Predicting Radiation Liver Injury Using MRI Perfusion

描述（由申请人提供）：大约三分之二的肝内癌患者存在不可切除的疾病。我们的研究表明，高剂量适形放疗联合化疗似乎可以延长不能切除的肝内癌患者的生存期。然而，进一步增加辐射剂量的尝试受到辐射诱导的肝病（RILD）的发展的限制。RILD的病理是静脉闭塞性疾病。过去，开发模型以估计发生RILD的可能性的努力主要基于正常肝脏的计划辐射剂量分布。这些分析表明，平均肝脏剂量增加与发生RILD的可能性相关。虽然这些模型允许安全输送比以前可能的辐射剂量高得多的辐射剂量，但它们也表明，单独基于物理剂量分布进行的预测并不能反映出个体患者的敏感性。如果在治疗前或治疗过程中能够更好地估计个体患者的敏感性，则可以将更高剂量的辐射安全地输送到肝脏相对耐辐射的患者的肿瘤，从而提高存活率而不增加并发症。由于RILD的基本病理生理学是静脉闭塞，因此我们提出了一个假设，即静脉灌注的早期监测有可能选择在症状性辐射诱导损伤发作之前具有灌注变化临床前体征的患者。为了响应NIH/NCI PAR-05-114，我们建议开发一个灌注模型，该模型允许我们根据放射治疗计划和放射治疗前和放射治疗期间的灌注值，预测放射治疗完成后解剖学分布的肝脏灌注变化。此外，我们比较了肝脏灌注估计动态对比增强MRI与吲哚菁绿色测量的标准肝功能指数。我们提出的方法是高度创新的，代表了一个新的范式，以调查在肝脏中的辐射毒性。它有可能评估和预测个人对辐射的敏感性。如果这项快速试验成功，我们可以将这项研究过渡到一项为期五年的研究。最终，我们可以使用这个灌注和剂量模型来指导个体放射治疗干预。我们以往的研究表明，高剂量适形放疗联合化疗似乎可以延长不能切除的肝内癌患者的生存期。然而，进一步增加辐射剂量的尝试受到辐射诱导的肝损伤的限制。我们的长期目标是发展一种新的影像学方法来预测放射性肝损伤。因此，对于耐受性较好的患者，可以安全地给予较高剂量的放射治疗，从而提高生存率。

DESCRIPTION (provided by applicant): Approximately two thirds of patients with intrahepatic cancer present with unresectable disease. Our studies show that high dose conformal radiation combined with chemotherapy appears to prolong the survival of patients with unresectable intrahepatic cancers. However, attempts to increase radiation dose still further have been limited by the development of radiation-induced liver disease (RILD). The pathology of RILD is veno-occlusive disease. In the past, efforts to develop models to estimate the likelihood of developing RILD have been based primarily on the planned radiation dose distribution for the normal liver. These analyses have demonstrated that increasing mean liver dose correlates with the likelihood of developing RILD. While these models have permitted the safe delivery of far higher doses of radiation than have previously been possible, they also suggest that there is a broad range of individual patient sensitivity that is not reflected by predictions made solely based on the physical dose distribution. If individual patient sensitivity could be better estimated before or during a course of treatment, it would permit higher doses of radiation to be delivered safely to the tumors of patients whose liver is relatively radiation resistant, thus improving survival without increasing complications. As the basic pathophysiology of RILD is venous occlusion, we develop the hypothesis that early monitoring of venous perfusion would have the potential to select patients with pre-clinical signs of perfusion changes prior to the onset of symptomatic radiation-induced injury. In response to NIH/NCI PAR-05-114, we propose to develop a perfusion model that allows us to predict anatomically distributed liver perfusion changes after the completion of radiation therapy based upon the radiation treatment plan and the values of perfusion prior to and during radiation therapy. Also, we compare the liver perfusion estimated by dynamic contrast enhanced MRI with a standard liver function index measured by Indocyanine green. Our proposed approach is highly innovative and represents a new paradigm to investigate radiation toxicity in the liver. It has potential to assess and predict individual sensitivity to radiation. If this quick trial is successful, we can transition this study into a five-years study. Eventually, we could use this perfusion and dose model to guide individual radiation therapy intervention. Our previous studies show that high dose conformal radiation combined with chemotherapy appears to prolong the survival of patients with unresectable intrahepatic cancers. However, attempts to increase radiation dose still further have been limited by radiation-induced liver injury. Our long term goal is to develop a new imaging approach for prediction of radiation-induced syptomatic liver injury. Therefore, higher dose of radiaton can be safely delivered to tumor in patients who can be better tolenrent to radiation, thereby improving survival.