The evolution of white matter microstructural changes after mild traumatic brain injury: A longitudinal DTI and NODDI study

E M Palacios; J P Owen; E L Yuh; M B Wang; M J Vassar; A R Ferguson; R Diaz-Arrastia; J T Giacino; D O Okonkwo; C S Robertson; M B Stein; N Temkin; S Jain; M McCrea; C L MacDonald; H S Levin; G T Manley; P Mukherjee; TRACK-TBI Investigators

doi:10.1126/sciadv.aaz6892

The evolution of white matter microstructural changes after mild traumatic brain injury: A longitudinal DTI and NODDI study

Sci Adv. 2020 Aug 7;6(32):eaaz6892. doi: 10.1126/sciadv.aaz6892. eCollection 2020 Aug.

Authors

E M Palacios¹, J P Owen², E L Yuh^{1

3}, M B Wang¹, M J Vassar^{3

4}, A R Ferguson^{3

4

5}, R Diaz-Arrastia⁶, J T Giacino^{7

8}, D O Okonkwo⁹, C S Robertson¹⁰, M B Stein^{11

12}, N Temkin¹³, S Jain¹², M McCrea¹⁴, C L MacDonald¹³, H S Levin¹⁵, G T Manley^{3

4}, P Mukherjee^{1

3

16}; TRACK-TBI Investigators

Affiliations

¹ Department of Radiology & Biomedical Imaging, UCSF, San Francisco, CA, USA.
² Department of Radiology, University of Washington, Seattle, WA, USA.
³ Brain and Spinal Cord Injury Center, Zuckerberg San Francisco General Hospital and Trauma Center, San Francisco, CA, USA.
⁴ Department of Neurological Surgery, UCSF, San Francisco, CA, USA.
⁵ San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA.
⁶ Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA.
⁷ Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital, Charlestown, MA, USA.
⁸ Department of Physical Medicine and Rehabilitation, Harvard Medical School, Boston, MA, USA.
⁹ Department of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
¹⁰ Department of Neurosurgery, Baylor College of Medicine, Houston, TX, USA.
¹¹ Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA.
¹² Department of Family Medicine & Public Health, University of California, San Diego, La Jolla, CA, USA.
¹³ Department of Neurological Surgery, University of Washington, Seattle, WA, USA.
¹⁴ Departments of Neurosurgery and Neurology, Medical College of Wisconsin, Milwaukee, WI, USA.
¹⁵ Department of Neurology, Baylor College of Medicine, Houston, TX, USA.
¹⁶ Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, USA.

Abstract

Neuroimaging biomarkers that can detect white matter (WM) pathology after mild traumatic brain injury (mTBI) and predict long-term outcome are needed to improve care and develop therapies. We used diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) to investigate WM microstructure cross-sectionally and longitudinally after mTBI and correlate these with neuropsychological performance. Cross-sectionally, early decreases of fractional anisotropy and increases of mean diffusivity corresponded to WM regions with elevated free water fraction on NODDI. This elevated free water was more extensive in the patient subgroup reporting more early postconcussive symptoms. The longer-term longitudinal WM changes consisted of declining neurite density on NODDI, suggesting axonal degeneration from diffuse axonal injury for which NODDI is more sensitive than DTI. Therefore, NODDI is a more sensitive and specific biomarker than DTI for WM microstructural changes due to mTBI that merits further study for mTBI diagnosis, prognosis, and treatment monitoring.

Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).

Publication types

Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, Non-U.S. Gov't

Grants and funding

U01 NS086090/NS/NINDS NIH HHS/United States