Bader Kenneth B, Flores Basterrechea Katia, Hendley Samuel A
Department of Radiology, University of Chicago, Chicago, IL, United States.
University of Nebraska Medical Center, Omaha, NE, United States.
Front Physiol. 2023 Jun 28;14:1225804. doi: 10.3389/fphys.2023.1225804. eCollection 2023.
For venous thrombosis patients, catheter-directed thrombolytic therapy is the standard-of-care to recanalize the occluded vessel. Limitations with thrombolytic drugs make the development of adjuvant treatments an active area of research. One potential adjuvant is histotripsy, a focused ultrasound therapy that lyses red blood cells within thrombus via the spontaneous generation of bubbles. Histotripsy has also been shown to improve the efficacy of thrombolytic drugs, though the precise mechanism of enhancement has not been elucidated. In this study, calculations were performed to determine the contribution of histotripsy-induced changes in thrombus diffusivity to alter catheter-directed therapy. An established and validated Monte Carlo calculation was used to predict the extent of histotripsy bubble activity. The distribution of thrombolytic drug was computed with a finite-difference time domain (FDTD) solution of the perfusion-diffusion equation. The FDTD calculation included changes in thrombus diffusivity based on outcomes of the Monte Carlo calculation. Fibrin degradation was determined using the known reaction rate of thrombolytic drug. In the absence of histotripsy, thrombolytic delivery was restricted in close proximity to the catheter. Thrombolytic perfused throughout the focal region for calculations that included the effects of histotripsy, resulting in an increased degree of fibrinolysis. These results were consistent with the outcomes of studies, suggesting histotripsy-induced changes in the thrombus diffusivity are a primary mechanism for enhancement of thrombolytic drugs.
对于静脉血栓形成患者，导管直接溶栓治疗是使闭塞血管再通的标准治疗方法。溶栓药物的局限性使得辅助治疗的开发成为一个活跃的研究领域。一种潜在的辅助治疗方法是组织超声破碎术，这是一种聚焦超声疗法，可通过气泡的自发产生来溶解血栓内的红细胞。组织超声破碎术也已被证明可提高溶栓药物的疗效，尽管增强的确切机制尚未阐明。在本研究中，进行了计算以确定组织超声破碎术引起的血栓扩散率变化对改变导管直接治疗的作用。使用已建立并经过验证的蒙特卡罗计算来预测组织超声破碎术气泡活动的程度。用灌注 - 扩散方程的有限差分时域（FDTD）解计算溶栓药物的分布。FDTD计算包括基于蒙特卡罗计算结果的血栓扩散率变化。使用溶栓药物的已知反应速率确定纤维蛋白降解情况。在没有组织超声破碎术的情况下，溶栓药物的递送局限于导管附近。对于包括组织超声破碎术影响的计算，溶栓药物灌注到整个焦点区域，导致纤维蛋白溶解程度增加。这些结果与研究结果一致，表明组织超声破碎术引起的血栓扩散率变化是增强溶栓药物的主要机制。
