We describe the development of a miniaturized broadband near-infrared spectroscopy system (bNIRS), which measures changes in cerebral tissue oxyhemoglobin ( [ HbO 2 ] ) 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 [ HbO 2 ] - Δ [ HHb ] ), blood volume ( Δ [ HbT ] = Δ [ HbO 2 ] + 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 ( H 1 ) 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 P 31 -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.

中文翻译：

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使用来自小型宽带近红外光谱系统的细胞色素c-氧化酶的测量值对新生儿临床前模型中的缺氧缺血性脑损伤的严重程度进行量化。

我们描述了微型宽带近红外光谱系统（bNIRS）的发展，该系统通过改变细胞色素c的氧化态来测量脑组织氧合血红蛋白（[HbO 2]）和脱氧血红蛋白（[HHb]）以及组织代谢的变化。 -氧化酶（[oxCCO]）。该系统基于小型光源和定制的微型光谱仪。在一项临床前研究中，我们对27例经历短暂性脑缺氧缺血（HI）的新生仔猪评估了该仪器。我们旨在量化HI损伤的恢复并评估损伤的严重程度。脑氧合（Δ[HbDiff] =Δ[HbO 2]-Δ[HHb]），血容量（Δ[HbT] =Δ[HbO 2] +Δ[HHb]）HI结束后长达30分钟的代谢和代谢（Δ[oxCCO]）均使用恢复分数（RF）算法以百分比的形式进行定量，该算法可量化信号相对于基线的恢复。接收器工作特性分析是在bNIRS-RF测量结果上进行的，与HI损伤后24小时测量的质子（H 1）磁共振光谱法（MRS）衍生的丘脑乳酸/ N-乙酰天冬氨酸（Lac / NAA）进行比较；Lac / NAA峰面积比是新生儿HI脑病婴儿神经发育结局的准确替代指标。基于Lac / NAA的HI预测的损伤严重程度，在30分钟内Δ[oxCCO] -RF截止阈值为79％，具有高灵敏度（100％）和特异性（93％）。注意到丘脑Lac / NAA有显着差异（p <0。基于该阈值阈值79％Δ[oxCCO] -RF，在两组之间进行0001）。严重损伤组（n = 13）的Δ[HbDiff] -RF（p = 0.0001）降低约30％，两组之间的Δ[HbT] -RF差异无统计学意义。HI后48小时，在严重损伤组中观察到P 31 -MRS测定的无机磷酸盐/可交换磷酸盐池（epp）显着更高（p = 0.01），磷酸肌酸/ epp降低（p = 0.003），表明持续的脑能量消耗。根据这些结果，在HI损伤后30分钟内，oxCCO回收率的bNIRS测量提供了脑损伤严重程度的非侵入性实时生物标记。0001），两组之间的[[HbT] -RF]差异无统计学意义。HI后48小时，在严重损伤组中观察到P 31 -MRS测定的无机磷酸盐/可交换磷酸盐池（epp）显着更高（p = 0.01），磷酸肌酸/ epp降低（p = 0.003），表明持续的脑能量消耗。根据这些结果，在HI损伤后30分钟内，oxCCO回收率的bNIRS测量提供了脑损伤严重程度的非侵入性实时生物标记。0001），两组之间的[[HbT] -RF]差异无统计学意义。HI后48小时，在严重损伤组中观察到P 31 -MRS测定的无机磷酸盐/可交换磷酸盐池（epp）显着更高（p = 0.01），磷酸肌酸/ epp降低（p = 0.003），表明持续的脑能量消耗。根据这些结果，在HI损伤后30分钟内，oxCCO回收率的bNIRS测量提供了脑损伤严重程度的非侵入性实时生物标记。