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Characterization of microvasculature in kidney transplant by super-resolution ultrasound imaging

Award Number: R01DK138998
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/09/2024
PERIOD OF PERFORMANCE END DATE: 03/31/2029

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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.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $568,357 )
2026	2026	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	2/26/2026	NON-COMPETING CONTINUATION	$568,357
														Subtotal = $568,357

Issue Date FY: 2025 ( Subtotal = $538,923 )
2025	2025	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	4/14/2025	NON-COMPETING CONTINUATION	$538,923
														Subtotal = $538,923

Issue Date FY: 2024 ( Subtotal = $505,741 )
2024	2024	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	5/9/2024	NEW	$505,741
														Subtotal = $505,741

Grand Total All Awards = $1,613,021

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Characterization of microvasculature in kidney transplant by super-resolution ultrasound imaging

Award Number: R01DK138998

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 05/09/2024

PERIOD OF PERFORMANCE END DATE: 03/31/2029

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