Ultrasound-induced thermal therapy of hyperplasia in hemodialysis access grafts

The blood flow path between a dialysis patient and dialysis machine -- the hemodialysis vascular access -- is a veritable lifeline for the patient. Vascular access dysfunction is the leading cause of morbitity and hospitalization in hemodialysis patients. Expanded polytetrafluoroethylene (ePTFE) vascular grafts fail at high rates due to the occlusive effects of neointimal hyperplasia. To develop a treatment to reduce or prevent neointimal hyperplasia in arteriovenous dialysis grafts, cell death from mild hyperthermia of bovine aortic endothelial cells cultured on ePTFE was investigated. Hyperthermia experiments showed increased sensitivity to cell death for cells cultured on ePTFE compared to cells cultured on a surrogate tissue surface. An apoptosis target temperature range (45-47°C), was identified from exposures producing a majority cell death and apoptosis detection experiments.;The use of focused ultrasound to heat implanted ePTFE grafts was modeled by combining acoustic finite-difference time-domain and COMSOLRTM Multiphysics heat transfer simulations. Beam propagations, acoustic power depositions and temperature profiles from 1.5- and 3.2-MHz transducers were modeled in a simplified fat, muscle, blood and ePTFE graft model. With 1.2 mm of neointimal hyperplasia modeled inside the graft, temperatures simulated at the graft-hyperplasia boundary reached the targeted apoptosis temperature range. Models without hyperplasia showed significant temperature rises occurring only within the ePTFE graft; however, these temperatures may prevent neointimal hyperplasia by exposing cells migrating through the graft into the lumen. Comparison of simulations to a physical model, accomplished using magnetic resonance temperature imaging during ultrasound exposure of an agar phantom-PTFE graft model, showed a temperature rise within 1°C of the simulation. Overall, results suggest focused ultrasound exposure may be able to control neointimal hyperplasia thickness through hyperthermia-induced apoptosis and maintain dialysis access for ePTFE vascular grafts.