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PreprintCited by 15Traumatic Brain Injury ResearchAdvanced Neuroimaging Techniques and ApplicationsAutomotive and Human Injury Biomechanics

The Evolution of White Matter Changes After Mild Traumatic Brain Injury: A DTI and NODDI Study

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Palacios, Eva M., Owen, Julia P, Yuh, Esther L., Wang, Maxwell B., Vassar, Mary J., Ferguson, Adam R., Diaz-Arrastia, Ramon, Giacino, Joseph T. +11 more·2018·bioRxiv (Cold Spring Harbor Laboratory)
DOI 10.1101/345629

Preprint — published as 10.1126/sciadv.aaz6892 · Paper page

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Abstract

Neuroimaging biomarkers show promise for improving precision diagnosis and prognosis after mild traumatic brain injury (mTBI), but none has yet been adopted in routine clinical practice. Biophysical modeling of multishell diffusion MRI, using the neurite orientation dispersion and density imaging (NODDI) framework, may improve upon conventional diffusion tensor imaging (DTI) in revealing subtle patterns of underlying white matter microstructural pathology, such as diffuse axonal injury (DAI) and neuroinflammation, that are important for detecting mTBI and determining patient outcome. With a cross-sectional and longitudinal design, we assessed structural MRI, DTI and NODDI in 40 mTBI patients at 2 weeks and 6 months after injury and 14 matched control participants with orthopedic trauma but not suffering from mTBI at 2 weeks. Self-reported and performance-based cognitive measures assessing postconcussive symptoms, memory, executive functions and processing speed were investigated in post-acute and chronic phase after injury for the mTBI subjects. Machine learning analysis was used to identify mTBI patients with the best neuropsychological improvement over time and relate this outcome to DTI and NODDI biomarkers. In the cross-sectional comparison with the trauma control group at 2 weeks post-injury, mTBI patients showed decreased fractional anisotropy (FA) and increased mean diffusivity (MD) on DTI mainly in anterior tracts that corresponded to white matter regions of elevated free water fraction (FISO) on NODDI, signifying vasogenic edema. Patients showed decreases from 2 weeks to 6 months in white matter neurite density on NODDI, predominantly in posterior tracts. No significant longitudinal changes in DTI metrics were observed. The machine learning analysis divided the mTBI patients into two groups based on their recovery. Voxel-wise group comparison revealed associations between white matter orientation dispersion index (ODI) and FISO with degree and trajectory of improvement within the mTBI group. In conclusion, white matter FA and MD alterations early after mTBI might reflect vasogenic edema, as shown by elevated free water on NODDI. Longer-term declines in neurite density on NODDI suggest progressive axonal degeneration due to DAI, especially in tracts known to be integral to the structural connectome. Overall, these results show that the NODDI parameters appear to be more sensitive to longitudinal changes than DTI metrics. Thus, NODDI merits further study in larger cohorts for mTBI diagnosis, prognosis and treatment monitoring.

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  • In patients with orthopedic trauma, increased f_fw and decreased NDI in WM are observed compared with controls at 2 weeks post-injury.

    “A longitudinal follow-up of patients with orthopedic trauma revealed increased f fw and decreased NDI in WM compared with controls at 2 weeks post-injury”

    From NODDI in clinical research (2020) · cites this paper as Palacios et al., 2018

    The Discussion identifies orthopedic trauma patients as the control group, not the group with these changes. It reports decreased NDI and increased free-water fraction (FISO) in patients with mTBI versus trauma controls at the early, 2-week time point. The supplied passages do not give page numbers. (LLM, conf=0.90)

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  • In patients with orthopedic trauma, NDI and f_fw decrease over time from 2 weeks to 6 months post-injury.

    “and decreased NDI and f fw over time from 2 weeks to 6 months (Palacios et al., 2018).”

    From NODDI in clinical research (2020) · cites this paper as Palacios et al., 2018

    The ‘Longitudinal analysis of mTBI patients at 2 weeks vs 6 months’ section reports decreases in NDI and FISO over that interval, but those results are for patients with mild traumatic brain injury. The Participants section identifies orthopedic trauma patients as controls; the paper does not report the claimed longitudinal decreases for them. Page numbers are unavailable in our copy. (LLM, conf=0.88)

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Authors
Palacios, E. M., Owen, J. P., Yuh, E. L., Wang, M. B., Vassar, M. J., Ferguson, A. R., Diaz-Arrastia, R., Giacino, J. T., Okonkwo, D. O., Robertson, C. S., Stein, M. B., Temkin, N., Jain, S., McCrea, M., Mac Donald, C. L., Levin, H. S., Manley, G. T., Mukherjee, P., & the TRACK-TBI Investigators
Affiliations
  • University of California, San Francisco (US)
  • University of Washington (US)
  • San Francisco General Hospital (US)
  • University of Pennsylvania (US)
  • Harvard University (US)
  • University of Pittsburgh Medical Center (US)
  • Baylor College of Medicine (US)
  • University of California San Diego (US)
  • Medical College of Wisconsin (US)
Corresponding author
Mukherjee, Pratik
ORCID
Venue
bioRxiv (Cold Spring Harbor Laboratory)
Publisher
openRxiv
Published
2018-06-14
DOI
10.1101/345629
OpenAlex
W2808408179
Cited by
15
References
5
Citations by year
2026: 1 · 2025: 1 · 2023: 1 · 2021: 3 · 2020: 6 · 2019: 2 · 2018: 1
Type
posted content
Language
en
Open access
Locations
bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
Funders
  • U.S. Department of Defense (W81XWH, W81XWH1420176, W81XWH‐14)
  • National Institutes of Health (NIH-R01, W81XWH)
  • National Institute of Neurological Disorders and Stroke (RC2NS069409, R01NS060776, U01NS086090)
Topics
  • Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Automotive and Human Injury Biomechanics
Keywords
mild traumatic brain injury, NODDI, diffusion tensor imaging, white matter microstructure, diffuse axonal injury, vasogenic edema, free water fraction, neurite density, orientation dispersion index, post-concussion symptoms, cognitive recovery, neuroinflammation, axonal degeneration, structural connectome, neuroimaging biomarkers

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