Myelin Imaging in Concussed High School Football Players

The lack of highly sensitive clinical neuroimaging and neuropsychiatric markers of subtle
changes due to mTBI makes it difficult to characterize injury severity and to predict
outcomes. White matter tracts in the brain, both myelinated and non-myelinated, are
susceptible to damage from impact-acceleration forces experienced during a TBI,5-7 and there
is evidence that significant white matter injury and myelin loss occurs in mTBI. In addition,
this damage may be chronic and can negatively affect neural processing speed and cognitive
function. Traditional anatomical and function MRI imaging sequences include clinical
sequences such as traditional T1 and T2 sequences, fluid-attenuated inversion recovery
(FLAIR), three-dimensional (3D) magnetization-prepared rapid gradient echo (MP-RAGE),
diffusion-weighted imaging (DWI) and gradient MRI. While a number of advanced imaging
techniques, notably magnetization transfer, diffusion tensor and quantitative T1 and T2
imaging (MTI, DTI, qT1 and qT2, respectively), have been used previously to study white
matter in neurosurgical diseases, these methods provide only indirect, non-specific
information related to myelin content. For example, these modalities can tell when there is
swelling that is affecting the movement of water, which may be indicative of a process that
would affect myelin, but they cannot give specific information about the amount of myelin
surrounding a nerve. An emerging multicomponent relaxometry technique, termed multicomponent
driven equilibrium single pulse observation of T1 and T2 (mcDESPOT), provides a voxel-wise
estimation ranging from 0 to 1 for myelin content, with higher values providing an indirect
marker of greater myelin integrity. Two studies have shown increased myelin after injury in
football and ice hockey players.8 DTI, which primarily gives information about the
myelin-axon bundle interactions, has shown decreased fractional anisotropy after
mTBI,myelin-axon bundle interactions, has shown decreased fractional anisotropy after mTBI,
indicating that the myelin that is present is less organized.8 Combining mcDESPOT and DTI
findings, it is possible to see a more nuanced picture of the remyelination process after
mTBI. In the present program, the investigators propose adding the mcDESPOT sequence to the
MRI scanner in accordance with the MRI manufacturer's technical requirements. Although the
sequences obtained for mcDESPOT are nearly identical sequences used in clinical practice, the
flip-angles are changed so that they cannot be read like a traditional image.

Rather, the data have to be post-processed by a computer in order to be able to derive myelin
information. The mcDESPOT sequences are FDA approved, and present no additional risk over
traditional clinical MRI sequences. Apolipoprotein E (ApoE) is a class of proteins involved
in the metabolism of fats in the body, and is important in Alzheimer's disease and
cardiovascular disease. How the body makes this protein is genetically coded in the APoE
gene. One form of this gene, APoE allele 4 (APoE4) is found in about 25% of the population,
but in 60% of patients with Alzheimer's dementia. Infants with this allele also show
decreased myelination at a young age. It is postulated that this defect affects the brain's
ability to myelinate and remyelinate, leading to decreased or disorganized myelination, which
then leads to an increased risk for development of dementia. This study aims to build upon
preliminary data collected by the principal investigator (PI) showing increased but
disorganized myelin in collegiate football players, by confirming and reproducing these
results in a larger population. This study will also add the component of genetic testing for
the APoE4 allele to see if there is a sub-segment of the study population that may be at
increased risk for brain injury after mTBI and subsequent findings in the research scans. The
mcDESPOT and genetic testing findings will also be correlated with routine neuropsychology
concussion assessment results.

Inclusion Criteria:

- Experimental Group

- Patient age range: 9th through 12th grade (high school)

- Male

- Right-handed

- Diagnosis of mTBI or concussion during a football game or training

- No significant co-morbidities

- Able to get an MRI

- Potential subject must be capable of giving informed consent or assent when
applicable

• Control Group

- Patient age range: 9th through 12th grade (high school)

- Male Right-handed

- Does not play contact sports (football, soccer, lacrosse)

- No significant co-morbidities

- Able to get an MRI

- Potential subject must be capable of giving informed consent or assent when
applicable

Exclusion Criteria:

- Unable to tolerate MRI scan