Background: Chronic kidney disease (CKD) encompasses a long-term decrease in function of the kidneys. CKD can progress to kidney failure or end-stage renal disease (ESRD), which is treated by hemodialysis or kidney transplant. Patient and renal graft survival rates have increased over the past two decades, but long- term survival of grafts is still an issue. Renal biopsy is the gold standard for diagnosis of kidney health, but is an invasive procedure, cannot be used frequently, and can cause complications. Noninvasive indicators of kidney disease including levels of serum creatinine, glomerular filtration rate, and classical medical imaging can provide certain insights into kidney disease state. Elasticity imaging methods can discriminate healthy versus diseased tissue based on different parameters measured in the tissue. We have found in the previous cycle of this grant that certain elastographic parameters are sensitive to different structural or physiological changes in renal allografts. Linear and nonlinear elastic mechanical properties were found to be sensitive to the presence of interstitial fibrosis while viscoelastic parameters were sensitive to inflammatory processes and tubular atrophy. Based on these findings, we propose the use of quantitative, noninvasive methods to perform a comprehensive multi-parametric elastographic evaluation of renal allografts to evaluate health of the transplanted kidney. Methods: Ultrasound shear wave-based methods use acoustic radiation force to ?push? the tissue and create shear waves. Ultrasound-based methods are used to detect the propagation of the shear waves through the tissue. The propagation velocity of the shear waves can be modified by several parameters including the elastic, viscoelastic, and nonlinear, mechanical properties in the tissue. We will use shear wave elastography (SWE) to measure elastic properties in the kidney using time-of-flight methods. Viscoelastic properties will be measured using a model-based approach by fitting shear wave velocity dispersion to rheological models or a model-free approach that involves extracting measurements of shear wave velocity and attenuation at various frequencies. Lastly, we will use a method called acoustoelasticity, which combines compression of the renal allograft and SWE measurements to estimate the nonlinear elastic modulus from shear modulus data obtained at various levels of applied stress. The parameters extracted from these measurements will be compared with structural (biopsy) and functional measures of kidney health (serum creatinine, estimated glomerular filtration rate, and Doppler ultrasound results) to elucidate how allograft disease changes these parameters. Establishing these relationships will provide a strong foundation for translating these elastographic measurement methods forward for widespread clinical use for assessment of renal allografts. The noninvasive nature of SWE measurements, available on many clinical ultrasound scanners, make them a strong candidate as a tool for reducing the number of biopsies, and to be used for frequent quantitative assessment and monitoring of patients? responses to treatment, which will lead to reduced healthcare costs and potentially improved patient outcomes. To accomplish these objectives, we propose the following Specific Aims.
Aims : 1) Evaluate the use of SWE to measure elastic mechanical properties for the noninvasive assessment of structural and functional changes in renal allografts. 2) Evaluate the use of SWE to measure viscoelastic mechanical properties to assess renal allograft fibrosis, inflammation, and function. 3) Evaluate the use of acoustoelasticity to measure nonlinear elastic mechanical properties to assess pathology and functional changes in renal allografts.
Successful completion of this research program will result in enhanced knowledge of the relationship of elastographic properties of renal allografts to nascent and well-developed rejection and fibrosis. Using a multi-parametric ultrasound-based shear wave elastography approach to measure the elastic, viscoelastic, and nonlinear mechanical properties of renal allografts and comparing those measurements to biopsy and clinical results will establish the relationships between renal structure and function changes and how they change mechanical properties of tissue. The noninvasive nature of ultrasound shear wave elastography makes it suitable for screening, for frequent assessment, and for monitoring patients undergoing therapeutic interventions to track treatment response.
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