Transcranial chronic optical access to longitudinally measure cerebral blood flow

• Published in: Journal of neuroscience methods 2021-02, Vol.350, p.109044-109044, Article 109044
• Main Authors: Hoover, Evelyn M., Crouzet, Christian, Bordas, Julianna M., Figueroa Velez, Dario X., Gandhi, Sunil P., Choi, Bernard, Lodoen, Melissa B.
• Format: Article
• Language: English
• Subjects: Animals; Brain; Brain - diagnostic imaging; Brain - surgery; Cerebral blood flow; Cerebrovascular Circulation; Circulation; Hemodynamics; In vivo imaging; Laser speckle imaging; Mice; Optical Imaging; Skull - diagnostic imaging; Skull - surgery; Surgery; Vasculature
• ISSN: 0165-0270; 1872-678X
• DOI: 10.1016/j.jneumeth.2020.109044

•Many pathological conditions can cause long-term negative effects on cerebral blood flow.•Laser speckle imaging enables minimally invasive measurement of cerebral blood flow in the mouse.•We developed a surgical technique that permits continuous and chronic optical access through the intact mouse skull.•This approach enables longitudinal bi-hemispheric imaging of cerebral blood vessels.•We measured cerebral blood flow through the mouse skull longitudinally for over 100 days. The regulation of cerebral blood flow is critical for normal brain functioning, and many physiological and pathological conditions can have long-term impacts on cerebral blood flow. However, minimally invasive tools to study chronic changes in animal models are limited. We developed a minimally invasive surgical technique (cyanoacrylate skull, CAS) allowing us to image cerebral blood flow longitudinally through the intact mouse skull using laser speckle imaging. With CAS we were able to detect acute changes in cerebral blood flow induced by hypercapnic challenge. We were also able to image cerebral blood flow dynamics with laser speckle imaging for over 100 days. Furthermore, the relative cerebral blood flow remained stable in mice from 30 days to greater than 100 days after the surgery. Previously, achieving continuous long-term optical access to measure cerebral blood flow in individual vessels in a mouse model involved invasive surgery. In contrast, the CAS technique presented here is relatively non-invasive, as it allows stable optical access through an intact mouse skull. The CAS technique allows researcher to chronically measure cerebral blood flow dynamics for a significant portion of a mouse’s lifespan. This approach may be useful for studying changes in blood flow due to cerebral pathology or for examining the therapeutic effects of modifying cerebral blood flow in mouse models relevant to human disease.