Catheter guided endovascular electric field ablation for thrombosis therapy.

 描述（由申请人提供）：静脉血栓形成（VT）是当今最普遍的医学问题之一，在美国估计每年发生约100万例。尽管有最好的药物治疗，但DVT通常不完全消退，导致临床表现为血栓后综合征（PTS）的纤维化变化。高达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，并在终末期出现静脉溃疡。我们建议开发具有柔性电极阵列的血管内导管，以输送可调的非热、低压、脉冲电场（即，不可逆电穿孔（IRE））以防止纤维化变化，从而可以发生凝块的增强的生理分解。DVT细胞的成功非热消融可能导致血栓的完全生理消退，从而降低PTS的发生率。我们建议在现实的3D生物打印血栓血管芯片模型中使用简单电极优化血管内非热IRE（目标1）。使用这些IRE参数，我们将制作带有柔性电极的导管原型，并在血栓形成的血管芯片模型（Aim 2）和大鼠DVT模型（Aim 3）中进行体内测试。本研究的成功完成将表明，通过涂覆有柔性电子器件的导管输送的脉冲非热IRE可以以微创方式防止凝块组织。

 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.