Modelling ultrasound-induced mild hyperthermia of hyperplasia in vascular grafts

Mark R Brinton,Alfred K Cheung,Yan-Ting E Shiu,Douglas A Christensen,Russell J Stewart

doi:10.1186/1742-4682-8-42

Abstract

BackgroundExpanded polytetrafluoroethylene (ePTFE) vascular grafts frequently develop occlusive neointimal hyperplasia as a result of myofibroblast over-growth, leading to graft failure. ePTFE exhibits higher ultrasound attenuation than native soft tissues. We modelled the selective absorption of ultrasound by ePTFE, and explored the feasibility of preventing hyperplasia in ePTFE grafts by ultrasound heating. Specifically, we simulated the temperature profiles of implanted grafts and nearby soft tissues and blood under ultrasound exposure. The goal was to determine whether ultrasound exposure of an ePTFE graft can generate temperatures sufficient to prevent cell growth on the graft without damaging nearby soft tissues and blood.MethodsUltrasound beams from two transducers (1.5 and 3.2 MHz) were simulated in two graft/tissue models, with and without an intra-graft cellular layer mimicking hyperplasia, using the finite-difference time-domain (FDTD) method. The resulting power deposition patterns were used as a heat source for the Pennes bioheat equation in a COMSOL® Multiphysics heat transfer model. 50°C is known to cause cell death and therefore the transducer powers were adjusted to produce a 13°C temperature rise from 37°C in the ePTFE.ResultsSimulations showed that both the frequency of the transducers and the presence of hyperplasia significantly affect the power deposition patterns and subsequent temperature profiles on the grafts and nearby tissues. While neither transducer significantly raised the temperature of the blood, the 1.5-MHz transducer was less focused and heated larger volumes of the graft and nearby soft tissues than the 3.2-MHz transducer. The presence of hyperplasia had little effect on the blood's temperature, but further increased the temperature of the graft and nearby soft tissues in response to either transducer. Skin cooling and blood flow play a significant role in preventing overheating of the native tissues.ConclusionsModelling shows that ultrasound can selectively heat ePTFE grafts and produce temperatures that cause cell death on the graft. The temperature increase in blood is negligible and that in the adjacent soft tissues may be minimized by skin cooling and using appropriate transducers. Therefore, ultrasound heating may have the potential to reduce neointimal hyperplasia and failure of ePTFE vascular grafts.

Highlights

Expanded polytetrafluoroethylene vascular grafts frequently develop occlusive neointimal hyperplasia as a result of myofibroblast over-growth, leading to graft failure. ePTFE exhibits higher ultrasound attenuation than native soft tissues
We modelled the selective absorption of ultrasound in ePTFE and the corresponding thermal profiles to determine whether ultrasound exposure can elevate the graft to temperatures capable of inflicting neointimal hyperplasia (NH) cell death without significantly damaging the nearby tissues and blood
Simulated pressure and power depositions for the 1.5- and 3.2-MHz transducers Our simulated pressure results showed that, while the focus was positioned at the rear graft wall for both transducers, the focal zone of the 1.5-MHz transducer spanned the width of the graft (Figure 2a) while the focal zone of the 3.2-MHz transducer covered only the rear graft wall (Figure 2b)

Summary

Introduction

Expanded polytetrafluoroethylene (ePTFE) vascular grafts frequently develop occlusive neointimal hyperplasia as a result of myofibroblast over-growth, leading to graft failure. ePTFE exhibits higher ultrasound attenuation than native soft tissues. Grafts are a useful form of vascular access in patients whose vasculature is insufficient to support a functional native AV fistula. The low primary patency rates of ePTFE grafts are attributed to their propensity to develop excessive cell growth in the graft lumen, preferentially near the graft-venous anastomosis site [4]. This growth, termed neointimal hyperplasia (NH), causes lumen stenosis that predisposes to thrombosis and occlusion. If the occurrence of NH could be prevented or reduced, the synthetic graft should be an excellent form of dialysis vascular access for the large population of dialysis patients whose vasculature cannot support a functional AV fistula

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