title: Functional and oxygen-metabolic photoacoustic microscopy of the awake mouse brain.
abstract: A long-standing challenge in optical neuroimaging has been the assessment of hemodynamics and oxygen metabolism in the awake rodent brain at the microscopic level. Here, we report first-of-a-kind head-restrained photoacoustic microscopy (PAM), which enables simultaneous imaging of the cerebrovascular anatomy, total concentration and oxygen saturation of hemoglobin, and blood flow in awake mice. Combining these hemodynamic measurements allows us to derive two key metabolic parameters-oxygen extraction fraction (OEF) and the cerebral metabolic rate of oxygen (CMRO2). This enabling technology offers the first opportunity to comprehensively and quantitatively characterize the hemodynamic and oxygen-metabolic responses of the mouse brain to isoflurane, a general anesthetic widely used in preclinical research and clinical practice. Side-by-side comparison of the awake and anesthetized brains reveals that isoflurane induces diameter-dependent arterial dilation, elevated blood flow, and reduced OEF in a dose-dependent manner. As a result of the combined effects, CMRO2is significantly reduced in the anesthetized brain under both normoxia and hypoxia, which suggests a mechanism for anesthetic neuroprotection. The head-restrained functional and metabolic PAM opens a new avenue for basic and translational research on neurovascular coupling without the strong influence of anesthesia and on the neuroprotective effects of various interventions, including but not limited to volatile anesthetics, against cerebral hypoxia and ischemia.
authors.affiliation: Department of Biomedical Engineering, University of Virginia, VA 22908, USA.
authors.forename: Rui
authors.initials: R
authors.lastname: Cao
authors.affiliation: Department of Anesthesiology, University of Virginia, VA 22908, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Biomedical Engineering, University of Virginia, VA 22908, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Ning
authors.affiliation: Department of Biomedical Engineering, University of Virginia, VA 22908, USA.
authors.forename: Naidi
authors.initials: N
authors.lastname: Sun
authors.affiliation: Department of Biomedical Engineering, University of Virginia, VA 22908, USA.
authors.forename: Tianxiong
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, University of Virginia, VA 22908, USA. Electronic address: zz3c@virginia.edu.
authors.forename: Zhiyi
authors.initials: Z
authors.lastname: Zuo
authors.affiliation: Department of Biomedical Engineering, University of Virginia, VA 22908, USA. Electronic address: songhu@virginia.edu.
authors.forename: Song
authors.initials: S
authors.lastname: Hu
mesh_terms: D000818:Animals; D001921:Brain / Q000098:blood supply / Q000000981:diagnostic imaging* / Q000378:metabolism*; D006439:Hemodynamics / Q000502:physiology; D008297:Male; D051379:Mice; D008853:Microscopy / Q000379:methods; D059906:Neuroimaging / Q000379:methods*; D000069336:Neurovascular Coupling / Q000502:physiology*; D061088:Photoacoustic Techniques; D014851:Wakefulness / Q000502:physiology
keywords: Anesthetic neuroprotection; Awake-brain imaging; Head-restrained photoacoustic microscopy; Hemodynamics; Oxygen metabolism