This study tested the viability of using MRI-guided transcranial focused ultrasound (MRgFUS) to modify the interstitial space in the living brain. As a non-invasive technique, success in generating spatially controlled, non-destructive changes could lead to clinical applications such as enhancing delivery of therapeutics and altering fluid and pressure dynamics. The research involved the use of computer simulations for treatment planning and MRI acoustic radiation force impulse imaging for target validation. Additionally, Evans blue dye or nanoparticle probes were utilized to assess changes in the interstitium.This dataset includes a variety of histological, acoustic simulation, and electrophysiological images and tabular data of compressional acoustic properties of skull and brain tissue and physiochemical properties of nanoparticles.