MRI-guided Ultrasonic Ablation of Pancreatic Cancer

描述(申请人提供)：这项研究的目标是设计、制造和初步的体外和体内测试胰腺癌的消融(破坏)系统，使用高强度超声波通过热热效应进行消融，这将使用MRTI(磁共振热成像)进行监测。胰腺癌的加热最终将通过在内窥镜超声(EUS)引导下将与MR兼容的超声输送装置(称为“敷贴器”)插入胰腺癌来完成。在将敷贴器插入胰腺癌后，患者将移除EUS内窥镜，将与MR兼容的敷贴器留在胰腺肿瘤内。这些敷贴器将由几个独立控制的高输出换能器组成，能够以3D适形方式加热胰腺癌的靶区。最终目标将是将胰腺癌的所有区域治疗到超过50摄氏度的消融温度，使用MRTI确保完全治疗，同时保留邻近结构，如肠道。在这项提案中，将在第一年进行适当设计的涂抹器的初步设计和体外测试，然后在第二年在猪模型上继续开发和测试。猪胰腺消融手术引起的急性(即刻)和慢性(长期)组织学变化将通过消融手术后切除的胰腺组织的组织学分析来评估。通过将组织学变化与胰腺治疗温度曲线相关联，正如MRTI所记录的那样，使用这些技术将可能评估有效的胰腺组织消融所需的热需求。除了MRTI用于胰腺消融的热监测外，许多先进的MR成像技术(T2加权、对比增强、磁化传递对比成像(MTC)和弥散加权成像(DWI))将用于消融手术后的胰腺成像，以确定这些技术在辨别消融后实际组织学变化方面的有效性。预计这些研究将为胰腺癌的局部消融提供一种高效、副作用极小的新技术，为胰腺癌的治愈或有效的姑息治疗提供一种全新的工具。公共卫生相关性：胰腺癌是一种常见的高度恶性的癌症，是美国癌症死亡的第四大原因，但确实没有非常好的治疗方法。我们建议开发一种图像引导的微创技术，在保留正常组织的同时完全摧毁胰腺癌。如果成功，这项技术可能会对这种目前没有有效治疗方法的毁灭性疾病提供有意义的治疗。

DESCRIPTION (provided by applicant): The goals of this study are the design, fabrication and initial in vitro and in vivo testing of a system for ablation (destruction) of pancreatic cancers, using high- intensity ultrasound to ablate via thermal heating effect, which will be monitored using MRTI (magnetic resonance thermal imaging). Heating of pancreatic cancers will ultimately be performed by insertion of MR-compatible ultrasonic delivery devices (called "applicators") into pancreatic cancers using endoscopic ultrasound (EUS) guidance. Following insertion of applicators into pancreatic cancers, patients will have the EUS endoscope removed, leaving MR-compatible applicators in place within the pancreatic tumor. These applicators will consist of several independently controlled high-output transducers capable of heating targeted regions of pancreatic cancer in a 3D conformal manner. The ultimate goal will be to treat all regions of pancreatic cancer to an ablative temperature in excess of 50 degrees centigrade, using MRTI to assure complete treatment, while sparing adjacent structures such as bowel. In this proposal, initial design and the in vitro testing of appropriately designed applicators will be performed in the first year, followed by continued development and testing in a swine model in the second year. Both acute (immediate) and chronic (longer-term) histologic changes caused by the ablative procedure in swine pancreata will be assessed by histologic analysis of resected pancreatic tissue after the ablative procedure. By correlating histologic changes with pancreatic treatment temperature profiles, as documented by MRTI, it will be possible to assess the desired thermal requirements for effective pancreatic tissue ablation using these techniques. In addition to MRTI for thermal monitoring of pancreatic ablation, a number of advanced MR imaging techniques (T2-weighted, contrast-enhanced, MTC (magnetization transfer contrast) and DWI (diffusion-weighted imaging) will be used to image the pancreas after the ablation procedure, in order to determine how effective these techniques are for discerning actual histologic changes following ablation. It is expected that these studies will result in a highly effective new technique for local ablation of pancreatic cancer with minimal side effects, providing an entirely new tool for cure or useful palliation of this disease. PUBLIC HEALTH RELEVANCE: Cancer of the pancreas is a common and highly malignant form of cancer that is the fourth leading cause of cancer death in the USA, but there are really no very good treatment methods. We propose the development of an image-guided minimally invasive technique to completely destroy pancreatic cancers while preserving normal tissues. If successful, the technique could be of great importance in providing meaningful treatment for a devastating disease for which there is no current effective treatment.