Abstract
We describe the development of a miniaturized broadband near-infrared spectroscopy system (bNIRS), which measures changes in cerebral tissue oxyhemoglobin ( [HbO2] ) and deoxyhemoglobin ([HHb]) plus tissue metabolism via changes in the oxidation state of cytochrome-c-oxidase ([oxCCO]). The system is based on a small light source and a customized mini-spectrometer. We assessed the instrument in a preclinical study in 27 newborn piglets undergoing transient cerebral hypoxia-ischemia (HI). We aimed to quantify the recovery of the HI insult and estimate the severity of the injury. The recovery in brain oxygenation ( Δ[HbDiff] = Δ[HbO2] - Δ[HHb] ), blood volume ( Δ[HbT] = Δ[HbO2] + Δ[HHb] ), and metabolism ( Δ[oxCCO] ) for up to 30 min after the end of HI were quantified in percentages using the recovery fraction (RF) algorithm, which quantifies the recovery of a signal with respect to baseline. The receiver operating characteristic analysis was performed on bNIRS-RF measurements compared to proton ( H1 ) magnetic resonance spectroscopic (MRS)-derived thalamic lactate/N-acetylaspartate (Lac/NAA) measured at 24-h post HI insult; Lac/NAA peak area ratio is an accurate surrogate marker of neurodevelopmental outcome in babies with neonatal HI encephalopathy. The Δ[oxCCO] -RF cut-off threshold of 79% within 30 min of HI predicted injury severity based on Lac/NAA with high sensitivity (100%) and specificity (93%). A significant difference in thalamic Lac/NAA was noticed ( p < 0.0001 ) between the two groups based on this cut-off threshold of 79% Δ[oxCCO] -RF. The severe injury group ( n = 13 ) had ∼ 30% smaller recovery in Δ[HbDiff] -RF ( p = 0.0001 ) and no significant difference was observed in Δ[HbT] -RF between groups. At 48 h post HI, significantly higher P31 -MRS-measured inorganic phosphate/exchangeable phosphate pool (epp) ( p = 0.01 ) and reduced phosphocreatine/epp ( p = 0.003 ) were observed in the severe injury group indicating persistent cerebral energy depletion. Based on these results, the bNIRS measurement of the oxCCO recovery fraction offers a noninvasive real-time biomarker of brain injury severity within 30 min following HI insult.