MRI-guided HIFU-mediated heating and lesion formation enhanced with phase-shift n

描述（由申请人提供）：MRI引导的HIFU介导的加热和病变形成通过相移纳米乳液增强MRI引导的高强度聚焦超声（HIFU）已显示出作为通过热机制非侵入性破坏实体瘤的方法的前景。虽然HIFU可以通过以高度的空间精度形成病变（即凝固组织）来破坏局部恶性肿瘤，但是治疗整个肿瘤可能需要数小时。这限制了MRI引导的HIFU癌症治疗的效率，并阻碍了其临床接受。已经证明，声空化（即，声驱动气泡）可以增加MRI引导的HIFU介导的组织中的加热和损伤形成的效率。我们已经开发了一种相移纳米乳液（PSNE）作为核声空化。通过优先在实体瘤中积累，PSNE将泡核定位于患病组织。PSNE可以声学地蒸发，并且所产生的气泡可以用于加速超声介导的加热，从而减少治疗大块肿瘤所需的时间。我们设计了一系列研究来评估局部气泡增强加热策略的有效性，并在实体瘤中产生可预测的病变。最后，MR成像和测温可用于监测气泡增强HIFU介导的加热，确保输送热消融所需的热剂量，并预测病变体积和位置。 公共卫生相关性：癌症是美国第二大死亡原因。本提案中概述的研究将开发使用聚焦超声局部治疗实体瘤的技术和方案，其不良副作用可忽略不计。最终，这项技术有可能减少肿瘤消退所需的治疗时间和数量，从而降低成本并改善癌症患者的护理。

DESCRIPTION (provided by applicant): MRI-guided HIFU-mediated heating and lesion formation enhanced with phase-shift nanoemulsions MRI-guided high intensity focused ultrasound (HIFU) has shown promise as a method for destroying solid tumors noninvasively through thermal mechanisms. While HIFU can destroy localized malignancies via the formation of lesions (i.e. coagulated tissue) with a high degree of spatial precision, it can take hours to treat an entire tumor. This has limited the efficiency of MRI-guided HIFU cancer therapy, and has hindered its acceptance clinically. It has been demonstrated that acoustic cavitation (i.e. acoustically-driven bubbles) can increase the efficiency of MRI-guided HIFU mediated heating and lesion formation in tissue. We have developed a phase-shift nanoemulsion (PSNE) to serve as nuclei for acoustic cavitation. By accumulating preferentially in solid tumors, the PSNE localize bubble nuclei to the diseased tissue. The PSNE can be vaporized acoustically, and the resultant bubbles can be used to accelerate ultrasound-mediated heating, thus reducing the time required for treatment of bulk tumors. We have designed a series of studies to evaluate the effectiveness of the strategy for localizing bubble-enhanced heating and producing predictable lesions in solid tumors. Finally, MR imaging and thermometry can be used to monitor bubble-enhanced HIFU-mediated heating, ensure that the required thermal dose for thermal ablation is delivered, and predict the lesion volume and location. PUBLIC HEALTH RELEVANCE: Cancer is the second leading cause of death in the United States. The research outlined in this proposal will develop technology and protocols for localized treatment of solid tumors using focused ultrasound with negligible adverse side effects. Ultimately, this technology has the potential to reduce the time and number of treatments required for tumor regression, thus reducing costs and improving cancer patient care.