UC Berkeley

Renal diseases that involve filtration function loss are usually diagnosed through measuring estimated glomerular filtration rate (eGFR) via blood tests such as blood urea nitrogen and serum creatinine level measurements. Although these methods allow quick assessment of renal function, it does not tell the cause of function loss and lacks adequate sensitivity due to the hyperfiltration by intact nephrons. These limitations become more critical in cases that involve progressive renal function loss such as acute kidney injury (AKI)-to-chronic kidney disease (CKD) transition and chronic graft function loss after renal transplantation, in which microstructural alterations often precede the change in blood marker levels. Biopsy remains the gold standard to pick up these tissue level damages, but the procedure is invasive and prone to sampling errors. Here, the use of novel molecular magnetic resonance imaging (MRI) technique called chemical exchange saturation transfer (CEST) imaging is demonstrated for noninvasively characterizing renal pathophysiology. Specifically, urea was studied as an imaging target and contrast agent of CEST MRI, as urea is a major metabolite responsible for controlling water reabsorption in the kidneys. Characterization of urea showed concentration and pH-dependent CEST contrast, and the feasibility of in vivo urea imaging was demonstrated with heightened CEST contrast in the inner medulla and papilla of the mouse kidneys after urea infusion. This method was further optimized for better quantification of urea by choosing the optimal time point of acquiring CEST data after urea infusion, removing T1 time effect on the CEST contrast and adopting multi-pool Lorentzian fitting. Lastly, this technique was applied to mouse renal disease models to test its diagnostic potential. Acute and chronic nephropathies were induced in mice, and the CEST data were longitudinally acquired along the disease progression. Since CEST data also reflects the presence of other mobile proteins, metabolites, and semi-solid macromolecules, the CEST contrast from these molecules were also analyzed in addition to urea. The urea CEST showed significant changes upon acute injury development, and the multiparametric CEST clearly distinguished acute and chronic nephropathies. Overall, CEST MRI can observe urea recycling in the mouse kidneys, and allows distinguishing different nephropathies along with other endogenous CEST contrast.