Responsive Nanoparticles to Enable a Focused Ultrasound-Stimulated Magnetic Resonance Imaging Spotlight.

Magnetic resonance imaging (MRI)-guided high-intensity focused ultrasound (HIFU) has been applied as a therapeutic tool in the clinic, and enhanced MRI contrast for depiction of target tissues will improve the precision and applicability of HIFU therapy. This work presents a "spotlight MRI" contrast enhancement technique, which combines four essential components: periodic HIFU stimulation, strong modulation of T1 caused by HIFU, rapid MRI signal collection, and spotlight MRI spectral signal processing. The T1 modulation is enabled by a HIFU-responsive nanomaterial based on mesoporous silica nanoparticles with Pluronic polymers (Poloxamers) and MRI contrast agents attached. With periodic HIFU stimulation in a precisely defined region containing the nanomaterial, strong periodic MRI T1-weighted signal changes are generated. Rapid MRI signal collection of the periodic signal changes is realized by a rapid dynamic 3D MRI technique, and spotlight MRI spectral signal processing creates modulation enhancement maps (MEM) that suppress background signal and spotlight the spatial location with nanomaterials experiencing HIFU stimulation. In particular, a framework is presented to analyze the trade-offs between different parameter choices for the signal processing method. The optimal parameter choices under a specific experimental setting achieved MRI contrast enhancement of more than 2 orders of magnitude at the HIFU focal point, compared to controls.