Characterizing ‘mild’ in traumatic brain injury with proton MR spectroscopy in the thalamus: Initial findings

Objective: Although most mild traumatic brain injury (mTBI) patients suffer any of several post-concussion symptoms suggestive of thalamic involvement, they rarely present with any MRI-visible pathology. The aim here, therefore, is to characterize their thalamic metabolite levels with proton MR spectroscopy (1H-MRS) compared with healthy controls. Methods: T1-weighted MRI and multi-voxel 1H-MRS were acquired at 3 Tesla from 20 mTBI (Glasgow Coma Scale score of 15–13) patients, 19–59 years old, 0–7 years post-injury; and from 17 age and gender matched healthy controls. Mixed model regression was used to compare patients and controls with respect to the mean absolute N-acetylaspartate (NAA), choline (Cho) and creatine (Cr) levels within each thalamus. Results: The mTBI-induced thalamic metabolite concentration changes were under ±13.0% for NAA, ±13.5% for Cr and ±18.8% for Cho relative to their corresponding concentrations in the controls: NAA: 10.08 ± 0.30 (mean ± standard error), Cr: 5.62 ± 0.18 and Cho: 2.08 ± 0.09 mM. These limits represent the minimal detectable differences between the two cohorts. Conclusion: The change in metabolic levels in the thalamus of patients who sustained clinically defined mTBI could be an instrumental characteristic of ‘mildness’. 1H-MRS could, therefore, serve as an objective laboratory indicator for differentiating ‘mild’ from more severe categories of head-trauma, regardless of the presence or lack of current clinical symptoms.

[1]  W M Brooks,et al.  Magnetic resonance spectroscopy in traumatic brain injury. , 2001, The Journal of head trauma rehabilitation.

[2]  R. Chan Sustained attention in patients with mild traumatic brain injury , 2005, Clinical rehabilitation.

[3]  K. Hall,et al.  Mild traumatic brain injury in an insured population: subjective complaints and return to employment. , 1992, Brain injury.

[4]  D. Streiner,et al.  The clinical significance of major depression following mild traumatic brain injury. , 2003, Psychosomatics.

[5]  I. Grant,et al.  Postconcussional disorder: time to acknowledge a common source of neurobehavioral morbidity. , 1994, The Journal of neuropsychiatry and clinical neurosciences.

[6]  Kyla Pennington,et al.  Differential responses in three thalamic nuclei in moderately disabled, severely disabled and vegetative patients after blunt head injury. , 2004, Brain : a journal of neurology.

[7]  D. McArthur,et al.  Epidemiologic aspects of brain injury. , 1996, Neurologic clinics.

[8]  B. Hart,et al.  Quantitative proton MRS predicts outcome after traumatic brain injury , 1999, Neurology.

[9]  S. Stein,et al.  Mild head injury: a plea for routine early CT scanning. , 1992, The Journal of trauma.

[10]  G. Manley,et al.  Volumetric proton spectroscopic imaging of mild traumatic brain injury. , 2004, AJNR. American journal of neuroradiology.

[11]  Peter M Rees Contemporary issues in mild traumatic brain injury. , 2003, Archives of physical medicine and rehabilitation.

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

[13]  J E Sniezek,et al.  Incidence of mild and moderate brain injury in the United States, 1991. , 1996, Brain injury.

[14]  R. Ruff,et al.  Miserable minority: emotional risk factors that influence the outcome of a mild traumatic brain injury. , 1996, Brain injury.

[15]  B. Gordon,et al.  Guidelines for the pharmacologic treatment of neurobehavioral sequelae of traumatic brain injury. , 2006, Journal of neurotrauma.

[16]  J. Povlishock,et al.  The pathobiology of traumatically induced axonal injury in animals and humans: a review of current thoughts. , 1995, Journal of neurotrauma.

[17]  Timothy Edward John Behrens,et al.  Non-invasive mapping of connections between human thalamus and cortex using diffusion imaging , 2003, Nature Neuroscience.

[18]  J. Povlishock,et al.  Neurobiology of Disease Identification and Characterization of Heterogeneous Neuronal Injury and Death in Regions of Diffuse Brain Injury: Evidence for Multiple Independent , 2022 .

[19]  E. Bigler,et al.  Ventricular dilation, cortical atrophy, and neuropsychological outcome following traumatic brain injury. , 1995, The Journal of neuropsychiatry and clinical neurosciences.

[20]  G. Dohrmann,et al.  Brain injury: Analysis of imaging modalities , 2002, Neurological research.

[21]  B. Condon,et al.  Early and late magnetic resonance imaging and neuropsychological outcome after head injury. , 1988, Journal of neurology, neurosurgery, and psychiatry.

[22]  D. Warden,et al.  Military TBI During the Iraq and Afghanistan Wars , 2006, The Journal of head trauma rehabilitation.

[23]  Ronald Ruff,et al.  Two Decades of Advances in Understanding of Mild Traumatic Brain Injury , 2005, The Journal of head trauma rehabilitation.

[24]  Ramona O Hopkins,et al.  Traumatic brain injury and atrophy of the cingulate gyrus. , 2002, The Journal of neuropsychiatry and clinical neurosciences.

[25]  A. Blamire,et al.  Evidence for cellular damage in normal-appearing white matter correlates with injury severity in patients following traumatic brain injury: A magnetic resonance spectroscopy study. , 2000, Brain : a journal of neurology.

[26]  H. Levin,et al.  Depression and Posttraumatic Stress Disorder at Three Months After Mild to Moderate Traumatic Brain Injury , 2001, Journal of clinical and experimental neuropsychology.

[27]  J.-K. Kang,et al.  Metabolic changes in pericontusional oedematous areas in mild head injury evaluated by 1H MRS. , 2000, Acta neurochirurgica. Supplement.

[28]  J. Bazarian,et al.  Mild traumatic brain injury in the United States, 1998–2000 , 2005, Brain injury.

[29]  S. Deb,et al.  Neuropsychiatric sequelae one year after a minor head injury , 1998, Journal of neurology, neurosurgery, and psychiatry.

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

[31]  H. Rusinek,et al.  Proton MR spectroscopy and MRI-volumetry in mild traumatic brain injury. , 2007, AJNR. American journal of neuroradiology.

[32]  R. Wood Understanding the 'miserable minority': a diasthesis-stress paradigm for post-concussional syndrome. , 2004, Brain injury.

[33]  B. Miller A review of chemical issues in 1H NMR spectroscopy: N‐acetyl‐l‐aspartate, creatine and choline , 1991, NMR in biomedicine.

[34]  R Stoyanova,et al.  3D multivoxel proton spectroscopy of human brain using a hybrid of 8th‐order hadamard encoding with 2D chemical shift imaging , 1998, Magnetic resonance in medicine.

[35]  J. Malec Mild traumatic brain injury. , 1997, Archives of physical medicine and rehabilitation.

[36]  R. Kreis Quantitative localized 1H MR spectroscopy for clinical use , 1997 .

[37]  M S Grady,et al.  The Use of Antibodies Targeted Against the Neurofilament Subunits for the Detection of Diffuse Axonal Injury in Humans , 1993, Journal of neuropathology and experimental neurology.

[38]  D. Sosin,et al.  Trends in death associated with traumatic brain injury, 1979 through 1992. Success and failure. , 1995, JAMA.

[39]  E. Bigler,et al.  Lesion volume, injury severity, and thalamic integrity following head injury. , 1996, Journal of neurotrauma.

[40]  Gadi Goelman,et al.  Optimizing the efficiency of high‐field multivoxel spectroscopic imaging by multiplexing in space and time , 2006, Magnetic resonance in medicine.

[41]  M. Uzan,et al.  Thalamic proton magnetic resonance spectroscopy in vegetative state induced by traumatic brain injury , 2003, Journal of neurology, neurosurgery, and psychiatry.

[42]  R. Kessler,et al.  The prevalence and distribution of major depression in a national community sample: the National Comorbidity Survey. , 1994, The American journal of psychiatry.

[43]  R. Lenkinski,et al.  Proton magnetic resonance spectroscopy for detection of axonal injury in the splenium of the corpus callosum of brain-injured patients. , 1998, Journal of neurosurgery.

[44]  J. Borg,et al.  Summary of the WHO Collaborating Centre for Neurotrauma Task Force on Mild Traumatic Brain Injury. , 2005, Journal of rehabilitation medicine.

[45]  V. Govindaraju,et al.  Automated spectral analysis III: Application to in Vivo proton MR Spectroscopy and spectroscopic imaging , 1998, Magnetic resonance in medicine.