Vol. 3 No. 3 - Sep 2017

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Can Hyperpolarized 13 C-Urea be Used to Assess Glomerular Filtration Rate? A Retrospective Study Christian Østergaard Mariager, Per Mose Nielsen, Haiyun Qi, Marie Schroeder, Lotte Bonde Bertelsen, and Christoffer Laustsen Department of Clinical Medicine, MR Research Centre, Aarhus University, Aarhus, Denmark Corresponding Author: Christoffer Laustsen, PhD Palle Juul-Jensens Boulevard 99, 8200 Aarhus N, Denmark; E-mail: Key Words: MRI, hyperpolarization, GFR Abbreviations: Glomerular filtration rate (GFR), magnetic resonance (MR), single-kidney GFR (skGFR), dynamic contrast-enhanced (DCE), arterial input function (AIF), Baumann–Rudin (BR), ischemia-reperfusion (I/R), magnetic resonance imaging (MRI), renal blood flow (RBF) This study investigated a simple method for calculating the single-kidney glomerular filtration rate (GFR) using dynamic hyperpolarized 13 C-urea magnetic resonance (MR) renography. A retrospective data analysis was applied to renal hyperpolarized 13 C-urea MR data acquired from control rats, prediabetic nephropathy rats, and rats in which 1 kidney was subjected to ischemia-reperfusion. Renal blood flow was determined by the model-free bolus differentiation method, GFR was determined using the Baumann–Rudin model method. Ref- erence single-kidney and total GFRs were measured by plasma creatinine content and compared to 1 H dy- namic contrast-enhanced estimated GFR and fluorescein isothiocyanate-inulin clearance GFR estimation. In healthy and prediabetic nephropathy rats, single-kidney hyperpolarized 13 C-urea GFR was estimated to be 2.5 6 0.7 mL/min in good agreement with both gold-standard inulin clearance GFR (2.7 6 1.2 ml/min) and 1 H dynamic contrast-enhanced estimated GFR (1.8 6 0.8 mL/min), as well as plasma creatinine mea- surements and literature findings. Following ischemia-reperfusion, hyperpolarized 13 C-urea revealed a signifi- cant reduction in single-kidney GFR of 57% compared with the contralateral kidney. Hyperpolarized 13 C MR could be a promising tool for accurate determination of GFR. The model-free renal blood flow and arterial input function-insensitive GFR estimations are simple to implement and warrant further translational adaptation. INTRODUCTION Glomerular filtration rate (GFR) measures are essential to the daily care of patients, as either an estimate or an exact quanti- fiable measure (1). GFR is often estimated by the serum creati- nine levels or creatinine clearance, derived from both blood and urine samples. Creatinine estimation is a relative insensitive marker of GFR owing to the GFR-dependent tubular secretion of creatinine (2). Inulin clearance is considered to be the most reproducible, quantitative index of renal function, as it not reabsorbed and thus transported freely to the urine. However, the specificity is lacking in both methods, as the total GFR can overshadow alterations in single kidney function or even in intrarenal differences (1). Nuclear medicine-based techniques remain the reference method for quantification of the single-kidney GFR (skGFR) (1); widespread application of these, however, has been limited by the ionizing radiation associated with the examination. Several magnetic resonance (MR)-based methods have emerged as al- ternative methods to quantify skGFR. Contrast-based methods, such as dynamic contrast-enhanced (DCE) MR, have been used to generate GFR analytical models in both experimental disease and in humans (3-6). Although the methods in general show great promise, the clinical translation is lacking. This may be largely because of the lack of general consensus on model standardization, a direct consequence of the complex system in question and the obtainable signal-to-noise ratio in MR. Recently, an alternative method for high-signal, contrast- enhanced MR has been introduced. By means of hyperpolariza- tion of tracers containing an MR-active nucleus, the MR signal available can be enhanced by 4 orders of magnitude. In this technique, the hyperpolarized tracer itself is the origin of the signal, thereby overcoming some of the challenges associated with traditional MR contrast agents. The novel technique of hyperpolarized MR has shown applicability in a broad range of biological applications including cancer, cardiovascular, brain, liver and kidney research (7-9), with the primary goal to inter- rogate organ-specific metabolic substrate selection associated with various disease states (10, 11). The technique enables the 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 146 TOMOGRAPHY.ORG | VOLUME 3 NUMBER 3 | SEPTEMBER 2017

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