Estimation of Multi-Component Flow in the Kidney with Multi-b-value Spectral Diffusion

Purpose: Examine the theory and potential clinical application of estimated intravoxel flow of separated perfusion, tubular flow, and diffusion from multi-b-value DWI in kidney allografts. Methods: Multi-b-value DWI (9 b-values; 0-800 s/mm2) from a kidney cortex is simulated with anisotropic and non-Gaussian (i.e. anomalous) vascular, tubular, and tissue components and analyzed with a Bayesian biexponential, least-squares triexponential, and spectral diffusion MRI. Comparison and application of biexponential, triexponential, and spectral diffusion fD is demonstrated in a two-center study of 54 kidney allografts patients (21F/33M, 48.8 SD 10.5years) and compared to fibrosis (Banff 2017 interstitial fibrosis and tubular atrophy score 0-6 from clinical biopsies of the renal cortex), impaired kidney function (CKD-EPI 2021 eGFR<45ml/min/1.73m2), and proteinuria. Results: Spectral diffusion fD demonstrated strong correlation to input fD of the simulated anisotropic and anomalous components. It agreed with both three-component diffusion and two-component diffusion. fD showed similar or improved agreement and correlation to input compared to individual parameters, and similar or improved agreement to corresponding bi- and triexponential models. In kidney allografts, spectral diffusion fD showed higher allograft fibrosis score had higher fD_tissue, impaired allograft function showed reduced fD_tubule, and fD_vascular negatively correlated with proteinuria across diagnostic groups of function and fibrosis. Conclusions: Spectral diffusion MRI with multi-Gaussian fD as a flow proxy separated different anomalous and anisotropic diffusion components of perfusion, tubular flow, and tissue diffusion and may hold clinical value in diffusion MRI of kidney pathophysiology.