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Purpose: To measure the arterial input function (AIF), an essential component of tracer kinetic analysis, in a population of patients using an optimized dynamic contrast-enhanced (DCE) imaging sequence and to estimate inter- and intrapatient variability. From these data, a representative AIF that may be used for realistic simulation studies can be extracted., Methods: Thirty-nine female patients were imaged on multiple visits before and during a course of neoadjuvant chemotherapy for breast cancer. A total of 97 T 1 -weighted DCE studies were analyzed including bookend estimates of T 1 and model-fitting to each individual AIF. Area under the curve and cardiac output were estimated from each first pass peak, and these data were used to assess inter- and intrapatient variability of the AIF., Results: Interpatient variability exceeded intrapatient variability of the AIF. There was no change in cardiac output as a function of MR visit (mean value 5.6 ± 1.1 L/min) but baseline blood T 1 increased significantly following the start of chemotherapy (which was accompanied by a decrease in hematocrit)., Conclusion: The AIF in an individual patient can be measured reproducibly but the variability of AIFs between patients suggests that use of a population AIF will decrease the precision of tracer kinetic analysis performed in cross-patient comparison studies. A representative AIF is presented that is typical of the population but retains the characteristics of an individually measured AIF., (© 2018 International Society for Magnetic Resonance in Medicine.)

Purpose: To evaluate an interleaved MRI sampling strategy that acquires both high temporal resolution (HTR) dynamic contrast-enhanced (DCE) data for quantifying breast tumor blood flow (TBF) and high spatial resolution (HSR) DCE data for clinical reporting, following a single standard injection of contrast agent., Methods: A simulation study was used to evaluate the performance of the interleaved technique under different conditions. In a prospective clinical study, 18 patients with primary breast cancer, who were due to undergo neoadjuvant chemotherapy (NACT), were examined using interleaved HTR and HSR DCE-MRI at 1.5 Tesla. Tumor regions of interest were analyzed with a two-compartment tracer kinetic model. Paired parameters (n = 10) from the data acquired before and post-cycle 2 of NACT were compared using the nonparametric Wilcoxon signed-rank test., Results: Simulations demonstrated that TBF was reliably estimated using the proposed strategy. The region of interest analysis revealed significant changes in TBF (0.81-0.43 mL/min/mL; P = 0.002) following two cycles of NACT. The HSR data were reported in the normal way and enabled the assessment of tumor volume, which decreased by 53% following NACT (P = 0.065)., Conclusions: TBF can be measured reliably using the proposed strategy without compromising a standard clinical protocol. Furthermore, in our feasibility study, TBF decreased significantly following NACT, whereas capillary permeability surface-area product did not. Magn Reson Med 79:317-326, 2018. © 2017 International Society for Magnetic Resonance in Medicine., (© 2017 International Society for Magnetic Resonance in Medicine.)

Background and Purpose: One of the protective actions of angiotensin converting enzyme-2 (ACE2) is the inactivation of angiotensin II. Expression and activity of ACE2 was reduced in glomeruli of diabetic patients and in animal models of diabetes. Recently the potential role of recombinant ACE2 administration in preventing diabetic nephropathy (DN) has been shown. Here we have tested the effects of the ACE2 activator, diminazene aceturate (DIZE), in a model of DN., Experimental Approach: Male Wistar rats were rendered diabetic using a single dose of streptozotocin (55 mg·kg -1 , i.p.). After 4 weeks, diabetic animals were divided into experimental groups and treated with DIZE, at a low dose (5 mg·kg -1 ·day -1 ), a high dose (15 mg·kg -1 ·day -1 ) and the high dose with of the AT 2 receptor antagonist PD123319 (10 mg·kg -1 ·day -1 ). At the end of the treatment , kidneys from all the groups were collected and processed separately for glomerular isolation, protein isolation, mRNA extraction and for immunohistochemical studies., Key Results: Treatment with DIZE restored ACE2 expression in glomeruli and increased expression of AT 2 receptors in whole kidney and isolated glomeruli of diabetic animals. DIZE administration reduced angiotensin II levels and increased angiotensin-(1-7) levels in diabetic kidney. However, PD123319 treatment reversed all these actions of DIZE., Conclusions and Implications: DIZE treatment reduced diabetes-induced renal damage as shown by reduction of fibrosis and apoptosis. These protective actions of DIZE were blocked by the AT 2 receptor antagonist. Taken together, these results suggest that DIZE protected against DN through the ACE2/angiotensin-(1-7)/ AT 2 receptor axis., (© 2017 The British Pharmacological Society.)