Focused Ultrasound Therapy Enhanced by Microbubbles

Focused Ultrasound Therapy Enhanced by Microbubbles

Abstracts T4. ACUCI 2017 TAIPEI Special Lecture T4-14-IN01 Where Physics Meets Biology: Quantifying the Biological Effects of Combination Treatments ...

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T4. ACUCI 2017 TAIPEI Special Lecture T4-14-IN01 Where Physics Meets Biology: Quantifying the Biological Effects of Combination Treatments of Focused Ultrasound Mediated Heating and Radiotherapy Gail ter Haar, Marcia Costa Therapy Ultrasound, Division of Radiation and Imaging, The Institute of Cancer Research, London, UKT4-14-IN01 Radiotherapy (RT) is widely used for treating many cancers. While it has been shown to be very effective in many cases, and its toxicity to normal tissues has been greatly reduced by the advent of image modulated RT, the hypoxic cells that are often found in central tumour regions remain resistant to killing by ionizing radiation. It is therefore of interest to investigate a combination treatment in which focused ultrasound is used to ablate these hypoxic regions. This strategy has been used in pre-clinical studies using a subcutaneously implanted human head and neck tumour (CALR) in immunosuppressed mice. Hypoxic regions were identified immediately prior to being targeted by ultrasound using photoacoustic imaging. RT-alone treatments (at 10 Gy) resulted in a 46% treatment response rate (full tumour remission or growth inhibition within a 60 day follow upperiod). This increased to 71% for ultrasound ablation of hypoxic regions before RT, and 86% when the ultrasound followed RT. These results will be discussed, as will their implications for future combination therapies. T4-14-IN02 Focused Ultrasound Therapy Enhanced by Microbubbles Kullervo Hynynen,1,2,3 Ryan M. Jones,1,2 Christopher N. Acconcia,1,2 Mark Santos,1,2 Meaghan A. O’Reilly,1,2 David Goertz1,2 1 Sunnybrook Research Institute, Toronto, Ontario, Canada, 2Department of Medical Biophysics, University of Toronto, 3Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada MRI guided focused ultrasound provides a completely noninvasive method for delivering energy deep in the body. This has been successfully exploited for thermal ablation of tissues and for locally enhanced drug delivery. The focal thermal ablation shows great promise in replacing many invasive surgeries with completely noninvasive procedure with much faster recovery time and reduced complications. However, treatments are relatively slow and acceleration would make these treatments clinically more acceptable. Animal research demonstrated that significant enhancement in the ablation efficiency can be achieved using microbubbles. Similarly, microbubbles enhance local drug delivery. However, the use of microbubbles carries a risk for bleeding and therefore exposures need to be controlled. We have used acoustic emissions from the bubble to control these exposures such that safe and reliable enhancement of ablation or drug delivery can be achieved. In this talk we will review our experience with bubble enhanced heating and drug delivery. T4-14-IN03 Microscale Ultrasonic Bioeffects and Their Biomedical Implications Hairong Zheng, PhD Paul C. Lauterbur Research Center for Biomedical Imaging, Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences E-mail: [email protected]


The gas-filled microbubbles oscillate and vibrate when a sonic energy field is applied and may reflect ultrasound waves. The intense radial oscillation of microbubbles makes them several thousand times more reflective than normal body tissues and emits significantly stronger acoustic signal. The unique acoustic property of microbubbles can be used as sensitive acoustic probes in molecular imaging when conjugated with certain a ligand or antibody. Moreover, due to the large surface area, microbubbles are wonderful tool as gene and drug carriers. More importantly, the bubbles were easily destroyed by ultrasound exposure, making it possible deliver drugs or genes to specific tissues by ultrasound-targeted microbubble destruction. All of these properties make microbubbles of many powerful emerging applications, such as molecular imaging, drug delivery and therapy. In this talk, we will present the current progresses on ultrasonic microbubbles as an ideal tool for ultrasound molecular imaging and ultrasound-mediated drug delivery. Moreover, precise transportation microbubbles and single cell to any specified location with MEMS technique by acoustic radiation force will also be discussed. T4-14-IN04 Therapeutic Applications of Microbubbles with Nanoparticle Encapsulation Pai-Chi Li Institute of Biomedical Electronics and Bioinformatics Department of Electrical Engineering, National Taiwan University E-mail: [email protected] New developments in imaging physics have found promising biomedical applications. One example is the combination of ultrasound and photoacoustics that has demonstrated new opportunities in both imaging and therapeutic applications with functionalized microbubbles playing a pivotal role. The microbubbles typically used in ultrasonic imaging as the contrast agent present unique mechanical properties and the associated acoustic cavitation has been exploited for therapeutic purposes. Similarly, gold nanoparticles (AuNPs) are found to be a good contrast agent for photoacoustic imaging for its bioconjugation capabilities. The efficient light absorption of AuNPs and abilities to tune their optical properties have also led to new photothermal therapy methods. New development in combined diagnosis with therapy for both modalities have also been introduced. AuNPs encapsulated with microbubbles (AuMBs) have been introduced as a photoacoustic and ultrasound dual-modality contrast agent. Applications can be extended to theranosis purpose. In a previous study, an enhanced delivery method of AuNPs is proposed by using microbubbles as a targeted carrier and by inducing acoustic cavitation to enhance permeability. At least 10 times improvement in AuNP delivery and twenty degrees of temperature elevation were achieved. An optical microscope which collects the two photon fluorescence emitted by AuNPs further confirms the enhanced delivery. Finally, in vivo delivery of AuNPs was demonstrated with laser-induced thermotherapy that showed hyperthermia (.45 C) with sonoporation. Therefore, controlled release of AuNPs is feasible with acoustic cavitation and the procedure can further improve therapeutic effects of the AuNPs. Such functionalized microbubbles can also be used by exploiting the radiosensitization effect of gold nanoparticles (AuNPs) to enhance the cell-killing of ionization on tumor cells. In our research, we utilized AuMBs together with ultrasound as a radiosensitizer. Pre-radiotherapy cavitation carried out by acoustic stimulation increased the permeability of cell membrane and intracellular uptake of AuNPs. Simultaneous measurement of cavitation during ultrasound treatment also confirmed the production of cavitation. After combined treatment of AuMBs and ultrasound, Huh7 cells, a notoriously radioresistant cancer cells, was exposed to various dose of irradiation by a 6-MV linear accelerator. Cologenic