Catheter guided endovascular electric field ablation for thrombosis therapy.

 描述(由申请人提供)：静脉血栓形成(VT)是当今最常见的医疗问题之一，估计在美国每年的发病率约为100万例。尽管有最好的药物治疗，但DVT往往不能完全消退，导致纤维化改变，临床表现为血栓后综合征(PTS)。多达60%的DVT患者发生PTS，这增加了DVT复发的风险，并可能严重影响生活质量，导致慢性静脉功能不全，并在晚期导致静脉溃疡。我们建议开发具有柔性电极阵列的血管内导管，以向静脉血栓提供可调节的非热、低电压、脉冲电场(即不可逆电穿孔(IRE))，以防止纤维化改变，从而增强血栓的生理性破裂。成功的非热消融DVT细胞可能导致血栓在生理上完全消退，从而降低PTS的发生率。我们建议在一个真实的3D生物打印的芯片上血栓模型中使用简单的电极来优化血管内非热IRE(目标1)。使用这些IRE参数，我们将使用柔性电极制作导管原型，并在血栓芯片上血管模型(AIM 2)和大鼠深静脉血栓模型(AIM 3)中对它们进行测试。这项研究的成功完成将表明，由涂有柔性电子设备的导管输送的脉冲、非热式IRE可以以最小的侵入性方式防止血栓机化。

 DESCRIPTION (provided by applicant): Venous thrombosis (VT) is among the most prevalent medical problems today with an estimated annual incidence of approximately 1 million cases in the United States. Despite best medical therapy, there is often incomplete resolution of the DVT leading to fibrotic changes that clinically manifest as post-thrombotic syndrome (PTS). Up to 60% of DVT patients develop PTS, which increases the risk for DVT recurrence and can severely impact the quality of life causing chronic venous insufficiency and, at end stage, venous ulcers. We propose to develop endovascular catheters with flexible electrode arrays to deliver tunable non-thermal, low-voltage, pulsed electric fields (i.e., irreversible electroporatio (IRE)) to venous thrombus to prevent fibrotic changes so that enhanced physiologic breakdown of the clot can occur. Successful non-thermal ablation of the DVT cells may lead to complete physiologic resolution of the thrombus, decreasing the incidence of PTS. We propose to optimize intravascular non-thermal IRE using simple electrodes in a realistic 3D bioprinted thrombosed vessel-on-a-chip model (Aim 1). Using these IRE parameters, we will prototype catheters with flexible electrodes and test them in the thrombosed vessel-on-a-chip model (Aim 2) and in vivo in a rat DVT model (Aim 3). Successful completion of this study will show that pulsed, non-thermal IRE delivered by catheters coated with flexible electronics can prevent clot organization in a minimally invasive manner.