Project Details
Description
ABSTRACT/SUMMARY
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.
Status | Finished |
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Effective start/end date | 7/7/12 → 3/31/24 |
Funding
- National Institute of Diabetes and Digestive and Kidney Diseases: $618,364.00
- National Institute of Diabetes and Digestive and Kidney Diseases: $413,576.00
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