TY - JOUR
T1 - Functional and oxygen-metabolic photoacoustic microscopy of the awake mouse brain
AU - Cao, Rui
AU - Li, Jun
AU - Ning, Bo
AU - Sun, Naidi
AU - Wang, Tianxiong
AU - Zuo, Zhiyi
AU - Hu, Song
N1 - Publisher Copyright:
© 2017 Elsevier Inc.
PY - 2017/4/15
Y1 - 2017/4/15
N2 - 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, CMRO2 is 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.
AB - 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, CMRO2 is 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.
KW - Anesthetic neuroprotection
KW - Awake-brain imaging
KW - Head-restrained photoacoustic microscopy
KW - Hemodynamics
KW - Oxygen metabolism
UR - http://www.scopus.com/inward/record.url?scp=85013197014&partnerID=8YFLogxK
U2 - 10.1016/j.neuroimage.2017.01.049
DO - 10.1016/j.neuroimage.2017.01.049
M3 - Article
C2 - 28111187
AN - SCOPUS:85013197014
SN - 1053-8119
VL - 150
SP - 77
EP - 87
JO - NeuroImage
JF - NeuroImage
ER -