Schematic diagrams of cerebrovascular reactivity (CVR) MRI using ACZ challenge. (A) procedures of ACZ-based mouse CVR experiments: animal preparation; pre- and post-injection MRI scans, blood preparation, high-performance liquid chromatography (HPLC) analysis of blood samples to determine plasma ACZ level, and final calculation of CVR. (B, C, and D) timelines for Study 1, Study 2 and Study 3, respectively. Regarding (B) and (C), an MRI session consisted of 30 PC scans (5 as baseline [12 min] and 25 as post-injection [60 min]). The injection took place at the beginning of 6th scan and lasted for about 1min. No-injection experiments also had 30 PC scans.