RESUMEN
Prior studies using pO(2) microelectrodes have shown that RSR13, an allosteric modifier of hemoglobin, increases tissue oxygenation in vivo. Recently, measurements of tissue oxygenation have been performed by many investigators using blood oxygen level-dependent magnetic resonance imaging (BOLD MRI). In this study, we tested the hypothesis that the BOLD MRI signal ratio in tumors will change after administration of RSR13. NCI-H460 human lung carcinoma cells were used as a xenograft in athymic nude mice. Mice with 1-cm(3) tumors in the flank were anesthetized and mounted on the MRI apparatus, and various doses of RSR13 were administered intraperitoneally (i.p.). MR images were then acquired at 10-min intervals for up to 60 min after injection. The effect of RSR13 on tumor response was studied using the same mouse xenograft model with tumor growth delay measurements. RSR13 increased the MRI signal ratio [Intensity(t)/Intensity(t = 0)] in a dose-dependent manner, with maximum increases occurring 30 min after RSR13 was administered. An RSR13 dose of 200 mg/kg proved to be optimum. Since the MRI signal ratio has been shown previously to be linearly related to tissue oxygenation, the changes in the MRI signal ratio can be attributed to changes in tumor oxygen levels. Using a 200-mg/kg dose of RSR13, with a 10-Gy dose of radiation administered to tumors 30 min later, enhancement of radiation-induced tumor growth delay by RSR13 was observed (enhancement factor = 2.8). Thus our MRI results support and verify the previously reported RSR13-induced increase in tumor oxygenation obtained using pO(2) microelectrodes. Based upon these results and other previous studies, the mechanism of enhancement of the effect of radiation by RSR13 probably involves an increase in tumor oxygenation.
Asunto(s)
Compuestos de Anilina , Carcinoma de Células Grandes/metabolismo , Hemoglobinas/metabolismo , Neoplasias Pulmonares/metabolismo , Oxígeno/metabolismo , Propionatos/farmacología , Fármacos Sensibilizantes a Radiaciones/farmacología , Regulación Alostérica , Animales , Humanos , Imagen por Resonancia Magnética , Ratones , Trasplante de Neoplasias , Células Tumorales CultivadasRESUMEN
Thiamine deficiency (TD) in rats produces lesions similar to those found in humans with Wernicke's encephalopathy, an organic mental disorder associated with alcoholism. Male Sprague-Dawley rats (n = 24) were deprived of thiamine in a regimen of thiamine-deficient chow and daily intraperitoneal injections of the thiamine antagonist pyrithiamine hydrobromide for 12 days (0.5 mg/kg). In rats with TD, significant changes were observed in the choline peak (reduction and dose-dependent recovery after thiamine replenishment), which was confirmed by the extraction study. Changes were mainly due to the reduction in glycerophosphorylcholine (GPC), suggesting that a reduction in GPC may be relevant to the primary biochemical lesion in TD. These data are compatible with the hypothesis that a decrease in choline compounds is the cause of the biochemical abnormalities that precede neuroanatomic damage characteristic of Wernicke's encephalopathy.
Asunto(s)
Encéfalo/fisiopatología , Metabolismo Energético/fisiología , Espectroscopía de Resonancia Magnética , Deficiencia de Tiamina/fisiopatología , Encefalopatía de Wernicke/fisiopatología , Animales , Colina/metabolismo , Modelos Animales de Enfermedad , Glicerilfosforilcolina/metabolismo , Masculino , Ratas , Ratas Sprague-Dawley , Deficiencia de Tiamina/patología , Encefalopatía de Wernicke/patologíaRESUMEN
Quantifiable MRI perfusion studies using the contrast agent Gd-DTPA require measurement or estimation of the tissue partition coefficient (lambda) for tracer kinetic modeling. Radiotracer techniques were used to obtain regional lambda measurements from the left ventricles of five dogs. Measurements were analyzed to determine whether spatial heterogeneity was a major component of lambda variability. No systematic variations were identified in terms of radial position, short-axis slice location, or wall position. The high lambda variability seen in this study and in cited data of others may be due in part to tissue heterogeneity in interstitial volume, plasma volume, and perfusate hematocrit.
Asunto(s)
Medios de Contraste/farmacocinética , Gadolinio DTPA/farmacocinética , Imagen por Resonancia Magnética/métodos , Miocardio/metabolismo , Función Ventricular , Animales , Velocidad del Flujo Sanguíneo , Perros , Modelos Teóricos , Perfusión/métodosRESUMEN
Thiamine deficiency (TD) in rats produces lesions similar to those found in humans suffering from Wernicke's encephalopathy, an organic mental disorder associated with alcoholism. Male Sprague-Dawley rats (n = 29) were deprived of thiamine via a regimen of thiamine-deficient chow and daily intraperitoneal injections of the thiamine antagonist pyrithiamine hydrobromide. Spectra were obtained by using the STEAM sequence. No significant change occurred in the ratio of Cr/NAA, while the ratio of Cho/NAA declined significantly (60 +/- 11%) on Day 14. Eleven rats received intraperitoneal injections of thiamine hydrochloride at the end of 12 days, and dose-dependent recovery in Cho/NAA was observed.
Asunto(s)
Encéfalo/metabolismo , Espectroscopía de Resonancia Magnética , Deficiencia de Tiamina/metabolismo , Trastorno Amnésico Alcohólico/metabolismo , Animales , Encéfalo/patología , Creatina/metabolismo , Dipéptidos/metabolismo , Relación Dosis-Respuesta a Droga , Ácido Glutámico/metabolismo , Masculino , Fosfocreatina/metabolismo , Ratas , Ratas Sprague-Dawley , Tiamina/uso terapéutico , Deficiencia de Tiamina/tratamiento farmacológico , Encefalopatía de Wernicke/metabolismoRESUMEN
The lack of a naturally occurring background signal from fluorine in magnetic resonance (MR) imaging makes fluorinated compounds potentially attractive candidates for tissue-specific MR contrast agents. Problems associated with the in vivo use of fluorinated compounds are toxicity, which limits the amount of agent that can be used; multiple resonance lines; and an excessively long T1, which leads to long sequence TRs and consequently long imaging times. Many fluorinated agents also possess complex MR spectra that result in chemical shift artifacts if not corrected. The authors demonstrate the use of an extracellular fluorinated agent with a single MR peak for selective imaging of a brain abscess in an animal model and show that the image signal per unit of acquisition time can be enhanced through the use of a T1 relaxation agent, gadolinium diethylenetriamine-pentaacetic acid (DTPA). Trifluoromethylsulfonate was administered at a fluorine-19 dose of 4 mmol/kg, and fluorine images of the induced abscess were acquired before and after the injection of a standard dose of Gd-DTPA (0.1 mmol/kg); non-section-selected projection images were used. Typical imaging times were less than 5 minutes. The signal enhancement factor achieved was approximately four (4.0 +/- 0.8) with use of a 500/12 (TR msec/TE msec) spin-echo sequence.
Asunto(s)
Medios de Contraste , Gadolinio , Aumento de la Imagen/métodos , Imagen por Resonancia Magnética/métodos , Compuestos Organometálicos , Ácido Pentético/análogos & derivados , Animales , Absceso Encefálico/diagnóstico , Flúor , Gadolinio DTPA , Espectroscopía de Resonancia Magnética , Meglumina , Mesilatos , Conejos , Infecciones Estafilocócicas/diagnóstico , Factores de TiempoRESUMEN
The objective of this study was to determine the short- and long-term radiographic, physiologic and histologic changes elicited in the lung of rabbits following the aspiration of commonly used radiographic contrast agents. All agents used, including nonionic agents, caused radiographically evident pulmonary edema which cleared by 24 hours. The contrast materials with higher osmolality, viscosity, and iodine content elicited the greatest physiologic and pathologic changes. No differences were found between an ionic and a nonionic agent with similar viscosities and iodine content, despite a lower osmolality in the nonionic agent. No contrast agent is innocuous when introduced into the lung.
Asunto(s)
Medios de Contraste/toxicidad , Pulmón/efectos de los fármacos , Edema Pulmonar/inducido químicamente , Animales , Bronquios , Medios de Contraste/administración & dosificación , Diatrizoato de Meglumina/administración & dosificación , Diatrizoato de Meglumina/toxicidad , Instilación de Medicamentos , Yohexol/administración & dosificación , Yohexol/toxicidad , Yotalamato de Meglumina/administración & dosificación , Yotalamato de Meglumina/toxicidad , Concentración Osmolar , ConejosRESUMEN
The intravoxel incoherent motion (IVIM) model of perfusion and diffusion imaging was applied to an in vivo canine model of unilateral renal artery stenosis and was compared with relative renal blood flow determination with radioactive microspheres. The percentage relative renal blood flow as determined with radioactive microspheres correlated closely with the percentage apparent diffusion coefficient. If this method can be adapted to human imaging, it may provide a noninvasive means for detecting renal artery stenosis.
Asunto(s)
Imagen por Resonancia Magnética , Obstrucción de la Arteria Renal/diagnóstico , Animales , Constricción Patológica , Perros , Obstrucción de la Arteria Renal/fisiopatología , Circulación RenalRESUMEN
The authors evaluated the effect of different iodinated contrast agents on the fallopian tube and adnexal tissue in 15 rabbits. Ethiodized oil, an oil-soluble agent, was used in five rabbits. The following water-soluble agents were used: iothalamate meglumine 30% (n = 3), iothalamate meglumine 60% (n = 3), and ioxilan (n = 4). The agents were injected through catheters placed in the fallopian tubes. Fallopian tubes and peritoneal cavities were histologically evaluated. The contralateral tube served as a control. Ioxilan and iothalamate meglumine 30% produced no pathologic response in the tube or peritoneal cavity. Iothalamate meglumine 60% was associated with mild inflammatory infiltrate, mucosal edema, giant cell reaction, and periovarian adhesions that were bilateral but more pronounced on the injected side. Use of ethiodized oil resulted in papillary fibrous adhesions on the ovarian surface, and fat granulomas were seen in the periovarian tissues. The safety of oil-based contrast agents for use in hysterosalpingography is therefore questioned. No significant differences were found among the water-soluble contrast agents.
Asunto(s)
Medios de Contraste/toxicidad , Trompas Uterinas/efectos de los fármacos , Anexos Uterinos/efectos de los fármacos , Enfermedades de los Anexos/inducido químicamente , Animales , Aceite Etiodizado/toxicidad , Enfermedades de las Trompas Uterinas/inducido químicamente , Femenino , Granuloma/inducido químicamente , Histerosalpingografía , Yohexol/toxicidad , Yotalamato de Meglumina/toxicidad , Conejos , Adherencias Tisulares/inducido químicamenteRESUMEN
A simple, inexpensive, non-magnetizable, pulsatile air-driven pump has been devised for use in magnetic resonance environments. The pump has a variable stroke volume and stroke rate, is easily cleaned and sterilized, requires relatively small priming volumes and causes no observable hemolysis when blood is used as the perfusate. This device is usable for phantoms, isolated organs or in situ preparations.
Asunto(s)
Corazón Auxiliar , Imagen por Resonancia Magnética/instrumentación , Animales , Diseño de Equipo , Corazón Auxiliar/economía , OvinosRESUMEN
It has been demonstrated that chromium (Cr) labeling significantly decreases the relaxation times of packed red blood cells (RBCs). In this study, the spin-lattice relaxation time (T1) of human red cells was shortened from 836 ms to 29 ms and the spin-spin relaxation time (T2) shortened from 134 ms to 18 ms, when the cells were labeled at a Cr incubation concentration of 50 mM. Labeling of canine cells at 50 mM resulted in a T1 of 36 ms and a T2 of 26 ms. A labeling concentration of 10 mM produced similar relaxation enhancement, with uptake of 47% of the available Cr, and was determined to be optimal. The enhancement of longitudinal and transverse relaxation rates (1/T1,-1/T2) per amount of hemoglobin-bound Cr are 6.9 s-1 mM-1 and 9.8 s-1 mM-1 respectively, different from those of a pure Cr+3 solution. Labeling cells at 10 mM decreased the survival half-time in vivo from 16.6 days to 4.7 days in dogs. No difference in red cell survival was found with the use of hetero-transfusion versus auto-transfusion of labeled RBCs. Significant shortening of the T1 (912 ms to 266 ms, P = .03) and T2 (90 ms to 70 ms, P = .006) of spleen and the T1 (764 ms to 282 ms, P = .005) and the T2 (128 ms to 86 ms, P = .005) of liver occurred when 10% of the RBC mass of dogs was exchanged with Cr labeled cells. Liver and spleen spin density changes (P greater than 0.23) and muscle spin density and relaxation changes (P greater than 0.4) were insignificant. The in vivo T1 of a canine spleen which had been infarcted did not change following transfusion with labeled cells, where the T1 of liver did shorten. We believe this preliminary study suggests that Cr labeled red cells may have the potential to become an intravascular magnetic resonance imaging contrast agent.
Asunto(s)
Radioisótopos de Cromo , Medios de Contraste , Eritrocitos , Imagen por Resonancia Magnética , Animales , Transfusión Sanguínea , Radioisótopos de Cromo/administración & dosificación , Perros , Eritrocitos/metabolismo , Hematócrito , Hemoglobinas , Humanos , Aumento de la Imagen/métodos , Isquemia/diagnóstico , Hígado/patología , Bazo/irrigación sanguínea , Bazo/patologíaRESUMEN
A consensus does not exist as to the optimal contrast agent for hysterosalpingography. This study was undertaken to evaluate the early and delayed inflammatory responses of the peritoneal surfaces to various types of iodinated contrast media. Guinea pigs received intraperitoneal injections of lactated Ringer solution, iothalamate meglumine, diatrizoate sodium, ioxilan, or ethiodized oil. The inflammatory response of the peritoneal surfaces was assessed at 1,7, and 30 days. Five animals were studied at each time point for each agent. No animals that received Ringer lactate or iothalamate meglumine had inflammation at any time. Ioxilan produced inflammation in two of five animals at 7 days and no inflammation at 1 or 30 days. Ethiodized oil produced no inflammation at 1 day; however, three animals had inflammation at 7 days, and all five had inflammation at 30 days. The 30-day group showed striking inflammatory response with granulomatous features. The authors recommend the continued use of meglumine-based water-soluble ionic contrast material for hysterosalpingography.
Asunto(s)
Medios de Contraste/toxicidad , Peritonitis/inducido químicamente , Animales , Diatrizoato/toxicidad , Aceite Etiodizado/toxicidad , Cobayas , Yohexol/análogos & derivados , Yohexol/toxicidad , Yotalamato de Meglumina/toxicidad , Peritonitis/patologíaRESUMEN
Acute mesenteric ischemic bowel disease is a common yet complex disorder with high morbidity and mortality rates predominantly caused by delayed diagnosis. We examined the role of magnetic resonance imaging (MRI) in the early detection of small bowel ischemia using the rabbit model. Surgical ligation of the appropriate arterial vascular supply to the ileum of 10 rabbits produced the ischemic compromise. The animals were imaged at different time intervals after the arterial occlusion. Multislice, T1 and T2-weighted images were obtained in axial and coronal planes. Abnormal findings of the dearterialized segment of bowel were visualized as early as 45 minutes after vascular occlusion. The findings consisted of: (1) bowel wall thickening, (2) two- to three-fold increase in signal intensity from bowel on T2-weighted images, and (3) isointensity or slightly increased signal intensity within the bowel wall on T1-weighted images. MRI appears to be a sensitive, noninvasive technique for the early detection of bowel ischemia in the rabbit animal model.