title: Ultrasound-aided Multi-parametric Photoacoustic Microscopy of the Mouse Brain.
abstract: High-resolution quantitative imaging of cerebral oxygen metabolism in mice is crucial for understanding brain functions and formulating new strategies to treat neurological disorders, but remains a challenge. Here, we report on our newly developed ultrasound-aided multi-parametric photoacoustic microscopy (PAM), which enables simultaneous quantification of the total concentration of hemoglobin (CHb), the oxygen saturation of hemoglobin (sO2), and cerebral blood flow (CBF) at the microscopic level and through the intact mouse skull. The three-dimensional skull and vascular anatomies delineated by the dual-contrast (i.e., ultrasonic and photoacoustic) system provide important guidance for dynamically focused contour scan and vessel orientation-dependent correction of CBF, respectively. Moreover, bi-directional raster scan allows determining the direction of blood flow in individual vessels. Capable of imaging all three hemodynamic parameters at the same spatiotemporal scale, our ultrasound-aided PAM fills a critical gap in preclinical neuroimaging and lays the foundation for high-resolution mapping of the cerebral metabolic rate of oxygen (CMRO2)-a quantitative index of cerebral oxygen metabolism. This technical innovation is expected to shed new light on the mechanism and treatment of a broad spectrum of neurological disorders, including Alzheimer's disease and ischemic stroke.
authors.affiliation: Department of Biomedical Engineering, University of Virginia, Charlottesville, VA 22908.
authors.forename: Bo
authors.initials: B
authors.lastname: Ning
authors.affiliation: Department of Biomedical Engineering, University of Virginia, Charlottesville, VA 22908.
authors.forename: Naidi
authors.initials: N
authors.lastname: Sun
authors.affiliation: Department of Biomedical Engineering, University of Virginia, Charlottesville, VA 22908.
authors.forename: Rui
authors.initials: R
authors.lastname: Cao
authors.affiliation: Department of Biomedical Engineering, University of Southern California, Los Angeles, CA 90089.
authors.forename: Ruimin
authors.initials: R
authors.lastname: Chen
authors.affiliation: Department of Biomedical Engineering, University of Southern California, Los Angeles, CA 90089.
authors.forename: K
authors.initials: K
authors.lastname: Kirk Shung
authors.affiliation: Department of Biomedical Engineering, University of Virginia, Charlottesville, VA 22908.
authors.forename: John A
authors.initials: JA
authors.lastname: Hossack
authors.affiliation: Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110.
authors.forename: Jin-Moo
authors.initials: JM
authors.lastname: Lee
authors.affiliation: Department of Biomedical Engineering, University of Southern California, Los Angeles, CA 90089.
authors.forename: Qifa
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Department of Biomedical Engineering, University of Virginia, Charlottesville, VA 22908.
authors.forename: Song
authors.initials: S
authors.lastname: Hu
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002560:Cerebrovascular Circulation; D006454:Hemoglobins / Q000378:metabolism; D051379:Mice; D033401:Microscopy, Acoustic; D010100:Oxygen / Q000378:metabolism*; D061088:Photoacoustic Techniques / Q000379:methods*; D014463:Ultrasonography
chemical_list: D006454:Hemoglobins; D010100:Oxygen