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

In this study, in vivo T2 heterogeneity of hyperpolarized [(13)C,(15)N(2)]urea in rat kidney has been investigated. Selective quenching of the vascular hyperpolarized (13)C signal with a macromolecular relaxation agent revealed that a long T2 component of the [(13)C,(15)N(2)]urea signal originated from the renal extravascular space, thus allowing the vascular and renal filtrate contrast agent pools of the [(13)C,(15)N(2)]urea to be distinguished via multiexponential analysis. The T2 response to induced diuresis and antidiuresis was determined using 2 imaging agents—hyperpolarized [(13)C,(15)N(2)]urea and hyperpolarized bis-1,1-(hydroxymethyl)-1-(13)C-cyclopropane-(2)H(8) (control agent). During antidiuresis, large T2 increases in the inner medulla and papilla were observed using the former agent only. Therefore, [(13)C,(15)N(2)]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 mm(3) resolution 3-dimensional encoding of urea by exploiting relaxation differences in the vascular and filtrate pools.