| Summary: | Near-infrared spectroscopy (NIRS) and diffuse correlation spectroscopy (DCS) measure cerebral hemodynamics, which in turn can be used to assess the cerebral metabolic rate of oxygen (CMRO<sub>2</sub>) and cerebral autoregulation (CA). However, current mathematical models for CMRO<sub>2</sub> estimation make assumptions that break down for cerebral perfusion pressure (CPP)-induced changes in CA. Here, we performed preclinical experiments with controlled changes in CPP while simultaneously measuring NIRS and DCS at rest. We observed changes in arterial oxygen saturation (~10%) and arterial blood volume (~50%) with CPP, two variables often assumed to be constant in CMRO<sub>2</sub> estimations. Hence, we propose a general mathematical model that accounts for these variations when estimating CMRO<sub>2</sub> and validate its use for CA monitoring on our experimental data. We observed significant changes in the various oxygenation parameters, including the coupling ratio (CMRO<sub>2</sub>/blood flow) between regions of autoregulation and dysregulation. Our work provides an appropriate model and preliminary experimental evidence for the use of NIRS- and DCS-based tissue oxygenation and metabolism metrics for non-invasive diagnosis of CA health in CPP-altering neuropathologies.
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