Development of a Quantitative Angiography Technique for Characterizing Hepatic Perfusion Changes in Response to Embolization

项目总结 肝癌是全球第四大癌症死亡原因。对于中期疾病，动脉内 治疗方法，如经动脉化疗栓塞术(TACE)，是主要的治疗方法。在TACE中，有针对性 化疗药物和栓塞剂颗粒阻断肿瘤供血动脉以增加这两种药物 并导致肿瘤坏死。TACE可以延长存活期，缓解症状，或者作为通往肝脏的桥梁。 移植。在TACE中，血管造影监测肿瘤残余血流是至关重要的，而且程度 停滞的程度直接影响患者的预后，包括生存。目前，没有客观的， 确定最佳栓塞点的标准化的术中方法。相反， 介入放射科医生依靠对血流停滞和血流灌注减少的目测评估来确定 何时结束栓塞术。这种主观评估是不可重现的，并可能导致 栓塞不足(肿瘤坏死不足)或过度栓塞(对周围肝组织的损害)， 最终会增加死亡率。 这项建议的目的是发展一种术中定量数字减影血管造影术。 (QDSA)技术，可表征栓塞后肝脏血流灌注的变化。建议数 该技术从TACE过程中常规获取的DSA图像中提取血流信息 程序。在我们的第一个目标中，我们将开发一种优化的qdsa方法来表征肝脏的变化。 动脉血流和灌注对栓塞术的反应。这将使用体外模型来完成。 并在活体猪模型中确定最佳成像参数，以表征血流减少的性质 作为对栓塞术的反应。然后，我们将在活体猪模型中对部分和 完全止血终点，并将使用qDSA的流量减少与血流灌注变化程度相关联 利用组织病理学。在第二个目标中，我们将使用兔肝肿瘤模型来关联血流减少与 QDSA与肿瘤内血流灌注变化程度及组织病理学反应有关。成功 这种技术的演示将作为第一个目标、标准化和程序内的 确定TACE终点的方法。这将显著提高安全和有效性 肝肿瘤治疗中的手术方法。

PROJECT SUMMARY Liver cancer is the 4th leading cause of cancer death worldwide. For intermediate-stage disease, intra-arterial therapies, such as transarterial chemoembolization (TACE), are the mainstay treatment. In TACE, targeted delivery of chemotherapeutic agents and embolic particles block tumor feeding arteries to increase both drug delivery and cause tumor necrosis. TACE can prolong survival, palliate symptoms, or serve as a bridge to liver transplantation. During TACE, angiographic monitoring of residual tumoral blood flow is critical and the degree of stasis achieved directly impacts patient outcomes, including survival. Currently, there are no objective, standardized intra-procedural methods for determining the optimal embolization endpoint. Instead, interventional radiologists rely on visual assessment of blood flow stasis and decreased perfusion to determine when to end an embolization. This subjective assessment is not reproducible and can lead to underembolization (insufficient tumor necrosis) or overembolization (damage to surrounding liver tissue), which can ultimately increase mortality. The objective of this proposal is to develop an intraprocedural quantitative digital subtraction angiography (qDSA) technique that can characterize hepatic perfusion changes in response to embolization. The proposed technique extracts blood flow information from DSA images that are routinely acquired during a TACE procedure. In our first aim, we will develop an optimized qDSA method that characterizes changes in hepatic arterial blood flow and perfusion in response to embolization. This will be done using in vitro phantom models and in vivo porcine models to identify optimal imaging parameters to characterize the nature of flow reduction in response to embolization. We will then perform embolizations in an in vivo porcine model to partial and complete stasis endpoints, and correlate the flow reduction using qDSA with the degree of perfusion changes using histopathology. In the second aim, we will use a rabbit liver tumor model to correlate flow reduction using qDSA with the degree of intratumoral perfusion changes and tissue response on histopathology. Successful demonstration of such a technique would serve as the first objective, standardized, and intra-procedural method for determining TACE endpoints. This would significantly improve the safety and efficacy of the procedure in the treatment of liver tumors.