Transcatheter Intra-arterial Perfusion MRI Monitoring of Liver Tumor Embolization

描述(由申请人提供)：这项建议的广泛、长期目标是改善不能切除的肝细胞癌(HCC)患者的预后。这些患者通常接受经导管动脉栓塞术(TAE)作为姑息治疗的一种形式。目前使用x射线数字减影血管造影进行动脉栓塞术，以评估每次注射栓塞剂后的血流减少。然而，DSA血流估计可能是高度主观的，并且不能很好地反映肿瘤的血流灌注。这项建议的目的是开发一种新的磁共振成像(MRI)技术，在TAE过程中反复监测肝脏肿瘤的血流灌注。建议的经导管动脉内灌注磁共振成像(TRIP-MRI)技术提供了在混合DSA/MRI程序套件中监测TAE过程中的血流灌注变化的可能性。对于TRIP-MRI，小剂量造影剂直接通过TAE导管注入，允许迭代药代动力学测量，以估计每次注射栓塞剂后的血流灌注变化。必须解决技术挑战，才能进行连续的定量TRIP-MRI测量，还需要进一步的研究，通过与有创金标准方法的比较来验证TRIP-MRI测量。拟议的研究将针对肝肿瘤动物模型(目标1和2)和肝细胞癌临床患者(目标3)中的以下特定目标：特定目标1：TRIP-MRI方法学的技术开发任务1：验证动脉内注射允许定量估计对比药代动力学的假设，而不需要直接测量肝远端动脉内的动脉输入功能。任务2：验证TRIP-MRI对比剂剂量可以在术中优化的假设，以允许较短的冲洗时间和有利于TAE监测的测量重复间隔。具体目标2：TRIP-MRI测量的定量验证任务1：测试TRIP-MRI测量可以准确量化肝肿瘤栓塞术中血流灌注减少的假设。任务2：验证手术中TRIP-MRI测量可以准确预测术后导管拔除后肿瘤血流减少的最终分数的假设。具体目标3：TRIP-MRI和DSA监测的栓塞性终点的临床比较任务1：检验定量TRIP-MRI灌注测量提供比传统DSA监测方法更可靠的TAE栓塞性终点的假设。任务2：通过与手术中定量的TRIP-MRI血流测量进行比较，验证DSA血流估计不能很好地反映肿瘤血流减少的假设。

DESCRIPTION (provided by applicant): The broad, long-term objective of this proposal is to improve the prognosis of patients with unresectable hepatocellular carcinoma (HCC). These patients commonly undergo transcatheter arterial embolization (TAE) as a form of palliative therapy. TAE is currently performed using x-ray DSA to estimate blood flow reductions after each injection of embolic material. However, DSA flow estimates may be highly subjective and poorly reflective of tumor perfusion. The objective of this proposal is to develop a new magnetic resonance imaging (MRI) technique to iteratively monitor liver tumor perfusion during TAE procedures. The proposed transcatheter intra-arterial perfusion MRI (TRIP-MRI) techniques offer the potential to monitor perfusion changes during TAE procedures within hybrid DSA/MRI procedure suites. For TRIP-MRI, small contrast doses are infused directly through the TAE catheter permitting iterative pharmacokinetic measurements to estimate perfusion changes after each injection of embolic material. Technical challenges must be resolved to permit serial quantitative TRIP-MRI measurements and further studies are required to validate TRIP-MRI measurements by comparison to invasive gold-standard methods. Proposed studies will address the following Specific Aims in a liver tumor animal model (Aims 1 and 2) and clinical patients with hepatocellular carcinoma (Aim 3): Specific Aim 1: Technical Development of TRIP-MRI Methodology Task 1: To test the hypothesis that intra-arterial injections permit quantitative estimation of contrast pharmacokinetics without needing to directly measure the arterial input function within distal hepatic arteries. Task 2: To test the hypothesis that TRIP-MRI contrast dose can be optimized intra-procedurally to permit short wash-out times and measurement repetition intervals conducive to TAE monitoring. Specific Aim 2: Quantitative Validation of TRIP-MRI Measurements Task 1: To test the hypothesis that TRIP-MRI measurements can accurately quantify intra-procedural perfusion reductions during liver tumor embolization. Task 2: To test the hypothesis that intra-procedural TRIP-MRI measurements can accurately predict the final fractional reduction to tumor perfusion after post-procedural catheter withdrawal. Specific Aim 3: Clinical Comparison of TRIP-MRI and DSA Monitored Embolic Endpoints Task 1: To test hypothesis that quantitative TRIP-MRI perfusion measurements provide a more reproducible estimation of TAE embolic endpoints than conventional DSA monitoring approaches. Task 2: To test the hypothesis that DSA flow estimates are poorly reflective of tumor perfusion reduction by comparison to quantitative intra-procedural TRIP-MRI perfusion measurements.