An automatic MEG low-frequency source imaging approach for detecting injuries in mild and moderate TBI patients with blast and non-blast causes

Traumatic brain injury (TBI) is a leading cause of sustained impairment in military and civilian populations. However, mild (and some moderate) TBI can be difficult to diagnose because the injuries are often not detectable on conventional MRI or CT. Injured brain tissues in TBI patients generate abnormal low-frequency magnetic activity (ALFMA, peaked at 1-4 Hz) that can be measured and localized by magnetoencephalography (MEG). We developed a new automated MEG low-frequency source imaging method and applied this method in 45 mild TBI (23 from combat-related blasts, and 22 from non-blast causes) and 10 moderate TBI patients (non-blast causes). Seventeen of the patients with mild TBI from blasts had tertiary injuries resulting from the blast. The results show our method detected abnormalities at the rates of 87% for the mild TBI group (blast-induced plus non-blast causes) and 100% for the moderate group. Among the mild TBI patients, the rates of abnormalities were 96% and 77% for the blast and non-blast TBI groups, respectively. The spatial characteristics of abnormal slow-wave generation measured by Z scores in the mild blast TBI group significantly correlated with those in non-blast mild TBI group. Among 96 cortical regions, the likelihood of abnormal slow-wave generation was less in the mild TBI patients with blast than in the mild non-blast TBI patients, suggesting possible protective effects due to the military helmet and armor. Finally, the number of cortical regions that generated abnormal slow-waves correlated significantly with the total post-concussive symptom scores in TBI patients. This study provides a foundation for using MEG low-frequency source imaging to support the clinical diagnosis of TBI.

[1]  B. Jennett,et al.  Assessment of coma and impaired consciousness. A practical scale. , 1974, Lancet.

[2]  L. Binder Persisting symptoms after mild head injury: a review of the postconcussive syndrome. , 1986, Journal of clinical and experimental neuropsychology.

[3]  N. Bohnen,et al.  Neuropsychological deficits in patients with persistent symptoms six months after mild head injury. , 1992, Neurosurgery.

[4]  AH Chowdhury,et al.  Assessment of coma and impaired consciousness : A critical review , 2009 .

[5]  Bruce D. McCandliss,et al.  Extent of Microstructural White Matter Injury in Postconcussive Syndrome Correlates with Impaired Cognitive Reaction Time: A 3T Diffusion Tensor Imaging Study of Mild Traumatic Brain Injury , 2008, American Journal of Neuroradiology.

[6]  Gregory A. Miller,et al.  Somatosensory System Deficits in Schizophrenia Revealed by MEG during a Median-Nerve Oddball Task , 2009, Brain Topography.

[7]  Agatha D. Lee,et al.  Acute and chronic changes in diffusivity measures after sports concussion. , 2011, Journal of neurotrauma.

[8]  B. Giordani,et al.  Disability caused by minor head injury. , 1981, Neurosurgery.

[9]  Kelvin O. Lim,et al.  Diffuse and spatially variable white matter disruptions are associated with blast-related mild traumatic brain injury , 2012, NeuroImage.

[10]  B. Rockstroh,et al.  Abnormal oscillatory brain dynamics in schizophrenia: a sign of deviant communication in neural network? , 2007, BMC psychiatry.

[11]  K. Yeates,et al.  Pediatric Sport-Related Concussion: A Review of the Clinical Management of an Oft-Neglected Population , 2006, Pediatrics.

[12]  P. Basser Inferring microstructural features and the physiological state of tissues from diffusion‐weighted images , 1995, NMR in biomedicine.

[13]  G. A. Miller,et al.  Spontaneous brain magnetic activity in schizophrenia patients treated with aripiprazole. , 1998, Psychopharmacology bulletin.

[14]  V. Haughton,et al.  Diffusion tensor MR imaging in diffuse axonal injury. , 2002, AJNR. American journal of neuroradiology.

[15]  A. C. Papanicolaou,et al.  Comparison of single current dipole and Magnetic Field Tomography analyses of the cortical response to auditory stimuli , 2005, Brain Topography.

[16]  A. Sorensen,et al.  Diffusion tensor imaging as potential biomarker of white matter injury in diffuse axonal injury. , 2004, AJNR. American journal of neuroradiology.

[17]  Jeffrey L. Elman,et al.  A novel integrated MEG and EEG analysis method for dipolar sources , 2007, NeuroImage.

[18]  J. Gotman,et al.  The electromicrophysiology of delta waves induced by systemic atropine , 1978, Brain Research.

[19]  J. Knott,et al.  The EEG in intrinsic supratentorial brain tumors: a comparative evaluation. , 1972, Electroencephalography and clinical neurophysiology.

[20]  G. Johnson,et al.  Short-term DTI predictors of cognitive dysfunction in mild traumatic brain injury , 2008, Brain injury.

[21]  J. Lewine,et al.  Objective Documentation of Traumatic Brain Injury Subsequent to Mild Head Trauma: Multimodal Brain Imaging With MEG, SPECT, and MRI , 2007, The Journal of head trauma rehabilitation.

[22]  K. Nagata,et al.  Topographic electroencephalographic study with power ratio index mapping in patients with malignant brain tumors. , 1985, Neurosurgery.

[23]  B. Rockstroh,et al.  Source distribution of neuromagnetic slow-wave activity in schizophrenic patients—effects of activation , 2003, Schizophrenia Research.

[24]  L. Jia Blast induced mild traumatic brain injury , 2010 .

[25]  H. Levin,et al.  Diffusion tensor imaging of acute mild traumatic brain injury in adolescents , 2008, Neurology.

[26]  Jan J. Heimans,et al.  Localization of Slow Wave Activity in Patients with Tumor-Associated Epilepsy , 2004, Brain Topography.

[27]  S. Okie Traumatic brain injury in the war zone. , 2005, The New England journal of medicine.

[28]  G. Johnson,et al.  Diffuse axonal injury in mild traumatic brain injury: a diffusion tensor imaging study. , 2005, Journal of neurosurgery.

[29]  M. Alexander Mild traumatic brain injury , 1995, Neurology.

[30]  S Taulu,et al.  MEG recordings of DC fields using the signal space separation method (SSS). , 2004, Neurology & clinical neurophysiology : NCN.

[31]  S. Taulu,et al.  Suppression of Interference and Artifacts by the Signal Space Separation Method , 2003, Brain Topography.

[32]  J. Stephen,et al.  Sources on the anterior and posterior banks of the central sulcus identified from magnetic somatosensory evoked responses using Multi‐Start Spatio‐Temporal localization , 2000, Human brain mapping.

[33]  J. Lagopoulos,et al.  Diffuse axonal injury in severe traumatic brain injury visualized using high-resolution diffusion tensor imaging. , 2007, Journal of neurotrauma.

[34]  Harvey S. Levin,et al.  Magnetic resonance imaging and computerized tomography in relation to the neurobehavioral sequelae of mild and moderate head injuries. , 1987, Journal of neurosurgery.

[35]  Erin D Bigler,et al.  Diffusion tensor imaging in the corpus callosum in children after moderate to severe traumatic brain injury. , 2006, Journal of neurotrauma.

[36]  B. Golomb,et al.  Prevalence and Psychological Correlates of Traumatic Brain Injury in Operation Iraqi Freedom , 2010, The Journal of head trauma rehabilitation.

[37]  Andrew J MacGregor,et al.  Injury-Specific Correlates of Combat-Related Traumatic Brain Injury in Operation Iraqi Freedom , 2011, The Journal of head trauma rehabilitation.

[38]  N R Temkin,et al.  One year psychosocial outcome in head injury , 1995, Journal of the International Neuropsychological Society.

[39]  E. Somersalo,et al.  Visualization of Magnetoencephalographic Data Using Minimum Current Estimates , 1999, NeuroImage.

[40]  Li Cui,et al.  Evaluation of signal space separation via simulation , 2007, Medical & Biological Engineering & Computing.

[41]  G. Houston,et al.  Microstructural brain injury in post-concussion syndrome after minor head injury , 2010, Neuroradiology.

[42]  Min Ho Chun,et al.  Usefulness of Diffusion Tensor Imaging for Evaluation of Motor Function in Patients With Traumatic Brain Injury: Three Case Studies , 2006, The Journal of head trauma rehabilitation.

[43]  J. Adams,et al.  Diffuse axonal injury in head injury: Definition, diagnosis and grading , 1989, Histopathology.

[44]  A. G. Osborn,et al.  White Matter Abnormalities in Mild Traumatic Brain Injury: A Diffusion Tensor Imaging Study , 2009 .

[45]  Horst A. Eiselt,et al.  Continuous Optimization Models , 1987 .

[46]  B. Rockstroh,et al.  Source distribution of neuromagnetic slow waves and MEG-delta activity in schizophrenic patients , 2001, Biological Psychiatry.

[47]  K. Matsuura,et al.  A robust reconstruction of sparse biomagnetic sources , 1997, IEEE Transactions on Biomedical Engineering.

[48]  King H. Yang,et al.  Blast related neurotrauma: a review of cellular injury. , 2008, Molecular & cellular biomechanics : MCB.

[49]  Psychosocial functioning at 1 month after head injury. , 1984, Neurosurgery.

[50]  Habib Benali,et al.  Diffusion tensor imaging and white matter lesions at the subacute stage in mild traumatic brain injury with persistent neurobehavioral impairment , 2011, Human brain mapping.

[51]  P Gloor,et al.  Brain lesions that produce delta waves in the EEG , 1977, Neurology.

[52]  J. Lewine,et al.  Magnetoencephalographic assessment of spontaneous brain activity in schizophrenia. , 1996, Psychopharmacology bulletin.

[53]  A. Rowan,et al.  Primer of EEG: With A Mini-Atlas , 2003 .

[54]  Alain Ptito,et al.  New Frontiers in Diagnostic Imaging in Concussive Head Injury , 2001, Clinical journal of sport medicine : official journal of the Canadian Academy of Sport Medicine.

[55]  J. Langlois,et al.  Traumatic brain injury in the United States; emergency department visits, hospitalizations, and deaths , 2006 .

[56]  Guy B. Williams,et al.  Diffusion tensor imaging in chronic head injury survivors: correlations with learning and memory indices , 2006, NeuroImage.

[57]  K. Gerold,et al.  Clinicopathological heterogeneity in the classification of mild head injury. , 1996, Neurosurgery.

[58]  B. Rockstroh,et al.  Focal temporoparietal slow activity in Alzheimer’s disease revealed by magnetoencephalography , 2002, Biological Psychiatry.

[59]  Valerian Kagan,et al.  Blast exposure in rats with body shielding is characterized primarily by diffuse axonal injury. , 2011, Journal of neurotrauma.

[60]  Cornelis J. Stam,et al.  The influence of brain tumor treatment on pathological delta activity in MEG , 2003, NeuroImage.

[61]  A. Walker Electroencephalography, Basic Principles, Clinical Applications and Related Fields , 1982 .

[62]  Seppo P. Ahlfors,et al.  New Six-Layer Magnetically-Shielded Room for MEG , 2002 .

[63]  Helmut Kober,et al.  Sources of spontaneous slow waves associated with brain lesions, localized by using the MEG , 2005, Brain Topography.

[64]  Anders M. Dale,et al.  Vector-based spatial–temporal minimum L1-norm solution for MEG , 2006, NeuroImage.

[65]  L. Binder,et al.  A review of mild head trauma. Part II: Clinical implications. , 1997, Journal of clinical and experimental neuropsychology.

[66]  Bruce J. Fisch,et al.  Fisch and Spehlmann's Eeg Primer: Basic Principles of Digital and Analog Eeg , 1999 .

[67]  Ernst Fernando Lopes Da Silva Niedermeyer,et al.  Electroencephalography, basic principles, clinical applications, and related fields , 1982 .

[68]  J. Lewine,et al.  Neuromagnetic assessment of pathophysiologic brain activity induced by minor head trauma. , 1999, AJNR. American journal of neuroradiology.

[69]  David F. Moore,et al.  In silico investigation of intracranial blast mitigation with relevance to military traumatic brain injury , 2010, Proceedings of the National Academy of Sciences.

[70]  William C Moss,et al.  Skull flexure from blast waves: a mechanism for brain injury with implications for helmet design. , 2008, Physical review letters.

[71]  Derick R. Peterson,et al.  Diffusion tensor imaging detects clinically important axonal damage after mild traumatic brain injury: a pilot study. , 2007, Journal of neurotrauma.

[72]  J. Adams,et al.  Diffuse axonal injury and traumatic coma in the primate , 1982, Annals of neurology.

[73]  Lewine Jd,et al.  Spike and slow wave localization by magnetoencephalography. , 1995 .

[74]  M. Raichle,et al.  Detection of blast-related traumatic brain injury in U.S. military personnel. , 2011, The New England journal of medicine.

[75]  P. Basser,et al.  Microstructural and physiological features of tissues elucidated by quantitative-diffusion-tensor MRI. , 1996, Journal of magnetic resonance. Series B.

[76]  Norbert Schuff,et al.  Advances in neuroimaging of traumatic brain injury and posttraumatic stress disorder. , 2009, Journal of rehabilitation research and development.

[77]  Seana Coulson,et al.  Magnetoencephalography reveals early activation of V4 in grapheme-color synesthesia , 2010, NeuroImage.

[78]  Sriram Vasudevan,et al.  Global white matter analysis of diffusion tensor images is predictive of injury severity in traumatic brain injury. , 2007, Journal of neurotrauma.

[79]  Khader M Hasan,et al.  Diffusion Tensor Imaging in Late Posttraumatic Epilepsy , 2005, Epilepsia.

[80]  M. Apuzzo,et al.  Birth and Evolution of the Football Helmet , 2004, Neurosurgery.

[81]  Josef Ling,et al.  Functional connectivity in mild traumatic brain injury , 2011, Human brain mapping.

[82]  Raul Coimbra,et al.  Integrated imaging approach with MEG and DTI to detect mild traumatic brain injury in military and civilian patients. , 2009, Journal of neurotrauma.

[83]  P Gloor,et al.  The cortical electromicrophysiology of pathological delta waves in the electroencephalogram of cats. , 1977, Electroencephalography and clinical neurophysiology.

[84]  L. Noble-Haeusslein,et al.  Traumatic Brain Injury: An Overview of Pathobiology with Emphasis on Military Populations , 2010 .

[85]  D. Pennell,et al.  Are functional deficits in concussed individuals consistent with white matter structural alterations: combined FMRI & DTI study , 2010, Experimental Brain Research.

[86]  R. Leahy,et al.  EEG and MEG: forward solutions for inverse methods , 1999, IEEE Transactions on Biomedical Engineering.

[87]  I Cernak,et al.  Ultrastructural and functional characteristics of blast injury-induced neurotrauma. , 2001, The Journal of trauma.

[88]  M. Wald,et al.  Traumatic brain injury in the United States; emergency department visits, hospitalizations, and deaths, 2002-2006 , 2010 .

[89]  K A Dunn,et al.  Traumatic brain injury in the United States: A public health perspective. , 1999, The Journal of head trauma rehabilitation.