Fiberoptic Probe For Hemodynamic Spectroscopy in Freely Moving Mice Shows Cerebrovascular Dysregulation In Alzheimers and Glioma Models

Significance: Cerebral vascular reactivity is critical parameters of brain homeostasis in health and disease, but the investigational value of brain oxymetry is diminished by anesthesia and mechanical fixation of the mouse scull. Aim: We needed to reduce the physical restrictivity of hemodynamic spectroscopy to enable cancer and Alzheimers disease (AD) studies in freely-moving mice. Approach: We combined spectroscopy, spectral analysis software and a magnetic, implantable device to measure vascular reactivity in unanesthetized, freely-moving mice. We measured cerebral blood volume fraction (CBVF) and oxygen saturation (SO2). Results: CBVF and SO2 demonstrated delayed cerebrovascular recovery from hypoxia in an orthotopic xenograft glioma model and we found increased CBVF during hypercapnia in a mouse model of AD compared to wild-type littermates. Conclusions: Our optomechanical approach to reproducibly getting light into and out of the brain enabled us to successfully measure CBVF and SO2 during hypercapnia in unanesthetized freely-moving mice. We present hardware and software enabling oximetric analysis of metabolic activity, which provides a safe and reliable method for rapid assessment of vascular reactivity in murine disease models as well as CBVF and SO2.