These results demonstrate that i.a. and i.v. therapy with prourokinase are equally effective in promoting reperfusion and inhibiting the development of focal ischemic injury in this rat embolic stroke model.
Background and Purpose-Spreading depressions (SDs) occur in experimental focal ischemia and contribute to lesion evolution. N-Methyl-D-aspartate (NMDA) antagonists inhibit SDs and reduce infarct size. The glycine site on the NMDA receptor complex offers a therapeutic target for acute focal ischemia, potentially devoid of many side effects associated with competitive and noncompetitive NMDA antagonists. We evaluated the effect of the glycine antagonist ZD9379 on SDs and brain infarction. Methods-Male Sprague-Dawley rats (nϭ18) weighing 290 to 340 g undergoing permanent middle cerebral artery occlusion (MCAO) were randomly and blindly assigned to receive drug or placebo: group 1 (pre-MCAO treatment group; nϭ5), a 5-mg/kg bolus of ZD9379 over 5 minutes followed by 5 mg/kg per hour drug infusion for 4 hours beginning 30 minutes before MCAO; group 2 (post-MCAO treatment group; nϭ7), a 5-mg/kg bolus of ZD9379 30 minutes after MCAO followed by 5 mg/kg per hour drug infusion for 4 hours; and group 3 (control group; nϭ6), vehicle for 5 hours beginning 30 minutes before MCAO. SDs were monitored electrophysiologically for 4.
Two model-independent measures of diffusion, the apparent diffusion coefficient (ADC) and return-to-the-origin probability enhancement (R) were compared for their ability to detect tissue necrosis in RIF-1 murine tumors. Both reflect the degree of restriction experienced by the endogenous water molecules; however, the ADC is calculated from the initial linear slope of the diffusion attenuation curve, while R is calculated from data that includes the non-monoexponential part of the curve. In spectroscopic studies (n ؍ 9), neither the ADC nor R showed a strong correlation with tumor volume. In imaging studies (n ؍ 14), ADC, R, and T 2 were calculated on a pixel-by-pixel basis. There, the mean ADC and mean R for the entire imaging slice showed reasonable correlation with necrotic tumor fraction (r 2 ؍ 0.679 and -0.665, respectively). The mean T 2 value yielded a poor correlation (r 2 ؍ 0.436). Regions-of-interest were chosen from areas identified as either necrotic or viable and the resulting sets of ADC and R-values were subjected to discriminant analysis to determine the identification error rate. The error was greater for R than for the ADC (P < 0.001). Therefore, in this application, the use of the non-monoexponential part of the diffusion attenuation curve does not provide additional identification power.Magn Reson Med 49:468 -478, 2003.
The object of this work is to develop a noninvasive method for detecting local tissue necrosis in RIF-1 murine tumors. The method is based on structural differences between necrotic and viable tissue. By probing the displacement of water molecules in a time, i, it is possible to gather information on the tissue structure. This can be exploited to detect local tissue necrosis in tumors. The return-to-the-origin probability derived from porous media theory is employed to detect local necrosis in tumor.
IntroductionThe ability to monitor the growth of necrotic regions in tumors is an important part of determining the efficacy of chemo-and radiation therapy of tumors. It allows evaluation of the treatment efficacy and affected areas during the time course of the treatment. Recent spectroscopic methods using the apparent diffusion coefficient (ADC) and the retum-to-
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