Abstract

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 (StO2) 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.

Highlights

  • An estimated 15 million babies are born prematurely each year and those with very low birth weights (VLBW < 1500 g) are at a high risk of neurodevelopmental impairment [1]

  • In this article, we report on the development of a hybrid diffuse correlation spectroscopy (DCS) and broadband near-infrared spectroscopy (B-NIRS) instrument capable of simultaneous monitoring of cerebral blood flow (CBF) and changes in the oxidation state of cytochrome c oxidase

  • This article reports on the development of a novel optical system that combines DCS and BNIRS to enable continuous monitoring of absolute cerebral blood flow and changes in the oxidation state of cytochrome c oxidase − two sensitive biomarkers of brain health

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Summary

Introduction

An estimated 15 million babies are born prematurely each year and those with very low birth weights (VLBW < 1500 g) are at a high risk of neurodevelopmental impairment [1]. Among the 63,000 VLBW infants born annually in the United States, 5-10% develop major disabilities such as cerebral palsy and 25-50% show other cognitive and behavioural deficits [2,3]. Ultrasound is used to detect brain damage that has already occurred, rather than detecting pathophysiological events that are indicative of oncoming injury. This speaks to the need for bedside methods capable of detecting CBF and metabolic fluctuations which could act as prognostic markers of brain injury

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