Enhanced thermal ablation of biomaterials using HIFU energized magnetic nanoparticles

CBET 1403356 Banerjee磁性纳米颗粒（mNP）增强高强度聚焦超声（HIFU）治疗的拟议研究结果将使肿瘤和肌瘤的消融能够在较低的声强度下完成。 较低的能量水平增加了HIFU手术的可控性，并降低了不良事件（如不希望的组织损伤）的可能性。 高强度聚焦超声手术结果的更高可预测性也有可能加快FDA对高强度聚焦超声系统的审查，从而更快地将新系统推向市场。 本研究的预期结果是一种非侵入性的方法，用于组织的热消融，这是更准确和更低的成本比目前的最先进的状态。本研究的长期目标是执行高强度聚焦超声（HIFU）在降低功率水平的热消融。HIFU肿瘤消融的挑战之一是施加大量能量，使得目标位置处的细胞快速坏死-而不施加太多强度，从而发生不受控制的空化或对健康组织的附带损伤。 与加热身体深处的肿瘤相关的另一个挑战是为目标提供足够的热量，而不会使换能器表面过热并导致皮肤灼伤。 如果开发出将焦点温度提高到较低换能器功率所需的高水平的方法，则可以减轻这些挑战。本研究的目的是使用纳米颗粒增强加热在降低的功率水平下实现有效消融的目标。本研究的中心假设是纳米粒子介导的HIFU消融将允许靶区域中的热沉积增加，从而减少对更高水平的HIFU功率的需求。 在强有力的初步数据的指导下，将通过追求两个特定目标来测试该假设：1）使用注入磁性纳米颗粒（mNP）的组织模拟材料内的远程温度测量来确定沿着能量沉积分布的损伤体积。 工作假设是，（铁磁性，特别是超顺磁性颗粒）将避免大规模空化，同时增强热剂量和损伤体积，并且这些热剂量和损伤体积可以使用逆方法和有限差分方案的组合在组织模型中从一组独特配置的远程热电偶非侵入性地确定;和2）使用显微计算机断层扫描（microCT）成像和组织病理学确定mNP灌注的离体组织中的病变体积。 这里的工作假设是mNP增强的microCT信号和组织病理学数据将允许我们将热剂量、损伤体积和空化阈值与从热电偶阵列方法获得的数据进行比较。 这种用于无创估计病变体积的声-热-纳米材料研究具有创新性，因为它使用mNP诱导加热来降低HIFU热消融领域的换能器功率。 本研究的意义在于，通过纳米粒子输注进行低功率HIFU手术的能力，可以更快速和可控地获得所需的病变，从而在临床环境中更广泛地使用这种手术，并获得更好的患者结局。 本研究的预期结果是一种生物相容性、无显著毒性、加热均匀准确、成本低且比现有技术更容易应用的方法。

CBET 1403356BanerjeeResults from the proposed research on magnetic nanoparticle (mNP)-enhanced high intensity focused ultrasound (HIFU) therapy will enable ablation of tumors and fibroids to be accomplished at lower acoustic intensities. The lower energy levels increase the controllability of the HIFU procedures and reduce the likelihood of adverse events such as undesired tissue damage. The higher predictability of the HIFU surgical outcomes also has the potential to expedite FDA review of the HIFU systems, bringing new systems to market more quickly. The anticipated outcome of this study is a non-invasive method for thermal ablation of tissue that is more accurate and lower cost than the current state of the art. The long-term goal of this research is to perform High Intensity Focused Ultrasound (HIFU) thermal ablation at reduced power levels. One of the challenges in HIFU tumor ablation is to apply a large amount of energy so that cells at the target location are rapidly necrosed - without applying so much intensity that uncontrolled cavitation or collateral damage to healthy tissue occurs. Another challenge associated with heating tumors deep in the body is providing sufficient heating to the target without overheating the transducer surface and causing skin burns. These challenges can be mitigated if methods are developed to raise the focal temperature to the high levels required with a lower transducer power. The objective of this study is to achieve the goal of effective ablation at reduced power levels using nanoparticle enhanced heating. The central hypothesis of this study is that nanoparticle mediated HIFU ablation will allow increased heat deposition in the target area, thus reducing the need for higher levels of HIFU power. Guided by strong preliminary data, this hypothesis will be tested by pursuing two specific aims: 1) To determine the lesion volume along with energy deposition profile, using remote temperature measurements within a magnetic-nanoparticles (mNPs) infused tissue-mimicking material. The working hypothesis is that the ablation with mNPs (ferromagnetic and, in particular, superparamagnetic particles) will avoid large-scale cavitation while enhancing the thermal-dose and lesion volume, and these thermal doses and lesion volumes can be determined noninvasively in tissue phantoms using the combination of an inverse method and finite differencing scheme from a set of uniquely configured remote thermocouples; and 2) To ascertain the lesion volumes in mNP perfused ex-vivo tissues, using micro-computed tomography (microCT) imaging and histo-pathology. The working hypothesis here is that the mNP- enhanced microCT signal and histopathology data will permit us to compare the thermal-dose, lesion volume and cavitation threshold with data obtained from the thermocouple array method. This acoustic-thermal-nanomaterial research for non-invasive estimation of lesion volume is innovative as it uses mNP induced heating to reduce transducer power in the field of HIFU thermal ablation. The significance of this research is that, with the ability to conduct lower-power HIFU procedures with nanoparticle infusion, the desired lesion can be obtained more rapidly and con-trollably, resulting in wider use of such procedure under clinical setting with better patient outcomes. The expected outcome of this study is a method that is biocompatible, absent of significant toxicity, accurate with uniform heating, low-cost, and more easily applied than the current state of the art.