Novel MRI Contrast Agent for Monitoring Thermal Ablation

描述（由申请人提供）：手术切除已被证明是继发性肝脏肿瘤的有效治疗方法，5年生存率在20- 30%之间。不幸的是，只有精选的患者是切除的候选人，它有一个相对较高的并发症发生率。约35%的患者出现轻微并发症，15%出现更严重的并发症，死亡率为2- 5%。此外，即使没有并发症，平均住院时间也在两周左右。微创热凝固肝肿瘤的方法已经消除了这些缺点中的一些，并已被证明是一种有效的替代治疗方法。接受这种热消融治疗的患者数量正在迅速增长，这项技术有望得到广泛应用。一种显著提高这些治疗的安全性和有效性的方法将是具有一种方法来容易地且可靠地在线量化已经达到足以引起热凝固的热暴露的组织。我们的假设是，在阈值温度水平下激活的新型磁共振成像（MRI）造影剂可用于可靠地成功监测肝肿瘤的热消融。该试剂由包封在脂质体壳中的顺磁性材料组成。当封装时，材料对MR信号强度的影响最小。脂质体壳在可以精确选择的温度（Tc）下经历相变，并且发生MR信号增强，这可以用标准成像方法容易地检测到。Tc为57？C，其是用于加热至少几秒的热凝固的近似阈值，因此信号强度增强指示被热消融的区域。由于灌注在热凝固后停止，因此任何释放的顺磁剂将在组织中保留较长时间，清楚地标记消融进展。我们对该制剂的初步体内试验已证实其基本功能。在这里，我们提出了在体内动物实验，以广泛表征其性能，并测试其有效性，在监测热消融肝肿瘤。这项研究将导致更有效和更安全的肝脏热消融治疗，并可能允许更困难的病例采用热消融方法进行可行的治疗，因为它将提供直接和可靠的治疗进展在线反馈。

DESCRIPTION (provided by applicant): Surgical resection has been shown to be an effective treatment for secondary liver tumors, with five-year survival rates between 20-30%. Unfortunately, only select patients are candidates for resection, and it has a relatively high complication rate. About 35% of patients suffer minor complications, 15% have more serious complications, and the mortality rate is 2-5%. In addition, the average hospital stay is about two weeks, even without complications. Minimally invasive methods to thermally coagulate liver tumors have eliminated some of these disadvantages and have been shown to be an effective alternative treatment. The number of patients who receive such thermal ablation treatments is growing rapidly, and this technology is poised to enter widespread use. A way to substantially improve the safety and effectiveness of these treatments would be to have a method to easily and reliably quantify the tissue online that has reached a sufficient thermal exposure to induce thermal coagulation. Our hypothesis is that a novel magnetic resonance imaging (MRI) contrast agent that is activated at a threshold temperature level can be used to reliably successfully monitor thermal ablation of liver tumors. This agent consists of paramagnetic material encapsulated in a liposome shell. When encapsulated, the material has a minimal effect on the MR signal intensity. The liposome shell undergoes a phase transition at a temperature (Tc) that can be precisely chosen, and MR signal enhancement occurs which can be easily detected with standard imaging methods. With a Tc of 57¿C, which is the approximate threshold for thermal coagulation for heating of at least a few seconds, the signal intensity enhancement thus indicates the regions that are thermally ablated. Since perfusion is halted after thermal coagulation, any released paramagnetic agent will remain in the tissue for an extended period of time, clearly marking the ablation progression. Our preliminary tests of this agent in vivo have demonstrated its basic functionally. Here, we propose in vivo animal experiments to extensively characterize its performance and to test its effectiveness in monitoring thermal ablation of liver tumors. This research will lead to more effective and safer thermal ablation treatments in liver, and perhaps allow more difficult cases to be feasibly treated with thermal ablation methods, since it would provide straightforward and reliable online feedback of the treatment progression.