Thermoresponsive Polymer-Modified SiO ₂ /Gadolinium-Diethylenetriamine Pentaacetic Acid Composite Nanoparticles for Magnetic Resonance Imaging-Guided Ultrasound-Modulated Contrast Enhancement at Human Body Temperatures

Magnetic Resonance Imaging (MRI) routinely uses contrast agents such as paramagnetic molecules to enhance T 1 -weighted images. In addition to imaging, MRI-guided high-intensity focused ultrasound (HIFU) has therapeutic applications such as identifying, heating, and ablating diseased tissue. We have shown that HIFU can also be used to enhance MR image contrast in a region of interest (i.e., create a “spotlight”) by modulating the HIFU intensity to interact with polymer-coated mesoporous silica nanoparticles (MSN) in the focused beam at around 32 °C. The polymer coating affects water access to an MRI contrast agent on the nanoparticle, and the modulated T 1 relaxation increases the signal-to-noise ratio of the region near the nanoparticle resulting in an amplified image contrast. In this article, we report the synthesis of a phase-change polymer, poly(2-oxazoline) (POx), with a lower critical solution temperature (LCST) of 40 °C when attached to a nanoparticle. The nanoparticle responds to HIFU-modulated temperature changes of ∼ 3 °C. MRI data acquisition is relatively fast (maximum of 100 s). The MRI contrast enhancement in the spotlighted region on the modulation enhancement map (MEM) compared to background increases 139-fold with the designed nanoparticle and HIFU modulation with respect to baseline T 1 -weighted MRI, and the enhancement fold of the designed nanoparticle is higher than that of a standard contrast agent or control nanoparticles. This nanoparticle-based amplification via HIFU, tuned to maximize the MRI contrast at body temperature, has the potential for increasing the precision of spotlighting fine features, such as small tumors and tumor margins, for disease management.