Novel MRI Contrast Agent for Monitoring Thermal Ablation

描述（申请人提供）：手术切除已被证明是治疗继发性肝脏肿瘤的有效方法，5年生存率在20-30%之间。不幸的是，只有经过筛选的患者才适合切除，而且其并发症发生率相对较高。约35%的患者有轻微并发症，15%的患者有较严重的并发症，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。微创热凝肝肿瘤的方法消除了这些缺点，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，这项技术有望进入广泛应用。大大提高这些治疗的安全性和有效性的一种方法是，有一种方法可以轻松可靠地在线量化已经达到足够热暴露以诱导热凝固的组织。我们的假设是，一种新型的磁共振成像（MRI）造影剂在阈值温度水平下被激活，可用于可靠地成功监测肝脏肿瘤的热消融。这种药剂由包裹在脂质体外壳中的顺磁性物质组成。当被封装时，材料对MR信号强度的影响很小。脂质体外壳在可精确选择的温度（Tc）下经历相变，并发生磁共振信号增强，这可以用标准成像方法轻松检测到。Tc为57°C，这是加热至少几秒钟后热凝固的近似阈值，因此信号强度增强表明热烧蚀区域。由于热凝后灌注停止，任何释放的顺磁剂将在组织中停留较长时间，清楚地标志着消融的进展。我们对这种药物的体内初步试验已经证明了它的基本功能。在这里，我们建议在体内进行动物实验，以广泛表征其性能，并测试其在监测肝脏肿瘤热消融方面的有效性。这项研究将导致更有效、更安全的肝脏热消融治疗，并可能使更困难的病例可以用热消融方法治疗，因为它将提供直接、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.