Early assessment of injury with optical markers in a piglet model of neonatal encephalopathy

Kelly Harvey-Jones; Frederic Lange; Vinita Verma; Gemma Bale; Christopher Meehan; Adnan Avdic-Belltheus; Mariya Hristova; Magdalena Sokolska; Francisco Torrealdea; Xavier Golay; Veronika Parfentyeva; Turgut Durduran; Alan Bainbridge; Ilias Tachtsidis; Nicola J Robertson; Subhabrata Mitra

doi:10.1038/s41390-023-02679-y

Early assessment of injury with optical markers in a piglet model of neonatal encephalopathy

Kelly Harvey-Jones, Frederic Lange, Vinita Verma, Gemma Bale, Christopher Meehan, Adnan Avdic-Belltheus, Mariya Hristova, Magdalena Sokolska, Francisco Torrealdea, Xavier Golay, Veronika Parfentyeva, Turgut Durduran, Alan Bainbridge, Ilias Tachtsidis, Nicola J Robertson, Subhabrata Mitra

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Abstract / Description of output

BACKGROUND: Opportunities for adjunct therapies with cooling in neonatal encephalopathy are imminent; however, robust biomarkers of early assessment are lacking. Using an optical platform of broadband near-infrared spectroscopy and diffuse correlation spectroscopy to directly measure mitochondrial metabolism (oxCCO), oxygenation (HbD), cerebral blood flow (CBF), we hypothesised optical indices early (1-h post insult) after hypoxia-ischaemia (HI) predicts insult severity and outcome.

METHODS: Nineteen newborn large white piglets underwent continuous neuromonitoring as controls or following moderate or severe HI. Optical indices were expressed as mean semblance (phase difference) and coherence (spectral similarity) between signals using wavelet analysis. Outcome markers included the lactate/N-acetyl aspartate (Lac/NAA) ratio at 6 h on proton MRS and TUNEL cell count.

RESULTS: CBF-HbD semblance (cerebrovascular dysfunction) correlated with BGT and white matter (WM) Lac/NAA (r 2 = 0.46, p = 0.004, r 2 = 0.45, p = 0.004, respectively), TUNEL cell count (r 2 = 0.34, p = 0.02) and predicted both initial insult (r 2 = 0.62, p = 0.002) and outcome group (r 2 = 0.65 p = 0.003). oxCCO-HbD semblance (cerebral metabolic dysfunction) correlated with BGT and WM Lac/NAA (r 2 = 0.34, p = 0.01 and r 2 = 0.46, p = 0.002, respectively) and differentiated between outcome groups (r 2 = 0.43, p = 0.01).

CONCLUSION: Optical markers of both cerebral metabolic and vascular dysfunction 1 h after HI predicted injury severity and subsequent outcome in a pre-clinical model.

IMPACT: This study highlights the possibility of using non-invasive optical biomarkers for early assessment of injury severity following neonatal encephalopathy, relating to the outcome. Continuous cot-side monitoring of these optical markers can be useful for disease stratification in the clinical population and for identifying infants who might benefit from future adjunct neuroprotective therapies beyond cooling.

Original language	English
Journal	Pediatric Research
Early online date	13 Jun 2023
DOIs	https://doi.org/10.1038/s41390-023-02679-y
Publication status	E-pub ahead of print - 13 Jun 2023

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s41390-023-02679-yFinal published version, 1.99 MBLicence: Creative Commons: Attribution (CC-BY)

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Harvey-Jones, K., Lange, F., Verma, V., Bale, G., Meehan, C., Avdic-Belltheus, A., Hristova, M., Sokolska, M., Torrealdea, F., Golay, X., Parfentyeva, V., Durduran, T., Bainbridge, A., Tachtsidis, I., Robertson, N. J., & Mitra, S. (2023). Early assessment of injury with optical markers in a piglet model of neonatal encephalopathy. Pediatric Research. Advance online publication. https://doi.org/10.1038/s41390-023-02679-y

@article{e0dffb67daec4215b0b9fe1a1edd13de,

title = "Early assessment of injury with optical markers in a piglet model of neonatal encephalopathy",

abstract = "BACKGROUND: Opportunities for adjunct therapies with cooling in neonatal encephalopathy are imminent; however, robust biomarkers of early assessment are lacking. Using an optical platform of broadband near-infrared spectroscopy and diffuse correlation spectroscopy to directly measure mitochondrial metabolism (oxCCO), oxygenation (HbD), cerebral blood flow (CBF), we hypothesised optical indices early (1-h post insult) after hypoxia-ischaemia (HI) predicts insult severity and outcome.METHODS: Nineteen newborn large white piglets underwent continuous neuromonitoring as controls or following moderate or severe HI. Optical indices were expressed as mean semblance (phase difference) and coherence (spectral similarity) between signals using wavelet analysis. Outcome markers included the lactate/N-acetyl aspartate (Lac/NAA) ratio at 6 h on proton MRS and TUNEL cell count.RESULTS: CBF-HbD semblance (cerebrovascular dysfunction) correlated with BGT and white matter (WM) Lac/NAA (r 2 = 0.46, p = 0.004, r 2 = 0.45, p = 0.004, respectively), TUNEL cell count (r 2 = 0.34, p = 0.02) and predicted both initial insult (r 2 = 0.62, p = 0.002) and outcome group (r 2 = 0.65 p = 0.003). oxCCO-HbD semblance (cerebral metabolic dysfunction) correlated with BGT and WM Lac/NAA (r 2 = 0.34, p = 0.01 and r 2 = 0.46, p = 0.002, respectively) and differentiated between outcome groups (r 2 = 0.43, p = 0.01). CONCLUSION: Optical markers of both cerebral metabolic and vascular dysfunction 1 h after HI predicted injury severity and subsequent outcome in a pre-clinical model.IMPACT: This study highlights the possibility of using non-invasive optical biomarkers for early assessment of injury severity following neonatal encephalopathy, relating to the outcome. Continuous cot-side monitoring of these optical markers can be useful for disease stratification in the clinical population and for identifying infants who might benefit from future adjunct neuroprotective therapies beyond cooling.",

author = "Kelly Harvey-Jones and Frederic Lange and Vinita Verma and Gemma Bale and Christopher Meehan and Adnan Avdic-Belltheus and Mariya Hristova and Magdalena Sokolska and Francisco Torrealdea and Xavier Golay and Veronika Parfentyeva and Turgut Durduran and Alan Bainbridge and Ilias Tachtsidis and Robertson, {Nicola J} and Subhabrata Mitra",

note = "{\textcopyright} 2023. The Author(s).",

year = "2023",

month = jun,

day = "13",

doi = "10.1038/s41390-023-02679-y",

language = "English",

journal = "Pediatric Research",

issn = "0031-3998",

publisher = "INT PEDIATRIC RESEARCH FOUNDATION, INC",

}

Harvey-Jones, K, Lange, F, Verma, V, Bale, G, Meehan, C, Avdic-Belltheus, A, Hristova, M, Sokolska, M, Torrealdea, F, Golay, X, Parfentyeva, V, Durduran, T, Bainbridge, A, Tachtsidis, I, Robertson, NJ & Mitra, S 2023, 'Early assessment of injury with optical markers in a piglet model of neonatal encephalopathy', Pediatric Research. https://doi.org/10.1038/s41390-023-02679-y

TY - JOUR

T1 - Early assessment of injury with optical markers in a piglet model of neonatal encephalopathy

AU - Harvey-Jones, Kelly

AU - Lange, Frederic

AU - Verma, Vinita

AU - Bale, Gemma

AU - Meehan, Christopher

AU - Avdic-Belltheus, Adnan

AU - Hristova, Mariya

AU - Sokolska, Magdalena

AU - Torrealdea, Francisco

AU - Golay, Xavier

AU - Parfentyeva, Veronika

AU - Durduran, Turgut

AU - Bainbridge, Alan

AU - Tachtsidis, Ilias

AU - Robertson, Nicola J

AU - Mitra, Subhabrata

PY - 2023/6/13

Y1 - 2023/6/13

N2 - BACKGROUND: Opportunities for adjunct therapies with cooling in neonatal encephalopathy are imminent; however, robust biomarkers of early assessment are lacking. Using an optical platform of broadband near-infrared spectroscopy and diffuse correlation spectroscopy to directly measure mitochondrial metabolism (oxCCO), oxygenation (HbD), cerebral blood flow (CBF), we hypothesised optical indices early (1-h post insult) after hypoxia-ischaemia (HI) predicts insult severity and outcome.METHODS: Nineteen newborn large white piglets underwent continuous neuromonitoring as controls or following moderate or severe HI. Optical indices were expressed as mean semblance (phase difference) and coherence (spectral similarity) between signals using wavelet analysis. Outcome markers included the lactate/N-acetyl aspartate (Lac/NAA) ratio at 6 h on proton MRS and TUNEL cell count.RESULTS: CBF-HbD semblance (cerebrovascular dysfunction) correlated with BGT and white matter (WM) Lac/NAA (r 2 = 0.46, p = 0.004, r 2 = 0.45, p = 0.004, respectively), TUNEL cell count (r 2 = 0.34, p = 0.02) and predicted both initial insult (r 2 = 0.62, p = 0.002) and outcome group (r 2 = 0.65 p = 0.003). oxCCO-HbD semblance (cerebral metabolic dysfunction) correlated with BGT and WM Lac/NAA (r 2 = 0.34, p = 0.01 and r 2 = 0.46, p = 0.002, respectively) and differentiated between outcome groups (r 2 = 0.43, p = 0.01). CONCLUSION: Optical markers of both cerebral metabolic and vascular dysfunction 1 h after HI predicted injury severity and subsequent outcome in a pre-clinical model.IMPACT: This study highlights the possibility of using non-invasive optical biomarkers for early assessment of injury severity following neonatal encephalopathy, relating to the outcome. Continuous cot-side monitoring of these optical markers can be useful for disease stratification in the clinical population and for identifying infants who might benefit from future adjunct neuroprotective therapies beyond cooling.

AB - BACKGROUND: Opportunities for adjunct therapies with cooling in neonatal encephalopathy are imminent; however, robust biomarkers of early assessment are lacking. Using an optical platform of broadband near-infrared spectroscopy and diffuse correlation spectroscopy to directly measure mitochondrial metabolism (oxCCO), oxygenation (HbD), cerebral blood flow (CBF), we hypothesised optical indices early (1-h post insult) after hypoxia-ischaemia (HI) predicts insult severity and outcome.METHODS: Nineteen newborn large white piglets underwent continuous neuromonitoring as controls or following moderate or severe HI. Optical indices were expressed as mean semblance (phase difference) and coherence (spectral similarity) between signals using wavelet analysis. Outcome markers included the lactate/N-acetyl aspartate (Lac/NAA) ratio at 6 h on proton MRS and TUNEL cell count.RESULTS: CBF-HbD semblance (cerebrovascular dysfunction) correlated with BGT and white matter (WM) Lac/NAA (r 2 = 0.46, p = 0.004, r 2 = 0.45, p = 0.004, respectively), TUNEL cell count (r 2 = 0.34, p = 0.02) and predicted both initial insult (r 2 = 0.62, p = 0.002) and outcome group (r 2 = 0.65 p = 0.003). oxCCO-HbD semblance (cerebral metabolic dysfunction) correlated with BGT and WM Lac/NAA (r 2 = 0.34, p = 0.01 and r 2 = 0.46, p = 0.002, respectively) and differentiated between outcome groups (r 2 = 0.43, p = 0.01). CONCLUSION: Optical markers of both cerebral metabolic and vascular dysfunction 1 h after HI predicted injury severity and subsequent outcome in a pre-clinical model.IMPACT: This study highlights the possibility of using non-invasive optical biomarkers for early assessment of injury severity following neonatal encephalopathy, relating to the outcome. Continuous cot-side monitoring of these optical markers can be useful for disease stratification in the clinical population and for identifying infants who might benefit from future adjunct neuroprotective therapies beyond cooling.

U2 - 10.1038/s41390-023-02679-y

DO - 10.1038/s41390-023-02679-y

M3 - Article

C2 - 37308684

SN - 0031-3998

JO - Pediatric Research

JF - Pediatric Research

ER -

Early assessment of injury with optical markers in a piglet model of neonatal encephalopathy

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