Mapping kidney tubule diameter ex vivo by diffusion MRI

Morozov, Darya; Parvin, Neda; Charlton, Jennifer R.; Bennett, Kevin M.

doi:10.1152/ajprenal.00369.2020

Cited by 4 publications

(2 citation statements)

References 47 publications

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“…Finally, comparison of experimental medullary radial diffusivities of the slow compartment with both analytical and simulation estimates of cylindrical tubule size both gave consistent results suggesting a diameter of ~34 μm. This is within the range of the expected tubular size scale, 37 though only a first‐order estimate that does not consider tubular permeability effects. Still, these preliminary results suggest further microstructural modeling of renal DWI data might be illuminating.…”

Section: Discussionmentioning

confidence: 58%

Cardiac Phase and Flow Compensation Effects on REnal Flow and Microstructure AnisotroPy MRI in Healthy Human Kidney

Sigmund

Mikheev

Brinkmann³

et al. 2022

Magnetic Resonance Imaging

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Background Renal diffusion‐weighted imaging (DWI) involves microstructure and microcirculation, quantified with diffusion tensor imaging (DTI), intravoxel incoherent motion (IVIM), and hybrid models. A better understanding of their contrast may increase specificity. Purpose To measure modulation of DWI with cardiac phase and flow‐compensated (FC) diffusion gradient waveforms. Study Type Prospective. Population Six healthy volunteers (ages: 22–48 years, five females), water phantom. Field Strength/Sequence 3‐T, prototype DWI sequence with 2D echo‐planar imaging, and bipolar (BP) or FC gradients. 2D Half‐Fourier Single‐shot Turbo‐spin‐Echo (HASTE). Multiple‐phase 2D spoiled gradient‐echo phase contrast (PC) MRI. Assessment BP and FC water signal decays were qualitatively compared. Renal arteries and velocities were visualized on PC‐MRI. Systolic (peak velocity), diastolic (end stable velocity), and pre‐systolic (before peak velocity) phases were identified. Following mutual information‐based retrospective self‐registration of DWI within each kidney, and Marchenko‐Pastur Principal Component Analysis (MPPCA) denoising, combined IVIM‐DTI analysis estimated mean diffusivity (MD), fractional anisotropy (FA), and eigenvalues (λi) from tissue diffusivity (Dt), perfusion fraction (fp), and pseudodiffusivity (Dp, Dp,axial, Dp,radial), for each tissue (cortex/medulla, segmented on b0/FA respectively), phase, and waveform (BP, FC). Monte Carlo water diffusion simulations aided data interpretation. Statistical Tests Mixed model regression probed differences between tissue types and pulse sequences. Univariate general linear model analysis probed variations among cardiac phases. Spearman correlations were measured between diffusion metrics and renal artery velocities. Statistical significance level was set at P < 0.05. Results Water BP and FC signal decays showed no differences. Significant pulse sequence dependence occurred for λ1, λ3, FA, Dp, fp, Dp,axial, Dp,radial in cortex and medulla, and medullary λ2. Significant cortex/medulla differences occurred with BP for all metrics except MD (systole [P = 0.224]; diastole [P = 0.556]). Significant phase dependence occurred for Dp, Dp,axial, Dp,radial for BP and medullary λ1, λ2, λ3, MD for FC. FA correlated significantly with velocity. Monte Carlo simulations indicated medullary measurements were consistent with a 34 μm tubule diameter. Data Conclusion Cardiac gating and flow compensation modulate of measurements of renal diffusion. Evidence Level 2 Technical Efficacy Stage 2

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Section: Discussionmentioning

confidence: 58%

Cardiac Phase and Flow Compensation Effects on REnal Flow and Microstructure AnisotroPy MRI in Healthy Human Kidney

Sigmund

Mikheev

Brinkmann³

et al. 2022

Magnetic Resonance Imaging

View full text Add to dashboard Cite

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“…Recently, glomerular ultrastructural features were shown to be predictive for clinical outcomes in proteinuric patients, confirming the powerful link between ultrastructure and functionality in the kidney. (11) Similarly, the cortical tubular epithelium is strictly polarized, forming continuous tubes with a mean diameter of 40 µm (12), equipped with different lengths of apical microvilli depending on the tubule type, increasing the surface area for transport and playing an essential role in mechanotransduction (13).…”

Section: Introductionmentioning

confidence: 99%

Ultrastructural comparison of human kidney organoids and human fetal kidneys reveals features of hyperglycemic culture

Schumacher

Joris

Griensven

et al. 2023

Preprint

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Induced pluripotent stem cell (iPSC)-derived kidney organoids have the potential for a large variety of applications. However, they do not persist long in culture, for which reasons are still unclear. Furthermore, their morphological maturation, an essential feature for kidney function, has not been sufficiently assessed. Kidney organoids are transcriptionally much alike end-of-first-trimester fetal kidneys and present many of the same cell types. From large transmission electron microscopy tilescans of specific regions of interest, we compared the ultrastructures of iPSC-derived kidney organoids at various timepoints to human fetal kidneys of the first trimester. Unlike healthy fetal kidneys, large glycogen deposits developed over time in all organoid cell types, but particularly in podocytes and in chondrocytes, one of the off-target populations that contaminate the culture. Deeper investigation showed that glycogen synthase kinase 3b (GSK3b;) levels and activation were diminished over time, correlated with the accumulation of glycogen. Activated YAP was strongly expressed and large lipid droplets accumulated over time in proximal tubules. Accordingly, EGFR signaling increased significantly over time. Mitochondria in glomeruli and tubules contained few or no cristae, indicating mitochondrial damage. Together these features are known for hyperglycemic cultures and diabetic nephropathy. Measuring the glucose concentration in the kidney organoid culture medium showed a concentration of 2.94 g/mL, which is considered an elevated, pre-diabetic-like concentration in vitro. In summary, our ultrastructural assessment of iPSC-derived kidney organoids using an age-matched fetal human reference allowed the evaluation of cellular morphology, and we identified intracellular features that can inform the cellular state, which is particularly important while physiological testing of organoids is limited.

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Probing Renal Microstructure and Function with Advanced Diffusion MRI: Concepts, Applications, Challenges, and Future Directions

Stabinska,

Wittsack,

Lerman

et al. 2023

Magnetic Resonance Imaging

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Diffusion measurements in the kidney are affected not only by renal microstructure but also by physiological processes (i.e., glomerular filtration, water reabsorption, and urine formation). Because of the superposition of passive tissue diffusion, blood perfusion, and tubular pre‐urine flow, the limitations of the monoexponential apparent diffusion coefficient (ADC) model in assessing pathophysiological changes in renal tissue are becoming apparent and motivate the development of more advanced diffusion‐weighted imaging (DWI) variants. These approaches take advantage of the fact that the length scale probed in DWI measurements can be adjusted by experimental parameters, including diffusion‐weighting, diffusion gradient directions and diffusion time. This forms the basis by which advanced DWI models can be used to capture not only passive diffusion effects, but also microcirculation, compartmentalization, tissue anisotropy. In this review, we provide a comprehensive overview of the recent advancements in the field of renal DWI. Following a short introduction on renal structure and physiology, we present the key methodological approaches for the acquisition and analysis of renal DWI data, including intravoxel incoherent motion (IVIM), diffusion tensor imaging (DTI), non‐Gaussian diffusion, and hybrid IVIM‐DTI. We then briefly summarize the applications of these methods in chronic kidney disease and renal allograft dysfunction. Finally, we discuss the challenges and potential avenues for further development of renal DWI.Level of Evidence5Technical EfficacyStage 2

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Mapping kidney tubule diameter ex vivo by diffusion MRI

Cited by 4 publications

References 47 publications

Cardiac Phase and Flow Compensation Effects on REnal Flow and Microstructure AnisotroPy MRI in Healthy Human Kidney

Cardiac Phase and Flow Compensation Effects on REnal Flow and Microstructure AnisotroPy MRI in Healthy Human Kidney

Ultrastructural comparison of human kidney organoids and human fetal kidneys reveals features of hyperglycemic culture

Probing Renal Microstructure and Function with Advanced Diffusion MRI: Concepts, Applications, Challenges, and Future Directions

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