Improving Ultrasound Pulse Wave Imaging for Prediction of Arteriovenous Fistula Maturation

摘要/总结 在美国，超过80万患者患有终末期肾病， 临床上估计肾小球滤过率（eGFR）<15 mL/kg/1.73m2，而正常eGFR >90 mL/kg/1.73m2。这种肾功能的严重丧失使得血液透析（HD）治疗成为一种过程， 在外部过滤血液以增强肾功能，这对于该患者群体的存活至关重要。 有效执行HD需要进入具有良好流动性、通畅性和 抗反复穿刺。临床上首选的方法是通过手术连接 高压桡动脉或肱动脉与低压头静脉或贵要静脉，以创建一个 动静脉瘘（AVF）。理想情况下，一旦创建AVF，流出静脉经历以下过程： 动脉化，体积流量急剧增加，向外增厚，形成成熟的AVF 一个理想的高清接入网站。不幸的是，AVF具有非常高的失败成熟率， 40%在创建后1年无法使用。AVF也可能需要几个月的时间才能成熟， 在成熟过程中可能难以评估，因此确定生物标志物至关重要， 在尽可能早的时间点预测AVF成熟，以推动介入治疗和AVF 继任计划 在这个项目中，我们建议检查AVF邻近血管的刚度作为一种可能的分类， 使用基于超声的脉搏波成像（PWI）的生物标志物。PWI利用了速度 机械激励通过管传播的速度与所述管的刚度有关 Moens-Korteweg方程。这样的机械激励是由脉动流连续提供的， 血管，并且可以使用超声成像。然而，想象这波 鲁棒地需要优异的时间和空间分辨率，因为脉管系统中的脉搏波以高速传播 在米每秒的数量级上，并且通常引起小的（<1 mm）变形，这使得PWI 困难重重，阻碍了其临床应用。最近提出了几种新的超声成像技术 该技术有望提高时空分辨率，包括时间对准平面波复合（TA- PWC）和梳状探测（CD），但这些尚未应用于美国PWI。 在具体目标1中，我们建议将TA-PWC和CD技术应用于PWI，并在 血管模型和离体和体内猪颈总动脉，以改善时空 超声波的分辨率在特定目标2中，我们计划应用PWI测量猪模型中的AVF刚度 并评估过去的硬度值和未来的替代品之间的关系 AVF的成熟，AVF硬度和组织学评估的纤维化之间的关系， PWI评估的AVF刚度与切除组织的机械测试之间的一致性。

ABSTRACT/SUMMARY Over 800,000 patients in the United States are suffering from end-stage renal disease, a condition defined clinically as an estimated glomerular filtration rate (eGFR) <15 mL/kg/1.73m2, compared to a normal eGFR >90 mL/kg/1.73m2. This profound loss of renal function makes hemodialysis (HD) treatment, a procedure where the blood is filtered externally to augment renal function, critical for the survival of this patient population. Performing HD efficiently requires access to a section of vasculature with excellent flow, patency, and resistance to repeated punctures. The clinically preferred method of creating such a site is by surgically joining the high-pressure radial or brachial artery with the low-pressure cephalic or basilic vein to create an arteriovenous fistula (AVF). Ideally, once an AVF is created, the outflow vein undergoes a process of arterialization, with a dramatic increase in volumetric flow and an outward thickening that makes a mature AVF an ideal HD access site. Unfortunately, AVFs have a remarkably high failure-to-mature rate, with as many as 40% being unusable 1 year after creation. AVFs can also take months to mature, and their failure probability can be difficult to assess during the maturation process, making it critical to identify biomarkers that are predictive of AVF maturation at the earliest possible timepoints to drive interventional treatments and AVF succession planning. In this project, we propose examining the stiffness of the AVF-adjacent vasculature as one possible class of biomarkers using ultrasound-based pulse wave imaging (PWI). PWI takes advantage of the fact that the speed at which a mechanical excitation propagates through a tube is related to the stiffness of that tube as described by the Moens-Korteweg equation. Such a mechanical excitation is provided continuously by pulsatile flow in blood vessels under in vivo conditions, and can be imaged using ultrasound. However, imaging this wave robustly requires excellent temporal and spatial resolution, as pulse waves in vasculature propagate at speeds on the order of meters per second and typically induce small (<1 mm) deformations, which has made PWI difficult and hampered its clinical adoption. Several new US imaging techniques have recently been proposed that promise to increase spatiotemporal resolution including Time-Aligned Plane Wave Compounding (TA- PWC) and Comb Detection (CD), but these have not yet been applied for US-based PWI. In Specific Aim 1, we propose to apply the TA-PWC and CD techniques to PWI and validate the results in vascular phantoms and both ex vivo and in vivo porcine common carotid arteries to improve the spatiotemporal resolution of ultrasound. In Specific Aim 2, we plan to apply PWI to measure AVF stiffness in porcine models of chronic kidney disease and assess the relationships between past values of stiffness and future surrogates of AVF maturation, the relationship between AVF stiffness and histologically-assessed fibrosis, and the agreement between PWI-assessed AVF stiffness and mechanical testing of excised tissue.