Myelin Water Fraction Is Transiently Reduced after a Single Mild Traumatic Brain Injury – A Prospective Cohort Study in Collegiate Hockey Players

Abstract

Impact-related mild traumatic brain injuries (mTBI) are a major public health concern, and remain as one of the most poorly understood injuries in the field of neuroscience. Currently, the diagnosis and management of such injuries are based largely on patient-reported symptoms. An improved understanding of the underlying pathophysiology of mTBI is urgently needed in order to develop better diagnostic and management protocols. Specifically, dynamic post-injury changes to the myelin sheath in the human brain have not been examined, despite ‘compromised white matter integrity’ often being described as a consequence of mTBI. In this preliminary cohort study, myelin water imaging was used to prospectively evaluate changes in myelin water fraction, derived from the T2 decay signal, in two varsity hockey teams (45 players) over one season of athletic competition. 11 players sustained a concussion during competition, and were scanned at 72 hours, 2 weeks, and 2 months post-injury. Results demonstrated a reduction in myelin water fraction at 2 weeks post-injury in several brain areas relative to preseason scans, including the splenium of the corpus callosum, right posterior thalamic radiation, left superior corona radiata, left superior longitudinal fasciculus, and left posterior limb of the internal capsule. Myelin water fraction recovered to pre-season values by 2 months post-injury. These results may indicate transient myelin disruption following a single mTBI, with subsequent remyelination of affected neurons. Myelin disruption was not apparent in the athletes who did not experience a concussion, despite exposure to repetitive subconcussive trauma over a season of collegiate hockey. These findings may help to explain many of the metabolic and neurological deficits observed clinically following mTBI.

What is the physiological time to recovery after concussion? A systematic review

“…These are inherently difficult to compare directly because of differences in study populations, methodology, time points and brain region of interest analysed. Among longitudinal studies, four used DTI26–29 and one used myelin water fraction (MWF) 30. One article found imaging consistent with clinical data, with radial diffusivity increased and fractional anisotropy (FA) decreased at post injury day 2 (PID) with normalisation by 14 days after injury 26.…”

“…However, others found changes in FA varied depending on region of interest and showed increased MD at chronic time points 31. MWF was reduced at 3 days after injury, tended to be decreased at day 14 and normalised by day 60 30. Diffusion kurtosis imaging showed changes from controls at 1 day after injury and persisting at day 8, but recovery of symptoms and cognition occurred between 1 and 8 days after injury 29…”

Myelin water imaging to detect demyelination and remyelination and its validation in pathology

“…Beyond MS, myelin water imaging has been used to study many other neurological disease applications include neuromyelitis optica , schizophrenia and first episode psychosis , phenylketonuria , autism , stroke , neurofibromatosis , Niemann–Pick disease , primary lateral sclerosis , amyotrophic lateral sclerosis , concussion , and Krabbe disease . Other spinal cord applications are also feasible, for example, a recent study of cervical spondylotic myelopathy demonstrated a correlation between MWF in the dorsal columns and functional measures of myelin through somatosensory evoked potential latency times .…”

Brain Myelin Water Fraction and Diffusion Tensor Imaging Atlases for 9‐10 Year‐Old Children

“…Myelin water fraction (MWF), defined as the fraction of the total signal which has T 2 < 40 milliseconds at 3 Tesla, has been histologically validated as a marker of myelin density in human tissue, 30–32 and has good scan‐rescan reproducibility (coefficient of variation 4% in cerebral white matter) 33 . MWI has been used to investigate myelin in a wide range of diseases including multiple sclerosis, neuromyelitis optica spectrum disorder, schizophrenia, Niemann‐Pick disease, prenatal alcohol exposure, amyotrophic and primary lateral sclerosis, Krabbe disease, autism, stroke, and traumatic brain injury 34–47 . Rapid myelination has been demonstrated in early childhood and adolescence using multicomponent driven equilibrium single pulse observation of T 1 and T 2 (mcDESPOT), an alternate approach to MWI using a steady‐state acquisition 48–53 .…”

“…33 MWI has been used to investigate myelin in a wide range of diseases including multiple sclerosis, neuromyelitis optica spectrum disorder, schizophrenia, Niemann-Pick disease, prenatal alcohol exposure, amyotrophic and primary lateral sclerosis, Krabbe disease, autism, stroke, and traumatic brain injury. [34][35][36][37][38][39][40][41][42][43][44][45][46][47] Rapid myelination has been demonstrated in early childhood and adolescence using multicomponent driven equilibrium single pulse observation of T 1 and T 2 (mcDESPOT), an alternate approach to MWI using a steadystate acquisition. [48][49][50][51][52][53] Adult multi-echo T 2 -based MWF atlases in both brain and cervical spinal cord have recently been published, 54,55 but, to our knowledge, no such atlases exist for children.…”