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Transcranial focused ultrasound stimulation (tFUS) is an effective noninvasive treatment modality for brain disorders with high clinical potential. However, the therapeutic effects of ultrasound neuromodulation are not widely explored due to limitations in preclinical systems. The current preclinical studies are head‐fixed, anesthesia‐dependent, and acute, limiting clinical translatability. Here, this work reports a general‐purpose ultrasound neuromodulation system for chronic, closed‐loop preclinical studies in freely behaving rodents. This work uses microelectromechanical systems (MEMS) technology to design and fabricate a small and lightweight transducer capable of artifact‐free stimulation and simultaneous neural recording. Using the general‐purpose system, it can be observed that state‐dependent ultrasound neuromodulation of the prefrontal cortex increases rapid eye movement (REM) sleep and protects spatial working memory to REM sleep deprivation. The system will allow explorative studies in brain disease therapeutics and neuromodulation using ultrasound stimulation for widespread clinical adoption. [ABSTRACT FROM AUTHOR]

• An MR-compatible system for mice MRI was fabricated via optimization of ultrasound transducer components. • EPI was conducted concurrently with ultrasound sonication using a 9.4 T high resolution MRI scanner. • Visualization of ultrasound-induced heat effects was shown as local EPI signal changes at the beam focus. Visualization of focused ultrasound in high spatial and temporal resolution is crucial for accurately and precisely targeting brain regions noninvasively. Magnetic resonance imaging (MRI) is the most widely used noninvasive tool for whole-brain imaging. However, focused ultrasound studies employing high-resolution (> 9.4 T) MRI in small animals are limited by the small size of the radiofrequency (RF) volume coil and the noise sensitivity of the image to external systems such as bulky ultrasound transducers. This technical note reports a miniaturized ultrasound transducer system packaged directly above a mouse brain for monitoring ultrasound-induced effects using high-resolution 9.4 T MRI. Our miniaturized system integrates MR-compatible materials with electromagnetic (EM) noise reduction techniques to demonstrate echo-planar imaging (EPI) signal changes in the mouse brain at various ultrasound acoustic intensities. The proposed ultrasound-MRI system will enable extensive research in the expanding field of ultrasound therapeutics. [ABSTRACT FROM AUTHOR]