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

描述（由申请人提供）：mri引导的高强度聚焦超声（HIFU）作为一种通过热机制无创破坏实体肿瘤的方法，已经显示出前景。虽然HIFU可以通过形成病变（即凝固组织）以高度的空间精度摧毁局部恶性肿瘤，但它可能需要数小时才能治疗整个肿瘤。这限制了mri引导下HIFU治疗癌症的效率，并阻碍了其在临床上的接受。已经证明，声空化（即声驱动气泡）可以提高mri引导下HIFU介导的加热和组织中病变形成的效率。我们开发了一种相移纳米乳（PSNE）作为声空化的核。通过在实体肿瘤中优先积累，PSNE将泡核定位到病变组织。PSNE可以在声学上汽化，产生的气泡可以用来加速超声介导的加热，从而减少治疗大块肿瘤所需的时间。我们设计了一系列的研究来评估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，确保提供热消融所需的热剂量，并预测病变体积和位置。

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.