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.