Abstract
PURPOSE: Examine the theory and potential clinical application of estimated intravoxel "flow" of separated perfusion, tubular flow, and tissue diffusion from multi-b-value DWI in kidney allografts. METHODS: Multi-b-value DWI (nine b-values; 0-800 s/mm(2)) 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 flow proxies as the product of signal fraction f and diffusion coefficient D , fD for each component, is demonstrated in a two-center study of 54 kidney allografts patients (21 females/33 males, 48.8 ± 10.5 years, NCT05058170) and compared to fibrosis (Banff 2017 interstitial fibrosis and tubular atrophy score 0-6 from clinical biopsies of the renal cortex), impaired kidney function (Chronic Kidney Disease Epidemiology Collaboration 2021 estimated glomerular filtration rate<45 mL/min/1.73 m(2)), and proteinuria (mg/24 h). RESULTS: Spectral diffusion fD demonstrated strong correlation to input fD of the simulated anisotropic and anomalous components. It agreed with both three-component diffusion ( y = 1.10x - 0.1 , R2 = 0.74 ) and two-component diffusion ( y = 1.01 + 0.2, R2 = 0.88 ). fD showed similar or improved agreement and correlation to input than the individual parameters f and D , and spectral diffusion showed similar or improved agreement than corresponding bi- and triexponential models. In kidney allografts, fD from spectral diffusion showed that allografts with higher fibrosis score had higher fDtissue (one-way analysis of variance F-statistic = 3.86, p = 0.02) and that allografts with impaired function had reduced fDtubule (Mann-Whitney U-test = -2.14, p = 0.04). Across diagnostic groups of function and fibrosis, fDvasc negatively correlated with proteinuria ( y = - 348x + 1144, p = 0.035 R2 = 0.82 ). 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.