RESUMO
The iodinated benzamide epidepride, which shows a picomolar affinity binding to dopamine D(2) receptors, has been designed for in vivo studies using SPECT. The aim of the present study was to apply a steady-state condition by the bolus/infusion approach with [(123)I]epidepride for the quantification of striatal and extrastriatal dopamine D(2) receptors in humans. In this way the distribution volume of the tracer can be determined from a single SPECT image and one blood sample. Based on bolus experiments, an algorithm using conventional convolution arguments for prediction of the outcome of a bolus/infusion (B/I) experiment was applied. It was predicted that a B/I protocol with infusion of one-third of the initial bolus per hour would be appropriate. Steady-state conditions were attained in extrastriatal regions within 3-4 h but the infusion continued up to 7 h in order to minimize the significance of individual differences in plasma clearance and binding parameters. A steady-state condition, however, could not be attained in striatal brain regions using a B/I protocol of 20 h, even after 11 h. Under near steady-state conditions a striatal:cerebellar ratio of 23 was demonstrated. Epidepride has a unique signal-to-noise ratio compared to [(123)I]IBZM but present difficulties for steady-state measurements of striatal regions. The bolus/infusion approach is particularly feasible for quantification of the binding potential in extrastriatal regions.
Assuntos
Encéfalo/metabolismo , Receptores de Dopamina D2/metabolismo , Adulto , Idoso , Benzamidas/administração & dosagem , Benzamidas/sangue , Benzamidas/farmacocinética , Encéfalo/diagnóstico por imagem , Meios de Contraste/administração & dosagem , Meios de Contraste/farmacocinética , Homeostase , Humanos , Radioisótopos do Iodo , Masculino , Pessoa de Meia-Idade , Pirrolidinas/administração & dosagem , Pirrolidinas/sangue , Pirrolidinas/farmacocinética , Distribuição Tecidual , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
The value of SPECT scanning in diagnosis and growth potential of vestibular schwannoma (VS) was investigated in a series of 29 patients. SPECT demonstrated all tumours > 0.8 cm3, but had limitations as a diagnostic modality of small intracanalicular tumours, when compared to gadolinium DTPA enhanced MR. SPECT was found to be valuable in determining VS growth potential as it reflects tumour vascularity, which is essential for tumour growth. A high radioactive tracer uptake in the tumour corresponded to high tumour vascularity, indicating a high growth rate and vice versa. It seems that we now have an in vivo functional radiological modality capable of providing data on VS vascularity and determination of growth potential in the individual tumour.
Assuntos
Neuroma Acústico/diagnóstico por imagem , Radioisótopos de Tálio , Tomografia Computadorizada de Emissão de Fóton Único , Doenças Vestibulares/diagnóstico por imagem , Adulto , Idoso , Transformação Celular Neoplásica , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Neuroma Acústico/irrigação sanguínea , Neuroma Acústico/patologia , Estudos Prospectivos , Radioisótopos de Tálio/metabolismo , Doenças Vestibulares/patologiaRESUMO
In the clinical setting it has been shown that activation will increase cerebral glucose uptake in excess of cerebral oxygen uptake. To study this phenomenon further, this study presents an experimental setup that enables precise determination of the ratio between cerebral uptake of glucose and oxygen in the awake rat. Global CBF was measured by the Kety-Schmidt technique, and the ratio between cerebral uptake rates for oxygen, glucose, and lactate was calculated from cerebral arterial-venous differences. During baseline conditions, rats were kept in a closed box designed to minimize interference. During baseline conditions CBF was 1.08 +/- 0.25 mL x g(-1) x minute(-1), and the cerebral oxygen to glucose uptake ratio was 5.5. Activation was induced by opening the sheltering box for 6 minutes. Activation increased CBF to 1.81 mL x g(-1) x minute(-1). During activation cerebral glucose uptake increased disproportionately to cerebral oxygen uptake, and the cerebral oxygen to glucose uptake ratio was 4.2. The accumulated excess glucose uptake during 6 minutes of activation amounted to 2.4 micromol/g. Activation was terminated by closure of the sheltering box. In the postactivation period, the cerebral oxygen to glucose uptake ratio rose to a maximum of 6.4. This response is exactly opposite to the excess cerebral glucose uptake observed during activation.
Assuntos
Encéfalo/irrigação sanguínea , Encéfalo/metabolismo , Circulação Cerebrovascular , Glucose/metabolismo , Consumo de Oxigênio , Animais , Glicemia/metabolismo , Pressão Sanguínea , Dióxido de Carbono/sangue , Cinética , Masculino , Oxigênio/sangue , Pressão Parcial , Ratos , Ratos Sprague-Dawley , Fluxo Sanguíneo RegionalAssuntos
Córtex Cerebral/diagnóstico por imagem , Flumazenil/análogos & derivados , Radioisótopos do Iodo , Tomografia Computadorizada de Emissão de Fóton Único , Doença de Alzheimer/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Receptores de GABA-A/análise , Sinapses/diagnóstico por imagemRESUMO
BACKGROUND AND PURPOSE: [123I]Iomazenil is a specific radioligand for the central benzodiazepine receptor that may be useful as an indicator of the intactness of cortical neurons after focal cerebral ischemia. We evaluated the binding of this receptor in reperfused cortex among patients with ischemic stroke to detect viable neurons in cortex that appeared structurally intact on conventional neuroimaging studies. METHODS: Fourteen patients were selected by (1) angiography within 24 hours of onset showing embolic occlusion of an intracranial artery, (2) cerebral blood flow showing ischemia of moderate severity in 12 cases and spontaneous reflow in 2 cases, and (3) thrombolysis with reperfusion within 24 hours in most cases. Thirty reperfused cortical areas that remained structurally intact, 7 infarcted cortical areas, and 6 contralateral cerebellar areas with reduced blood flow were selected as regions of interest to estimate receptor binding 5 days to 23 months after the stroke. A two-compartment model was used to compute the distribution volume (Vd) of iomazenil in relative units, with Vd proportional to benzodiazepine receptor concentration. The side-to-side asymmetry ratio of Vd was calculated. RESULTS: The mean asymmetry ratio was 0.89 +/- 0.11 (range, 0.64 to 1.05), 0.50 +/- 0.15 (range, 0.23 to 0.67), and 0.97 +/- 0.05 (range, 0.90 to 1.04) in reperfused cortex, infarcted cortex, and contralateral cerebellum, respectively. Compared with unity, both reperfused cortex and infarcted cortex showed significant decrease of Vd (P < .001). Contralateral cerebellum showing diaschisis had no reduction of Vd. On MRI, obtained 3 or 6 months after the stroke, mild cortical atrophy was observed in two reperfused areas where the asymmetry ratio was moderately reduced (0.64 and 0.80). CONCLUSIONS: The reduction of benzodiazepine receptor concentration in reperfused cortex that remained structurally intact is likely to be the result of injury involving only a limited number of neurons (ie, incomplete infarction). Our data suggest that the degree of viability of ischemic cortex apparently salvaged by early reperfusion can be quantified by iomazenil.
Assuntos
Córtex Cerebral/diagnóstico por imagem , Infarto Cerebral/diagnóstico por imagem , Flumazenil/análogos & derivados , Embolia e Trombose Intracraniana/diagnóstico por imagem , Radioisótopos do Iodo , Idoso , Cerebelo/diagnóstico por imagem , Cerebelo/patologia , Córtex Cerebral/patologia , Infarto Cerebral/patologia , Circulação Cerebrovascular , Feminino , Flumazenil/metabolismo , Humanos , Embolia e Trombose Intracraniana/patologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Compostos de Organotecnécio , Oximas , Receptores de GABA-A/análise , Receptores de GABA-A/metabolismo , Reperfusão , Tecnécio Tc 99m Exametazima , Fatores de Tempo , Tomografia Computadorizada de Emissão de Fóton Único , Tomografia Computadorizada por Raios X , Radioisótopos de XenônioRESUMO
Thallium chloride 201Tl combined with SPECT was performed in a series of 29 patients with neuroradiological evidence of vestibular schwannoma (VS). The relative tumor uptake (U) and relative tumor concentration (C) of the radiotracer 201Tl was determined, and the cerebellum served as a reference. The relative tracer concentration and uptake were correlated to tumor volume determined by gadolinium DTPA enhanced MR, to prediagnostic duration of symptoms, to tumor vascularity expressed by the average number of intratumoral vessels using the endothelial marker CD31, and to the proliferative activity in the tumors expressed by positive staining with the monoclonal antibody MIB-1 for Ki-67. A positive 201TI enhancement was detected in 17 tumors (n = 17). Tumors U and C were statistically unrelated to tumor volume (p = 0.236 and p = 0.439). SPECT demonstrated all tumors > 0.8 cm3, but it had its limitation as a diagnostic modality of small intracanalicular tumors, when compared with gadolinium DTPA enhanced MR. Relating U and C in all tumors (n = 29) and the prospectively registered data on the prediagnostic duration of symptoms, a statistical significance was found (p = 0.012 and p = 0.015). No statistically significant correlation was observed between U and C and the proliferative activity of the tumors expressed by positive staining with the monoclonal antibody MIB-1 for Ki-67 (p = 0.063 and p = 0.086). A statistically significant correlation was noted between C and U in the operated group (n = 12) and tumor vascularity expressed by the average number of the intratumoral vessels (p = 0.003 and p = 0.014). SPECT was found to be superior to MR in determining VS growth potentials as it expresses tumor vascularity, which is essential for tumor growth. It seems that we now have an in vivo functional radiological modality capable of providing data on VS vascularity and determination of growth potential in the individual tumor. A high radioactive tracer uptake in the tumor corresponded to high tumor vascularity, indicating a high growth rate and vice versa.
Assuntos
Neuroma Acústico/diagnóstico por imagem , Radioisótopos de Tálio , Tálio , Tomografia Computadorizada de Emissão de Fóton Único , Nervo Vestibular/diagnóstico por imagem , Adulto , Idoso , Anticorpos Monoclonais , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Neuroma Acústico/diagnóstico , Neuroma Acústico/patologia , Nervo Vestibular/patologiaRESUMO
PET (positron emission tomography) and SPECT (single photon emission computed tomography) are isotopic methods in which the distribution is registered of radiolabelled tracers given in such small amounts that they are without effect on the organism or the organism's disposal of them. Thus, a series of important biological processes in the intact organism can be studied. The methods have been used in many disciplines but in particular for neurobiological research on the brain--e.g., the brain's regional blood circulation and mapping of the brain's functional structure. The methods have also been used in the investigation of glucose and amino acid metabolism in the brain and receptor conditions.
Assuntos
Mapeamento Encefálico , Tomografia Computadorizada de Emissão de Fóton Único , Tomografia Computadorizada de Emissão , Aminoácidos/metabolismo , Encéfalo/metabolismo , Circulação Cerebrovascular/fisiologia , Glucose/metabolismo , Humanos , NeurobiologiaRESUMO
During dynamic exercise, mean blood velocity (Vmean) in the middle cerebral artery (MCA) demonstrates a graded increase to work rate and reflects regional cerebral blood flow. At a high work rate, however, vasoactive levels of plasma catecholamines could mediate vasoconstriction of the MCA and thereby elevate Vmean at a given volume flow. To evaluate transcranial Doppler-determined Vmean at high plasma catecholamine levels, seven elite cyclists performed a maximal performance test on a bicycle ergometer. Results were compared with those elicited during five incremental exercise bouts and during rhythmic handgrip when plasma catecholamines are low. During rhythmic handgrip the Vmean was elevated by 21 +/- 3% (mean +/- SE), which was not statistically different from that established during moderate cycling. However, at the highest submaximal and maximal work intensities on the bicycle ergometer. Vmean increased by 31 +/- 3% and 48 +/- 4%, respectively, and this was significantly higher compared to handgrip (P < 0.05). During maximal cycling, plasma adrenaline increased from 0.21 +/- 0.04 nmol L-1 at rest to 4.18 +/- 1.46 nmol L-1, and noradrenaline increased from 0.79 +/- 0.08 to 12.70 +/- 1.79 nmol L-1. These levels were 12- to 16-fold higher than those during rhythmic handgrip (adrenaline: 0.34 +/- 0.03 nmol L-1; noradrenaline: 0.78 +/- 0.05 nmol L-1). The increase in Vmean during intense ergometer cycling conforms to some middle cerebral artery constriction elicited by plasma catecholamines. Such an influence is unlikely during rhythmic handgrip compared with low intensity cycling.
Assuntos
Velocidade do Fluxo Sanguíneo/fisiologia , Artérias Cerebrais/fisiologia , Epinefrina/sangue , Exercício Físico/fisiologia , Norepinefrina/sangue , Adulto , Altitude , Ciclismo/fisiologia , Circulação Cerebrovascular/fisiologia , Força da Mão , Hemodinâmica/fisiologia , Humanos , Fluxometria por Laser-Doppler , Respiração/fisiologia , Ultrassonografia Doppler TranscranianaRESUMO
Iodine-123 labelled iomazenil (IMZ) is a specific tracer for the GABAA receptor, the dominant inhibitory synapse of the brain. The cerebral distribution volume (Vd) of IMZ may be taken as a quantitative measure of these synapses in Alzheimer's disease (AD), where synaptic loss tends indiscriminately to affect all cortical neurons, albeit more so in some areas than in others. In this pilot study we measured Vd in six patients with probable AD and in five age-matched controls using a brain-dedicated single-photon emission tomography scanner allowing all cortical levels to be sampled simultaneously. Reduced values were found in all regions except in the occipital (visual) cortex. In particular, temporal and parietal cortex Vd was significantly (P<0.02) reduced: temporal Vd averaged 69 ml/ml in normals and 51 ml/ml in AD, and parietal Vd averaged 71 ml/ml in normals and 48 ml/ml in AD. These results accord well with emission tomographic studies of blood flow or labelled glucose. This supports the idea that while only measuring a subpopulation of synapses, the IMZ method reflects synaptic loss and hence functional loss in AD. The method constitutes an in vivo version of synaptic quantitation that in histopathological studies has been shown to correlate closely with the mental deterioration in AD.
Assuntos
Doença de Alzheimer/diagnóstico por imagem , Córtex Cerebral/diagnóstico por imagem , Flumazenil/análogos & derivados , Radioisótopos do Iodo , Doença de Alzheimer/patologia , Estudos de Casos e Controles , Córtex Cerebral/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Receptores de GABA-A/análise , Sinapses/patologia , Tomografia Computadorizada de Emissão de Fóton ÚnicoAssuntos
Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/tratamento farmacológico , Encéfalo/diagnóstico por imagem , Fibrinolíticos/uso terapêutico , Terapia Trombolítica , Tomografia Computadorizada de Emissão de Fóton Único , Doença Aguda , Humanos , Compostos de Organotecnécio , Oximas , Ensaios Clínicos Controlados Aleatórios como Assunto , Tecnécio Tc 99m ExametazimaRESUMO
BACKGROUND: The concept of selective vulnerability or selective loss o f individual neurons, with survival of glial and vascular elements as one of the consequences of a systemic ischemic-hypoxic insult (eg, transient cardiac arrest or severe hypotension), has been recognized for decades. In contrast, selective neuronal death as one of the lesions that may develop in the brain after occluding an intracranial artery is an idea not readily acknowledged in the current medical literature dealing with human stroke. SUMMARY OF REVIEW: A review of pertinent publications reveals that selective neuronal injury after middle cerebral artery occlusion was observed in autopsy specimens over 40 years ago, although its pathogenesis remains unclear. Recent observations in both humans and animals suggest that selective neuronal necrosis (rather than infarct) is the consequence of either a short-term arterial occlusion or permanent occlusion accompanied by ischemia of moderate severity. During the acute and subacute states of an ischemic stroke, the loss of a limited number of neurons (ie, incomplete infarction) does not result in structural changes discernible by either CT or conventional MRI. However, the loss of a selected number of neurons may be demonstrable in vivo by calculating the corresponding loss of benzodiazepine receptors. The use of specific radiotracers in combination with single-photon emission CT or positron emission tomography allows demonstration of a decrease in gamma-aminobutyric acid-ergic receptor sites at places where many neurons have been lethally injured. CONCLUSIONS: We aim to alert physicians to the potential development of incomplete brain infarctions in patients with intracranial arterial occlusions. Recognizing incomplete infarcts is particularly important in the context of stroke therapy with thrombolytic and neuroprotective agents. This brain lesion is likely to be the consequence of an arterial occlusion with a resultant ischemia of moderate severity (eg, regional blood flows in the range of 15 to 20 mL x 100 g-1 x min-1).
Assuntos
Encéfalo/patologia , Infarto Cerebral/patologia , Infarto Cerebral/fisiopatologia , Transtornos Cerebrovasculares/patologia , Transtornos Cerebrovasculares/fisiopatologia , Neurônios/patologia , Animais , Autopsia , Infarto Cerebral/diagnóstico , Humanos , Embolia e Trombose Intracraniana/fisiopatologia , Imageamento por Ressonância Magnética , Reperfusão , Tomografia Computadorizada por Raios XRESUMO
The fractional increase in cerebral blood flow (CBF) velocity (VCBF) from the control value with 5-min steps of isocapnic hypoxia and hyperoxic hypercapnia was measured by transcranial Doppler in six sea-level native men before and during a 5-day sojourn at 3,810 m altitude to determine whether cerebral vasoreactivity to low arterial O2 saturation (SaO2) gradually increased [as does the hypoxic ventilatory response (HVR)] or diminished (adapted, in concert with known slow fall of CBF) at altitude. A control resting PCO2 value was chosen each day during preliminary hyperoxia to set ventilation at 140 ml.kg-1.min-1 for this and the parallel HVR study, attempting to establish control cerebrospinal fluid (CSF) and brain extracellular fluid pH values unaltered by acclimatization. The relationship of CBF to SaO2 was nonlinear, steepening at a lower SaO2. A hyperbolic equation was used to describe hypoxic cerebrovascular reactivity: fractional VCBF = x[60/ (SaO2-40)-1], where X is the fractional increase of VCBF at 70%.X rose from 0.346 +/- 0.104 (SD) at sea level to 0.463 +/- 0.084 on altitude day 5 (P < 0.05 by paired t-test, justified by the a priori experimental plan). For comparison with CO2 sensitivity, from these X values, we estimate the rise in CBF in response to a 1% fall in SaO2 at 80% to be 1.30% at sea level and 1.74% after 5 days at altitude. CBF sensitivity to increased end-tidal PCO2 rose from 4.01 +/- 0.62%/Torr at sea level to 5.12 +/- 0.79%/Torr on day 5 (P < 0.05), as expected, at the lower PCO2 due to the logarithmic relationship of PCO2 to CSF pH. This change was not significant after correction to log PCO2. We conclude that the cerebral vascular response to acute isocapnic hypoxia may increase during acclimatization at high altitude. The mechanism is unknown but is presumably unrelated to the parallel carotid chemosensitization that, in these subjects, increased the HVR by 60% in the same 5-day period from 0.91 +/- 0.38 to 1.46 +/- 0.59 l.min-1.% fall in SaO2-1).
Assuntos
Altitude , Velocidade do Fluxo Sanguíneo/fisiologia , Circulação Cerebrovascular/fisiologia , Hipóxia/fisiopatologia , Adulto , Idoso , Humanos , Hipercapnia/fisiopatologia , Masculino , Pessoa de Meia-Idade , Fatores de TempoAssuntos
Encéfalo/diagnóstico por imagem , Radioisótopos de Carbono , Radioisótopos do Iodo , Receptores de GABA-A/análise , Tomografia Computadorizada de Emissão de Fóton Único , Tomografia Computadorizada de Emissão , Animais , Flumazenil/análogos & derivados , Moduladores GABAérgicos , Meia-Vida , HumanosAssuntos
Processamento de Imagem Assistida por Computador/métodos , Medicina Nuclear/métodos , Animais , Humanos , Processamento de Imagem Assistida por Computador/estatística & dados numéricos , Matemática , Modelos Biológicos , Medicina Nuclear/estatística & dados numéricos , Tomografia Computadorizada de Emissão/métodos , Tomografia Computadorizada de Emissão/estatística & dados numéricos , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Tomografia Computadorizada de Emissão de Fóton Único/estatística & dados numéricosRESUMO
Stroke-in-progression, SIP, occurs in about 30% of patients with acute stroke and negatively affects the prognosis and mortality. The underlying caused are thought to be clot propagation, cerebral haemorrhage or oedema. In some cases these rather obvious mechanisms cannot be demonstrated, and other variables such as a decrease in blood pressure must be considered as major factors. In this paper the basic haemodynamic mechanisms of cerebral blood flow and the relevant pathophysiology of focal cerebral infarcts are described with emphasis on the penumbra. In addition, available clinical studies are reviewed and current treatment discussed. Our main conclusion is that to assure sufficient collateral flow a high perfusion pressure must be maintained, and we advocate withholding antihypertensive therapy during the acute phase of focal cerebral ischaemia.