Non-invasive measurement of a metabolic marker of infant brain function

Siddiqui, Maheen F.; Lloyd‐Fox, Sarah; Kaynezhad, Pardis; Tachtsidis, Ilias; Johnson, Mark H.; Elwell, Clare E.

doi:10.1038/s41598-017-01394-z

Cited by 29 publications

(23 citation statements)

References 26 publications

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“…New developments in fNIRS technology will further allow us to monitor both hemodynamic and metabolic responses during newborn functional activation, with broadband instruments able to measure metabolic marker, cytochrome-c-oxidase (Bale et al, 2014 ). This metabolic marker has shown to have increased brain specificity (Kolyva et al, 2014 ; de Roever et al, 2017 ), enabling us to investigate hemodynamic metabolic coupling during neuronal activity (Bale et al, 2016 ; Siddiqui et al, 2017 ). Finally, developments in analysis techniques, such as short-separation techniques to remove scalp effects (Gagnon et al, 2011 ) enable improved data analysis.…”

Section: Discussionmentioning

confidence: 99%

Investigation of the Pattern of the Hemodynamic Response as Measured by Functional Near-Infrared Spectroscopy (fNIRS) Studies in Newborns, Less Than a Month Old: A Systematic Review

Roever

Bale

Mitra

et al. 2018

Front. Hum. Neurosci.

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It has been 20 years since functional near-infrared spectroscopy (fNIRS) was first used to investigate the evoked hemodynamic response to a stimulus in newborns. The hemodynamic response to functional activation is well-established in adults, with an observed increase in concentration change of oxygenated hemoglobin (Δ[HbO2]) and decrease in deoxygenated hemoglobin (Δ[HHb]). However, functional studies in newborns have revealed a mixed response, particularly with Δ[HHb] where an inconsistent change in direction is observed. The reason for this heterogeneity is unknown, with potential explanations arising from differing physiology in the developing brain, or differences in instrumentation or methodology. The aim of this review is to collate the findings from studies that have employed fNIRS to monitor cerebral hemodynamics in term newborn infants aged 1 day−1 month. A total of 46 eligible studies were identified; some studies investigated more than one stimulus type, resulting in a total of 51 reported results. The NIRS parameters reported varied across studies with 50/51 cases reporting Δ[HbO2], 39/51 reporting Δ[HHb], and 13/51 reporting total hemoglobin concentration Δ[HbT] (Δ[HbO2] + Δ[HHb]). However, of the 39 cases reporting Δ[HHb] in graphs or tables, only 24 studies explicitly discussed the response (i.e., direction of change) of this variable. In the studies where the fNIRS responses were discussed, 46/51 cases observed an increase in Δ[HbO2], 7/51 observed an increase or varied Δ[HHb], and 2/51 reported a varied or negative Δ[HbT]. An increase in Δ[HbO2] and decrease or no change in Δ[HHb] was observed in 15 studies. By reviewing this body of literature, we have identified that the majority of research articles reported an increase in Δ[HbO2] across various functional tasks and did not report the response of Δ[HHb]. Confirming the normal, healthy hemodynamic response in newborns will allow identification of unhealthy patterns and their association to normal neurodevelopment.

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Section: Discussionmentioning

confidence: 99%

Investigation of the Pattern of the Hemodynamic Response as Measured by Functional Near-Infrared Spectroscopy (fNIRS) Studies in Newborns, Less Than a Month Old: A Systematic Review

Roever

Bale

Mitra

et al. 2018

Front. Hum. Neurosci.

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“…Data analysis was carried out in MATLAB (Mathworks, USA). A detailed description of the data analysis pipeline is described elsewhere [11]. Valid experimental trials were determined using looking time.…”

Section: Methodsmentioning

confidence: 99%

Changes in Cytochrome-C-Oxidase Account for Changes in Attenuation of Near-Infrared Light in the Healthy Infant Brain

Siddiqui

Lloyd‐Fox

Kaynezhad

et al. 2018

Advances in Experimental Medicine and Biology

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A novel multi-wavelength broadband near infrared spectroscopy (NIRS) system has been employed to simultaneously measure haemodynamic changes alongside changes in cellular oxygen utilization by measurement of oxidation state of mitochondrial enzyme cytochrome-c-oxidase (oxCCO). The aim of this study was to investigate the role of oxCCO in neural responses to functional activation in infants. Studies were performed using a NIRS broadband system in 33 typically developing infants aged between 4 and 6 months. Responses were recorded over the right temporal lobe while infants were presented with engaging videos containing social and non-social content. Changes in the concentration of oxyhaemoglobin (Δ[HbO]), deoxyhaemoglobin (Δ[HHb]) and Δ[oxCCO] were calculated using changes in attenuation of light at 120 wavelengths between 780 and 900 nm using the UCLn algorithm. The algorithm was also used to fit (a) HbO and HHb spectra (2 component fit) and (b) HbO, HHb and oxCCO (3 component fit) to the change in attenuation occurring within an experimental block in different participants. Residuals resulting from these two fits were compared with oxidized-minus reduced CCO spectrum, calculated using the CCO specific extinction coefficient. A significant increase in oxCCO was found in response to the social stimuli (maximum increase 0.238 ± 0.13 μM). Residuals analysis showed that the best fits were achieved when oxCCO was included as a tissue chromophore. These results are the first reported significant change in oxCCO to stimulus-evoked activation in infants and may reveal vital information about oxygen metabolism during functional activation in the developing human brain.

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“…Fibreless systems are also likely to play an increasingly important role in neurodevelopment studies given the additional flexibility they provide for imaging brain function in naturalistic environments, especially for typically and atypically developing young infants and toddlers. Recent studies have demonstrated the first measurement of oxCCO changes during functional activation in the infant brain using a single source detector system [12], and further work is already underway to deliver spatially resolved measures of oxCCO to investigate links between mitochondrial and metabolic dysfunction in infants at high risk of autism [13,14].…”

Section: Discussionmentioning

confidence: 99%

A Fibreless Multiwavelength NIRS System for Imaging Localised Changes in Cerebral Oxidised Cytochrome C Oxidase

Highton

Chitnis²,

Brigadoi

et al. 2018

Advances in Experimental Medicine and Biology

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Measurement of the oxidation state of cytochrome c oxidase (oxCCO) can inform directly on neuronal metabolism. Conventionally this has been measured in vivo using benchtop broadband near infrared spectroscopy (NIRS) systems. Spatially resolved measures of oxCCO have recently been made possible using a multichannel fibre-based broadband NIRS system. We describe the use of a fibreless multiwavelength NIRS system using light emitting diodes (LED) designed specifically to image localised changes in oxCCO and hence neuronal metabolism. A fibreless system consisting of four modules, each containing two LED sources and four photodiode detectors, was developed. Each LED source contained eight LED dies (780, 811, 818, 842, 850, 882, 891 and 901 nm) assembled in an area of 1.5 × 1.5 mm. A well-established hyperoxia protocol was used to evaluate the oxCCO spatially resolved measurement capabilities of the system and, subsequently, its imaging capabilities were tested using a functional activation paradigm. A multi-spectral image reconstruction approach was used to provide images of Δ[HbO], Δ[HHb] and Δ[oxCCO] from the multi-distance, multi-channel optical datasets. This novel fibreless multiwavelength NIRS system allows imaging of localised changes in oxCCO in the human brain, and has potential for development as an inexpensive, wearable, continuous monitor of cerebral energetics in a range of experimental and clinical scenarios.

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Non-invasive measurement of a metabolic marker of infant brain function

Cited by 29 publications

References 26 publications

Investigation of the Pattern of the Hemodynamic Response as Measured by Functional Near-Infrared Spectroscopy (fNIRS) Studies in Newborns, Less Than a Month Old: A Systematic Review

Investigation of the Pattern of the Hemodynamic Response as Measured by Functional Near-Infrared Spectroscopy (fNIRS) Studies in Newborns, Less Than a Month Old: A Systematic Review

Changes in Cytochrome-C-Oxidase Account for Changes in Attenuation of Near-Infrared Light in the Healthy Infant Brain

A Fibreless Multiwavelength NIRS System for Imaging Localised Changes in Cerebral Oxidised Cytochrome C Oxidase

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