Transcranial chronic optical access to longitudinally measure cerebral blood flow

Background: 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. New method: 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. Results: 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. Comparison with existing methods: 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. Conclusions: 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.