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Dynamic susceptibility contrast (DSC) perfusion-weighted imaging (PWI) is widely used in clinical settings for the radiological diagnosis of brain tumor. The signal change in brain tissue in gradient echo-based DSC PWI is much higher than in spin echo-based DSC PWI. Due to its exquisite sensitivity, gradient echo-based sequence is the preferred method for imaging of all tumors except those near the base of the skull. However, high sensitivity also comes with a dynamic range problem. It is not unusual for blood volume to increase in gene-mediated cytotoxic immunotherapy-treated glioblastoma patients. The increase of fractional blood volume sometimes saturates the MRI signal during first-pass contrast bolus arrival and presents signal truncation artifacts of various degrees in the tumor when a significant amount of blood exists in the image pixels. It presents a hidden challenge in PWI, as this signal floor can be either close to noise level or just above and can go no lower. This signal truncation in the signal intensity time course is a significant issue that deserves attention in DSC PWI. In this paper, we demonstrate that relative cerebral blood volume and relative cerebral blood flow (rCBF) are underestimated due to signal truncation in DSC perfusion, in glioblastoma patients. We propose the use of second-pass tissue residue function in rCBF calculation using least-absolute-deviation deconvolution to avoid the underestimation problem. [ABSTRACT FROM AUTHOR]

Background: The intravenous co-infusion of labradimil, a metabolically stable bradykinin B2 receptor agonist, has been shown to temporarily enhance the transvascular delivery of small chemotherapy drugs, such as carboplatin, across the blood-brain tumor barrier. It has been thought that the primary mechanism by which labradimil does so is by acting selectively on tumor microvasculature to increase the local transvascular flow rate across the blood-brain tumor barrier. This mechanism of action does not explain why, in the clinical setting, carboplatin dosing based on patient renal function over-estimates the carboplatin dose required for target carboplatin exposure. In this study we investigated the systemic actions of labradimil, as well as other bradykinin B2 receptor agonists with a range of metabolic stabilities, in context of the local actions of the respective B2 receptor agonists on the blood-brain tumor barrier of rodent malignant gliomas. Methods: Using dynamic contrast-enhanced MRI, the pharmacokinetics of gadolinium-diethyltriaminepentaacetic acid (Gd-DTPA), a small MRI contrast agent, were imaged in rodents bearing orthotopic RG-2 malignant gliomas. Baseline blood and brain tumor tissue pharmacokinetics were imaged with the 1st bolus of Gd-DTPA over the first hour, and then reimaged with a 2nd bolus of Gd-DTPA over the second hour, during which normal saline or a bradykinin B2 receptor agonist was infused intravenously for 15 minutes. Changes in mean arterial blood pressure were recorded. Imaging data was analyzed using both qualitative and quantitative methods. Results: The decrease in systemic blood pressure correlated with the known metabolic stability of the bradykinin B2 receptor agonist infused. Metabolically stable bradykinin B2 agonists, methionine-lysine-bradykinin and labradimil, had differential effects on the transvascular flow rate of Gd-DTPA across the blood-brain tumor barrier. Both methionine-lysine-bradykinin and labradimil increased the blood half-life of Gd-DTPA sufficiently enough to increase significantly the tumor tissue Gd-DTPA area under the time-concentration curve. Conclusion: Metabolically stable bradykinin B2 receptor agonists, methionine-lysine-bradykinin and labradimil, enhance the transvascular delivery of small chemotherapy drugs across the BBTB of malignant gliomas by increasing the blood half-life of the co-infused drug. The selectivity of the increase in drug delivery into the malignant glioma tissue, but not into normal brain tissue or skeletal muscle tissue, is due to the inherent porous nature of the BBTB of malignant glioma microvasculature. [ABSTRACT FROM AUTHOR]