Exploration of Ultrasound-Activated Bubbles as a Switchable MRI Contrast Agent

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Micro- and nanobubbles have been used in ultrasound imaging to highlight diseased tissue, specifically tumors, to aid physicians in detecting disease. These bubbles can also be filled with therapeutic drugs, and popped using ultrasound energy when they are at the desired location. While these bubble-based contrast agents make tumors easier to see on ultrasound images, it can still be challenging to recognize anatomical structures in ultrasound images due to the relatively poor soft tissue contrast of this modality. Ultrasound imaging is also limited in penetration depth at the higher frequencies needed for imaging, which can make some applications including body imaging challenging. On the other hand, Magnetic Resonance Imaging (MRI) is able to image large organs such as the liver with exquisite contrast and complete coverage. The drawback of MRI is that its low sensitivity makes the detection of small cancerous lesions challenging, and treatment of the tumor cannot be initiated non-invasively with MRI. The goal of this project is to explore the use of ultrasound-activated nanobubbles as a switchable MRI contrast agent to enable the rapid and effective detection and treatment of metastatic disease. Here, the effect of the presence of micro- and/or nanobubbles, both with and without the application of ultrasound energy, on the MRI signal will be tested. We hypothesize that the mere presence of small bubbles will have little impact on the MRI signal, but that the MRI signal can be dramatically altered on a rapid timescale by applying ultrasound energy to the bubbles. The formulation of the bubbles will be revisited to maximize their ability to alter the surrounding magnetic field and thus affect the MRI signal, and various forms of MRI data collection will be tested to enable rapid localization of the bubbles. Note that the switchable nature of this contrast agent, which is truly unique in MRI, will have a profound impact on how the MRI data can be collected, opening the door for innovative strategies for acquiring data and generating images. This exploratory project will pave the way for testing of this novel switchable MRI contrast agent in vivo for robust detection and efficient treatment of small metastatic tumors. Note that the team includes an expert on nanobubble design for ultrasound contrast agents, an MRI physicist renowned for developing innovative data collection and image reconstruction methods, and a second MRI physicist who has both the experience in combined MRI/ultrasound and access to the tools needed to perform this work.