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 pathological findings from kidney biopsies. Biopsies, usually taken from the kidney cortex, are invasive and prone to sampling error. Tools to directly and noninvasively measure tubular pathology could provide a new approach to assess kidney health. This study used diffusion magnetic resonance imaging (dMRI) as a noninvasive 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 dMRI 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. dMRI detected heterogeneity in the distribution of tubules within the kidney cortex of mice with acute kidney injury compared with control mice. We conclude that dMRI can be used to measure the distribution of tubule diameters in the kidney cortex ex vivo and that dMRI may provide a new noninvasive biomarker of tubular pathology.