Measurement of Renal Viscoelastic Properties with Ultrasound

摘要/总结 背景：慢性肾脏病（CKD）包括肾脏功能的长期下降。 CKD可进展为肾衰竭或终末期肾病（ESRD），可通过血液透析或 肾脏移植在过去的二十年里，患者和肾移植物的存活率有所提高，但长期以来- 移植物的长期存活仍然是一个问题。肾活检是诊断肾脏健康的金标准，但 这是一种侵入性手术，不能经常使用，并且可能导致并发症。非侵入性指标 肾脏疾病，包括血清肌酐水平、肾小球滤过率和经典医学成像 可以提供对肾脏疾病状态的某些见解。弹性成像方法可以区分健康 基于在组织中测量的不同参数来比较患病组织。我们发现，在过去的 这一周期授予某些弹性成像参数是敏感的不同结构或生理 移植肾的变化。线性和非线性弹性力学性能被发现是敏感的 间质纤维化的存在，而粘弹性参数对炎症过程敏感， 肾小管萎缩基于这些发现，我们建议使用定量的，非侵入性的方法来执行 一项全面的多参数弹性成像评估肾移植物，以评估健康的 移植的肾脏方法：基于超声剪切波的方法利用声辐射力“推动” 并产生剪切波。基于超声的方法用于检测剪切的传播 波穿过组织。剪切波的传播速度可以通过几个参数来修改 包括组织中的弹性、粘弹性和非线性机械特性。我们将使用横波 弹性成像（SWE），以使用飞行时间方法测量肾脏中的弹性特性。粘弹性 将使用基于模型的方法，通过将剪切波速度色散拟合到 流变学模型或涉及提取剪切波速度测量值的无模型方法 以及在各种频率下的衰减。最后，我们将使用一种称为声弹性的方法， 肾脏移植物的压缩和SWE测量，以从 剪切模量数据在不同水平的施加应力。从中提取的参数 将测量结果与肾脏健康的结构（活检）和功能测量结果（血清 肌酐、估计的肾小球滤过率和多普勒超声结果），以阐明 疾病改变了这些参数。建立这些关系将为以下方面奠定坚实的基础： 将这些弹性成像测量方法转化为广泛的临床应用， 肾移植SWE测量的无创性，可用于许多临床超声 扫描仪，使他们成为一个强有力的候选人，作为一种工具，减少活检的数量，并用于 频繁的定量评估和监测患者对治疗的反应，这将导致 降低了医疗保健成本，并可能改善患者的治疗效果。为了实现这些目标，我们 提出以下具体目标。目的：1）评价使用SWE测量弹性力学 用于非侵入性评估肾移植物的结构和功能变化的特性。2)评价 使用SWE测量粘弹性机械特性以评估肾移植物纤维化，炎症， 和功能3)评估使用声弹性测量非线性弹性力学性能， 评估移植肾的病理和功能变化。

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.