Decrease in myelin water fraction of global white matter and white matter tracts in traumatic brain injury (TBI).
Bretta Russell-Schulz1, Irene Vavasour2, Jing Zhang2, Alex MacKay1,3, Shaun Porter4, Delrae Fawcett5, Ivan Torres5, William Panenka5, Lara Boyd6, and Naznin Virji-Babul4

1UBC MRI Research Centre, Radiology, University of British Columbia, Vancouver, BC, Canada, 2Radiology, University of British Columbia, Vancouver, BC, Canada, 3Physics & Astronomy, University of British Columbia, Vancouver, BC, Canada, 4Physical Therapy, University of British Columbia, Vancouver, Canada, 5Psychiatry, University of British Columbia, Vancouver, Canada, 6Physical Therapy, University of British Columbia, Vancouver, BC, Canada


Chronic traumatic brain injury (TBI) was examined using myelin water fraction (MWF) in global white matter and tracts for subjects undergoing intensive cognitive training (Arrowsmith Program) compared to age and gender matched controls. MWF was significantly lower in TBI subjects and correlations were found between MWF and cognitive scores of fluid and crystallized ability. However, after 3 months of cognitive training no significant differences were found in MWF in TBI subjects.


Traumatic brain injury (TBI) is the most common cause of death in the first half of life, and a prime contributor to disability throughout the lifespan. It can result in a wide range of symptoms that can have long-term effects and is a risk factor for development of neurodegenerative diseases1. It results in known white matter (WM) changes, even in its mild forms2. Myelin water fraction (MWF) is used as a marker for myelin content and has been found to be decreased in normal appearing white matter in neurodegenerative diseases such as multiple sclerosis compared to controls3. MWF has previously been shown to decrease post-concussion and then recover after 2 months4. Here we examine chronic differences in MWF within a heterogeneous group of TBI participants compared to matched controls. Given the ability of MWF to detect recovery, we also re-examined these participants following an intensive cognitive improvement program over 3 months as developed by the Eaton-Arrowsmith Group5.


Participants were recruited as part of a study to evaluate the impact of an intensive cognitive intervention program (Arrowsmith) in adults with TBI. Six TBI subjects and six gender and age matched controls participated in the study, demographics given in Table 1. TBI subjects underwent a 3 month Arrowsmith intervention. Cognitive testing (NIH Toolbox Cognitive Battery)6 and MRI scans were performed. MRI scans were done on a 3T Philips scanner; a 3DT1 scan was completed for anatomical information and a 48-echo Gradient and Spin Echo (GRASE) sequence with echo spacing 8 ms was used to acquire a multi-component T2 decay curve for MWF determination7,8. MWF maps were determined from the GRASE data using a locally written function in matlab. MWF images and 3DT1s were registered to MNI space using FSL. Global white matter (WM) was segmented and pre-existing regions of interest (ROI), from the JHU tract atlas in FSL were used to segment specific tracts: anterior thalamic radiation (ATR), corpus callosum (CC), corticospinal tract (CST), superior and interior longitudinal fasciculus (SLF and ILF respectively). MWF means were compared using a Mann-Whitney U Test between TBI and controls and corrected for multiple comparisons using a Bonferroni-Holm correction at baseline. MWFs for TBI at month 3 followup were also compared to baseline MWFs. Correlations between MWF and cognitive scores were examined using Pearson Correlations (n=9; n=5 TBI, n=4 control).


Baseline results showed both qualitative (visual inspection) and quantitatively decreased global WM MWF in TBI subjects compared to age and gender matched healthy controls at baseline (Figure 1). TBI subjects had significantly lower MWF than controls in global WM (p=0.0087) (Figure 2a), ATR (p=0.0087), CC (p=0.0043), ILF (p=0.0043) and SLF (p=0.0022) (Figure 3). Within the TBI cohort, month 3 results showed no significant difference in MWF from baseline in all ROIs, nor in global WM MWF (Figure 2a). Individual TBI-control pairs of WM MWFs are shown in Figure 2b, where the x axis shows pairings with increasing age. MWF in all ROIs, except CST, correlated positively with a measure of declarative memory, Age Adjusted Picture Sequence Memory Test (PSMT) score (r=0.68-0.77, p<0.05), and MWF in the ILF and SLF correlated positively with a measure of premorbid cognitive function, Age Adjusted Oral Reading Recognition Test (ORRT) score (r=0.77, p<0.02 and r=0.74, p<0.03 respectively) across TBI and controls. Global WM was also found to be significantly positively correlated (r=0.73 and 0.71, p<0.02) with these cognitive measures (Figure 4).


Decreased MWF in chronic TBI may be due to myelin loss or injury. Correlation between increasing years of education and higher MWF in healthy controls is known9; this could have influenced the differences observed between controls and TBI as the controls had more years of education. Correlations between cognitive scores and MWFs show promise that MWF could be use as a biomarker of TBI related deficits in cognitive function. Oral Reading Recognition Test is a measure of crystallized ability and Picture Sequence Memory Test is considered to be a strong measure of fluid ability6, suggesting that MWF may be indexing both aspects of cognitive ability. Three months of cognitive training did not results in a significant difference in MWF. Cognitive change in subjects undergoing the cognitive intervention will be evaluated. 5 TBI subjects will continue with treatment for another 3 months and follow-up month 6 scans will be completed along with cognitive scores. As well, controls will be rescanned at month 3 and month 6.


This project is funded by MITACS in partnership with the Eaton-Arrowsmith group.


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3. Laule C, Vavasour IM, Moore GRW, et al. Water content and myelin water fraction in multiple sclerosis: A T2 relaxation study. J Neurol. 2004;251:284-293.

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5. Arrowsmith Program. Accessed October 30, 2015.

6. Slotkin J, Nowinski C, Hays R, et al. NIH Toolbox: Scoring and Interpretation Guide. September 18, 2012. Accessed October 30, 2015.

7. Prasloski T, Rauscher A, MacKay AL, et al. Rapid whole cerebrum myelin water imaging using a 3D GRASE sequence . NeuroImage. 2012;63:533-539.

8. Zhang J, Vavasour I, Kolind S, et al. Advanced Myelin Water Imaging Techniques for Rapid Data Acquisition and Long T2 Component Measurements . Proceedings of the 23rd Annual Meeting of the International Society of Magnetic Resonance in Medicine; 2015: 30 May-5 June. Toronto, Ontario, Canada (Abstract #:824).

9. Lang DJM, Yip E, MacKay AL, et al. 48 echo T2 myelin imaging of white matter in first-episodeschizophrenia: Evidence for aberrant myelination. NeuroImage: Clinical. 2014;6:408-414.


Figure 1: Myelin water fraction images of controls and TBI subject pairs at baseline.

Figure 2: Global white matter MWF for healthy controls at baseline and TBI subjects at baseline and month 3 a) for group comparison and b) for all TBI-control pairs at baseline and Month 3 treatment with increasing age of TBI subject along x-axis.

Figure 3: Myelin water fraction in different brain tracts significantly different between TBI subjects and their control matches at baseline.

Figure 4: Correlation between global white matter MWF and Age Adjusted Oral Reading Recognition Test and Age Adjusted Picture Sequence scores across TBI and control subjects at baseline.

Table 1: Baseline subject demographics where MVA=Motor Vehicle Accident, MC=Multiple Concussions and TBI Severity is based on Loss of Consciousness Scale.

Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)