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experiments, a significant reduction of BP
ND
was observed on days
1 and 3 (up to 30–50%) in CCI rats, but there was no significant
difference on days 7 and 26. A similar reduction of
a
7-nAChR
binding on days 1 and 3 and recovery on days 7 and 25 was seen in
the PET experiments. Evaluation of the cortical tissue demonstrated
that neuronal
a
7-nAChR’s are present in the sham, but are reduced
in the ipsilateral hemisphere after CCI. In conclusion, there is
significant reduction in expression of
a
7-nAChR’s early (1d, 3d)
after TBI, as measured by PET imaging, biodistribution, and im-
munohistochemistry. Validation of this non-invasive (PET) imaging
of
a
7-nAChR binding after TBI in preclinical models will facilitate
understanding of the pathogenesis of TBI, and could lead to clinical
translation for diagnosis, prognosis and drug development after
human TBI.
Keywords: nicotinic acetylcholine receptor
B6-08
DECREASED CEREBRAL BLOOD FLOW IS ASSOCIATED
WITH WORSE COGNITIVE OUTCOME AFTER RE-
PETITIVE CONCUSSIONS IN MICE
Michael Whalen
, Erin Buckley, Homa Sadeghian, Julianne Golinski,
Lauren McAllister, Maria Franceschini
Massachusetts General Hospital, Pediatrics, Boston, USA
Objectives:
Repetitive concussions may result in long-term cognitive
deficits that might be mitigated by adequate rest intervals between
injuries. However, biomarkers of safe rest intervals remain undefined.
Decreased cerebral blood flow (CBF) may be one such physiological
biomarker. Using a mouse closed head injury (CHI) model of human
concussion and diffuse correlation spectroscopy, we explored the ef-
fects of single and repetitive CHI on cortical CBF index and cognitive
outcome.
Methods:
Mice under isoflurane anesthesia were subjected to CHI
by weight drop (54 g, 38 in drop height). Sham-injured controls re-
ceived anesthesia alone. CBF was assessed at various times before and
after CHI by diffuse correlation spectroscopy. Cognitive function was
assessed after the final CHI using a version of the Morris water maze
(MWM).
Results:
After a single CHI, CBF was reduced by 35
–
4% at 4 h
and returned to pre-injury levels by 24 h. After 5 CHI spaced 1 day
apart, CBF was reduced from pre-injury levels 4 h after each injury
by approximately 20% but returned to pre-injury levels by 72 h after
the final CHI and remained at pre-injury levels after 2.5 weeks. A
single CHI did not induce MWM deficits, however, repetitive CHI
led to significant deficits compared to sham (p
<
0.001). After re-
petitive CHI, lower CBF measured both pre-injury and 4 hours after
the third CHI was associated with worse performance in the MWM
(p
<
0.01). Similar relationships were not observed between cogni-
tive deficits and CBF measured 4h, 72h, or 2.5 weeks after the final
CHI.
Conclusions:
Closed head injuries sustained by mice result in
transient decreases in cortical CBF. Decreased cortical CBF may be a
marker of an acute vulnerable period in which further injuries lead to
long-term cognitive deficits. Diffuse correlation spectroscopy is a
promising tool to interrogate the relationship between concussions and
return to play interval in preclinical models as well as concussed
patients.
Keywords: Concussion, diffuse correlation spectroscopy, cerebral
blood flow, mice
B6-09
MRI FINDINGS IN ACUTE TBI: INTER-RATER RELIA-
BILITY USING NIH COMMON DATA ELEMENTS
Katrin Rabiei, Sarah Murphy, Beth Costine, Paul Caruso, Monica
Shifman,
Ann-Christine Duhaime
Massachusetts General Hospital, Harvard Medical School, Pediatric
Neurosurgery, Boston, USA
Objective:
The NIH-sponsored Common Data Elements (CDE) for
Traumatic Brain Injury effort was designed to standardize data col-
lected across centers to facilitate pooling of data and better-powered
clinical studies. A standard dictionary of terms applied to specific
pathoanatomic lesions seen on CT or MRI was published, encom-
passing lesions seen in all ages of patients from infancy through
maturity.
1
MRI has advantages in children, involving no radiation
exposure and providing improved sensitivity for many parenchymal
lesions. We reviewed a series of acute MRI’s obtained on children
treated for TBI in our Pediatric Intensive Care Unit to measure inter-
rater reliability of injury characterization using the CDE imaging
dictionary.
Methods:
79 consecutive children treated for TBI in our Pediatric
Intensive Care Unit undergoing early brain MRI were identified.
Using the CDE neuroimaging definitions dictionary, the initial MRI
was assessed and scored by two independent reviewers without
knowledge of clinical factors or other imaging results (e.g., CT). After
an initial practice set, 20 MRI’s were scored independently and results
compared. Scores included ‘‘absent’’, ‘‘present’’, or ‘‘indeterminate’’,
and location for each lesion seen on each MRI. Inter-rater reliability
was calculated using weighted kappa statistics.
Results:
All patients (ages 1 month - 17 years) had MRI’s within 2
days of injury. Agreement was ‘‘perfect’’ for cervicomedullary/brain
stem lesion (1.00), ‘‘very good’’ for subdural hemorrhage (0.833),
‘‘good’’ for extra-axial hemorrhage (0.714), intraventricular hemor-
rhage (0.787), diffuse axonal injury (0.787), edema (0.655), midline
shift (0.643), and hypoxia/ischemia (0.62), and ‘‘moderate’’ for epi-
dural hematoma (0.588) and subarachnoid hemorrhage (0.559). Most
differences occurred with very small (
<
1 cm) lesions. Skull fracture
showed ‘‘fair’’ agreement (0.267).
Conclusions:
MRI can characterize major acute TBI in children
with high inter-rater reliability using the NIH Common Data Elements
pathoanatomic definitions. These tools will enable reliable data col-
lection and analysis across centers for comparative effectiveness and
interventional trials for patients of all ages.
Keywords: Common Data Elements, Clinical trials, MRI, inter-
rater reliability
B6-10
IN VIVO GLUCO-CEST MRI DETECTS METABOLIC CRISIS
IN MILD TRAUMATIC BRAIN INJURY
Tsang-Wei Tu
, Rashida Williams, Neekita Jikaria, L. Christine
Turtzo, Joseph A. Frank
National Institute of Health, Radiology and Imaging Sciences, Be-
thesda, USA
TBI results in an instant perturbation to cerebral glucose metabolism
impairing longterm cognition. FDG-PET is the major imaging mo-
dality to track matabolic changes in brain. The drawbacks of PET
1
Arch Phys Med Rehabil. 2010 Nov;91(11):1661–1666.
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