RESUMEN
BACKGROUND AND OBJECTIVES: Measurement of GFR is important for the management of chronic kidney disease (CKD). Although bolus administration of radiocontrast agents is commonly used to measure GFR, the optimal duration of sampling to assess their plasma clearance is unknown. The purpose of this study was to evaluate whether the duration of plasma sampling influences precision and estimation of GFR. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: GFR was measured by sampling plasma 12 times over 5 h in 56 patients with CKD (mean age 64 yr, 98% men, 79% Caucasian, 34% diabetics, estimated GFR 31.8 +/- 14.2 ml/min/1.73 m(2)). In a subset of 12 patients we measured GFR by sampling plasma 17 times over 10 h. RESULTS: Short sampling intervals considerably overestimated GFR measured using total plasma iothalamate clearance, especially in larger patients. In the higher estimated GFR group (>30 ml/min/1.73 m(2)), the 5-h GFR was 17% higher and 2-h GFR 54% higher compared with the 10-h GFR, which averaged 40.3 ml/min/1.73 m(2). In the lower estimated GFR group (<30 ml/min/1.73 m(2)), the 5-h GFR was 36% higher and 2-h GFR 126% higher compared with the 10-h GFR, which averaged 22.2 ml/min/1.73 m(2). Short sampling duration also reduced the precision of the estimated GFR from 1.67% for 10-h GFR, to 3.48% for 5-h GFR, and to 7.07% for 2-h GFR. CONCLUSIONS: GFR measured over a longer duration with multiple plasma samples spanning the distribution and elimination phases may improve precision and provide a better measure of renal function.
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Medios de Contraste/farmacocinética , Tasa de Filtración Glomerular , Yotalamato de Meglumina/farmacocinética , Enfermedades Renales/diagnóstico , Riñón/fisiopatología , Anciano , Enfermedad Crónica , Medios de Contraste/administración & dosificación , Femenino , Humanos , Inyecciones Intravenosas , Yotalamato de Meglumina/administración & dosificación , Enfermedades Renales/fisiopatología , Masculino , Persona de Mediana Edad , Modelos Biológicos , Valor Predictivo de las Pruebas , Reproducibilidad de los ResultadosRESUMEN
El objetivo del presente trabajo es exponer un grupo de compuestos iodados con tres y seis átomos de iodo en su molécula que son derivados del ácido benzoico y son utilizados en Radiología como medios de contraste de gran interés clínico. Se estudian sus constantes físico-químicas y las ventajas que presentan los contrastes no iónicos sobre los iónicos. Se describen también los posibles efectos colaterales indeseables en un pequeño pero importante número de pacientes que pueden producirse por su inyección intravascular (AU)
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Humanos , Medios de Contraste/efectos adversos , Compuestos de Yodo/efectos adversos , Yohexol/farmacocinética , Metrizamida/farmacocinética , Yotalamato de Meglumina/farmacocinética , Diatrizoato de Meglumina/toxicidad , Espectroscopía de Resonancia Magnética/métodosRESUMEN
PURPOSE: To investigate pharmacokinetic and physiologic factors that determine the time to peak intravenous contrast medium enhancement in computed tomographic (CT) and magnetic resonance (MR) angiography in the porcine mid-abdominal aorta. MATERIALS AND METHODS: Four pigs were imaged repeatedly in seven to eight sets: For each set, 20 dynamic CT scans were obtained at a fixed aortic level after intravenous injection of contrast medium. From a physiologically based compartment model, aortic contrast enhancement curves were generated by varying contrast medium injection duration from 1 to 40 seconds. Contrast enhancement curves and times to peak aortic enhancement from the experiment and model were compared. Time to peak aortic enhancement obtained from the injection with the shortest duration was considered the time to peak test bolus contrast enhancement. Mathematic and pharmacokinetic analyses were performed to investigate factors that determine peak enhancement. RESULTS: Empiric and compartmental model times to peak aortic enhancement were in good agreement. Time to peak aortic enhancement corresponded to the weighted sum of injection duration and time to peak test bolus enhancement. With increasing injection duration, the relative contribution of injection duration to peak aortic enhancement time increased. When injection duration was longer than time to peak test bolus enhancement, time to peak aortic enhancement increased linearly with injection duration and occurred shortly after completion of injection. However, when injection duration was shorter than time to peak test bolus enhancement, time to peak aortic enhancement was determined predominantly by time to peak test bolus enhancement and only gradually increased with injection duration. CONCLUSION: Time to peak aortic enhancement is determined by the relative contributions of injection duration and contrast medium traveling time and may well be explained by contrast medium volumetric inflow and recirculation physiology.
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Medios de Contraste/farmacocinética , Angiografía por Resonancia Magnética , Tomografía Computarizada por Rayos X , Angiografía , Animales , Aorta Abdominal/anatomía & histología , Medios de Contraste/administración & dosificación , Inyecciones Intravenosas , Yotalamato de Meglumina/administración & dosificación , Yotalamato de Meglumina/farmacocinética , Porcinos , Factores de TiempoRESUMEN
PURPOSE: To determine if multiphasic injection provides uniform, prolonged vascular contrast medium enhancement at computed tomographic (CT) angiography. MATERIALS AND METHODS: With a computer-based, compartmental model of the cardiovascular system, theoretic analysis was performed to estimate an injection algorithm for uniform, prolonged vascular enhancement. For algorithm validation, four pigs were scanned after intravenous injection of 50 or 70 mL of contrast medium (282 mg of iodine per milliliter). Uni-, bi-, and multiphasic injection schemes were tested. In most cases, the initial injection rate was 2 mL/sec. In each CT study, 27 dynamic images were acquired every 2 seconds at a fixed mid-abdominal aortic level. Time-enhancement curves were calculated. Injection duration, peak aortic enhancement, and enhancement uniformity (duration of enhancement achieved within 90% of the peak [90% DCE]) were evaluated. RESULTS: Theoretic and experimental results agreed well. Compared with uniphasic injection, biphasic injection resulted in more prolonged enhancement but generated two enhancement peaks with a valley between, and multiphasic injection yielded more uniform and prolonged enhancement. With 50- and 70-mL multiphasic injections, respectively, injection duration increased by 32% and 51%, peak enhancement decreased by 19% and 18%, and 90% DCE increased by 81% and 94%. CONCLUSION: Uniform, prolonged vascular enhancement, which is desirable for CT angiography and essential for steady-state quantification of blood volume in organs, can be achieved with multiphasic injection.
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Angiografía , Medios de Contraste/administración & dosificación , Yotalamato de Meglumina/administración & dosificación , Intensificación de Imagen Radiográfica , Tomografía Computarizada por Rayos X , Animales , Aortografía , Simulación por Computador , Medios de Contraste/farmacocinética , Relación Dosis-Respuesta a Droga , Humanos , Inyecciones Intravenosas , Yotalamato de Meglumina/farmacocinética , Modelos Cardiovasculares , Sensibilidad y Especificidad , PorcinosRESUMEN
BACKGROUND: To evaluate the relative effect of rate of injection and volume of contrast medium on aortic, portal, and hepatic enhancement during computed tomography (CT). METHODS: Thirty-eight nonincremental CT examinations were performed in three mini-pigs by using a combination of three different volumes (1.5, 2, and 3 mL/kg) and five different rates (1.5, 3, 4.5, 6, and 7.5 mL/s) of contrast material injection. Time-density enhancement curves of the aorta, portal vein, and liver were plotted over time for each rate of injection, each volume of contrast, and each volume-rate combination. In addition, aortic, portal, and liver peak enhancements, time-to-peak enhancements, optimal scanning intervals, and contrast enhancement indices were calculated for each volume-rate combination. RESULTS: Higher rates of injection increased peak aortic enhancement but had no effect on peak portal or hepatic enhancement. This result may be explained by the dilution of the bolus of contrast medium in the splanchnic circulation. When the results of a 6-mL/s injection of 1.5 mL/kg of contrast material were compared with a 3-mL/s injection of 2 mL/kg, maximum aortic enhancement increased by 32%, whereas maximum liver enhancement decreased by 35%. CONCLUSION: An increase in the rate of contrast injection results in an increase of peak aortic enhancement even when the total iodine load is decreased. However, an increase of the rate of contrast injection does not increase maximum liver enhancement, which is related to the total iodine dose injected. Therefore, one cannot compensate a decrease in the iodine load by an increase in injection rate in contrast-enhanced CT of the liver.
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Medios de Contraste/administración & dosificación , Yotalamato de Meglumina/administración & dosificación , Hígado/diagnóstico por imagen , Vena Porta/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Animales , Aortografía/métodos , Medios de Contraste/farmacocinética , Relación Dosis-Respuesta a Droga , Inyecciones Intravenosas , Yotalamato de Meglumina/farmacocinética , Hígado/irrigación sanguínea , Porcinos , Porcinos EnanosRESUMEN
PURPOSE: To investigate the effect of injection rate of contrast medium on aortic and hepatic peak enhancement at computed tomography. MATERIALS AND METHODS: Early pharmacokinetics of contrast enhancement was analyzed theoretically and simulated with a compartment model. Contrast enhancement curves were generated from the model at different injection rates (0.5-10.0 mL/sec). Time-enhancement curves were measured. The effect of contrast medium injection rate on the time and magnitude of peak enhancement was evaluated and validated empirically in pigs. RESULTS: Theoretic predictions and experimental results were in good agreement. Time to aortic peak enhancement was the sum of injection duration and bolus transfer time of contrast medium from the injection site to the aorta. Time to hepatic peak enhancement was the sum of injection duration and time to equilibrium. The magnitude of peak enhancement increased with the injection rate, but the increase was different in the aorta and liver. CONCLUSION: Use of injection rates above 2 mL/sec did not substantially increase hepatic peak enhancement but helped increase the magnitude of arterial enhancement and temporal separation of arterial and venous phases of enhancement for dual-phase spiral CT.
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Medios de Contraste/administración & dosificación , Medios de Contraste/farmacocinética , Hígado/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Animales , Aortografía , Humanos , Inyecciones Intravenosas/métodos , Yotalamato de Meglumina/administración & dosificación , Yotalamato de Meglumina/farmacocinética , Modelos Biológicos , Porcinos , Factores de TiempoRESUMEN
OBJECTIVE: Our goal was to assess the accuracy of estimating the time course of the arterial plasma concentration of meglumine iothalamate from cranial CT images of different vascular structures in the brain. MATERIALS AND METHODS: Dynamic CT studies of transcapillary transport in various brain lesions were analyzed. Vascular structures in the brain were identified and classified in three categories: arteries, veins, and venous sinuses. Systemic venous blood samples were taken prior to the infusion of meglumine iothalamate and 10 min after completion of the infusion and used as a calibration for the volume averaging fraction of the image of each vascular structure. A time course of plasma meglumine iothalamate concentration for each of the vascular categories in the CT images was obtained and compared with a variety of methods. RESULTS: Significant differences were found for measurement of plasma meglumine iothalamate concentration from different vascular categories. There was also a disparity between the volume averaging fraction that we calculated and what would be expected due to the measured systemic hematocrit for all vascular structures. CONCLUSION: The use of images of veins and venous sinuses consistently underestimated the arterial concentration around the peak values. Correcting the imaged venous sinus values with the measured systemic hematocrit was even less reliable. The most accurate method of determining arterial plasma concentration of meglumine iothalamate from CT images of brain was to correct the identified arterial vessels for volume averaging.
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Encéfalo/diagnóstico por imagen , Yotalamato de Meglumina/farmacocinética , Tomografía Computarizada por Rayos X , Arterias Cerebrales , Venas Cerebrales , Medios de Contraste , Senos Craneales , HumanosRESUMEN
During this study the absorption rates of two contrast media were measured in double-blind design. 33 patients received lopamidol (Solutrast 300), and 30 patients Meglumine iothalamate (Conray 60). A regular absorption of the contrast media during ERC, ERP and ERCP could be stated. With reference to the absorption rates a slight, but for statistically not significant advantage for the contrast medium lopamidol could be ascertained. During ERC the absorption rates ranged from 0.4 to 30%, during ERP from 2.2 to 18.8% and during ERCP from 1.0 and 30.0%. Consequently the endoscopist always has to take into account an anaphylactoid reaction due to the systemic absorption of contrast media which, compared to other examinations with contrast media, happens relatively seldom.
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Colangiopancreatografia Retrógrada Endoscópica , Medios de Contraste/farmacocinética , Yopamidol/farmacocinética , Yotalamato de Meglumina/farmacocinética , Adulto , Anciano , Anciano de 80 o más Años , Conductos Biliares/metabolismo , Método Doble Ciego , Femenino , Humanos , Masculino , Tasa de Depuración Metabólica , Persona de Mediana EdadRESUMEN
A quantity that often must be determined in physiological imaging studies is the blood concentration of the tracer over time. This is usually performed by direct arterial or venous blood sampling. We studied the relationship between the concentration of meglumine iothalamate in arterial blood and values determined from voxels containing large blood vessels in a series of CT images at the same location over time. After correction for volume averaging based on a single venous blood sample, there was an excellent correlation between the two blood curves. Differences between the curves were shown to be inconsequential by a simulation of transcapillary transport determinations. We thus conclude that determination of plasma concentration from CT images is a reliable technique for CT transcapillary transport studies.
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Encéfalo/diagnóstico por imagen , Yotalamato de Meglumina/farmacocinética , Tomografía Computarizada por Rayos X , Animales , Sangre , Volumen Sanguíneo , Arteria Braquial , Capilares , Difusión , Perros , Femenino , Vena Femoral , Antebrazo/irrigación sanguínea , Hematócrito , Bombas de Infusión , Yotalamato de Meglumina/administración & dosificación , Modelos Estructurales , Factores de Tiempo , Tomografía Computarizada por Rayos X/métodos , VenasRESUMEN
We present a quantitative method for determining a blood-to-tissue influx constant (K1), a tissue-to-blood efflux constant (k2), and tissue plasma vascular space (Vp) that uses a computed tomographic (CT) scanner to make tissue and plasma measurements of the concentration of an iodinated compound. Meglumine iothalamate was infused intravenously over time periods of 0.5-5 min, up to 49 CT scans were obtained at one brain level, and arterial plasma was sampled over a 30- to 40-min period. K1, k2, and Vp were calculated for each voxel of the 320 x 320 matrix, using a two-compartment pharmacokinetic model and nonlinear least-squares regression. The method was used in dogs with avian sarcoma virus-induced brain tumors. As many as four studies on different days were done in the same animal. In tumor-free cortex, K1 of meglumine iothalamate was 2.4 +/- 1.7 microliter g-1 min-1 (mean +/- SD) and Vp was 3.4 +/- 0.5 ml 100 g-1. Mean whole-brain tumor K1 values ranged from 3.3 to 97.9 microliters g-1 min-1; k2 ranged from 0.032 to 0.27 min-1; and Vp ranged from 1.1 to 11.4 ml 100 g-1. These values were reproducible in serial experiments in single animals. Independent verification of K1 values was obtained with quantitative autoradiographic measurements of alpha-aminoisobutyric acid, which has similar physicochemical properties to meglumine iothalamate. The CT methodology is capable of demonstrating regional variation of transcapillary transport in brain tumors and may be of value in the study of human brain tumors.
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Neoplasias Encefálicas/metabolismo , Capilares/metabolismo , Yotalamato de Meglumina/farmacocinética , Sarcoma/metabolismo , Tomografía Computarizada por Rayos X/métodos , Ácidos Aminoisobutíricos/farmacocinética , Animales , Autorradiografía , Virus del Sarcoma Aviar , Transporte Biológico , Encéfalo/metabolismo , Neoplasias Encefálicas/sangre , Neoplasias Encefálicas/diagnóstico por imagen , Perros , Humanos , Recién Nacido , Sarcoma/sangre , Sarcoma/diagnóstico por imagenRESUMEN
The rate at which water-soluble chemotherapeutic drugs enter brain tumors can be extremely variable. The ability to measure or predict the rate of drug entry may have an important role in treatment. We have developed a method that uses information from contrast-enhanced computed tomographic scans to measure quantitatively the rate of transcapillary transport of iodinated compounds in brain tumors. In a group of 10 patients with brain tumors, we obtained serial measurements of tissue (Am) and arterial plasma (Cp) iodine concentration from timed computed tomographic scans done over 30 minutes, after intravenous infusion of meglumine iothalamate (Conray-60). These measurements were analyzed with a two-compartment pharmacokinetic model and nonlinear least-squares regression methods to obtain K1, a blood-to-tissue transfer constant; k2, a tissue-to-blood rate constant; and Vp, tissue plasma vascular volume. Images of K1, k2, and Vp were reconstructed after calculating these values for each 0.8 x 0.8 x 5-mm volume element of the original data. Mean whole tumor K1 values varied from 2.0 mu 1 gm-1 min-1 in a thalamic astrocytoma to 33.9 mu 1 gm-1 min-1 in a glioblastoma multiforme. The value of k2 varied from 0.034 to 0.108 min-1, and Vp varied from 2.4 to 7.9 ml 100 gm-1. In tumor-free brain, the K1 of meglumine iothalamate was 2.9 mu 1 gm-1 min-1; k2 was 0.058 min-1; and Vp was 2.1 ml 100 gm-1.(ABSTRACT TRUNCATED AT 250 WORDS)
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Neoplasias Encefálicas/metabolismo , Permeabilidad Capilar , Adulto , Anciano , Autorradiografía , Transporte Biológico , Neoplasias Encefálicas/irrigación sanguínea , Neoplasias Encefálicas/diagnóstico por imagen , Femenino , Humanos , Yotalamato de Meglumina/farmacocinética , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Rayos XRESUMEN
Whether hyperosmotic blood-brain barrier (BBB) disruption is a technique that can be used to increase permeability of brain-tumor capillaries and thereby transiently increase drug delivery to the brain tumor is controversial. Nine virally induced brain tumors were studied in seven dogs, before and after hyperosmotic BBB disruption with 1.4 osmolar mannitol. Each dog was studied with computerized tomography (CT) after administration of the water-soluble tracer meglumine iothalamate. Each study lasted 30 minutes. A baseline CT scan and 35 to 40 additional CT scans were obtained to provide a time-related measurement of the amount of meglumine iothalamate in tissue (Am(t], and 30 plasma samples were collected to provide the time-related measurement of meglumine iothalamate in plasma (Cp(t]. The data were analyzed by three different methods: 1) a two-compartment model and nonlinear curve fitting were used to calculate K1 (blood-to-tissue or influx constant), k2 (tissue-to-blood or efflux constant), and Vp (plasma vascular space); 2) K1 values were calculated with a two-compartment model, assuming no efflux, at the time point for each CT scan; and 3) a "tissue advantage ratio" was calculated that expressed the ratio of tissue uptake of meglumine iothalamate at each time point, comparing values before and after BBB disruption. Regardless of which method of data analysis was used, there was a marked and significant increase in transcapillary transport of meglumine iothalamate to tumor-free brain regions, while there was only a small, transient, and insignificant increase to the brain tumors. Although there were often marked increases in delivery to cortex in the same hemisphere as the tumors, there was no significant increase to brain immediately surrounding the tumors, perhaps due to altered circulatory dynamics in this region. These data raise serious questions as to the wisdom of using this technique to increase drug delivery to brain tumors in patients and strongly support the continued study of this technique in experimental brain tumors before it is used in patients.
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Barrera Hematoencefálica/efectos de los fármacos , Neoplasias Encefálicas/metabolismo , Permeabilidad Capilar , Manitol/farmacología , Animales , Encéfalo/metabolismo , Perros , Yotalamato de Meglumina/administración & dosificación , Yotalamato de Meglumina/farmacocinética , Modelos Cardiovasculares , Concentración OsmolarRESUMEN
The contrast medium dose used in CT renal function analysis corresponds to about 1 ml/kg body weight at a measurement interval of 5 or 10 minutes. In the present study the dependence of "CT clearance" on dosage and time was examined in 12 healthy subjects. The amount of clearance was directly proportional to the employed contrast medium dose and to the length of the measurement interval. On account of the superior signal-to-noise ratio, the higher dose (1 ml/kg body weight) will continue to be preferred in future. The measurement interval can be limited to 10 minutes.
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Medios de Contraste/farmacocinética , Yotalamato de Meglumina/farmacocinética , Pruebas de Función Renal/métodos , Tomografía Computarizada por Rayos X , Adulto , Medios de Contraste/administración & dosificación , Femenino , Humanos , Yotalamato de Meglumina/administración & dosificación , Riñón/diagnóstico por imagen , Riñón/fisiología , Masculino , Valores de Referencia , Factores de TiempoRESUMEN
In this study methods for the assay of the iodine-containing radiographic contrast agents metrizoate, amidotrizoate and iothalamate found in serum and urine have been developed. The method involved reverse-phase high-pressure liquid chromatography with spectrophotometric detection. This technique was used to compare the clearance of these agents, in a group of healthy female volunteers, after a single small-dose injection (5 ml, 2275-3235 mg). In the period 0-4 h after injection, serum elimination was approximated by a two-compartment model. However, a full description of drug fate in the body required at least three compartments. Plasma clearance was significantly different between agents with means of 191, 130, 144 and 121 ml/min for metrizoate, amidotrizoate, iothalamate and iohexol, respectively, whereas no difference was found between the renal/plasma clearance ratio. Protein binding measured with equilibrium dialysis did not suggest binding to serum proteins by any of these agents irrespective of concentration.