Imaging Renal Urea Handling in Rats at Millimeter Resolution Using Hyperpolarized Magnetic Resonance Relaxometry

Abstract

In this study, in vivo T2 heterogeneity of hyperpolarized [13C,15N2]urea in rat kidney has been investigated. Selective quenching of the vascular hyperpolarized 13C signal with a macromolecular relaxation agent revealed that a long T2 component of the [13C,15N2]urea signal originated from the renal extravascular space, thus allowing the vascular and renal filtrate contrast agent pools of the [13C,15N2]urea to be distinguished via multiexponential analysis. The T2 response to induced diuresis and antidiuresis was determined using 2 imaging agents—hyperpolarized [13C,15N2]urea and hyperpolarized bis-1,1-(hydroxymethyl)-1-13C-cyclopropane-2H8 (control agent). During antidiuresis, large T2 increases in the inner medulla and papilla were observed using the former agent only. Therefore, [13C,15N2]urea relaxometry is sensitive to the following 2 steps of the renal urea handling process: glomerular filtration process and inner medullary urea transporter-A1- and urea transporter-A3-mediated urea concentrating process. To aid multiexponential data analysis, simple motion correction and subspace denoising algorithms are presented. Furthermore, a T2-edited, ultralong echo time sequence was developed for sub-2 mm3 resolution 3-dimensional encoding of urea by exploiting relaxation differences in the vascular and filtrate pools.