Significance: Near-infrared spectroscopy (NIRS) combined with diffuse correlation spectroscopy (DCS) provides a noninvasive approach for monitoring cerebral blood flow (CBF), oxygenation, and oxygen metabolism. However, these methods are vulnerable to signal contamination from the scalp. Our work evaluated methods of reducing the impact of this contamination using time-resolved (TR) NIRS and multidistance (MD) DCS. Aim: The magnitude of scalp contamination was evaluated by measuring the flow, oxygenation, and metabolic responses to a global hemodynamic challenge. Contamination was assessed by collecting data with and without impeding scalp blood flow. Approach: Experiments involved healthy participants. A pneumatic tourniquet was used to cause scalp ischemia, as confirmed by contrast-enhanced NIRS, and a computerized gas system to generate a hypercapnic challenge. Results: Comparing responses acquired with and without the tourniquet demonstrated that the TR-NIRS technique could reduce scalp contributions in hemodynamic signals up to 4 times (rSD = 3 cm) and 6 times (rSD = 4 cm). Similarly, blood flow responses from the scalp and brain could be separated by analyzing MD DCS data with a multilayer model. Using these techniques, there was no change in metabolism during hypercapnia, as expected, despite large increases in CBF and oxygenation. Conclusion: NIRS/DCS can accurately monitor CBF and metabolism with the appropriate enhancement to depth sensitivity, highlighting the potential of these techniques for neuromonitoring.

Preterm infants born with very low birth weights are at a high risk of brain injury, in part because the premature brain is believed to be prone to periods of low cerebral blood flow (CBF). Tissue damage is likely to occur if reduction in CBF is sufficient to impair cerebral energy metabolism for extended periods. Therefore, a neuromonitoring method that can detect reductions in CBF, large enough to affect metabolism, could alert the neonatal intensive care team before injury occurs. In this report, we present the development of an optical system that combines diffuse correlation spectroscopy (DCS) for monitoring CBF and broadband near-infrared spectroscopy (B-NIRS) for monitoring the oxidation state of cytochrome c oxidase (oxCCO) – a key biomarker of oxidative metabolism. The hybrid instrument includes a multiplexing system to enable concomitant DCS and B-NIRS measurements while avoiding crosstalk between the two subsystems. The ability of the instrument to monitor dynamic changes in CBF and oxCCO was demonstrated in a piglet model of neonatal hypoxia-ischemia (HI). Experiments conducted in eight animals, including two controls, showed that oxCCO exhibited a delayed response to ischemia while CBF and tissue oxygenation (S_tO₂) responses were instantaneous. These findings suggest that simultaneous neuromonitoring of perfusion and metabolism could provide critical information regarding clinically significant hemodynamic events prior to the onset of brain injury.

During cardiac surgery with cardiopulmonary bypass (CPB), adequate maintenance of cerebral blood flow (CBF) is vital in preventing postoperative neurological injury – i.e. stroke, delirium, cognitive impairment. Reductions in CBF large enough to impact cerebral energy metabolism can lead to tissue damage and subsequent brain injury. Current methods for neuromonitoring during surgery are limited. This study presents the clinical translation of a hybrid optical neuromonitor for continuous intraoperative monitoring of cerebral perfusion and metabolism in ten patients undergoing non-emergent cardiac surgery with non-pulsatile CPB. The optical system combines broadband near-infrared spectroscopy (B-NIRS) to measure changes in the oxidation state of cytochrome c oxidase (oxCCO) – a direct marker of cellular energy metabolism – and diffuse correlation spectroscopy (DCS) to provide an index of cerebral blood flow (CBFi). As the heart was arrested and the CPB-pump started, increases in CBFi (88.5 ± 125.7%) and significant decreases in oxCCO (−0.5 ± 0.2 µM) were observed; no changes were noted during transitions off CPB. Fifteen hypoperfusion events, defined as large and sustained reductions in CPB-pump flow rate, were identified across all patients and resulted in significant decreases in perfusion and metabolism when mean arterial pressure dropped to 30 mmHg or below. The maximum reduction in cerebral blood flow preceded the corresponding metabolic reduction by 18.2 ± 15.0 s. Optical neuromonitoring provides a safe and non-invasive approach for assessing intraoperative perfusion and metabolism and has potential in guiding patient management to prevent adverse clinical outcomes.

This study presents the characterization of dynamic cerebrovascular reactivity (CVR) in healthy adults by a hybrid optical system combining time-resolved (TR) near-infrared spectroscopy (NIRS) and diffuse correlation spectroscopy (DCS). Blood flow and oxygenation (oxy- and deoxy-hemoglobin) responses to a step hypercapnic challenge were recorded to characterize dynamic and static components of CVR. Data were acquired at short and long source-detector separations (r_SD) to assess the impact of scalp hemodynamics, and moment analysis applied to the TR-NIRS to further enhance the sensitivity to the brain. Comparing blood flow and oxygenation responses acquired at short and long r_SD demonstrated that scalp contamination distorted the CVR time courses, particularly for oxyhemoglobin. This effect was significantly diminished by the greater depth sensitivity of TR NIRS and less evident in the DCS data due to the higher blood flow in the brain compared to the scalp. The reactivity speed was similar for blood flow and oxygenation in the healthy brain. Given the ease-of-use, portability, and non-invasiveness of this hybrid approach, it is well suited to investigate if the temporal relationship between CBF and oxygenation is altered by factors such as age and cerebrovascular disease.

A major concern with preterm birth is the risk of neurodevelopmental disability. Poor cerebral circulation leading to periods of hypoxia is believed to play a significant role in the etiology of preterm brain injury, with the first three days of life considered the period when the brain is most vulnerable. This study focused on monitoring cerebral perfusion and metabolism during the first 72 h after birth in preterm infants weighing less than 1500 g. Brain monitoring was performed by combining hyperspectral near-infrared spectroscopy to assess oxygen saturation and the oxidation state of cytochrome c oxidase (oxCCO), with diffuse correlation spectroscopy to monitor cerebral blood flow (CBF). In seven of eight patients, oxCCO remained independent of CBF, indicating adequate oxygen delivery despite any fluctuations in cerebral hemodynamics. In the remaining infant, a significant correlation between CBF and oxCCO was found during the monitoring periods on days 1 and 3. This infant also had the lowest baseline CBF, suggesting the impact of CBF instabilities on metabolism depends on the level of blood supply to the brain. In summary, this study demonstrated for the first time how continuous perfusion and metabolic monitoring can be achieved, opening the possibility to investigate if CBF/oxCCO monitoring could help identify preterm infants at risk of brain injury.

Post-hemorrhagic ventricular dilatation (PHVD) is characterized by a build-up of cerebral spinal fluid (CSF) in the ventricles, which increases intracranial pressure and compresses brain tissue. Clinical interventions (i.e., ventricular taps, VT) work to mitigate these complications through CSF drainage; however, the timing of these procedures remains imprecise. This study presents Neonatal NeuroMonitor (NNeMo), a portable optical device that combines broadband near-infrared spectroscopy (B-NIRS) and diffuse correlation spectroscopy (DCS) to provide simultaneous assessments of cerebral blood flow (CBF), tissue saturation (S_tO₂), and the oxidation state of cytochrome c oxidase (oxCCO). In this study, NNeMo was used to monitor cerebral hemodynamics and metabolism in PHVD patients selected for a VT. Across multiple VTs in four patients, no significant changes were found in any of the three parameters: CBF increased by 14.6 ± 37.6% (p = 0.09), S_tO₂ by 1.9 ± 4.9% (p = 0.2), and oxCCO by 0.4 ± 0.6 µM (p = 0.09). However, removing outliers resulted in significant, but small, increases in CBF (6.0 ± 7.7%) and oxCCO (0.1 ± 0.1 µM). The results of this study demonstrate NNeMo’s ability to provide safe, non-invasive measurements of cerebral perfusion and metabolism for neuromonitoring applications in the neonatal intensive care unit.