Ultrasound Localization Microscopy to Assess the Intrarenal Microvasculature in Autosomal Dominant Polycystic Kidney Disease

Abstract

Background: In vitro studies in individuals with autosomal dominant polycystic kidney disease (ADPKD) have shown extensive intrarenal microvascular remodeling. However, analyses have been limited to the time of kidney failure due to the invasive nature of current methodologies to assess the intrarenal microvasculature. We hypothesized that super-resolution ultrasound microvascular imaging, known as ultrasound localization microscopy, enabled by high-frame-rate ultrasound imaging and microbubble localization and tracking post-processing techniques, would safely, reliably and reproducibly assess the intrarenal microvasculature in individuals with ADPKD at an early stage of the disease. Methods: We prospectively enrolled young (<40 years of age), well-characterized, early-stage (eGFR >90 mL/min/1.73m 2 ) individuals with ADPKD and sex-age 1:1 matched controls (n = 17 each) and assessed the intrarenal microvasculature using ultrasound localization microscopy. We determined the inter-sonographer reliability, intra-observer repeatability, and inter-observer reproducibility of microvascular parameters in both groups, as well as the day-to-day variability in the control group. Microvascular parameters were correlated with structural (total kidney volume) and functional (eGFR) markers in individuals with ADPKD. Results: Ultrasound localization microscopy provided a super-resolved map of the intrarenal microvasculature in ADPKD and matched controls. Intrarenal microvascular parameters (e.g., vessel density) were quantified in a safe, reliable (intraclass correlation coefficients (ICC) 0.96, 95% confidence interval (CI) 0.91 - 0.98), reproducible (ICC 0.96, 95% CI 0.93 - 0.98) and repeatable (coefficient of variations (CV) 3.6%) manner. In control individuals, the day-to-day variability of most parameters was low, with CV ranging from 1.8% to 10.7%. Microvascular parameters differed in individuals with ADPKD compared to controls, despite preserved eGFR. Interestingly, cortical vessel density and its derived perfusion correlated directly with eGFR, while tortuosity indices presented an inverse correlation. Conclusions: Ultrasound localization microscopy provided a safe and reliable in vivo assessment of the human intrarenal microvasculature.

Affiliated Institutions

• Mayo Clinic US
• Third Affiliated Hospital of Sun Yat-sen University CN
• Mayo Clinic in Arizona US

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