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1.
Phys Med Biol ; 65(10): 105011, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32235057

RESUMO

Positron emission tomography (PET) has been used for dose verification in charged particle therapy. The causes of washout of positron emitters by physiological functions should be clarified for accurate dose verification. In this study, we visualized the distribution of irradiated radioactive beams, 11C and 15O beams, in the rabbit whole-body using our original depth-of-interaction (DOI)-PET prototype to add basic data for biological washout effect correction. Time activity curves of the irradiated field and organs were measured immediately after the irradiations. All data were corrected for physical decay before further analysis. We also collected expired gas of the rabbit during beam irradiation and the energy spectrum was measured with a germanium detector. Irradiated radioactive beams into the brain were distributed to the whole body due to the biological washout process, and the implanted 11C and 15O ions were concentrated in the regions which had high blood volume. The 11C-labelled 11CO2 was detected in expired gas under the 11C beam irradiation, while no significant signal was detected under the 15O beam irradiation as a form of C15O2. Results suggested that the implanted 11C ions form molecules that diffuse out to the whole body by undergoing perfusion, then, they are incorporated into the blood-gas exchange in the respiratory system. This study provides basic data for modelling of the biological washout effect.


Assuntos
Encéfalo/diagnóstico por imagem , Encéfalo/efeitos da radiação , Radioisótopos de Carbono/metabolismo , Modelos Biológicos , Radioisótopos de Oxigênio/metabolismo , Tomografia por Emissão de Pósitrons , Animais , Radioisótopos de Carbono/farmacocinética , Radioisótopos de Oxigênio/farmacocinética , Coelhos , Distribuição Tecidual
2.
Phys Med Biol ; 64(20): 205012, 2019 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-31530751

RESUMO

Measured cross sections for the production of the PET isotopes [Formula: see text], [Formula: see text] and [Formula: see text] from carbon and oxygen targets induced by protons (40-220 [Formula: see text]) and carbon ions (65-430 [Formula: see text]) are presented. These data were obtained via activation measurements of irradiated graphite and beryllium oxide targets using a set of three scintillators coupled by a coincidence logic. The measured cross sections are relevant for the PET particle range verification method where accurate predictions of the [Formula: see text] emitter distribution produced by therapeutic beams in the patient tissue are required. The presented dataset is useful for validation and optimization of the nuclear reaction models within Monte Carlo transport codes. For protons the agreement of a radiation transport calculation using the measured cross sections with a thick target PET measurement is demonstrated.


Assuntos
Radioisótopos de Carbono/metabolismo , Radioterapia com Íons Pesados , Radioisótopos de Oxigênio/metabolismo , Imagens de Fantasmas , Tomografia por Emissão de Pósitrons/métodos , Terapia com Prótons , Humanos , Método de Monte Carlo , Dosagem Radioterapêutica
3.
Ann Neurol ; 85(6): 875-886, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30937950

RESUMO

OBJECTIVE: Accurate identification of the ischemic penumbra, the therapeutic target in acute clinical stroke, is of critical importance to identify patients who might benefit from reperfusion therapies beyond the established time windows. Therefore, we aimed to validate magnetic resonance imaging (MRI) mismatch-based penumbra detection against full quantitative positron emission tomography (15 O-PET), the gold standard for penumbra detection in acute ischemic stroke. METHODS: Ten patients (group A) with acute and subacute ischemic stroke underwent perfusion-weighted (PW)/diffusion-weighted MRI and consecutive full quantitative 15 O-PET within 48 hours of stroke onset. Penumbra as defined by 15 O-PET cerebral blood flow (CBF), oxygen extraction fraction, and oxygen metabolism was used to validate a wide range of established PW measures (eg, time-to-maximum [Tmax]) to optimize penumbral tissue detection. Validation was carried out using a voxel-based receiver-operating-characteristic curve analysis. The same validation based on penumbra as defined by quantitative 15 O-PET CBF was performed for comparative reasons in 23 patients measured within 48 hours of stroke onset (group B). RESULTS: The PW map Tmax (area-under-the-curve = 0.88) performed best in detecting penumbral tissue up to 48 hours after stroke onset. The optimal threshold to discriminate penumbra from oligemia was Tmax >5.6 seconds with a sensitivity and specificity of >80%. INTERPRETATION: The performance of the best PW measure Tmax to detect the upper penumbral flow threshold in ischemic stroke is excellent. Tmax >5.6 seconds-based penumbra detection is reliable to guide treatment decisions up to 48 hours after stroke onset and might help to expand reperfusion treatment beyond the current time windows. ANN NEUROL 2019;85:875-886.


Assuntos
Imagem de Difusão por Ressonância Magnética/métodos , Radioisótopos de Oxigênio/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/metabolismo , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Imagem Multimodal/métodos
4.
Neurology ; 90(17): e1452-e1460, 2018 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-29572282

RESUMO

OBJECTIVE: Extensive cortical ß-amyloid (Aß positivity) has been linked to cognitive decline, but the clinical significance of elevations in Aß within the negative range is unknown. METHODS: We examined amyloid and cognitive trajectories (memory, executive function) in 142 cognitively normal older individuals enrolled in the Alzheimer's Disease Neuroimaging Initiative who were Aß-negative at baseline and who had at least 2 [18F]-florbetapir PET scans over 3.9 ± 1.4 years. We determined whether Aß accumulation was associated with longitudinal changes in memory or executive function. RESULTS: Among baseline-negative individuals, florbetapir slope (mean annual increase 0.002 ± 0.008 standardized uptake value ratio units/y) was not related to age, sex, education, APOE4 status, baseline memory or executive function, temporoparietal glucose metabolism, baseline hippocampal volume, or hippocampal volume change; but it was related to higher baseline cortical florbetapir, indicating that Aß accumulation was ongoing at baseline in those who accumulated during the study. Over the course of follow-up, 13 individuals converted to florbetapir+ and 14 nearly nonoverlapping individuals converted to mild cognitive impairment or Alzheimer disease. Amyloid accumulation among baseline-negative individuals was associated with poorer longitudinal memory performance (p = 0.019), but it was not associated with changes in executive function. Reducing the sample to individuals with at least 3 timepoints to estimate the florbetapir slope strengthened the relationship further between florbetapir accumulation and memory decline (p = 0.007). CONCLUSIONS: Memory decline accompanies Aß accumulation in otherwise healthy, Aß-negative older adults. Amyloid increases within the negative range may represent the earliest detectable indication of pathology with domain-specific cognitive consequences.


Assuntos
Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/metabolismo , Amiloide/metabolismo , Transtornos da Memória/diagnóstico por imagem , Transtornos da Memória/metabolismo , Idoso , Idoso de 80 Anos ou mais , Compostos de Anilina/metabolismo , Etilenoglicóis/metabolismo , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Radioisótopos de Oxigênio/metabolismo , Tomografia por Emissão de Pósitrons , Estudos Retrospectivos , Fatores de Tempo
5.
J Cereb Blood Flow Metab ; 38(5): 780-792, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-28595496

RESUMO

CBF, OEF, and CMRO2 images can be quantitatively assessed using PET. Their image calculation requires arterial input functions, which require invasive procedure. The aim of the present study was to develop a non-invasive approach with image-derived input functions (IDIFs) using an image from an ultra-rapid O2 and C15O2 protocol. Our technique consists of using a formula to express the input using tissue curve with rate constants. For multiple tissue curves, the rate constants were estimated so as to minimize the differences of the inputs using the multiple tissue curves. The estimated rates were used to express the inputs and the mean of the estimated inputs was used as an IDIF. The method was tested in human subjects ( n = 24). The estimated IDIFs were well-reproduced against the measured ones. The difference in the calculated CBF, OEF, and CMRO2 values by the two methods was small (<10%) against the invasive method, and the values showed tight correlations ( r = 0.97). The simulation showed errors associated with the assumed parameters were less than ∼10%. Our results demonstrate that IDIFs can be reconstructed from tissue curves, suggesting the possibility of using a non-invasive technique to assess CBF, OEF, and CMRO2.


Assuntos
Algoritmos , Doenças Cardiovasculares/diagnóstico por imagem , Interpretação de Imagem Assistida por Computador/métodos , Neuroimagem/métodos , Tomografia por Emissão de Pósitrons/métodos , Circulação Cerebrovascular , Feminino , Humanos , Masculino , Oxigênio/metabolismo , Radioisótopos de Oxigênio/metabolismo , Compostos Radiofarmacêuticos , Água/metabolismo
6.
Stroke ; 48(8): 2136-2141, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28663515

RESUMO

BACKGROUND AND PURPOSE: The oxygen extraction fraction (OEF) is an effective metric to evaluate metabolic reserve in chronic ischemia. However, OEF is considered to be accurately measured only when using positron emission tomography (PET). Thus, we investigated whether OEF maps generated by magnetic resonance quantitative susceptibility mapping (QSM) at 7 Tesla enabled detection of OEF changes when compared with those obtained with PET. METHODS: Forty-one patients with chronic stenosis/occlusion of the unilateral internal carotid artery or middle cerebral artery were examined using 7 Tesla-MRI and PET scanners. QSM images were obtained from 3-dimensional T2*-weighted images, using a multiple dipole-inversion algorithm. OEF maps were generated based on susceptibility differences between venous structures and brain tissues on QSM images. OEF ratios of the ipsilateral middle cerebral artery territory against the contralateral side were calculated on the QSM-OEF and PET-OEF images, using an anatomic template. RESULTS: The OEF ratio in the middle cerebral artery territory showed significant correlations between QSM-OEF and PET-OEF maps (r=0.69; P<0.001), especially in patients with a substantial increase in the PET-OEF ratio of 1.09 (r=0.79; P=0.004), although showing significant systematic biases for the agreements. An increased QSM-OEF ratio of >1.09, as determined by receiver operating characteristic analysis, showed a sensitivity and specificity of 0.82 and 0.86, respectively, for the substantial increase in the PET-OEF ratio. Absolute QSM-OEF values were significantly correlated with PET-OEF values in the patients with increased PET-OEF. CONCLUSIONS: OEF ratios on QSM-OEF images at 7 Tesla showed a good correlation with those on PET-OEF images in patients with unilateral steno-occlusive internal carotid artery/middle cerebral artery lesions, suggesting that noninvasive OEF measurement by MRI can be a substitute for PET.


Assuntos
Angiografia Digital/métodos , Isquemia Encefálica/diagnóstico por imagem , Mapeamento Encefálico/métodos , Angiografia por Ressonância Magnética/métodos , Consumo de Oxigênio/fisiologia , Radioisótopos de Oxigênio , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/metabolismo , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Radioisótopos de Oxigênio/metabolismo , Estudos Prospectivos
7.
Anal Biochem ; 529: 171-178, 2017 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-27568551

RESUMO

In the last decade, in vivo oxygen-17 (17O) MRS has evolved into a promising MR technique for noninvasively studying oxygen metabolism and perfusion in aerobic organs with the capability of imaging the regional metabolic rate of oxygen and its changes. In this chapter, we will briefly review the methodology of the in vivo17O MRS technique and its recent development and applications; we will also discuss the advantages of the high/ultrahigh magnetic field for 17O MR detection, as well as the challenges and potential of this unique MRS method for biomedical research of oxygen metabolism, mitochondrial function and tissue energetics in health and disease.


Assuntos
Encéfalo/metabolismo , Imagem por Ressonância Magnética/métodos , Espectroscopia de Ressonância Magnética/métodos , Mitocôndrias/metabolismo , Radioisótopos de Oxigênio/análise , Animais , Humanos , Modelos Biológicos , Consumo de Oxigênio , Radioisótopos de Oxigênio/metabolismo , Perfusão
8.
Int J Radiat Oncol Biol Phys ; 92(2): 453-9, 2015 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-25817530

RESUMO

PURPOSE: This work was a proof-of-principle study for the evaluation of oxygen-15 ((15)O) production as an imaging target through the use of positron emission tomography (PET), to improve verification of proton treatment plans and to study the effects of perfusion. METHODS AND MATERIALS: Dynamic PET measurements of irradiation-produced isotopes were made for a phantom and rabbit thigh muscles. The rabbit muscle was irradiated and imaged under both live and dead conditions. A differential equation was fitted to phantom and in vivo data, yielding estimates of (15)O production and clearance rates, which were compared to live versus dead rates for the rabbit and to Monte Carlo predictions. RESULTS: PET clearance rates agreed with decay constants of the dominant radionuclide species in 3 different phantom materials. In 2 oxygen-rich materials, the ratio of (15)O production rates agreed with the expected ratio. In the dead rabbit thighs, the dynamic PET concentration histories were accurately described using (15)O decay constant, whereas the live thigh activity decayed faster. Most importantly, the (15)O production rates agreed within 2% (P>.5) between conditions. CONCLUSIONS: We developed a new method for quantitative measurement of (15)O production and clearance rates in the period immediately following proton therapy. Measurements in the phantom and rabbits were well described in terms of (15)O production and clearance rates, plus a correction for other isotopes. These proof-of-principle results support the feasibility of detailed verification of proton therapy treatment delivery. In addition, (15)O clearance rates may be useful in monitoring permeability changes due to therapy.


Assuntos
Músculo Esquelético/metabolismo , Radioisótopos de Oxigênio/metabolismo , Imagens de Fantasmas , Tomografia por Emissão de Pósitrons/métodos , Terapia com Prótons , Animais , Fenômenos Bioquímicos , Estudos de Viabilidade , Método de Monte Carlo , Músculo Esquelético/efeitos da radiação , Radioisótopos de Oxigênio/análise , Radioisótopos de Oxigênio/química , Permeabilidade , Terapia com Prótons/instrumentação , Coelhos , Coxa da Perna , Tomografia Computadorizada por Raios X/métodos
9.
Ann Nucl Med ; 26(8): 644-55, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22797841

RESUMO

OBJECTIVES: (15)O-water-perfusable tissue fraction (PTF) has been shown to be a potential index for assessing myocardial viability in PET, an alternative to (18)F-fluorodeoxyglucose (FDG). This study aimed to directly compare these two independent methods in assessing myocardial viability in patients with abnormal wall motion. METHODS: PET study was performed on 16 patients with previous myocardial infarction, before coronary artery bypass graft operation (CABG). The protocol included a (15)O-carbonmonoxide static, a (15)O-water dynamic and an (18)F-FDG dynamic scan, during the euglycemic hyperinsulinemic clamp. Echocardiography was performed at the time of PET and 5-12 months after the CABG, and the wall motion recovery was evaluated on segmental and global bases. Consistency between PTF and (18)F-FDG was evaluated visually and also in a quantitative manner. Predictive values for the wall motion recovery were also compared between the two approaches. RESULTS: The image quality of (18)F-FDG was superior to that of (15)O-water. The qualitative PTF showed significantly smaller defects than (18)F-FDG, and the quantitative PTF showed slightly greater values than (18)F-FDG in the infarcted region. The two methods were, however, consistent visually and also quantitatively. The predictive values of the wall motion recovery were almost equal between the two approaches. The absolute (18)F-FDG uptake was varied in normal segments, and predictive values for the wall motion recovery by the absolute (18)F-FDG was less (accuracy: 80 %) compared with those by the relative (18)F-FDG (accuracy: 87 %) and the quantitative PTF (accuracy: 89 %). CONCLUSION: Despite the small sample size, PTF appears to give consistent results with the (18)F-FDG approach, and might be an alternative viability assessment.


Assuntos
Fluordesoxiglucose F18/metabolismo , Reperfusão Miocárdica , Miocárdio/metabolismo , Miocárdio/patologia , Sobrevivência de Tecidos , Água/metabolismo , Adulto , Idoso , Transporte Biológico , Doença da Artéria Coronariana/metabolismo , Doença da Artéria Coronariana/patologia , Doença da Artéria Coronariana/fisiopatologia , Doença da Artéria Coronariana/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Revascularização Miocárdica , Radioisótopos de Oxigênio/metabolismo , Valor Preditivo dos Testes , Recuperação de Função Fisiológica
10.
Nucl Med Biol ; 37(1): 77-83, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20122672

RESUMO

INTRODUCTION: The aim of this study was to develop an injectable (15)O-O(2) system using hemoglobin-containing vesicles (HbV), a type of artificial red blood cell, and to investigate the feasibility of (15)O(2)-labeled HbV ((15)O(2)-HbV) to measure cerebral metabolic rate of oxygen (CMRO(2)) in rats. METHODS: The direct bubbling method was combined with vortexing to enhance labeling efficiency of HbV with (15)O-O(2) gas. L-Cysteine was added as a reductant to protect hemoglobin molecules in HbV from oxidation at different concentrations, and labeling efficiencies were also compared. Measurement of cerebral blood flow (CBF) and CMRO(2) in five normal rats was performed using a small animal PET scanner after the injection of H(2)(15)O and (15)O(2)-HbV to evaluate the precision of hemodynamic parameters quantitatively. RESULTS: The labeling efficiency of HbV was significantly increased when vortexing and bubbling were combined compared with the simple bubbling method (P<.05). The most efficient method for labeling was bubbling of (15)O-O(2) combined with vortexing and the addition of 2.8 mM L-cysteine in HbV solution. The mean radioactivity of 214.4+/-7.8 MBq/mL HbV was obtained using this method. PET scans using (15)O(2)-HbV and H(2)(15)O yielded a mean CMRO(2) value of 6.8+/-1.4 (mL/min per 100 g) in rats with normal CBF of 51.4+/-7.9 (mL/min per 100 g). CONCLUSION: Addition of l-cysteine to HbV and simple direct bubbling of (15)O-O(2) gas combined with vortexing was the most efficient method for preparation of (15)O(2)-HbV. The present injectable system using (15)O(2)-HbV was successfully utilized to measure CMRO(2) in rats, indicating that this new method could be useful for animal models to measure oxygen metabolism in the brain.


Assuntos
Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Hemoglobinas/metabolismo , Marcação por Isótopo/métodos , Lipossomos/metabolismo , Oxigênio/metabolismo , Animais , Automação , Injeções , Cinética , Radioisótopos de Oxigênio/administração & dosagem , Radioisótopos de Oxigênio/metabolismo , Tomografia por Emissão de Pósitrons , Ratos , Ratos Sprague-Dawley
11.
J Pharmacol Exp Ther ; 332(2): 429-36, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19910538

RESUMO

An artificial oxygen carrier, liposome-encapsulated hemoglobin (LEH), protective in a rodent stroke model, was quantitatively evaluated in monkeys. Serial positron emission tomography studies using the steady-state (15)O-gas inhalation method were performed to quantify O(2) metabolism, which was compared based on the infarction extent and immunohistochemical evaluation in 19 monkeys undergoing middle cerebral artery occlusion (3 h), infusion of various LEH doses (n = 11), empty liposome (n = 4), or saline (n = 4) 5 min after the onset of ischemia, and reperfusion for 5 h. There was no significant difference in O(2) metabolism until 3 h after reperfusion, when the cerebral metabolic rate of O(2) (CMRO(2)) was significantly less suppressed in the cortex [mild suppression in CMRO(2) (71-100%) of preischemic ipsilateral control as in the ischemic penumbra: 64.7 +/- 14.3% in empty liposome versus 32.4 +/- 7.9% in LEH (2 ml/kg) treatment, P < 0.05] but not in basal ganglia. Immunohistochemical studies showed a reciprocal expression of microtubular-associated protein II expression in the cortex and LEH deposition in basal ganglia, suggesting the LEH perfusion, but not deposition, afforded the protection. Dose-response studies revealed that as little as 0.4 ml/kg LEH (24 mg/kg hemoglobin) was effective in preserving CMRO(2), whereas 2 and 10 ml/kg were protective in significantly reducing the area of infarction as well, by 66 and 56%, respectively, compared with animals receiving saline. CMRO(2) and histological integrity were better preserved early after 3-h occlusion and reperfusion of the middle cerebral artery of monkeys receiving LEH early after onset of ischemia.


Assuntos
Hemoglobinas/administração & dosagem , Hemoglobinas/farmacologia , Infarto da Artéria Cerebral Média/tratamento farmacológico , Animais , Gânglios da Base/diagnóstico por imagem , Gânglios da Base/metabolismo , Gânglios da Base/patologia , Gasometria , Glicemia/efeitos dos fármacos , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/metabolismo , Córtex Cerebral/patologia , Modelos Animais de Doenças , Hemodinâmica/efeitos dos fármacos , Hemoglobinas/metabolismo , Lipossomos , Macaca fascicularis , Proteínas Associadas aos Microtúbulos/metabolismo , Radioisótopos de Oxigênio/metabolismo , Tomografia por Emissão de Pósitrons
12.
Ann Nucl Med ; 23(6): 533-9, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19529979

RESUMO

OBJECTIVE: For diagnosing patients with ischemic cerebrovascular disease, non-invasive count-based method with (15)O(2) and H (2) (15) O positron-emission tomography (PET) data is widely used to measure asymmetric increases in oxygen extraction fraction (OEF). For shortening study time, we have proposed dual-tracer autoradiographic (DARG) protocol in which (15)O(2) gas and C(15)O(2) gas are sequentially administrated within short period. In this paper, we evaluated feasibility of the non-invasive count-based method with the DARG protocol. METHODS: Twenty-three patients [67.8 +/- 9.9 (mean +/- SD) years] with chronic unilateral brain infarction were examined by the use of measurements of asymmetric OEF elevation. As DARG protocol, (15)O(2) and C(15)O(2) gases were inhaled with 5-min interval and dynamic PET data were acquired for 8 min. Quantitative OEF (qOEF) image was computed with PET data and arterial input function. Ratio image of (15)O(2) and C(15)O(2) phases of PET data was computed as count-based OEF (cbOEF) image. The asymmetric indices (AI) of qOEF (qOEF-AI) and cbOEF (cbOEF-AI) were obtained from regions of interest symmetric placed on left and right sides of cerebral hemisphere. To optimize the summation time of PET data for the cbOEF image, qOEF and cbOEF images with various summation times were compared. RESULTS: Image quality of cbOEF image was better than that of qOEF image. The best correlation coefficient of 0.94 was obtained when the cbOEF image was calculated from 0 to 180 s of (15)O(2) summed image and 340 to 440 s of C(15)O(2) summed image. CONCLUSION: Using the appropriate summation time, we obtained the cbOEF image with good correlation with qOEF image, which suggests non-invasive cbOEF image can be used for evaluating the degree of misery perfusion in patients with chronic unilateral brain infarction. The count-based method with DARG protocol has a potential to dramatically reduce the examination time of (15)O PET study.


Assuntos
Infarto Encefálico/diagnóstico , Infarto Encefálico/metabolismo , Consumo de Oxigênio , Idoso , Autorradiografia , Infarto Encefálico/diagnóstico por imagem , Dióxido de Carbono/administração & dosagem , Dióxido de Carbono/metabolismo , Doença Crônica , Estudos de Viabilidade , Feminino , Humanos , Masculino , Radioisótopos de Oxigênio/administração & dosagem , Radioisótopos de Oxigênio/metabolismo , Tomografia por Emissão de Pósitrons , Traçadores Radioativos , Fatores de Tempo
13.
Ann Nucl Med ; 23(4): 363-71, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19360455

RESUMO

OBJECTIVE: Cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO(2)), oxygen extraction fraction (OEF), and cerebral blood volume (CBV) are quantitatively measured with PET with (15)O gases. Kudomi et al. developed a dual tracer autoradiographic (DARG) protocol that enables the duration of a PET study to be shortened by sequentially administrating (15)O(2) and C(15)O(2) gases. In this protocol, before the sequential PET scan with (15)O(2) and C(15)O(2) gases ((15)O(2)-C(15)O(2) PET scan), a PET scan with C(15)O should be preceded to obtain CBV image. C(15)O has a high affinity for red blood cells and a very slow washout rate, and residual radioactivity from C(15)O might exist during a (15)O(2)-C(15)O(2) PET scan. As the current DARG method assumes no residual C(15)O radioactivity before scanning, we performed computer simulations to evaluate the influence of the residual C(15)O radioactivity on the accuracy of measured CBF and OEF values with DARG method and also proposed a subtraction technique to minimize the error due to the residual C(15)O radioactivity. METHODS: In the simulation, normal and ischemic conditions were considered. The (15)O(2) and C(15)O(2) PET count curves with the residual C(15)O PET counts were generated by the arterial input function with the residual C(15)O radioactivity. The amounts of residual C(15)O radioactivity were varied by changing the interval between the C(15)O PET scan and (15)O(2)-C(15)O(2) PET scan, and the absolute inhaled radioactivity of the C(15)O gas. Using the simulated input functions and the PET counts, the CBF and OEF were computed by the DARG method. Furthermore, we evaluated a subtraction method that subtracts the influence of the C(15)O gas in the input function and PET counts. RESULTS: Our simulations revealed that the CBF and OEF values were underestimated by the residual C(15)O radioactivity. The magnitude of this underestimation depended on the amount of C(15)O radioactivity and the physiological conditions. This underestimation was corrected by the subtraction method. CONCLUSIONS: This study showed the influence of C(15)O radioactivity in DARG protocol, and the magnitude of the influence was affected by several factors, such as the radioactivity of C(15)O, and the physiological condition.


Assuntos
Monóxido de Carbono/química , Circulação Cerebrovascular , Oxigênio/metabolismo , Artefatos , Autorradiografia , Monóxido de Carbono/metabolismo , Simulação por Computador , Humanos , Modelos Biológicos , Radioisótopos de Oxigênio/química , Radioisótopos de Oxigênio/metabolismo , Tomografia por Emissão de Pósitrons , Traçadores Radioativos , Radioatividade , Sensibilidade e Especificidade , Coloração e Rotulagem , Técnica de Subtração
14.
Angew Chem Int Ed Engl ; 47(47): 8998-9033, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18988199

RESUMO

Positron emission tomography (PET) is a powerful and rapidly developing area of molecular imaging that is used to study and visualize human physiology by the detection of positron-emitting radiopharmaceuticals. Information about metabolism, receptor/enzyme function, and biochemical mechanisms in living tissue can be obtained directly from PET experiments. Unlike magnetic resonance imaging (MRI) or computerized tomography (CT), which mainly provide detailed anatomical images, PET can measure chemical changes that occur before macroscopic anatomical signs of a disease are observed. PET is emerging as a revolutionary method for measuring body function and tailoring disease treatment in living subjects. The development of synthetic strategies for the synthesis of new positron-emitting molecules is, however, not trivial. This Review highlights key aspects of the synthesis of PET radiotracers with the short-lived positron-emitting radionuclides (11)C, (18)F, (15)O, and (13)N, with emphasis on the most recent strategies.


Assuntos
Marcação por Isótopo , Tomografia por Emissão de Pósitrons , Radioisótopos/química , Radioisótopos de Carbono/química , Radioisótopos de Carbono/metabolismo , Radioisótopos de Flúor/química , Radioisótopos de Flúor/metabolismo , Humanos , Radioisótopos de Nitrogênio/química , Radioisótopos de Nitrogênio/metabolismo , Radioisótopos de Oxigênio/química , Radioisótopos de Oxigênio/metabolismo , Tomografia por Emissão de Pósitrons/instrumentação , Tomografia por Emissão de Pósitrons/métodos , Tomografia por Emissão de Pósitrons/estatística & dados numéricos , Radioisótopos/metabolismo
15.
Neuroscience ; 156(4): 932-8, 2008 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-18786619

RESUMO

Hyperoxic therapy for cerebral ischemia is suspected to reduce cerebral blood flow (CBF), due to the vasoconstrictive effect of oxygen on cerebral arterioles. We hypothesized that vasodilation predominates when 5% CO(2) is added to the inhaled oxygen (carbogen). Therefore, we used positron emission tomography (PET) to measure CBF and cerebral metabolic rate of oxygen (CMRO(2)) during inhalation of test gases (O(2), CO(2), carbogen and atmospheric air) in 10 healthy volunteers. Arterial blood gases were recorded during administration of each gas. The data were analyzed with volume-of-interest and voxel-based statistical methods. Inhalation of CO(2) or carbogen significantly increased global CBF, whereas pure oxygen decreased global CBF. The CMRO(2) generally remained unchanged, except in white matter during oxygen inhalation relative to condition of atmospheric air inhalation. The volume-of-interest results were confirmed by statistical cluster analysis. Oxygen and carbogen were equally potent in increasing oxygen saturation of arterial blood (Sa(O2)). The present data demonstrate that inhalation of carbogen increases both CBF and Sa(O2) in healthy adults. In conclusion we speculate that carbogen inhalation is sufficient for optimal oxygenation of healthy brain tissue, whereas carbogen induces concomitant increases of CBF and Sa(O2).


Assuntos
Encéfalo/metabolismo , Dióxido de Carbono/administração & dosagem , Circulação Cerebrovascular/fisiologia , Inalação , Oxigênio/administração & dosagem , Radiossensibilizantes/administração & dosagem , Adulto , Idoso , Velocidade do Fluxo Sanguíneo , Gasometria , Encéfalo/anatomia & histologia , Encéfalo/diagnóstico por imagem , Química Encefálica , Mapeamento Encefálico , Feminino , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Radioisótopos de Oxigênio/metabolismo , Tomografia por Emissão de Pósitrons
16.
Phys Med Biol ; 53(19): 5385-404, 2008 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-18765889

RESUMO

The beta-microprobe is a simple and versatile technique complementary to small animal positron emission tomography (PET). It relies on local measurements of the concentration of positron-labeled molecules. So far, it has been successfully used in anesthetized rats for pharmacokinetics experiments and for the study of brain energetic metabolism. However, the ability of the technique to provide accurate quantitative measurements using (18)F, (11)C and (15)O tracers is likely to suffer from the contribution of 511 keV gamma rays background to the signal and from the contribution of positrons from brain loci surrounding the locus of interest. The aim of the present paper is to provide a method of evaluating several parameters, which are supposed to affect the quantification of recordings performed in vivo with this methodology. We have developed realistic voxelized phantoms of the rat whole body and brain, and used them as input geometries for Monte Carlo simulations of previous beta-microprobe reports. In the context of realistic experiments (binding of (11)C-Raclopride to D2 dopaminergic receptors in the striatum; local glucose metabolic rate measurement with (18)F-FDG and H(2)O(15) blood flow measurements in the somatosensory cortex), we have calculated the detection efficiencies and corresponding contribution of 511 keV gammas from peripheral organs accumulation. We confirmed that the 511 keV gammas background does not impair quantification. To evaluate the contribution of positrons from adjacent structures, we have developed beta-Assistant, a program based on a rat brain voxelized atlas and matrices of local detection efficiencies calculated by Monte Carlo simulations for several probe geometries. This program was used to calculate the 'apparent sensitivity' of the probe for each brain structure included in the detection volume. For a given localization of a probe within the brain, this allows us to quantify the different sources of beta signal. Finally, since stereotaxic accuracy is crucial for quantification in most microprobe studies, the influence of stereotaxic positioning error was studied for several realistic experiments in favorable and unfavorable experimental situations (binding of (11)C-Raclopride to D2 dopaminergic receptors in the striatum; binding of (18)F-MPPF to 5HT1A receptors in the dorsal raphe nucleus).


Assuntos
Encéfalo/metabolismo , Modelos Anatômicos , Método de Monte Carlo , Radioisótopos/metabolismo , Incerteza , Animais , Radioisótopos de Carbono/química , Elétrons , Fluordesoxiglucose F18/metabolismo , Radioisótopos de Oxigênio/metabolismo , Racloprida/química , Racloprida/metabolismo , Ratos , Sensibilidade e Especificidade
17.
Brain Res ; 1212: 18-24, 2008 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-18445493

RESUMO

Hypertension is a major stroke risk factor and is correlated with worse outcome after stroke. Thus, the effects of hypertension on cerebral hemodynamics and metabolism within an hour after stroke must be evaluated in detail. Cerebral blood flow (CBF), oxygen extraction fraction (OEF), cerebral metabolic rate for oxygen (CMRO2) and cerebral metabolic rate for glucose (CMRglc) were measured 1 h after the occlusion of the right middle cerebral artery (MCA) in male spontaneously hypertensive rats (SHR) and male normotensive Wistar Kyoto rats (WKY). Physiological responses were determined by positron emission tomography (PET) using 15O-H2O and radiolabeled 15O-O2 blood (methodology previously developed in this laboratory) and by autoradiography (ARG) using 18F-FDG. The right hemisphere of SHR showed lower CBF values than the left hemisphere after stroke (right: 0.17+/-0.07 mL/min/g; left: 0.29+/-0.08 mL/min/g), CMRO2 (right: 2.55+/-0.80 mL/min/100 g; left: 4.11+/- 0.84 mL/min/100 g) and CMRglc (right: 52.4+/-16.2 mg/min/100 g; left: 65.6+/-10.2 mg/min/100 g). WKY rats exhibited significant decreases only in CBF and CMRO2. These results suggest greater underlying physiologic disturbances in SHR. Also, the occlusion significantly reduced CBF in both hemispheres of SHR compared with WKY, suggesting a disturbance of the autoregulatory mechanism in SHR. In summary, our results indicate that hypertension intensifies metabolic disturbances after the onset of stroke, at least in the first hour. Therefore, we suggest that hypertension not only increases the incidence of stroke but also exacerbates stroke-mediated damage.


Assuntos
Circulação Cerebrovascular/fisiologia , Infarto da Artéria Cerebral Média/diagnóstico por imagem , Infarto da Artéria Cerebral Média/patologia , Radioisótopos de Oxigênio/metabolismo , Tomografia por Emissão de Pósitrons , Análise de Variância , Animais , Autorradiografia , Tempo de Circulação Sanguínea/métodos , Glucose/metabolismo , Masculino , Oxigênio/metabolismo , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY
18.
Biol Psychiatry ; 64(4): 327-35, 2008 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-18423575

RESUMO

BACKGROUND: Neuroimaging studies report that individuals with posttraumatic stress disorder show abnormal responses in the amygdala and medial prefrontal cortex (mPFC)/anterior cingulate cortex (ACC) during exposure to traumatic reminders. However, neural responses arising in the early aftermath of a traumatic event have not been studied. METHODS: Twenty-two motor vehicle collision survivors and 12 nontraumatized control subjects participated. Regional cerebral blood flow (rCBF) was measured using [(15)O]-H(2)O positron emission tomography (PET) at rest and as subjects listened to scripts of traumatic and neutral events. Self-report measures rated emotional responses to the scripts; standardized assessments (Impact of Events--Revised) evaluated acute stress symptoms at scanning and at 3-month follow-up. Most subjects improved symptomatically. RESULTS: At rest, trauma subjects showed hyperperfusion in right mPFC/ACC and hypoperfusion in right amygdala compared with control subjects. In trauma subjects, listening to trauma scripts versus neutral scripts resulted in decreased flow in the right amygdala and left amygdala/perirhinal cortex, and symptom scores correlated negatively with right hippocampal flow changes. Symptom improvement at 3 months correlated negatively with rCBF changes in right perirhinal cortex and hippocampus during the trauma versus neutral script contrast. Subjective disturbance during the trauma versus neutral contrast correlated positively with rCBF changes in right amygdala and left mPFC. Functional connectivity analyses of rCBF changes during trauma versus neutral scripts demonstrated left amygdala coupling with right ACC and bilateral anterior insula, as well as coupling between the amygdala and contralateral hippocampus. CONCLUSIONS: In recently traumatized subjects functional interactions between the amygdala, perirhinal cortex and ACC/mPFC that occur during exposure to traumatic reminders may underlie adaptive/recuperative processes.


Assuntos
Acidentes de Trânsito/psicologia , Mapeamento Encefálico , Circulação Cerebrovascular/fisiologia , Tomografia por Emissão de Pósitrons , Transtornos de Estresse Pós-Traumáticos/diagnóstico por imagem , Adulto , Tonsila do Cerebelo/diagnóstico por imagem , Tonsila do Cerebelo/patologia , Feminino , Humanos , Processamento de Imagem Assistida por Computador/métodos , Masculino , Pessoa de Meia-Idade , Radioisótopos de Oxigênio/metabolismo , Psicometria/métodos , Fluxo Sanguíneo Regional/fisiologia
19.
Acta Neurol Scand ; 117(5): 317-23, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-17927800

RESUMO

OBJECTIVES: Parkinson's disease (PD) may be associated with increased energy metabolism in overactive regions of the basal ganglia. Therefore, we hypothesized that treatment with the N-methyl-d-aspartate receptor (NMDAR) antagonist memantine would decrease regional cerebral blood flow (rCBF) and oxygen metabolism in the basal ganglia of patients with early-stage PD. METHODS: Quantitative positron emission tomography (PET) recordings were obtained with 15O]water and 15O]oxygen in 10 patients, scanned first in a baseline condition, and again 6 weeks after treatment with a daily dose of 20 mg memantine. Dynamic PET data were analyzed using volume of interest and voxel-based approaches. RESULTS: The treatment evoked rCBF decreases in basal ganglia, and in several frontal cortical areas. The regional cerebral metabolic rate of oxygen (rCMRO2) did not decrease in any of the a priori defined regions, and consequently the oxygen extraction fraction was increased in these regions. Two peaks of significantly decreased rCMRO2 were detected near the frontal poles in both hemispheres, using a posteriori voxel-based analysis. CONCLUSIONS: Although we did not find the predicted decrease in basal ganglia oxygen consumption, our data suggest that treatment with memantine actively modulates neuronal activity and/or hemodynamic response in basal ganglia of PD patients. This finding may be relevant to the putative neuroprotective properties of NMDAR antagonists.


Assuntos
Antiparkinsonianos/uso terapêutico , Circulação Cerebrovascular/efeitos dos fármacos , Memantina/uso terapêutico , Oxigênio/metabolismo , Doença de Parkinson , Idoso , Encéfalo/diagnóstico por imagem , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Feminino , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Radioisótopos de Oxigênio/metabolismo , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo , Tomografia por Emissão de Pósitrons/métodos
20.
J Cereb Blood Flow Metab ; 24(2): 191-201, 2004 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-14747746

RESUMO

Whereas postmortem ischemic damage is common in head injury, antemortem demonstration of ischemia has proven to be elusive. Although 15O positron emission tomography may be useful in this area, the technique has traditionally analyzed data within regions of interest (ROIs) to improve statistical accuracy. In head injury, such techniques are limited because of the lack of a priori knowledge regarding the location of ischemia, coexistence of hyperaemia, and difficulty in defining ischemic cerebral blood flow (CBF) and cerebral oxygen metabolism (CMRO2) levels. We report a novel method for defining disease pathophysiology following head injury. Voxel-based approaches are used to define the distribution of oxygen extraction fraction (OEF) across the entire brain; the standard deviation of this distribution provides a measure of the variability of OEF. These data are also used to integrate voxels above a threshold OEF value to produce an ROI based upon coherent physiology rather than spatial contiguity (the ischemic brain volume; IBV). However, such approaches may suffer from poor statistical accuracy, particularly in regions with low blood flow. The magnitude of these errors has been assessed in modeling experiments using the Hoffman brain phantom and modified control datasets. We conclude that this technique is a valid and useful tool for quantifying ischemic burden after traumatic brain injury.


Assuntos
Lesões Encefálicas/fisiopatologia , Isquemia Encefálica/fisiopatologia , Encéfalo/metabolismo , Radioisótopos de Oxigênio/metabolismo , Tomografia Computadorizada de Emissão/métodos , Adulto , Encéfalo/anatomia & histologia , Lesões Encefálicas/patologia , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/patologia , Circulação Cerebrovascular , Feminino , Humanos , Oxigênio/química , Oxigênio/metabolismo , Fluxo Sanguíneo Regional
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