Functional MRI Monitoring of Hepatic Chemoembolization

描述（由申请人提供）：本申请的广泛、长期目标是改善不可切除的肝细胞癌（HCC）患者的预后。磁共振成像（MRI）被推荐用于肝细胞癌患者经导管动脉化疗栓塞（TACE）的监测。一种四维经导管动脉灌注加权(TRIP)-MRI技术，使用3个空间和1个时间维度，将用于测量治疗时肿瘤灌注的定量变化。这些定量的、绝对的灌注变化将与临床结果、x线数字减影血管造影（DSA）终点和组织标本上的肿瘤血管生成标志物相关。其基本原理是确定灌注在TACE期间发挥的关键作用，作为确定治疗终点的手段。研究将在相同的前瞻性队列中进行，100例HCC患者已经计划使用混合mr -介入性放射学DSA手术套件进行TACE。该套件包含1.5T MRI扫描仪和DSA装置。特异性Aim 1将TACE期间肿瘤灌注变化与临床结果联系起来。假设TACE期间定量4D TRIP-MRI灌注水平的基线和间隔降低可以预测未来的临床结果。这些临床结果将通过MRI的常规解剖大小变化来评估；利用改进的扩散加权MRI技术检测水迁移率的功能变化；生存而生存;和毒性。健康相关性将是通过测量治疗的绝对灌注变化来优化TACE结果。特异性Aim 2将把TACE期间的DSA终点与灌注变化和临床结果联系起来。假设TACE期间的DSA终点与定量4D TRIP-MRI灌注变化无关，也不能预测临床结果。健康相关性是使用外部客观标准来查看特定的DSA终点是否可以并且应该在治疗期间靶向。特异性Aim 3将把TACE期间的灌注变化与肿瘤血管生成和临床结果联系起来。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前肝活检标本和可用的肝移植体上进行测量。假设VEGF和HIF-11的基线组织水平与TACE后的临床结果相关；TACE期间的4D TRIP-MRI灌注变化预测了组织VEGF和HIF-11在肝移植体上的未来表达。公共卫生相关性健康相关性是观察基线组织血管生成标志物如何影响结果，并确定哪些TACE终点最有可能诱导血管生成。与公共卫生相关的是确定血液流向肿瘤在肝癌治疗过程中所起的核心作用。我们假设在治疗期间测量这种血流量可以用来帮助预测对治疗的反应。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.