MRI-guided Ultrasonic Ablation of Pancreatic Cancer

描述（由申请方提供）：本研究的目的是设计、制造和初步体外和体内测试胰腺癌消融（破坏）系统，使用高强度超声通过热效应进行消融，并使用MRTI（磁共振热成像）进行监测。胰腺癌的加热最终将通过使用内窥镜超声（EUS）引导将MR兼容的超声递送装置（称为“施用器”）插入胰腺癌中来执行。将施源器插入胰腺癌后，患者将取出EUS内窥镜，将MR兼容施源器留在胰腺肿瘤内。这些施源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域。最终目标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。在本提案中，将在第一年对适当设计的施源器进行初始设计和体外试验，然后在第二年继续在猪模型中进行开发和试验。将通过对消融术后切除的胰腺组织进行组织学分析，评估由消融术在猪胰腺中引起的急性（即刻）和慢性（长期）组织学变化。通过将组织学变化与胰腺治疗温度曲线相关联（如MRTI所记录），可以评估使用这些技术进行有效胰腺组织消融所需的热要求。除了用于胰腺消融热监测的MRI外，还将使用许多先进的MR成像技术（T2加权、对比增强、MTC（磁化传递对比）和DWI（弥散加权成像））对消融术后的胰腺进行成像，以确定这些技术在识别消融后实际组织学变化方面的有效性。预计这些研究将产生一种非常有效的胰腺癌局部消融新技术，副作用最小，为治愈或有效缓解这种疾病提供了一种全新的工具。公共卫生相关性：胰腺癌是一种常见且高度恶性的癌症，是美国癌症死亡的第四大原因，但确实没有很好的治疗方法。我们建议开发一种图像引导的微创技术，以完全破坏胰腺癌，同时保留正常组织。如果成功的话，这项技术可能在为目前没有有效治疗方法的毁灭性疾病提供有意义的治疗方面非常重要。

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.