Project Summary/Abstract Fatal or impairing neurological diseases, including movement disorders, brain cancers, psychological disorders, epilepsies, malformations, and memory disorders, impose heavy burdens on both individuals and society at large. Transcranial magnetic resonance guided focused ultrasound surgery (tMRgFUS) is an extremely promising, minimally invasive treatment modality for neurological diseases whereby sound waves are focused to a specific region of the brain. Because it is noninvasive, the efficacy of tMRgFUS procedure heavily relies on the accuracy and information content of the guidance technology. This study proposes to improve the treatment efficacy of nearly all tMRgFUS surgeries by eliminating a ubiquitous impediment to accurate and information-rich guidance MRI: the acoustic coupling medium. Interactions between the coupling media and guidance imaging impede tMRgFUS efficacy and translation. For example, while FDA-approved tMRgFUS treatments for essential tremor and Parkinson’s disease can rely on real-time patient feedback to compensate for errors in guidance MR imaging, other tMRgFUS indications cannot access patient feedback because either the patient is unconscious, or the consequences of treatment errors appear only days later. In these cases, guidance imaging errors imposed by the coupling bath cannot be compensated and degrade treatment efficacy To meet this need, our study proposes a dilute, iron-based coupling media (IBCM) that will eliminate coupling- media-induced errors in MRI guidance imaging while maintaining the coupling and cooling functionality critical to acoustic transmission. The specific aims of the study are as follows. Aim 1: Develop novel surface–modified iron oxide nanoparticles for an IBCM. Dilute, aqueous, surface- modified iron oxide nanoparticles can accelerate MRI signal decay such that, during image acquisition, a coupling medium will contribute negligible effects to guidance imaging. However, aqueous nanoparticles also agglomerate and seed treatment-impeding cavitation nucleation in the prefocal acoustic field. This aim will develop novel surface-modified particles that, upon suspension, accelerate MRI signal decay without promoting prefocal nucleation. Aim 2: Investigate the effects of IBCM suspension fluid properties on cavitation nucleation. Fluid properties play a critical role in particle suspension, acoustic coupling, subject cooling, and cavitation nucleation. This aim will investigate cavitation nucleation within the IBCM and how suspension fluid properties, such as pH, temperature, gas content, and flow state, can modify or suppress the nucleation process while maintaining suspension, coupling, and cooling capabilities. Aim 3: Enhance MRI guidance for tMRgFUS through the use of an IBCM. This aim will quantify the value of the IBCM designed in Aims 1 and 2 for tMRgFUS by measuring image quality metrics derived from guidance MRI scans of human subjects. This aim will also develop novel MRI guidance techniques that were previously rendered impossible due to severe image corruptions imposed by the acoustic coupling medium. The resulting IBCM will improve image quality for nearly all guidance techniques employed during, or undergoing development for, tMRgFUS, by rendering the acoustic coupling medium invisible to the MRI scanner without sacrificing necessary acoustic coupling and cooling functionality.

Project Narrative Fatal or impairing neurological diseases, including movement disorders, brain cancers, psychological disorders, epilepsies, malformations, and memory disorders, impose heavy burdens on both individuals and society at large. Transcranial magnetic resonance guided focused ultrasound surgery (tMRgFUS) is an extremely promising, minimally invasive treatment modality for neurological diseases whereby sound waves are focused to a specific region of the brain and elicit a number of beneficial effects such as heating, immune-modulation, neuromodulation, and blood-brain-barrier disruption. Our experience has identified an opportunity to improve the treatment efficacy of tMRgFUS by resolving a ubiquitous impediment to accurate and information-rich guidance imaging: the acoustic coupling medium. This study will develop and validate a new acoustic coupling medium that promotes more accurate and information-rich guidance during tMRgFUS.