Results 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.
