Predicting Radiation Liver Injury Using MRI Perfusion

描述(申请人提供)：大约三分之二的肝内癌患者存在无法切除的疾病。我们的研究表明，大剂量适形放射联合化疗似乎可以延长不能切除的肝癌患者的生存时间。然而，由于放射性肝病(RILD)的发展，进一步增加辐射剂量的尝试受到了限制。RILD的病理为静脉闭塞型疾病。在过去，开发模型来估计发生RILD的可能性的努力主要是基于正常肝脏的计划辐射剂量分布。这些分析表明，增加平均肝脏剂量与发生RILD的可能性相关。虽然这些模型允许安全地提供比以前可能的高得多的辐射剂量，但它们也表明，仅基于物理剂量分布做出的预测没有反映出广泛的个体患者敏感性。如果能在治疗前或疗程中更好地评估患者个体的敏感性，这将允许将更高剂量的辐射安全地传递到肝脏相对耐辐射的患者的肿瘤，从而在不增加并发症的情况下提高存活率。由于RILD的基本病理生理学基础是静脉闭塞，我们提出的假设是，早期监测静脉血流灌注将有可能在症状性放射损伤开始之前选择具有临床前血流灌注变化迹象的患者。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期间的灌注值来预测放射治疗完成后肝脏血流灌注的解剖分布变化。此外，我们还比较了动态增强MRI评估的肝脏灌注量与吲哚青绿测量的标准肝功能指数。我们提出的方法是高度创新的，代表了一种研究肝脏辐射毒性的新范式。它具有评估和预测个体对辐射的敏感性的潜力。如果这一快速试验成功，我们可以将这项研究转变为为期五年的研究。最终，我们可以使用这个灌流和剂量模型来指导个体化放射治疗干预。我们以前的研究表明，大剂量适形放射联合化疗似乎可以延长不能切除的肝癌患者的生存时间。然而，进一步增加辐射剂量的尝试受到辐射引起的肝损伤的限制。我们的长期目标是开发一种新的影像方法来预测辐射诱导的症状性肝损伤。因此，高剂量的放射可以安全地输送到患者的肿瘤，这些患者可以更好地耐受辐射，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.