Improving Ultrasound Pulse Wave Imaging for Prediction of Arteriovenous Fistula Maturation

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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.