Mapping cortical haemodynamics during neonatal seizures using diffuse optical tomography: A case study

Seizures in the newborn brain represent a major challenge to neonatal medicine. Neonatal seizures are poorly classified, under-diagnosed, difficult to treat and are associated with poor neurodevelopmental outcome. Video-EEG is the current gold-standard approach for seizure detection and monitoring. Interpreting neonatal EEG requires expertise and the impact of seizures on the developing brain remains poorly understood. In this case study we present the first ever images of the haemodynamic impact of seizures on the human infant brain, obtained using simultaneous diffuse optical tomography (DOT) and video-EEG with whole-scalp coverage. Seven discrete periods of ictal electrographic activity were observed during a 60 minute recording of an infant with hypoxic–ischaemic encephalopathy. The resulting DOT images show a remarkably consistent, high-amplitude, biphasic pattern of changes in cortical blood volume and oxygenation in response to each electrographic event. While there is spatial variation across the cortex, the dominant haemodynamic response to seizure activity consists of an initial increase in cortical blood volume prior to a large and extended decrease typically lasting several minutes. This case study demonstrates the wealth of physiologically and clinically relevant information that DOT–EEG techniques can yield. The consistency and scale of the haemodynamic responses observed here also suggest that DOT–EEG has the potential to provide improved detection of neonatal seizures.

[1]  Theodore H. Schwartz,et al.  In vivo optical mapping of epileptic foci and surround inhibition in ferret cerebral cortex , 2001, Nature Medicine.

[2]  Hongtao Ma,et al.  Spatiotemporal Dynamics of Perfusion and Oximetry during Ictal Discharges in the Rat Neocortex , 2009, The Journal of Neuroscience.

[3]  D. Boas,et al.  HomER: a review of time-series analysis methods for near-infrared spectroscopy of the brain. , 2009, Applied optics.

[4]  R. Grebe,et al.  Haemodynamic changes during seizure-like activity in a neonate: A simultaneous AC EEG-SPIR and high-resolution DC EEG recording , 2009, Neurophysiologie Clinique/Clinical Neurophysiology.

[5]  A Villringer,et al.  Near-infrared spectroscopy: does it function in functional activation studies of the adult brain? , 2000, International journal of psychophysiology : official journal of the International Organization of Psychophysiology.

[6]  M. Nolan,et al.  Cot-side electroencephalography for outcome prediction in preterm infants: observational study , 2010, Archives of Disease in Childhood: Fetal and Neonatal Edition.

[7]  M Wolf,et al.  How to detect and reduce movement artifacts in near-infrared imaging using moving standard deviation and spline interpolation , 2010, Physiological measurement.

[8]  G. Somjen Mechanisms of spreading depression and hypoxic spreading depression-like depolarization. , 2001, Physiological reviews.

[9]  Simon R. Arridge,et al.  A 4D neonatal head model for diffuse optical imaging of pre-term to term infants , 2014, NeuroImage.

[10]  M. Schweiger,et al.  A finite element approach for modeling photon transport in tissue. , 1993, Medical physics.

[11]  M J Painter,et al.  Neonatal seizures: electroclinical dissociation. , 1991, Pediatric neurology.

[12]  Hongtao Ma,et al.  Focal Increases in Perfusion and Decreases in Hemoglobin Oxygenation Precede Seizure Onset in Spontaneous Human Epilepsy , 2007, Epilepsia.

[13]  L. D. de Vries,et al.  Treatment of neonatal seizures. , 2013, Seminars in fetal & neonatal medicine.

[14]  David A. Boas,et al.  A temporal comparison of BOLD, ASL, and NIRS hemodynamic responses to motor stimuli in adult humans , 2006, NeuroImage.

[15]  Abraham Z. Snyder,et al.  Atlas-based head modeling and spatial normalization for high-density diffuse optical tomography: In vivo validation against fMRI , 2014, NeuroImage.

[16]  Brian R White,et al.  Neonatal hemodynamic response to visual cortex activity: high-density near-infrared spectroscopy study. , 2010, Journal of biomedical optics.

[17]  Arno Klein,et al.  A reproducible evaluation of ANTs similarity metric performance in brain image registration , 2011, NeuroImage.

[18]  Daniel Rueckert,et al.  A dynamic 4D probabilistic atlas of the developing brain , 2011, NeuroImage.

[19]  Simon R Arridge,et al.  Methods in diffuse optical imaging , 2011, Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences.

[20]  S. Bahar,et al.  Temporal Dependence in Uncoupling of Blood Volume and Oxygenation during Interictal Epileptiform Events in Rat Neocortex , 2005, The Journal of Neuroscience.

[21]  R. Oozeer,et al.  Continuous 4-channel EEG monitoring: a guide to interpretation, with normal values, in preterm infants. , 1987, Neuropediatrics.

[22]  Robert Oostenveld,et al.  FieldTrip: Open Source Software for Advanced Analysis of MEG, EEG, and Invasive Electrophysiological Data , 2010, Comput. Intell. Neurosci..

[23]  L. S. Vries,et al.  Clinical Management of Seizures in Newborns , 2013, Pediatric Drugs.

[24]  David A. Boas,et al.  Twenty years of functional near-infrared spectroscopy: introduction for the special issue , 2014, NeuroImage.

[25]  Gunnar Naulaers,et al.  Effect of Treatment of Subclinical Neonatal Seizures Detected With aEEG: Randomized, Controlled Trial , 2010, Pediatrics.

[26]  R. Clancy,et al.  Neurologic outcome after electroencephalographically proven neonatal seizures. , 1991, Pediatrics.

[27]  Geraldine Boylan,et al.  Treatment of neonatal seizures , 2007, Archives of Disease in Childhood - Fetal and Neonatal Edition.

[28]  Abraham Z. Snyder,et al.  A quantitative spatial comparison of high-density diffuse optical tomography and fMRI cortical mapping , 2012, NeuroImage.

[29]  D. Louis Collins,et al.  Non-local MRI upsampling , 2010, Medical Image Anal..

[30]  Hamid Dehghani,et al.  Retinotopic mapping of adult human visual cortex with high-density diffuse optical tomography , 2007, Proceedings of the National Academy of Sciences.

[31]  R. Graf,et al.  Propagation of cortical spreading depolarization in the human cortex after malignant stroke , 2013, Neurology.

[32]  D. Delpy,et al.  A frequency multiplexed near infra-red topography system for imaging functional activation in the brain , 2004 .

[33]  A Villringer,et al.  Systemic Nitric Oxide Synthase Inhibition Does Not Affect Brain Oxygenation during Cortical Spreading Depression in Rats: A Noninvasive Near-Infrared Spectroscopy and Laser-Doppler Flowmetry Study , 1996, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[34]  F Henry-Le Bros,et al.  Cerebral blood flow and metabolism, L Edvinsson, E Mackenzie, J McCulloch. Raven Press, Paris (1993) , 1994 .

[35]  S. Bahar,et al.  Intrinsic optical signal imaging of neocortical seizures: the ‘epileptic dip’ , 2006, Neuroreport.

[36]  Colin Studholme,et al.  Decreased cerebral blood flow during seizures with ictal SPECT injections , 2000, Epilepsy Research.

[37]  R. Yuste,et al.  Feedforward Inhibition Contributes to the Control of Epileptiform Propagation Speed , 2007, The Journal of Neuroscience.

[38]  Louis Lemieux,et al.  Mapping hemodynamic correlates of seizures using fMRI: A review , 2013, Human brain mapping.

[39]  Hannah C. Glass,et al.  Neonatal seizures , 2009, Current treatment options in neurology.

[40]  Ferenc Domoki,et al.  Seizure-Induced Alterations in Cerebrovascular Function in the Neonate , 2008, Developmental Neuroscience.

[41]  F. Wallois,et al.  EEG-NIRS in epilepsy in children and neonates , 2010, Neurophysiologie Clinique/Clinical Neurophysiology.

[42]  T. Schwartz,et al.  Dynamic Neurovascular Coupling and Uncoupling during Ictal Onset, Propagation, and Termination Revealed by Simultaneous In Vivo Optical Imaging of Neural Activity and Local Blood Volume , 2012, Cerebral cortex.

[43]  David A. Boas,et al.  Further improvement in reducing superficial contamination in NIRS using double short separation measurements , 2014, NeuroImage.

[44]  Anthony J. Strong,et al.  Association of seizures with cortical spreading depression and peri-infarct depolarisations in the acutely injured human brain , 2008, Clinical Neurophysiology.

[45]  John S. Ebersole,et al.  Localizing value of scalp EEG spikes: A simultaneous scalp and intracranial study , 2007, Clinical Neurophysiology.

[46]  A. Villringer,et al.  Beyond the Visible—Imaging the Human Brain with Light , 2003, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[47]  H. Frndova,et al.  Seizure burden is independently associated with short term outcome in critically ill children. , 2014, Brain : a journal of neurology.

[48]  David A. Boas,et al.  Tetrahedral mesh generation from volumetric binary and grayscale images , 2009, 2009 IEEE International Symposium on Biomedical Imaging: From Nano to Macro.

[49]  M. Schweiger,et al.  Diffuse optical tomography with spectral constraints and wavelength optimization. , 2005, Applied optics.

[50]  Stefan A. Carp,et al.  Somatosensory evoked changes in cerebral oxygen consumption measured non-invasively in premature neonates , 2014, NeuroImage.

[51]  A. A. Leão,et al.  SPREADING DEPRESSION OF ACTIVITY IN THE CEREBRAL CORTEX , 1944 .

[52]  C. Stafstrom The March of Epileptic Activity across Cortex is Limited (for a While) by the Powerful Forces of Surrounding Inhibition , 2007, Epilepsy currents.

[53]  D. Boas,et al.  Diffuse optical tomography system to image brain activation with improved spatial resolution and validation with functional magnetic resonance imaging. , 2006, Applied optics.

[54]  David A. Boas,et al.  Factors affecting the accuracy of near-infrared spectroscopy concentration calculations for focal changes in oxygenation parameters , 2003, NeuroImage.

[55]  Jeremy C. Hebden,et al.  Transient haemodynamic events in neurologically compromised infants: A simultaneous EEG and diffuse optical imaging study , 2011, NeuroImage.

[56]  E. Okada,et al.  Monte Carlo prediction of near-infrared light propagation in realistic adult and neonatal head models. , 2003, Applied optics.

[57]  M. Lauritzen,et al.  Spreading and Synchronous Depressions of Cortical Activity in Acutely Injured Human Brain , 2002, Stroke.

[58]  A. Blasi,et al.  Illuminating the developing brain: The past, present and future of functional near infrared spectroscopy , 2010, Neuroscience & Biobehavioral Reviews.

[59]  Simon R. Arridge,et al.  Three-dimensional whole-head optical tomography of passive motor evoked responses in the neonate , 2006, NeuroImage.

[60]  David A. Boas,et al.  A Systematic Comparison of Motion Artifact Correction Techniques for Functional Near-Infrared Spectroscopy , 2012, Front. Neurosci..

[61]  A D B Disease in Childhood: , 1936, Nature.

[62]  Taeun Chang,et al.  The American Clinical Neurophysiology Society's Guideline on Continuous Electroencephalography Monitoring in Neonates. , 2011, Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society.

[63]  P. House,et al.  EEG Infraslow Activity in Absence and Partial Seizures , 2008, Clinical EEG and neuroscience.

[64]  L C Pinto,et al.  Neonatal seizures: background EEG activity and the electroclinical correlation in full-term neonates with hypoxic-ischemic encephalopathy. Analysis by computer-synchronized long-term polygraphic video-EEG monitoring. , 2001, Epileptic disorders : international epilepsy journal with videotape.

[65]  S. Smith EEG in the diagnosis, classification, and management of patients with epilepsy , 2005, Journal of Neurology, Neurosurgery & Psychiatry.

[66]  A. Dunn,et al.  Peri-infarct depolarizations lead to loss of perfusion in ischaemic gyrencephalic cerebral cortex. , 2006, Brain : a journal of neurology.

[67]  Martin Schweiger,et al.  The Toast++ software suite for forward and inverse modeling in optical tomography , 2014, Journal of biomedical optics.

[68]  A. Strong,et al.  Depolarisation phenomena in traumatic and ischaemic brain injury. , 2005, Advances and technical standards in neurosurgery.

[69]  R. Guillet,et al.  Electrographic seizures in neonates correlate with poor neurodevelopmental outcome , 2000, Neurology.

[70]  J Connell,et al.  Continuous EEG monitoring of neonatal seizures: diagnostic and prognostic considerations. , 1989, Archives of disease in childhood.

[71]  Robert Oostenveld,et al.  The five percent electrode system for high-resolution EEG and ERP measurements , 2001, Clinical Neurophysiology.

[72]  Diffuse Optical Tomography , 2006, QELS 2006.

[73]  P. Marquet,et al.  In vivo local determination of tissue optical properties: applications to human brain. , 1999, Applied optics.

[74]  J. Ebersole,et al.  Intracranial EEG Substrates of Scalp EEG Interictal Spikes , 2005, Epilepsia.

[75]  James J. Riviello,et al.  Neonatal Seizures and EEG: Electroclinical Dissociation and Uncoupling , 2004 .

[76]  M. Lauritzen,et al.  Clinical Relevance of Cortical Spreading Depression in Neurological Disorders: Migraine, Malignant Stroke, Subarachnoid and Intracranial Hemorrhage, and Traumatic Brain Injury , 2011, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[77]  Vince D. Calhoun,et al.  EEGIFT: Group Independent Component Analysis for Event-Related EEG Data , 2011, Comput. Intell. Neurosci..

[78]  Hongtao Ma,et al.  Preictal and Ictal Neurovascular and Metabolic Coupling Surrounding a Seizure Focus , 2011, The Journal of Neuroscience.

[79]  Martin Wolf,et al.  General equation for the differential pathlength factor of the frontal human head depending on wavelength and age , 2013, Journal of biomedical optics.

[80]  Deborah Stevenson Homer (review) , 2012 .