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. Lipton, Namhee Kim, Young K. Park, Miriam B. Hulkower, Tova M. Gardin, Keivan Shifteh, Mimi Kim, Molly E. Zimmerman, Richard B. Lipton, Craig A. Branch

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)329-342
Number of pages14
JournalBrain Imaging and Behavior
Volume6
Issue number2
DOIs
StatePublished - Jun 2012

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Brain Concussion
Anisotropy
Wounds and Injuries
Health Insurance Portability and Accountability Act
Parietal Lobe
Diffusion Tensor Imaging
Corpus Callosum
Frontal Lobe
Temporal Lobe
Informed Consent
Individuality
Brain Injuries
Anatomy
Healthy Volunteers
White Matter
Pathology
Brain

Keywords

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

ASJC Scopus subject areas

  • Clinical Neurology
  • Psychiatry and Mental health
  • Neurology
  • Cognitive Neuroscience
  • Cellular and Molecular Neuroscience
  • Behavioral Neuroscience
  • Radiology Nuclear Medicine and imaging

Cite this

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title = "Robust detection of traumatic axonal injury in individual mild traumatic brain injury patients: Intersubject variation, change over time and bidirectional changes in anisotropy",
abstract = "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.",
keywords = "Diffusion tensor imaging (DTI), Image processing and analysis, Mild traumatic brain injury (mTBI), MRI, Traumatic axonal injury (TAI)",
author = "Lipton, {Michael L.} and Namhee Kim and Park, {Young K.} and Hulkower, {Miriam B.} and Gardin, {Tova M.} and Keivan Shifteh and Mimi Kim and Zimmerman, {Molly E.} and Lipton, {Richard B.} and Branch, {Craig A.}",
year = "2012",
month = "6",
doi = "10.1007/s11682-012-9175-2",
language = "English (US)",
volume = "6",
pages = "329--342",
journal = "Brain Imaging and Behavior",
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TY - JOUR

T1 - Robust detection of traumatic axonal injury in individual mild traumatic brain injury patients

T2 - Intersubject variation, change over time and bidirectional changes in anisotropy

AU - Lipton, Michael L.

AU - Kim, Namhee

AU - Park, Young K.

AU - Hulkower, Miriam B.

AU - Gardin, Tova M.

AU - Shifteh, Keivan

AU - Kim, Mimi

AU - Zimmerman, Molly E.

AU - Lipton, Richard B.

AU - Branch, Craig A.

PY - 2012/6

Y1 - 2012/6

N2 - 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.

AB - 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.

KW - Diffusion tensor imaging (DTI)

KW - Image processing and analysis

KW - Mild traumatic brain injury (mTBI)

KW - MRI

KW - Traumatic axonal injury (TAI)

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JO - Brain Imaging and Behavior

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