平板探测器CT灌注成像在肝癌TACE治疗中实时动态监测肿瘤血流动力学状态的研究

Hepatocellular carcinoma (HCC) is one of major malignant tumors that threaten human health. Transarterial chemoembolization (TACE) is the primary intervention treatment for hepatocellular carcinoma. TACE necrotizes tumor tissues by embolization of tumor feeding artery. However, one drawbacks of TACE is that it is difficult to control the degree of embolization,and there is lack of reliable guide line to evaluate embolization efficacy. Flat Detector (FD) equipped angiographic systems are increasingly used in daily routine recently. The introduction of FD equipped C-arm systems improved 3-D imaging with the possibility to obtain high-quality 3-D vascular imaging. Using this equipment, it is now possible to obtain CT like images (Flat Detector computed tomography, FD-CT) within the angio suite. There have been some evidences that FD-CT could provide a means to measure the cerebral hemodynamics at accuracy comparable to that of CT perfusion imaging. The ability to measure cerebral perfusion in an angiographic suite where it is possible to use immediately all available therapeutic techniques might, simply by saving time from initial assessment to intervention, add value to the management of patients with ischemic strokes. As a result, it is not unreasonable to propose that hepatic hemodynamics may be observed by FD-CT. But as far as we know, there are no published reports on the feasibility of measurements of hepatic hemodynamics by this technique. So, in this study we intend to measure changes of perfusion parameters in rabbit VX2 liver tumor models before and after TACE by using FD-CT technique. We will test the hypothesis that in patients with HCC, perfuison values of liver parenchyma or tumor tissues could be measured by using FD-CT and that these measurements would correlate with those made by using standard CT techniques. Real-time dynamic monitoring of the degree of tumor embolization will be applied. We are to assess the relationships between the degree of tumor embolization, different hemodynamic changes in tumor tissues and prognosis of tumors after TACE. The progress of tumor after TACE will be followed up.We expect to find the optimum embolic end points for TACE in this study. Furthermore, preliminary clinical application of this new technology will be carried out in patients with HCC who would accept TACE treatment. The study will provide theoretical and practical basis to promote clinical application of this technology. The success of this project will provide a new assessment and monitoring system for TACE treatment for HCC. There will be important clincal significance for improving the treatment of HCC.

肝癌是威胁人类健康的主要恶性肿瘤之一，肝动脉化疗栓塞（TACE）是肝癌的主要介入治疗手段。TACE的主要原理是通过栓塞肿瘤供血动脉以达到使肿瘤缺血坏死的目的，其缺点之一是难以控制肿瘤的栓塞程度，栓塞疗效评估缺乏可靠的衡量指标。通过平板探测器C型臂血管造影系统可得到类似传统CT的组织血流灌注参数图，故本研究拟利用此项技术测量兔VX2肝癌TACE前后的血流灌注参数变化，分析该灌注参数与传统CT灌注成像所得灌注值间的关系，实时动态监测肿瘤栓塞程度，评估不同栓塞程度与肿瘤内部血流动力学改变和预后之间的关系，评价TACE后肿瘤的进展情况，寻找最佳的栓塞终点，并将此新技术初步运用于临床行TACE治疗的肝癌患者，为该技术的临床推广提供理论和实践基础。本研究项目的成功将会为肝癌的TACE治疗提供新的评估和监测体系，对于提高肝癌治疗效果具有深远的临床意义。

肝动脉化疗栓塞（TACE）是目前肝癌的主要介入治疗手段。TACE的主要原理是通过栓塞肿瘤供血动脉以达到使肿瘤缺血坏死的目的，其缺点是难以控制肿瘤的栓塞程度，栓塞疗效评估缺乏可靠的衡量指标。为了解决这一难题,本项目中我们进行一系列研究，获得了重要进展和成果。.我们成功建立了兔VX2肝癌模型，分析平板探测器CT灌注（FD-CTP）和传统CT灌注（CTP）所得血容量(BV)值之间的关系。两者得到的BV灌注图像均比较满意，匹配性良好。BV灌注图上VX2肿瘤显示为“红环状”强化模式，所以本课题中分别测量肿瘤高灌注环和低灌注中心的BV值，高灌注环和低灌注中心的FD-BV和CTP-BV值之间相关性和一致性强。我们通过动物实验分析肿瘤栓塞程度与预后的关系，寻找最佳栓塞点。我们首先将动物模型根据预计栓塞程度进行定性分组，TACE治疗前常规行FD-CTP,完成栓塞后，待动物肝内血流状态稳定后，再次进行FD-CTP成像获得灌注参数值，并与栓塞前的进行比较，根据灌注值变化程度再次对实验动物进行栓塞程度定量分组，随后对上述两种分组方法与肿瘤预后之间的关系进行分析。结果提示定量的大部栓塞可以明显提高肝肿瘤预后，FD-CTP可以指导肝癌TACE的治疗。.我们研究了TACE术中FD-CTP所得的BV值与VX2肝癌血管生成之间的关系。首先在导管室内测量兔VX2肝肿瘤模型的BV值，获取肝肿瘤标本后，通过免疫组化方法测量肿瘤的微血管密度（MVD）和血管内皮生长因子（VEGF）的表达情况，结果发现肿瘤BV值与MVD和VEGF分级之间均存在良好相关性。FD-CTP技术评估肿瘤血管生成的能力对于肝肿瘤的TACE治疗有重要的潜在意义，该技术能在导管室内TACE术中直接实时动态监测肝肿瘤的BV值和血管生成情况，医师可以根据结果及时调整TACE和抗血管生成药物治疗方案,及时了解治疗效果，具有重大临床应用前景。.我们还将FD-CTP技术运用于肝癌拟行TACE治疗的患者，测量FD-CTP和CTP测得BV值之间的关系，所得结果与动物实验结果相似，两种技术所得BV灌注图匹配良好，BV值之间相关性和一致性良好。而且，FD-CTP较传统CTP可能会更多地显示一些较小的、不易发现的肿瘤病灶。研究提示FD-CTP能客观评估TACE治疗中肝肿瘤的血流动力学变化，有望帮助优化肝癌的介入诊疗。