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.
Highlights
The brain accounts for more than 20% of our oxygen consumption at the resting state[1]
photoacoustic microscopy (PAM) is insensitive to sO2 at 532 nm, a near-isosbestic point of hemoglobin where the optical absorption coefficients of oxy- and deoxy-hemoglobin (HbO2 and HbR, respectively) are equal
Fluctuations in the PAM signal acquired at 532 nm encode both the Brownian motion and the flow of red blood cells (RBCs)[21]
Summary
The brain accounts for more than 20% of our oxygen consumption at the resting state[1]. By measuring the total concentration of hemoglobin (CHb), the oxygen saturation of hemoglobin (sO2), and blood flow at selected locations in feeding arteries and draining veins, Yao et al previously demonstrated PAM of the total metabolic rate of oxygen in the tumor-bearing mouse ear[19] and recently extended it to measure relative CMRO2 changes in the electrically stimulated mouse brain[20] Encouraging, this method is not readily applicable for high-resolution CMRO2 imaging, because the three parameters were not simultaneously quantified and the cerebral blood flow (CBF) was not measured at the same spatial scale as the other two parameters. With the future development of complementary algorithms to extend the three parameters to the tissue level, the ultrasound-aided multi-parametric PAM will enable us to derive microscopic CMRO2 using the Fick’s law
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