In this work, we present a new method for predicting changes in tumor vascularity using only one flip angle in dynamic contrast-enhanced (DCE) imaging. The usual DCE approach finds the tissue initial T 1 value T 1 (0) prior to injection of a contrast agent. We propose finding changes in the tissue contrast agent uptake characteristics pre-and postdrug treatment by fixing T 1 (0). Using both simulations and imaging pre-and postadministration of caffeine, we find that the relative change (NR50) in the median of the cumulative distribution (R50) is almost independent of T 1 (0). Fixing T 1 (0) leads to a concentration curve c(t) more robust to the presence of noise than calculating T 1 (0). Consequently, the NR50 for the tumor remains roughly the same as the ideal NR50 when T 1 (0) is exactly known. Further, variations in eating habits are shown to create significant changes in the R50 response for both liver and muscle. In conclusion, analyzing data with fixed T 1 (0) leads to a more stable measure of changes in NR50 and does not require knowl- Dynamic contrast-enhanced MRI (DCE-MRI) is a method for imaging the physiology of the microcirculation. A series of recent clinical studies have shown that DCE-MRIbased measures correlate well with tumor angiogenesis. DCE-MRI is performed after the administration of an intravenous contrast agent, gadolinium-DTPA, to noninvasively assess tumor vascular characteristics. Recently, DCE-MRI has been used to assess antiangiogenic cancer drug effectiveness in Phase I pharmaceutical trials (1-3) by acquiring data before and after drug treatment. The contrast enhancement patterns on DCE-MRI are influenced by tumor angiogenesis, as reflected by elevated vascular endothelial growth factor (VEGF) expression. Therefore, they become valuable indicators for assessing tumor angiogenic activity (4,5) and tumor neovascularization in vivo in hepatocellular carcinoma patients (6,7). The use of DCE has been so important that one would be hesitant to continue testing a drug in the absence of any volume or vascular changes appearing in DCE-MRI unless the patients' survival increased (8).Despite its promise, there are problems in the acquisition and processing of DCE data. Repeatability has been a major problem (9 -11). Given the wide clinical use of DCE-MRI, this is an important issue that must be directly addressed. One approach is to improve the methodology itself with more rapid high-resolution respiratory free scanning methods (12). And this will happen with the advent of parallel imaging (13,14). The other is to better process existing data.From our review of many DCE-MRI experiments and projects at the MRI Research facility in the Department of Radiology at Wayne State University, we have found that the causes of most of the DCE errors are related to noise in the T 1 estimates and to physiologic changes in the blood flow (BF) from one day to the next. Normally, an estimate for the baseline T 1 (referred to here as T 1 (0)) is obtained from multiple flip angle (FA) images (15). Any inconsist...

To investigate further the antiangiogenic potential of sunitinib for renal cell carcinoma (RCC) treatment, its effects on tumor vasculature were monitored by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) using an orthotopic KCI-18 model of human RCC xenografts in nude mice. Tumor-bearing mice were treated with various doses of sunitinib, and vascular changes were assessed by DCE-MRI and histologic studies. Sunitinib induced dose-dependent vascular changes, which were observed both in kidney tumors and in normal kidneys by DCE-MRI. A dosage of 10 mg/kg per day caused mild changes in Gd uptake and clearance kinetics in kidney tumors. A dosage of 40 mg/kg per day induced increased vascular tumor permeability with Gd retention, probably resulting from the destruction of tumor vasculature, and also caused vascular alterations of normal vessels. However, sunitinib at 20 mg/kg per day caused increased tumor perfusion and decreased vascular permeability associated with thinning and regularization of tumor vessels while mildly affecting normal vessels as confirmed by histologic diagnosis. Alterations in tumor vasculature resulted in a significant inhibition of KCI-18 RCC tumor growth at sunitinib dosages of 20 and 40 mg/kg per day. Sunitinib also exerted a direct cytotoxic effect in KCI-18 cells in vitro. KCI-18 cells and tumors expressed vascular endothelial growth factor receptor 2 and platelet-derived growth factor receptor beta molecular targets of sunitinib that were modulated by the drug treatment. These data suggest that a sunitinib dosage of 20 mg/kg per day, which inhibits RCC tumor growth and regularizes tumor vessels with milder effects on normal vessels, could be used to improve blood flow for combination with chemotherapy. These studies emphasize the clinical potential of DCE-MRI in selecting the dose and schedule of antiangiogenic compounds.

The aim of this study was to design a system to diagnose chronic stress, based on blunted reactivity of the autonomic nervous system (ANS) to cognitive load (CL). The system concurrently measures CL-induced variations in pupil diameter (PD), heart rate (HR), pulse wave amplitude (PWA), galvanic skin response (GSR), and breathing rate (BR). Measurements were recorded from 58 volunteers whose stress level was identified using the State-Trait Anxiety Inventory. Number-multiplication questions were used as CLs. HR, PWA, GSR, and PD were significantly (p < 0.05) changed during CL. CL-induced changes in PWA (16.87 ± 21.39), GSR (- 13.71 ± 7.86), and PD (11.56 ± 9.85) for non-stressed subjects (n = 36) were significantly different (p < 0.05) from those in PWA (2.92 ± 12.89), GSR (- 6.87 ± 9.54), and PD (4.51 ± 10.94) for stressed subjects (n = 22). ROC analysis for PWA, GSR, and PD illustrated their usefulness to identify stressed subjects. By inputting all features to different classification algorithms, up to 91.7% of sensitivity and 89.7% of accuracy to identify stressed subjects were achieved using 10-fold cross-validation. This study was the first to document blunted CL-induced changes in PWA, GSR, and PD in stressed subjects, compared to those in non-stressed subjects. Preliminary results demonstrated the ability of our system to objectively detect chronic stress with good accuracy, suggesting the potential for monitoring stress to prevent dangerous stress-related diseases. Graphical abstract Chronic stress degrads the autonomic nervous system reaction to cognitive loads. Measurement of reduced changes in physiological signals during asking math questions was useful to identify people with high STAI score (stressed subjects).

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