A multifunctional theranostic ultrasound platform for remote magnetogenetics and expanded blood-brain barrier opening

作者：Alec J. Batts, Fotios N. Tsitsos, Jeannette Ingabire, Guillaume Duret, Samantha Gorman, Deny Tsakri, Rebecca L. Noel, Robin Ji, Nancy Kwon, Quoc-Khanh Pham, Linlin Zhang, Gang Bao, Jacob T. Robinson, Elisa E. Konofagou · 发表于：Brain stimulation · 年份：2025 · DOI：10.1016/j.brs.2025.10.006 · 被引用次数：4 · 研究领域：Ultrasound and Hyperthermia Applications、Nanoparticle-Based Drug Delivery、Ultrasound and Cavitation Phenomena

INTRODUCTION: Brain stimulation techniques are critical for unraveling the innerworkings of complex neuronal pathways governing both normal physiological function and pathologic states in neurological disorders. Focused ultrasound (FUS) is an emerging technique poised to significantly alter central nervous system (CNS) drug delivery and neuroscience research through non-invasive means. Magnetogenetics is a brain stimulation technique which may benefit from FUS technology in that alternating magnetic fields (AMF), like FUS, can pass through the skull without requiring surgery. METHODOLOGY: Magnetogenetics involves the deposition of superparamagnetic iron-oxide nanoparticles (SPIONs) and overexpression of thermoreceptor transmembrane proteins (e.g. TRPV1 and TRPA1) in the brain. When an external AMF is applied, SPIONs generate local heating, which can activate thermoreceptors, depolarize the cell membrane and trigger action potentials in neurons. Monitoring neuronal activation by a magnetogenetics approach can be facilitated by the co-expression of genetically-encoded voltage indicators (GEVI), which enable fluorescence-based detection of membrane depolarization. However, traditional surgical methods used to introduce these components into the brain are invasive and highly focal, precluding investigation of brain-wide neuronal pathways. RESULTS: Here, we demonstrate that our recently developed, flexible configuration for FUS therapy and ultrasound imaging, called theranostic ul...