Blood oxygen level-dependent (BOLD) MRI is increasingly used to assess renal tissue oxygenation during disease based on the transverse relaxation rate (R2*). (KX) sodium pentobarbital (PB) or 2 2 2 (TBE). A significant effect of anesthetic agent on R2* was observed in all tissue layers of the kidney including the cortex outer stripe of the outer medulla (OSOM) BIO-acetoxime inner stripe of the outer medulla (ISOM) and inner medulla (IM). Pairwise significant differences in R2* between specific agents were found in the cortex OSOM and ISOM with the largest difference observed in the ISOM between 1.5% Iso (26.6 ± 1.7 s-1) and KX (66.0 ± 7.1 s-1). The difference between 1% Iso and KX in the ISOM was not abolished when KX was administered with supplemental 100% O2 or when 1% Iso was delivered in 21% O2 indicating that the portion of inspired oxygen did not account for observed differences. Our results indicate that the choice of anesthesia has a large influence around the observed R2* in mouse kidney and anesthetic effects must be considered in the design and interpretation of renal BOLD MRI studies. Graphical abstract We evaluated the influence four commonly used anesthetics on renal R2* in mice. The choice of anesthetic agent significantly affected R2* in all tissue layers of the kidney and observed differences were not attributed BIO-acetoxime to differences in inhaled oxygen between volatile and injectable brokers. The results indicate that anesthetic effects must be considered for preclinical renal BOLD MRI. Introduction Renal oxygenation is determined by the balance of oxygen (O2) delivery and consumption (1). Although renal perfusion accounts for ～25% of the cardiac output the kidneys are vulnerable to hypoxic injury particularly within the medulla which normally functions at a low partial pressure of oxygen (pO2). This is due to a combination of factors including low medullary perfusion relative to that of the cortex arterial-to-venous shunting of O2 through diffusion between countercurrent vessels and the high aerobic demand associated with reabsorption of sodium. Accumulating evidence has implicated hypoxia in the pathogenesis of BIO-acetoxime acute kidney injury as well as chronic diseases including end-stage renal disease (2 3 diabetic nephropathy (4 5 and hypertension (6). Therefore there is desire for developing noninvasive clinical methods for evaluating renal oxygenation. Blood oxygen level-dependent (BOLD) MRI provides a method for non-invasive assessment of renal oxygenation based on the apparent transverse relaxation rate (R2*) of renal tissue (7). Because deoxyhemoglobin is usually paramagnetic (8) an increase in intravascular deoxyhemoglobin concentration leads to an increased R2*. Assuming the intravascular and parenchymal pO2 are in equilibrium R2* therefore serves as a surrogate for tissue oxygenation. BOLD MRI has been applied to a variety of renal diseases both clinically and in preclinical small animal models (for reviews observe Li et al. (9) and Zhang et al. (10)). An important consideration for BOLD MRI in animals is the effect of anesthesia on functional measures such as R2*. General anesthesia is needed for preclinical imaging but is known to produce several reversible physiologic changes in the kidney including changes in blood flow BIO-acetoxime glomerular filtration and sodium excretion (11). These effects may alter O2 delivery and/or demand leading to a change in pO2 and consequently R2*. Importantly the magnitude of the perturbation of R2* may depend on the specific anesthetic agent used as each has different biochemical targets. However comparative studies on the effects of different anesthetics on renal R2* are lacking and there is currently no recommended standard of anesthesia for BOLD MRI studies. The purpose of this study is to evaluate the influence of several commonly used anesthetic brokers on renal R2* in healthy mice. Because inhaled brokers are typically delivered Rabbit polyclonal to ALS2CL. with 100% O2 while only room air is usually provided for injected brokers we also investigated whether the portion of inspired oxygen (FiO2) could explain differences in R2* between these brokers. Our results show that the choice of anesthetic has a significant effect on R2* in all parts of the kidney and spotlight the importance of concern of anesthetic effects in the BIO-acetoxime design and analysis of renal BOLD MRI studies. Experimental Animal handling.