Vol. 3 No. 4 - Dec 2017

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Experimental MRI Monitoring of Renal Blood Volume Fraction Variations En Route to Renal Magnetic Resonance Oximetry Andreas Pohlmann 1 , Kathleen Cantow 2 , Till Huelnhagen 1 , Dirk Grosenick 3 , Joa # o dos Santos Periquito 1 , Laura Boehmert 1 , Thomas Gladytz 3 , Sonia Waiczies 1 , Bert Flemming 2 , Erdmann Seeliger 2 , and Thoralf Niendorf 1,4,5 1 Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin Ultrahigh Field Facility (B.U.F.F.), Berlin, Germany; 2 Institute of Physiology and Center for Cardiovascular Research, Charité – Universitätsmedizin Berlin, Campus Charité Mitte, Berlin, Germany; 3 Physikalisch-Technische-Bundesanstalt (PTB), Berlin, Germany; 4 Experimental and Clinical Research Center, Charité Medical Faculty and the Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany; and 5 Deutsches Zentrum für Herz- Kreislauf-Forschung (DZHK; German Centre for Cardiovascular Research), Berlin, Germany Corresponding Author: Andreas Pohlmann, PhD Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Robert Rössle Str. 10, 13125 Berlin, Germany; E-mail: Key Words: kidney, oxygenation, blood volume fraction, magnetic resonance imaging, blood oxygenation level dependent (BOLD), ultrasmall superparamagnetic iron oxide (USPIO) Abbreviations: Acute kidney injury (AKI), blood volume fraction (BVf), free induction decay (FID), magnetic resonance imaging (MRI), oxygen saturation of hemoglobin (SO 2 ), ultrasmall superparamagnetic iron oxide (USPIO), near-infrared spectroscopy (NIRS), signal-to-noise ratio (SNR), time-of-flight (TOF), venous occlusion (VO), radiofrequency (RF), repetition time (TR), echo time (TE), regions of interest (ROIs), multiecho gradient-echo (MGE), multi-spin echo (MSME) Diagnosis of early-stage acute kidney injury (AKI) will benefit from a timely identification of local tissue hyp- oxia. Renal tissue hypoxia is an early feature in AKI pathophysiology, and renal oxygenation is increasingly being assessed through T 2 * -weighted magnetic resonance imaging (MRI). However, changes in renal blood volume fraction (BVf) confound renal T 2 * . The aim of this study was to assess the feasibility of intravascular contrast-enhanced MRI for monitoring renal BVf during physiological interventions that are concomitant with variations in BVf and to explore the possibility of correcting renal T 2 * for BVf variations. A dose-dependent study of the contrast agent ferumoxytol was performed in rats. BVf was monitored throughout short-term oc- clusion of the renal vein, which is known to markedly change renal blood partial pressure of O 2 and BVf. BVf calculated from MRI measurements was used to estimate oxygen saturation of hemoglobin (SO 2 ). BVf and SO 2 were benchmarked against cortical data derived from near-infrared spectroscopy. As estimated from magnetic resonance parametric maps of T 2 and T 2 * , BVf was shown to increase, whereas SO 2 was shown to decline during venous occlusion (VO). This observation could be quantitatively reproduced in test– retest scenarios. Changes in BVf and SO 2 were in good agreement with data obtained from near-infrared spectroscopy. Our findings provide motivation to advance multiparametric MRI for studying AKIs, with the ultimate goal of translating MRI-based renal BVf mapping into clinical practice en route noninvasive renal magnetic resonance oximetry as a method of assessing AKI and progression to chronic damage. INTRODUCTION Kidney diseases are a global health burden with steadily increas- ing incidence (1-4), leading to an estimated worldwide death toll of 2 million per year from AKI (5-7). The currently available methods of assessing risk and therapeutic options for AKI are limited (5, 6, 8-10). Although a number of biochemical markers are being evaluated for use in diagnosis, risk assessment, and prognosis of AKI, there are currently no specific biomarkers that permit point-of-care diagnosis for early-stage AKI (4, 11, 12). Transla- tional approaches for the assessment of early-stage AKI and for the study of renoprotective strategies are urgently required (13-16). Strategies under consideration include novel imaging techniques that may be customized to probe early stages of AKI (12, 16-18). Early features in the pathophysiology of AKI that could lend themselves to detection by noninvasive magnetic resonance (MR) imaging include renal tissue hypoperfusion and hypoxia— factors that are also important during the progression from AKI to chronic kidney diseases (16, 19-25). An imbalance between renal oxygen supply and demand appears to also play a prominent role in the pathophysiology of diabetic nephropathy (26). Renal oxy- genation can be indirectly assessed through the blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI) con- trast (27), which can be observed through measurements of effec- tive transversal relaxation time T 2 * . Indeed, mapping of renal T 2 * (or its reciprocal, R 2 * 5 1/T 2 * ) is an established MRI method that is increasingly being used to study kidney disorders (28-30). RESEARCH ARTICLE ABSTRACT © 2017 The Authors. Published by Grapho Publications, LLC This is an open access article under the CC BY-NC-ND license ( ISSN 2379-1381 188 TOMOGRAPHY.ORG | VOLUME 3 NUMBER 4 | DECEMBER 2017

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