Estimation of multicomponent 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 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 kidneycortex is simulated with anisotropic and non-Gaussian (i.e., anomalous) vas-cular, tubular, and tissue components and analyzed with a Bayesian biexpo-nential, least-squares triexponential, and spectral diffusion MRI. Comparisonand application of biexponential, triexponential, and spectral diffusion flowproxies as the product of signal fraction f and diffusion coefficient D, fD foreach component, is demonstrated in a two-center study of 54 kidney allograftspatients (21 females/33 males, 48.8 ± 10.5 years, NCT05058170) and comparedto fibrosis (Banff 2017 interstitial fibrosis and tubular atrophy score 0–6 fromclinical biopsies of the renal cortex), impaired kidney function (Chronic Kid-ney Disease Epidemiology Collaboration 2021 estimated glomerular filtrationrate<45 mL/min/1.73 m(2)), and proteinuria (mg/24 h). RESULTS: Spectral diffusion fD demonstrated strong correlation to input fD ofthe simulated anisotropic and anomalous components. It agreed with boththree-component diffusion (y = 1.10x − 0.1, R(2) = 0.74) and two-component dif-fusion (y = 1.01 + 0.2, R(2) = 0.88). fD showed similar or improved agreementand correlation to input than the individual parameters f and D, and spectraldiffusion showed similar or improved agreement than corresponding bi- andtriexponential models. In kidney allografts, fD from spectral diffusion showedthat allografts with higher fibrosis score had higher fD(tissue) (one-way analysis ofvariance F-statistic = 3.86, p = 0.02) and that allografts with impaired functionhad reduced fD(tubule) (Mann–Whitney U-test = −2.14, p = 0.04). Across diagnostic groups of function and fibrosis, fD(vasc) negatively correlated with proteinuria(y = −348x + 1144, p = 0.035 R(2) = 0.82). CONCLUSIONS: Spectral diffusion MRI with multi-Gaussian fD as a flow proxyseparated different anomalous and anisotropic diffusion components of perfu-sion, tubular flow, and tissue diffusion and may hold clinical value in diffusionMRI of kidney pathophysiology.