Functional MRI Monitoring of Hepatic Chemoembolization

描述(由申请人提供)：这项应用的广泛、长期目标是改善不能切除的肝细胞癌(HCC)患者的预后。磁共振成像(MRI)被建议用于监测肝细胞癌患者的肝动脉化疗栓塞术(TACE)。一种4维经导管动脉内灌注加权(TRIP)-MRI技术，使用3个空间维度和1个时间维度，将被用来测量治疗时肿瘤血流灌注的定量变化。这些定量的、绝对的血流灌注变化将与临床结果、X射线数字减影血管造影术(DSA)终点和组织标本上的肿瘤血管生成标记物相关。其基本原理是确定灌注在TACE中作为确定治疗终点的一种手段所起的关键作用。研究将在相同的前瞻性队列中进行，其中100名肝癌患者已经计划接受TACE，使用混合MR介入放射学DSA程序套件。这套设备包括一台1.5T核磁共振扫描仪和一台DSA设备。特异靶1将TACE期间肿瘤的血流变化与临床结果相关联。据推测，TACE期间定量4D Trip-MRI灌注水平的基线和间隔减少可以预测未来的临床结果。这些临床结果将通过MRI上常规解剖大小的变化、使用改进的扩散加权MRI技术的水流动性的功能变化、存活率和毒性来评估。与健康相关的将是通过测量治疗的绝对血流灌注变化来优化TACE的结果。特定的目标2将使TACE期间的DSA终点与血流灌注变化和临床结果相关。我们假设TACE期间的DSA终点与定量的4D Trip-MRI血流灌注变化无关，也不能预测临床结果。与健康相关的是使用外部客观标准来确定特定的DSA终点是否可以并且应该在治疗期间成为靶点。特异靶3将TACE过程中的血流变化与肿瘤血管生成和临床结果相关联。血管生成蛋白--血管内皮生长因子(VEGF)和缺氧诱导因子-11(HIF-11)将在TACE前的肝活检标本和可用的肝移植上进行检测。本研究假设肝组织中VEGF和HIF-11的基线水平与TACE术后的临床结果相关；TACE过程中4D TRIP-MRI血流灌注的变化可以预测肝组织中VEGF和HIF-11的未来表达。公共卫生相关性与健康相关的是了解基线组织血管生成标记物如何影响预后，并确定哪些TACE终点最有可能诱导血管生成。与公共健康相关的是确定流向肿瘤的血液在肝癌治疗过程中所起的核心作用。我们推测，在治疗过程中测量这种血流量可以帮助预测治疗的反应。这一信息可能会改善未来肝癌患者的预后。

DESCRIPTION (provided by applicant): The broad, long-term objective of this application is to improve the prognosis of patients with unresectable hepatocellular carcinoma (HCC). Magnetic resonance imaging (MRI) is proposed to monitor transcatheter arterial chemoembolization (TACE) of patients with HCC. A 4-dimensional transcatheter intraarterial perfusion weighted (TRIP)-MRI technique, using 3 spatial and 1 time dimension, will be used to measure quantitative changes in tumor perfusion at the time of therapy. These quantitative, absolute changes in perfusion will be correlated with clinical outcomes, x-ray digital subtraction angiography (DSA) endpoints, and tumor angiogenic markers on tissue specimens. The rationale is to determine the pivotal role that perfusion plays during TACE as a means of determining endpoints for therapy. Studies will be performed within the same prospective cohort of 100 patients with HCC already scheduled to undergo TACE using a hybrid MR-interventional radiology DSA procedure suite. This suite contains both a 1.5T MRI scanner and a DSA unit. Specific Aim 1 will correlate tumor perfusion changes during TACE with clinical outcomes. It is hypothesized that baseline and interval reductions in quantitative 4D TRIP-MRI perfusion levels during TACE can predict future clinical outcomes. These clinical outcomes will be assessed by conventional anatomic size changes on MRI; functional changes in water mobility using an improved diffusion weighted MRI technique; survival; and toxicity. The health relevance will be to optimize TACE outcomes by measuring absolute perfusion changes for therapy. Specific Aim 2 will correlate DSA endpoints during TACE with perfusion changes and clinical outcomes. It is hypothesized that DSA endpoints during TACE do not correlate with quantitative 4D TRIP-MRI perfusion changes and do not predict clinical outcomes. The health relevance is to use external objective standards to see if a specific DSA endpoint can and should be targeted during therapy. Specific Aim 3 will correlate perfusion changes during TACE with tumor angiogenesis and clinical outcomes. Angiogenic proteins-- vascular endothelial growth factor (VEGF) and hypoxia inducible factor-11 (HIF-11) will be measured on pre-TACE liver biopsy specimens and on available liver explants. It is hypothesized that baseline tissue levels of VEGF and HIF-11 correlate with clinical outcomes after TACE; and that 4D TRIP-MRI perfusion changes during TACE predict future expression of tissue VEGF and HIF-11 on liver explants. PUBLIC HEALTH RELEVANCE The health relevance is to see how baseline tissue angiogenic markers affect outcome and to determine which TACE endpoints are most likely to induce angiogenesis. The relevance to public health is to determine the central role that blood flow to tumors plays during treatment of liver cancer. We postulate that measurement of this blood flow during treatment can be used to help predict response to therapy. This information might improve the prognosis of future patients with liver cancer.