Near-infrared spectroscopy (NIRS) measurements of tissue oxygen saturation (StO2) are frequently used during vascular and cardiac surgeries as a non-invasive means of assessing brain health; however, signal contamination from extracerebral tissues remains a concern. As an alternative, hyperspectral (hs)NIRS can be used to measure changes in the oxidation state of cytochrome c oxidase (ΔoxCCO), which provides greater sensitivity to the brain given its higher mitochondrial concentration versus the scalp. The purpose of this study was to evaluate the depth sensitivity of the oxCCO signal to changes occurring in the brain and extracerebral tissue components. The oxCCO assessment was conducted using multi-distance hsNIRS (source-detector separations = 1 and 3 cm), and metabolic changes were compared to changes in StO2. Ten participants were monitored using an in-house system combining hsNIRS and diffuse correlation spectroscopy (DCS). Data were acquired during carotid compression (CC) to reduce blood flow and hypercapnia to increase flow. Reducing blood flow by CC resulted in a significant decrease in oxCCO measured at rSD = 3 cm but not at 1 cm. In contrast, significant changes in StO2 were found at both distances. Hypercapnia caused significant increases in StO2 and oxCCO at rSD = 3 cm, but not at 1 cm. Extracerebral contamination resulted in elevated StO2 but not oxCCO after hypercapnia, which was significantly reduced by applying regression analysis. This study demonstrated that oxCCO was less sensitive to extracerebral signals than StO2.

Combining diffuse correlation spectroscopy (DCS) and near-infrared spectroscopy (NIRS) permits simultaneous monitoring of multiple cerebral hemodynamic parameters related to cerebral autoregulation; however, interpreting these optical measurements can be confounded by signal contamination from extracerebral tissue.Aim: We aimed to evaluate extracerebral signal contamination in NIRS/DCS data acquired during transient hypotension and assess suitable means of separating scalp and brain signals.Approach: A hybrid time-resolved NIRS/multidistance DCS system was used to simultaneously acquire cerebral oxygenation and blood flow data during transient orthostatic hypotension induced by rapid-onset lower body negative pressure (LBNP) in nine young, healthy adults. Changes in microvascular flow were verified against changes in middle cerebral artery velocity (MCAv) measured by transcranial Doppler ultrasound.Results: LBNP significantly decreased arterial blood pressure (−18% AE 14%), scalp blood flow (>30%), and scalp tissue oxygenation (all p ≤ 0.04 versus baseline). However, implementing depth-sensitive techniques for both DCS and timeresolved NIRS indicated that LBNP did not significantly alter microvascular cerebral blood flow and oxygenation relative to their baseline values (all p ≥ 0.14). In agreement, there was no significant reduction in MCAv (8% AE 16%; p ¼ 0.09). Conclusion:Transient hypotension caused significantly larger blood flow and oxygenation changes in the extracerebral tissue compared to the brain. We demonstrate the importance of accounting for extracerebral signal contamination within optical measures of cerebral hemodynamics during physiological paradigms designed to test cerebral autoregulation.

Significance: Hyperspectral near-infrared spectroscopy (hsNIRS) combined with diffuse correlation spectroscopy (DCS) provides a noninvasive approach for monitoring cerebral blood flow (CBF), the cerebral metabolic rate of oxygen (CMRO 2 ) and the oxidation state of cytochromec-oxidase (oxCCO). CMRO 2 is calculated by combining tissue oxygen saturation (S t O 2 ) with CBF, whereas oxCCO can be measured directly by hsNIRS. Although both reflect oxygen metabolism, a direct comparison has yet to be studied. Aim:We aim to investigate the relationship between CMRO 2 and oxCCO during periods of restricted oxygen delivery and lower metabolic demand.Approach: A hybrid hsNIRS/DCS system was used to measure hemodynamic and metabolic responses in piglets exposed to cerebral ischemia and anesthetic-induced reductions in brain activity.Results: Although a linear relationship was observed between CMRO 2 and oxCCO during ischemia, both exhibited a nonlinear relationship with respect to CBF. In contrast, linear correlation was sufficient to characterize the relationships between CMRO 2 and CBF and between the two metabolic markers during reduced metabolic demand. Conclusions:The observed relationship between CMRO 2 and oxCCO during periods of restricted oxygen delivery and lower metabolic demand indicates that the two metabolic markers are strongly correlated.

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