Brain Imaging and Behavior

, Volume 6, Issue 2, pp 329–342 | Cite as

Robust detection of traumatic axonal injury in individual mild traumatic brain injury patients: Intersubject variation, change over time and bidirectional changes in anisotropy

  • Michael L. LiptonEmail author
  • Namhee Kim
  • Young K. Park
  • Miriam B. Hulkower
  • Tova M. Gardin
  • Keivan Shifteh
  • Mimi Kim
  • Molly E. Zimmerman
  • Richard B. Lipton
  • Craig A. Branch


To identify and characterize otherwise occult inter-individual spatial variation of white matter abnormalities across mild traumatic brain injury (mTBI) patients. After informed consent and in compliance with Health Insurance Portability and Accountability Act (HIPAA), Diffusion tensor imaging (DTI) was performed on a 3.0 T MR scanner in 34 mTBI patients (19 women; 19–64 years old) and 30 healthy control subjects. The patients were imaged within 2 weeks of injury, 3 months after injury, and 6 months after injury. Fractional anisotropy (FA) images were analyzed in each patient. To examine white matter diffusion abnormalities across the entire brain of individual patients, we applied Enhanced Z-score Microstructural Assessment for Pathology (EZ-MAP), a voxelwise analysis optimized for the assessment of individual subjects. Our analysis revealed areas of abnormally low or high FA (voxel-wise P-value < 0.05, cluster-wise P-value < 0.01(corrected for multiple comparisons)). The spatial pattern of white matter FA abnormalities varied among patients. Areas of low FA were consistent with known patterns of traumatic axonal injury. Areas of high FA were most frequently detected in the deep and subcortical white matter of the frontal, parietal, and temporal lobes, and in the anterior portions of the corpus callosum. The number of both abnormally low and high FA voxels changed during follow up. Individual subject assessments reveal unique spatial patterns of white matter abnormalities in each patient, attributable to inter-individual differences in anatomy, vulnerability to injury and mechanism of injury. Implications of high FA remain unclear, but may evidence a compensatory mechanism or plasticity in response to injury, rather than a direct manifestation of brain injury.


Mild traumatic brain injury (mTBI) MRI Diffusion tensor imaging (DTI) Traumatic axonal injury (TAI) Image processing and analysis 



Computerized tomography


Diffusion tensor imaging


Enhanced Z-score


Enhanced Z-score microstructural assessment for pathology


Fractional anisotropy


Glasgow Coma Scale


Gaussian Random Field


Health Insurance Portability and Accountability Act


Institutional Review Board


Johns Hopkins University


Montreal Neurological Institute


Magnetic resonance


Mild traumatic brain injury


Receiver operating characteristic


Standard deviation


Traumatic axonal injury


Traumatic brain injury


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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Michael L. Lipton
    • 1
    • 2
    • 3
    • 4
    • 8
    Email author
  • Namhee Kim
    • 1
    • 2
  • Young K. Park
    • 1
    • 9
  • Miriam B. Hulkower
    • 1
  • Tova M. Gardin
    • 1
    • 8
  • Keivan Shifteh
    • 8
  • Mimi Kim
    • 5
  • Molly E. Zimmerman
    • 6
  • Richard B. Lipton
    • 5
    • 6
  • Craig A. Branch
    • 1
    • 2
    • 7
  1. 1.The Gruss Magnetic Resonance Research CenterAlbert Einstein College of Medicine of Yeshiva UniversityBronxUSA
  2. 2.Department of RadiologyAlbert Einstein College of Medicine of Yeshiva UniversityBronxUSA
  3. 3.Department of Psychiatry & Behavioral SciencesAlbert Einstein College of Medicine of Yeshiva UniversityBronxUSA
  4. 4.The Dominick P Purpura Department of NeuroscienceAlbert Einstein College of Medicine of Yeshiva UniversityBronxUSA
  5. 5.Department of Epidemiology and Population HealthAlbert Einstein College of Medicine of Yeshiva UniversityBronxUSA
  6. 6.The Saul R. Korey Department of NeurologyAlbert Einstein College of Medicine of Yeshiva UniversityBronxUSA
  7. 7.Department of Physiology & BiophysicsAlbert Einstein College of Medicine of Yeshiva UniversityBronxUSA
  8. 8.The Department of RadiologyMontefiore Medical CenterBronxUSA
  9. 9.Hofstra North Shore-LIJ School of Medicine at Hofstra University, North Shore-Long Island Jewish Health SystemManhassetUSA

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