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 determination^7,8. 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.