Myelin water fraction decrease in mild traumatic brain injury

Abstract

32The increased incidence of reported traumatic brain injury (TBI) and its potentially serious long-term 33 consequences have enormous clinical and societal impacts. The diffuse and continually evolving 34 secondary changes after TBI make it challenging to evaluate the changes in brain-behaviour 35relationships. In this study we used myelin water imaging to evaluate changes in myelin water fraction 36 (MWF) in individuals with chronic brain injury and evaluated their cognitive status using the NIH 37Toolbox Cognitive Battery. Twenty-two adults with mild or severe brain injury and twelve age, gender 38 and education matched healthy controls took part in this study. We found a significant decrease in 39 global white matter MWF in individuals with mild TBI compared to the healthy controls. Significantly 40 lower MWF was evident in most white matter ROIs examined including the corpus callosum 41 (separated into genu, body and splenium), minor forceps, right anterior thalamic radiation, left inferior 42 longitudinal fasciculus; and right and left superior longitudinal fasciculus and corticospinal tract. No 43 significant correlations were found between MWF in mild TBI and the cognitive measures. These 44 results show for the first time the loss of myelin in chronic mild TBI. 45 46 Every year about 160,000 Canadians sustain brain injuries, the most prevalent causes being falls and 47 motor vehicle accidents (MVA) (Brain Injury Canada). An impact to the head results in an immediate 48and direct insult to the brain, setting off a complex cascade of metabolic and neurochemical events. 49These effects can lead to long-term changes in brain physiology leading to cognitive, motor and 50 affective dysfunction (1-3). Over a lifetime, repeated brain trauma or a single moderate or severe TBI 51 is associated with an increased incidence of multiple neuropsychiatric conditions and is a significant 52 risk factor for developing neurodegenerative disorders (4,5). The diffuse and continually evolving 53 secondary changes that are the hallmark of TBI have made it extremely challenging to evaluate brain-54 behavior relationships. Neurodegeneration has been found in the chronic phases after TBI(6) and 55 detected using atrophy measures, however conventional neuroimaging tools (such as CT and MRI) 56 cannot detect the widespread and often subtle changes in structure and function that occur in the brain 57following TBI (7). The long-term effects of a mild TBI (mTBI) are less clear than more severe head 58injuries and neuroimaging findings are less consistent (8,9). Thus advanced MR imaging techniques are 59 increasingly being used to examine and monitor changes in the brain following TBI (10-12). 60 61Physiologically, movement of the brain within the skull causes shearing/stretching of the axons and 62initiates a cascade of molecular events which disrupts normal brain cell function. Metabolic changes 63 occur rapidly following axonal strain, altering the permeability of sodium channels, resulting in an 64 increase in intra-axonal calcium ...