Integration of non-invasive deep tissue microwave thermometry in the VectRx hyperthermia device in a transgenic liver tumor pig model

项目总结/摘要 NeoTherma Oncology（NTO/www.example.com）开发了一种新型非侵入性医疗设备 局部提供轻度高温（HT）作为标准治疗的辅助治疗， 腹部深部肿瘤VectRx ™设备被FDA命名为“突破性”， 在临床前研究中证明了其能够安全地加热腹部器官（胰腺、肝脏、肾脏、脾脏） 健康的猪FDA根据这些数据批准了VectRx的研究器械豁免， 缺乏有效的胰腺癌大型动物肿瘤模型。NTO已在人类早期启动了第一个 在马里兰州医学中心进行的可行性研究（EFS），以收集初始安全性和性能 胰腺癌患者的数据。 在EFS的同时，NTO将与科罗拉多大学博尔德分校的研究人员合作， 微波温度计（MT）可用于非侵入性地测量深部组织中的温度。 这一发展是基于检测黑体辐射与温度成正比的能力， 在从皮肤到深层器官的不同组织深度发射。MT的成功整合将有效地 提高VectRx的临床效用。这将解决有限的可用性、访问、高 成本、后勤问题和对专业人员的依赖，如磁共振 温度测定法一系列MT和辐射计将被设计、制造并集成到VectRx中， 潜在的VectRx线圈调整，以1）实现有源和无源MT的兼容设计， 在VectRx内（打开和关闭）; 2）管理MT的任何潜在发热、线圈失谐、电场和H场模式 VectRx操作期间的完整性。在共同开发和优化之后，MT的性能将 在肝细胞癌（HCC）Oncopig模型中建立，精确度目标为1.5 ° C。HCC是一个 生存率低的疾病，只有一小部分（15%）新诊断的患者有资格接受 由于诊断较晚，治疗效果不佳。该模型适用于NTO的深层指示管线 腹部肿瘤，NTO之前已经完成了VectRx设备的安装， 与伊利诺伊大学的兽医团队在3只HCC Oncopigs中进行了初步工作，以优化超声- 引导手术放置光纤探头，用于关联MT测量的温度。 尽管温和HT的好处是众所周知的，但由于技术原因，它在美国尚未被广泛采用。 目前的技术局限于解决深部、难以加热的肿瘤以及缺乏测温。在这 第一阶段项目，我们将证明，这些关键的缺陷可以克服，通过整合新的 微波温度技术与VectRx，提供了先进的创新示范 大型动物肿瘤模型中深部组织HT的温度监测。

Project Summary/Abstract NeoTherma Oncology (NTO/www.neothermaoncology.com) has developed a novel non-invasive medical device that delivers mild hyperthermia (HT) loco-regionally as adjuvant therapy to standard of care treatment of abdominal deep-seated tumors. The VectRx™ device, designated “Breakthrough” by the FDA, has demonstrated its ability to safely heat abdominal organs (pancreas, liver, kidney, spleen) in pre-clinical studies in healthy swine. FDA approved an investigational device exemption for VectRx on the basis of these data and the lack of a validated large animal tumor model for pancreatic cancer. NTO has initiated a First in Human early feasibility study (EFS) study at the University of Maryland Medical Center to collect initial safety and performance data in pancreatic cancer patients. In parallel to the EFS, NTO will collaborate with University of Colorado-Boulder researchers who have developed a microwave thermometer (MT) that could be utilized to non-invasively measure temperatures in deep tissue. This development is based on the ability to detect the black body radiation proportional to temperature that is emitted at different tissue depths from skin to deep organ. Successful integration of the MTs will effectively improve the clinical utility of VectRx. This will address challenges posed by the limited availability, access, high cost, logistical concerns and reliance on specialized personnel, as is the case with magnetic resonance thermometry. A series of MTs and a radiometer will be designed, fabricated, and integrated into VectRx with potential VectRx coil adjustments to 1) achieve compatible designs of active and passive MTs with operation within VectRx (on and off); 2) manage any potential heating of the MTs, coil detuning, E-field and H-field pattern integrity during VectRx operation. Following co-development and optimization, the MTs’s performance will be established in a hepatocellular carcinoma (HCC) Oncopig model with an accuracy goal of 1.5°C. HCC is a disease with low survival rates and only a small fraction (15%) of newly diagnosed patients are eligible for curative treatments due to late diagnosis. The model is relevant to NTO’s indication pipeline of deep-seated abdominal tumors, and NTO has previously completed installation of the VectRx device and performed preliminary work in 3 HCC Oncopigs with the veterinary team at the University of Illinois to optimize ultrasound- guided surgical placement of fiberoptic probes that will be used to correlate temperatures measured by the MTs. Despite the known benefits of mild HT, it has not been widely adopted in the US because of the technical limitations of current technologies to address deep, hard to heat tumors and the lack of thermometry. In this Phase I project, we will demonstrate that these critical deficiencies can be overcome through integration of novel microwave-based temperature techniques with VectRx, providing an innovative demonstration of advanced temperature monitoring of HT in deep tissue in a large animal tumor model.