Ultrasound-aided Multi-parametric Photoacoustic Microscopy of the Mouse Brain

• Published in: Scientific reports Vol. 5; no. 1; p. 18775
• Main Authors: Ning, Bo, Sun, Naidi, Cao, Rui, Chen, Ruimin, Kirk Shung, K., Hossack, John A., Lee, Jin-Moo, Zhou, Qifa, Hu, Song
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 21-12-2015; Nature Publishing Group
• Subjects: 631/1647/245/1859; 631/1647/245/2226; 639/624/1107/328; Alzheimer's disease; Animals; Blood flow; Brain - metabolism; Brain - pathology; Brain mapping; Cerebral blood flow; Cerebrovascular Circulation; Hemoglobin; Hemoglobins - metabolism; Humanities and Social Sciences; Ischemia; Metabolic rate; Metabolism; Mice; Microscopy; Microscopy, Acoustic; multidisciplinary; Neurodegenerative diseases; Neuroimaging; Neurological diseases; Neurological disorders; Oxygen; Oxygen - metabolism; Photoacoustic Techniques - methods; Science; Skull; Stroke; Sulfur dioxide; Ultrasonic imaging; Ultrasonography; Ultrasound
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep18775

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 (C
Hb
), the oxygen saturation of hemoglobin (sO
2
) 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 (CMRO
2
)—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.