Characterization of microvasculature in kidney transplant by super-resolution ultrasound imaging - PROJECT SUMMARY End-stage kidney disease (ESKD) affects a significant number of patients in the U.S. (>785,000 in 2018), and presents substantial medical, social, and economic challenges. Kidney transplantation is the preferred treatment for ESKD. However, there is a pressing unmet clinical need for better methods that allow for noninvasive, accurate, and frequent characterization and monitoring of kidney allograft injury. Such methods are critical for enhancing long-term allograft survival and improving the quality of life for the kidney transplant recipients. The change of kidney parenchymal microvasculature and perfusion has been shown to play a vital role in the progression of allograft injury, while noninvasive tools for imaging and quantification of allograft microvasculature are still lacking. In this project, we will develop a novel noninvasive, robust, and translatable super-resolution ultrasound imaging (SRUI) technology. This technology aims to provide imaging and quantification of parenchymal microvasculature to enable reliable assessment of allograft injuries. In our pilot patient study of transplant kidneys, parameters derived from SRUI correlate strongly with pathology (r ≥ 0.9). Aim 1: Technical development. We will advance and optimize the novel SRUI technology for kidney allograft imaging and quantification. New signal enhancement and localization methods will be developed to improve the overall performance of SRUI in clinical settings. We will advance the SRUI to 3D to enable more comprehensive assessments of the graft microvasculature. We will develop novel quantitative SRUI metrics, including microvascular density, tortuosity, flow speed, cortex perfusion and micro-resistive index. Aim 2: Clinical patient study. We will study 158 patients to investigate the value of SRUI for kidney allograft assessment using biopsy histology as validation. The association of SRUI metrics with histological injuries will be assessed. The ability of SRUI, conventional ultrasound, and clinical measures (eGFR, proteinuria) to distinguish between kidney allografts with varying degrees of histological injuries will be evaluated. We will also assess the inter-sonographer reproducibility of the SRUI technology in a subset of 46 patients. Aim 3: Longitudinal follow-up study. We will conduct a longitudinal follow-up study in 62 patients to assess the efficacy of SRUI in monitoring and predicting the progression of allograft injury, using biopsy histology as validation. The association of changes in SRUI metrics with the changes in histological injuries from 1-year to 2-year post-transplant will be assessed. We will study if SRUI metrics or combined metrics at 1-year post- transplant, or the changes of these metrics from 1-year to 2-year, can distinguish between allografts without and with histological worsening during this period. Successful completion of this project will lead to a noninvasive, accessible, cost-effective, and translatable tool to address the critical clinical need for reliable and frequent characterization of allograft in transplant recipients.
