Mapping kidney tubule diameter ex vivo by diffusion MRI.

Tubular pathologies are a common feature of kidney disease. Current metrics to assess kidney health, in vivo or in transplant, are generally based on urinary or serum biomarkers and pathologic findings from kidney biopsies. Biopsies, usually taken from kidney cortex, are invasive and prone to sampling error. Tools to directly and non-invasively measure tubular pathology could provide a new approach to assess kidney health. This study uses diffusion magnetic resonance imaging (dMRI) as a non-invasive tool to measure the size of the tubular lumen in ex vivo, perfused kidneys. We first used Monte-Carlo simulations to demonstrate that dMRI is sensitive to restricted tissue water diffusion at the scale of the kidney tubule. We applied dMRI and biophysical modeling to examine the distribution of tubular diameters in ex vivo, fixed kidneys from mice, rats, and a human donor. The biophysical model to fit the dMRI signal was based on a superposition of freely diffusing water and water diffusing inside infinitely long cylinders of different diameters. Tubular diameters measured by MRI were within 10% of those measured by histology within the same tissue. Finally, we applied dMRI to investigate kidney pathology in a mouse model of folic-acid induced acute kidney injury (AKI). dMRI detected heterogeneity in the distribution of tubules within kidney cortex of AKI mice compared to the control group. We conclude that dMRI can be used to measure the distribution of tubule diameters in the kidney cortex ex vivo and dMRI may provide a new non-invasive biomarker of tubular pathology.