104 / 198
AIF supports our plan to use this method in the future for traumatic
brain injury studies. The loss of correlation in smaller ROIs is likely
due to a lack of smoothing of the blood vessels with the higher res-
olution DSC-PWI; the standard deviation is much higher than in the
pCASL data. In summary, the dual-injection DSC-PWI method pro-
vides a reliable, high resolution measurement of CBF, which could be
useful in TBI.
Keywords: Cerebral blood flow, Perfusion weighted imaging, Ar-
terial spin labeling, Validation
B7 Poster Session IV - Group B: Neuropathology
B7-01
CLINICOPATHOLOGICAL FINDINGS IN 100 FORMER NFL
PLAYERS
Ann McKee
, P Kiernan, L Murphy, J Mez, T Solomon, D Daneshvar,
P Montenigro, C Nowinski, L Goldstein, R Cantu, D Katz, N Kowall,
R Stern, V Alvarez, T Stein
Boston University, Neurology, Boston, USA
In 2008, a brain bank was created by Boston University School of
Medicine, VA Boston, and Sports Legacy Institute to better understand
the long-term effects of repetitive mild brain trauma (RBT). To date, 255
brains have been harvested from individuals exposed to RBT through
sports, military service or other means, including 100 former National
Football League (NFL) players. NFL players ranged in age from 23–
98 yrs at death, mean 65 yrs: 76%Caucasian, 23%African American, 1%
Pacific Islander. The mean age at first exposure to football: 12 yrs, mean
total playing yrs: 17, mean yrs in the NFL: 7. 80 of the 84 (95%) neu-
ropathologically analyzed were diagnosed with CTE (mean stage III
(max IV)) using criteria (McKee, 2013) recently confirmed by the First
NIH Consensus Conference to Define the Neuropathological Criteria
for the Diagnosis of CTE,
http://www.ninds.nih.gov/research/tbi/ReportFirstNIHConsensusConference.htm. Players with CTE played
every position except kicker. 50 (63%) were diagnosed with pure CTE,
37% had co-morbid neurodegeneration. Of those with pure CTE, 2% had
no symptoms (mean age at death 48 yrs). 20% presented with mixed
behavioral and cognitive changes (mean onset: 45 yrs, age at death:
57 yrs), 48% presented with behavior and mood changes (mean onset:
39 yrs, age at death: 63 yrs), 24% presented with cognitive changes (mean
onset: 56 yrs, age at death: 71 yrs). The overwhelming majority of this
sample of former NFL players had at least stage II CTE. However,
ascertainment bias is a recognized limitation of brain donor cohorts, even
when inclusion criteria are based solely on exposure, and caution must be
used in interpreting the high frequency of CTE in this sample. The precise
clinicopathological characterization of this NFL cohort will provide
valuable information to aid in the future detection, management, and
treatment of CTE in living individuals.
Keywords: Trauma, Tau protein, Football, Sports
B7-02
EARLY CHRONIC TRAUMATIC ENCEPHALOPATHY IN
YOUNG ATHLETES AFTER CONCUSSIVE HEAD INJURY
AND A MOUSE MODEL OF IMPACT CONCUSSION
Lee Goldstein
1
, Chad Tagge
1
, Andrew Fisher
1
, Amanda Gaudreau
1
,
Mark Wojnarowicz
1
, Olga Minaeva
1
, Juliet Moncaster
1
, Noel Casey
1
,
Garth Hall
2
, Robin Cleveland
3
, William Moss
4
, Thor Stein
5
, Patric
Stanton
6
, Ann McKee
5
1
BU School of Medicine, Molecular Aging & Development Labora-
tory, Boston, MA, USA
2
University of Massachusetts Lowell, Biological Sciences, Lowell,
MA, USA
3
University of Oxford, Engineering Science, Oxford, UK
4
Lawrence Livermore National Laboratory, Physics, Livermore, CA,
USA
5
Boston VA Medical Center, Neurology Services, Boston, MA, USA
6
NY Medical College, Cell Biology and Anatomy, Valhalla, NY, USA
The mechanisms by which head injury induces acute concussion and
chronic sequelae are not known. We examined postmortem brains
from young athletes after concussive head injury and found paren-
chymal contusion, myelinated axonopathy, microvasculopathy, neu-
roinflammation, neurodegeneration, and phosphorylated tauopathy
consistent with early chronic traumatic encephalopathy (CTE). We
developed a biofidelic mouse model of impact concussion that induces
non-skull deforming head acceleration, acute concussion, and trau-
matic brain injury (TBI) in unanesthetized C57BL/6 mice. Impacted
mice exhibited contralateral circling, limb weakness, locomotor ab-
normalities, and impaired balance that recapitulates human concus-
sion. Neurological function rapidly returned to baseline, but markers
of early CTE persisted long after recovery. Impact concussion induced
blood-brain barrier disruption, neuroinflammation, impaired hippo-
campal axonal conduction, and defective long-term potentiation
(LTP) of synaptic transmission in prefrontal cortex. Kinematic anal-
ysis revealed head acceleration sufficient to induce concussion, TBI,
and CTE-linked pathology. Notably, concussion did not correlate with
CTE markers or chronic sequelae. Concussion was observed follow-
ing impact injury but not blast exposure under conditions of compa-
rable head kinematics. Dynamic modeling revealed greater brain shear
stress during impact compared to blast neurotrauma. These results
indicate that while acute concussion and chronic sequelae may be
triggered by the same insult, the pathophysiological responses un-
derpinning these effects engage distinct mechanisms and time do-
mains. Concussion per se is neither necessary nor sufficient to trigger
acute brain injury and chronic sequelae, including CTE. These results
suggest that the critical variable of clinical relevance is neurotrauma
exposure (hits).
Keywords: chronic traumatic encephalopathy, traumatic brain in-
jury, concussion, impact, blast, neurotrauma
B7-03
INJECTABLE FIDUCIAL MARKER IN MRI GUIDED PA-
THOLOGY OF BRAIN INJURY
Allison Griffin
1
, Gunjan Parikh
3,2
, John Ostuni
2
, Anita Moses
1
, Nancy
Edwards
2
, Govind Nair
2
, Abhik Ray-Chaudhury
2
, Lawrence Latour
2
1
CNRM/HJF/NIH, NINDS/SB, Bethesda, USA
2
NIH, NINDS, Bethesda, USA
3
University of Maryland, Shock Trauma, Baltimore, MD
There has been growing interest in pathology underlying focal MRI
abnormalities, such as traumatic microbleeds, in efforts to increase
sensitivity of MRI based diagnosis. MRI has been used to guide
sectioning of brain tissue, however co-localization of MRI and his-
tology is not trivial. Here we introduce the use of an injectable
fiducial marker combined with a 3D-printed structure for imaging
and sectioning of the brain, to reduce ambiguity of MRI guided
pathology. Acrylic paint containing iron oxide was chosen as an
injectable fiducial. Two donated fixed specimens were used for this
work; coronal sections to verify the fiducial, and whole brain for
A-68