TY - JOUR
T1 - 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
AU - Kaynezhad, Pardis
AU - Mitra, Subhabrata
AU - Bale, Gemma
AU - Bauer, Cornelius
AU - Lingam, Ingran
AU - Meehan, Christopher
AU - Avdic-Belltheus, Adnan
AU - Martinello, Kathryn A.
AU - Bainbridge, Alan
AU - Robertson, Nicola J.
AU - Tachtsidis, Ilias
PY - 2019/11
Y1 - 2019/11
N2 - 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.
AB - 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.
KW - broadband near-infrared spectroscopy
KW - cytochrome-c-oxidase
KW - hypoxia-ischemia
KW - near-infrared spectroscopy
KW - neonatal encephalopathy
UR - http://www.scopus.com/inward/record.url?scp=85077511483&partnerID=8YFLogxK
U2 - 10.1117/1.NPh.6.4.045009
DO - 10.1117/1.NPh.6.4.045009
M3 - Article
AN - SCOPUS:85077511483
SN - 2329-423X
VL - 6
JO - Neurophotonics
JF - Neurophotonics
IS - 4
M1 - 045009
ER -