Transcatheter Intra-arterial Perfusion MRI Monitoring of Liver Tumor Embolization

描述（由申请人提供）：该提案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。这些患者通常接受经导管动脉栓塞（TAE）作为姑息治疗的一种形式。TAE目前使用X射线DSA进行，以估计每次注射栓塞材料后的血流减少。然而，DSA流量估计可能是高度主观的，并且对肿瘤灌注的反映较差。本提案的目的是开发一种新的磁共振成像（MRI）技术，用于在TAE手术期间迭代监测肝脏肿瘤灌注。申报的经导管动脉内灌注MRI（TRIP-MRI）技术提供了在混合DSA/MRI手术套件中监测TAE手术期间灌注变化的可能性。对于TRIP-MRI，通过TAE导管直接输注小剂量造影剂，允许迭代药代动力学测量，以估计每次注射栓塞材料后的灌注变化。必须解决技术挑战，以允许连续定量TRIP-MRI测量，并需要进一步的研究，以验证TRIP-MRI测量相比，侵入性金标准方法。拟定研究将在肝肿瘤动物模型（目的1和2）和肝细胞癌临床患者（目的3）中解决以下特定目的：特定目的1：TRIP-MRI方法学的技术开发任务1：检验动脉内注射允许定量估计造影剂药代动力学而无需直接测量远端肝动脉内的动脉输入功能的假设。任务二：旨在检验TRIP-MRI造影剂剂量可在术中优化以允许较短的洗脱时间和测量重复间隔有利于TAE监测的假设。具体目标二：TRIP-MRI测量的定量验证任务1：检验TRIP-MRI测量可以准确量化肝肿瘤栓塞期间术中灌注减少的假设。任务二：旨在检验术中TRIP-MRI测量可准确预测术后导管撤回后肿瘤灌注的最终分数降低的假设。具体目标3：TRIP-MRI和DSA灌注栓塞终点的临床比较任务1：检验以下假设：定量TRIP-MRI灌注测量提供了比传统DSA监测方法更可重现的TAE栓塞终点估计。任务二：通过与定量术中TRIP-MRI灌注测量值相比，检验DSA流量估计值对肿瘤灌注减少的反映不佳的假设。

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.