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

In vivo spin spin relaxation time (T2) heterogeneity of hyperpolarized [13C,15N2]urea in the rat kidney was 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 multi-exponential analysis. The T2 response to induced diuresis and antidiuresis was performed with two imaging agents: hyperpolarized [13C,15N2]urea and a control agent hyperpolarized bis-1,1-(hydroxymethyl)-1-13C-cyclopropane-2H8. Large T2 increases in the inner-medullar and papilla were observed with the former agent and not the latter during antidiuresis. Therefore, [13C,15N2]urea relaxometry is sensitive to two steps of the renal urea handling process: glomerular filtration and the inner-medullary urea transporter (UT)-A1 and UT-A3 mediated urea concentrating process. Simple motion correction and subspace denoising algorithms are presented to aid in the multi exponential data analysis. Furthermore, a T2-edited, ultra long echo time sequence was developed for sub-2 mm3 resolution 3D encoding of urea by exploiting relaxation differences in the vascular and filtrate pools.