Ultrasound Localization Microscopy (ULM) for Noninvasive Ultrastructural Assessment of Microvascular Dynamics up to the Glomeruli

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Background: Vascular impairment is a major cause of kidney injury but invasive tissue biopsies are still often necessary. ULM enables non-invasive ultra high-dimensional monitoring of vascular dynamics up to the scale of individual glomeruli opening new avenues for the assessment of kidney disease. Methods: Contrast-enhanced ultrasound (CEUS) using intravenously applied microbubbles (MBs) and a clinical scanner was performed in adult kidney transplants and native neonatal kidneys. Post-processing including motion correction was done using a computational framework. ULM findings were correlated with routine biopsy results and clinical data. Results: Localizing and tracking of individual MBs enabled ultra-high dimensional reconstruction of kidney vasculature up to capillary scale. Geometrical filtering of slow MB tracks enabled non-invasive visualization and quantification of glomeruli in the renal cortex. In patients with pathological biopsy, reduced counts of glomeruli were detected. Conclusion: We present the successful translation of ULM to kidneys from both adult and neonatal patients including motion correction algorithms showing clinical feasibility even in vulnerable patient cohorts. ULM-based assessment of kidney disease may offer an alternative to invasive kidney biopsies.Figure 1 ULM in kidney allograftsFigure 2 ULM in neonatal kidneys

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