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14 November 2019 Quantification of the severity of hypoxic-ischemic brain injury in a neonatal preclinical model using measurements of cytochrome-c-oxidase from a miniature broadband-near-infrared spectroscopy system
Pardis Kaynezhad, Subhabrata Mitra, Gemma Bale, Cornelius Bauer, Ingran Lingam, Christopher Meehan, Adnan Avdic-Belltheus, Kathryn A. Martinello, Alan Bainbridge, Nicola J. Robertson, Ilias Tachtsidis
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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.

CC BY: © The Authors. Published by SPIE under a Creative Commons Attribution 4.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.
Pardis Kaynezhad, Subhabrata Mitra, Gemma Bale, Cornelius Bauer, Ingran Lingam, Christopher Meehan, Adnan Avdic-Belltheus, Kathryn A. Martinello, Alan Bainbridge, Nicola J. Robertson, and Ilias Tachtsidis "Quantification of the severity of hypoxic-ischemic brain injury in a neonatal preclinical model using measurements of cytochrome-c-oxidase from a miniature broadband-near-infrared spectroscopy system," Neurophotonics 6(4), 045009 (14 November 2019). https://doi.org/10.1117/1.NPh.6.4.045009
Received: 12 July 2019; Accepted: 14 October 2019; Published: 14 November 2019
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Cited by 18 scholarly publications.
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KEYWORDS
Spectroscopy

Injuries

Brain

Traumatic brain injury

Signal attenuation

Tissue optics

Chromophores

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