Diffuse optical imaging of the neonatal brain

Detecting brain injury that can lead to cerebral palsy in the newborn remains a significant challenge.  In the Evelyn Perinatal Imaging Centre (Rosie Hospital, Cambridge University Hospitals NHS Foundation Trust), researchers are developing diffuse optical imaging (DOI) techniques to measure in vivo haemodynamic correlates to neural function in the newborn brain  [1].  DOI uses multiple optical fibre bundles that emit and detect light in the near-infrared spectrum and these are attached to a cap that is placed on the subject’s head to acquire data.  This technique is advantageous in the infant population, as it is portable and can be used in the neonatal intensive care unit at the cot-side providing a potentially clinically useful prognostic neuroimaging tool.  Potential clinical uses for DOI include investigating functional connectivity [2] or functional activation [3].  We have also combined DOI with EEG simultaneously to investigate the relationship between neural activity and cerebral blood flow (neurovascular coupling) in pathological states such as hypoxic-ischaemic brain injury [4].  With a newly installed MRI in the imaging centre, there is potential to also combine DOI with MRI to provide a more comprehensive picture of brain structure and function in infants.

Raw DOI data is subject to multiple offline signal processing steps including motion artefact correction and consideration of non-cerebral systemic physiological noise [5].  To reconstruct images, structural information is required by either the subject’s own anatomical MRI image, or an anatomical atlas.  One approach to solving the forward model is to spatially register the location of the DOI optical fibre bundles on the head to the anatomical model producing a finite element mesh.  A multispectral linear reconstruction approach can be used to solve the inverse problem to reconstruct DOI images.  The steps in signal processing can vary among research groups and have potential to be optimised to produce more accurate high quality images of haemodynamic activity.

As DOI is an emerging research tool, there is no gold standard approach to statistical inference of DOI images.  Most approaches have been adopted from fMRI including the general linear mixed effect model for modelling functional activation, and seed-based analysis or independent component analysis to investigate functional connectivity [6].  With multi-modal data such as combining DOI with EEG or MRI, this will create further mathematical and statistical challenges before DOI can be used to provide clinically useful biomarkers of brain injury for clinicians.

[1] https://neolabresearch.com/

[2] Ferradal SL, Liao SM, Eggebrecht AT, Shimony JS, Inder TE, Culver JP, Smyser CD. 2016. Functional Imaging of the Developing Brain at the Bedside Using Diffuse Optical Tomography. Cereb Cortex 26:1558-1568.

[3] Liao SM, Ferradal SL, White BR, Gregg N, Inder TE, Culver JP. 2012. High-density diffuse optical tomography of term infant visual cortex in the nursery. J Biomed Opt 17:081414.

[4] Singh H, Cooper RJ, Wai Lee C, Dempsey L, Edwards A, Brigadoi S, Airantzis D, Everdell N, Michell A, Holder D, Hebden JC, Austin T. 2014. Mapping cortical haemodynamics during neonatal seizures using diffuse optical tomography: A case study. Neuroimage Clin 5:256-265.

[5] Scholkmann F, Kleiser S, Metz AJ, Zimmermann R, Pavia JM, Wolf U, Wolf M. 2014. A review on continuous wave functional near-infrared spectroscopy and imaging instrumentation and methodology. NeuroImage 85:6–27

[6] Tak S, Ye JC. 2013. Statistical analysis of fNIRS data: A comprehensive review. NeuroImage 85:72-91

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