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
N1 - © 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.
PY - 2019/10
Y1 - 2019/10
N2 - 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.
AB - 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.
U2 - 10.1117/1.NPh.6.4.045009
DO - 10.1117/1.NPh.6.4.045009
M3 - Article
C2 - 31737744
VL - 6
SP - 045009
JO - Neurophotonics
JF - Neurophotonics
SN - 2329-423X
IS - 4
ER -