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

TL;DR

This study uses hyperpolarized 13C urea MRI to investigate renal urea handling in rats at millimeter resolution, revealing heterogeneity in T2 relaxation times that reflect urea transport processes and enabling high-resolution imaging of kidney structures.

Contribution

The paper introduces novel hyperpolarized 13C MRI techniques with multi-exponential T2 analysis and ultra-long echo time imaging to study renal urea dynamics at high spatial resolution.

Findings

T2 heterogeneity distinguishes vascular and extravascular urea pools.

Urea T2 increases during antidiuresis in inner medulla and papilla.

New imaging methods achieve sub-2 mm^3 resolution of renal structures.

Abstract

\textit{In vivo} spin spin relaxation time ($T_2$) heterogeneity of hyperpolarized \textsuperscript{13}C urea in the rat kidney was investigated. Selective quenching of the vascular hyperpolarized \textsuperscript{13}C signal with a macromolecular relaxation agent revealed that a long-$T_2$ component of the \textsuperscript{13}C urea signal originated from the renal extravascular space, thus allowing the vascular and renal filtrate contrast agent pools of the \textsuperscript{13}C urea to be distinguished via multi-exponential analysis. The $T_2$ response to induced diuresis and antidiuresis was performed with two imaging agents: hyperpolarized \textsuperscript{13}C urea and a control agent hyperpolarized bis-1,1-(hydroxymethyl)-1-\textsuperscript{13}C-cyclopropane-$^2\textrm{H}_8$. Large $T_2$ increases in the inner-medullar and papilla were observed with the former agent and not the latter during antidiuresis suggesting that $T_2$ relaxometry may be used to monitor the inner-medullary urea transporter (UT)-A1 and UT-A3 mediated urea concentrating process. Two high resolution imaging techniques - multiple echo time averaging and ultra-long echo time sub-2 mm$^3$ resolution 3D imaging - were developed to exploit the particularly long relaxation times observed.