t-test).
Adult↗
Assessment of myocardial viability with 201Tl SPET and reinjection technique: a quantitative approach.
The definition of viable myocardium after an acute myocardial infarction (MI) is important as it will determine which therapeutic option will be best for the patient. In 201Tl scintigraphy it has been shown that late redistribution (8-24 h) or reinjection may help to identify viable myocardium which does not appear to reperfuse on the 4 h redistribution image. In a prospective study 20 patients with a persistent defect seen on both stress and redistribution images were imaged after reinjection of 201Tl. On visual analysis a total of 180 segments were studied, 85 were normal, 18 reperfused at redistribution and a further nine (in six patients) after reinjection. Bull's-eye analysis at stress demonstrated a mean defect size of 279 pixels, S.D. +/- 74. After redistribution, there was no significant change in mean defect size (227 +/- 96 pixels). At reinjection, there was a significant reduction in mean defect size (189 +/- 107 pixels) (P < 0.05, paired 't'-test). Quantification shows a significant reduction in defect size between stress and reinjection. The use of the 201Tl reinjection technique in patients with a fixed perfusion deficit on stress and redistribution images improves the detection of viable myocardium and is to be preferred to a method of redistribution analysis alone.
Adult↗
Vasodilator myocardial perfusion imaging: demonstration of local electrophysiological changes of ischaemia.
OBJECTIVE: To examine the incidence and severity of myocardial ischaemia provoked in the course of perfusion scintigraphy by coronary vasodilators using endocardial recordings of steady state monophasic action potentials as an independent marker of early localised myocardial ischaemia. PATIENTS: 31 men undergoing routine cardiac catheterisation for investigation of chest pain were studied. SETTING: A tertiary cardiac referral centre. DESIGN: Single site monophasic action potentials were recorded from the left or right ventricle or both (50 recording sites) during intravenous infusion of dipyridamole (0.015 mg/kg/min) for four minutes. Heart rate was held constant with atrial pacing at 20% above the patient's resting rate. Technetium-99m hexakis-2-methoxy-2-methylpropyl-isonitrile (MIBI) was administered four minutes after dipyridamole, and single photon emission tomographic imaging was performed an hour later. Rest images were obtained the next day (two day, two dose protocol). Recordings were divided into three groups based on the scintigraphic perfusion characteristics and coronary anatomical data for the action potential recording site: group 1--recordings from areas with a normal perfusion pattern (n = 30), group 2--recordings from areas with a perfusion defect and subtended by significantly narrowed coronary arteries without obvious angiographic collateral supply (n = 10), and group 3--recordings from areas with a perfusion defect and subtended by occluded arteries with angiographically evident collaterals from adjacent vessels (n = 10). RESULTS: There were changes in the duration of the monophasic action potential indicative of ischaemia--that is, shortening of duration of steady state action potential--in 18 of the 20 recordings from areas of abnormal perfusion. Peak changes were apparent eight minutes from the start of the dipyridamole infusion. Mean (SEM) values for duration of the action potential between control and peak effect at eight minutes were 276.5 (5.3) ms v 276.6 (5.4) for group 1 (NS), 289.6 (4.7) ms v 278.4 (4.9) ms for group 2 (p less than 0.001), and 269.6 (5.7) ms v 242.0 (4.4) for group 3 (p less than 0.0001). These changes were significantly different between the three groups (p less than 0.01). ST segment changes on the surface electrocardiogram were seen in only eight patients, all with areas of viable myocardium supplied by collateral vessels. CONCLUSIONS: These data provide strong evidence for the presence of myocardial ischaemia in regions of reversible perfusion defects induced by dipyridamole. This study also shows that such ischaemia is more intense and more likely to be seen when myocardial viability is dependent on collateral circulation.
Action Potentials↗
Effect of vigabatrin on striatal dopamine receptors: evidence in humans for interactions of GABA and dopamine systems.
Vigabatrin is a specific gamma-aminobutyric acid transaminase inhibitor. The clinical use of this drug in the treatment of epilepsy has been sporadically linked to the development of psychosis. Using 123I-IBZM, a specific dopamine D2 receptor ligand and single photon emission tomography (SPET), one month of treatment with vigabatrin was associated with a decrease in specific binding of 123I-IBZM to D2 receptors in the left hemisphere basal ganglia. This change may provide one explanation for the development of psychosis in vulnerable patients.
Adolescent↗
Creutzfeldt-Jakob disease in recipients of human growth hormone in the United Kingdom: a clinical and radiographic study.
In the past 3 years there have been five further cases, in addition to one case reported in 1985, of Creutzfeldt-Jakob disease in recipients of human growth hormone in the United Kingdom. The clinical findings of two of these cases are described, demonstrating a typical presentation with a predominantly cerebellar syndrome at onset which is not commonly a presenting feature of sporadic Creutzfeldt-Jakob disease. In one case a 99mTc hexamethylpropylenamine single photon emission tomographic scan showed marked impairment of tracer uptake in the basal ganglia and cerebral cortex at a time when the clinical picture was predominantly cerebellar. This technique may be useful in early diagnosis. In the other case post mortem examination of the brain showed prominent amyloid deposition in the cerebellum, which has not been described previously in pituitary-hormone related Creutzfeldt-Jakob disease. The previously published cases of growth hormone-related Creutzfeldt-Jakob disease are reviewed and reasons for the particular clinical pattern seen are discussed.
Adult↗
The role of nuclear medicine in neurology and psychiatry.
Nuclear medicine has a place in the study of brain trauma, brain tumours, stroke, dementia epilepsy and depression. The development of new tracers labelled with widely available radionuclides, such as technetium-99m (99Tc) and iodine-123, has played a key role here. Practical methodology can now be implemented in the routine setting. Additional applications are reviewed in the context of brain death, encephalitis, post-viral fatigue syndrome, Parkinson's disease and schizophrenia.
Brain↗
Basics and recommendations for brain SPECT. Task Group "Neurology" of the European Association of Nuclear Medicine.
In this article guidelines for single-photon emission computerized tomography (SPECT) of the brain are presented by the Task Group "Neurology" of the European Association of Nuclear Medicine (EANM). Under separate headings are discussed: the pathophysiologic principles of various brain diseases, pharmacokinetics and pharmacodynamics of various radiopharmaceuticals, physical principles of SPECT imaging, computerized data processing, clinical protocols and the evaluation of SPECT results.
Brain↗
High resolution SPECT, small deep infarcts and diaschisis.
Eighteen cases of lacunar infarction are presented. Six of these cases had a purely motor clinical deficit. All the cases were studied by serial high resolution SPECT (single photon emission computerized tomography) using 99Tcm HMPAO. The degree and extent of the changes in cerebral perfusion consistent with diaschisis were noted and these compared with the severity of the clinical deficit at presentation and over time. No significant correlation between diaschisis and the clinical state was found at any stage. The nature, aetiology and importance of diaschisis are discussed and it is suggested that caution should be exercised in attributing clinical features to diaschisis simply because it may be present.
Aged↗
Single photon emission tomography in growth-hormone related Creutzfeldt-Jakob disease.
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Adult↗