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lesion sites, but only in the three patients with APOE
e
4 haplotypes. Non-
leucotomized schizophrenic patients showed no significant pathology.
Massive chronic axonal damage in white matter, as produced in
leucotomy, leads to abnormal
tau
in neurons and astrocytes in gray
matter adjacent to the lesion in the distinctive pattern resembling
CTE. These data suggest that chronic neuronal deafferentation alone
leads to abnormal
tau
accumulation. Because leucotomy lacks ex-
ternal cortical impact, the data suggest that selective accumulation of
tau
at depths of sulci may be related to underlying axonal damage
rather than mechanical stresses during TBI. Lastly, only patients with
the APOE
e
4 haplotype formed
b
-amyloid plaques.
Keywords: CTE, Axonal injury, tau, neuropathology
S12-05
TRAUMATIC AXONAL INJURY IN THE LIVING HUMAN
BRAIN: CONCORDANCE OF MICRODIALYSIS AND AD-
VANCED MRI APPROACHES
S Magnoni
2
, C Mac Donald
1
, TJ Esparza
1
, V Conte
2
, J Sorrell
1
, M
Macri
2
, G Bertani
2
, R Biffi
2
, A Costa
2
, B Sammons
1
, A Snyder
1
,
J Shimony
1
, F Triulzi
2
, N Stocchetti
2
,
David Brody
1
1
Washington University, Neurology, St. Louis, USA
2
Ospedale Maggiore Policlinico, Anesthesia-Intensive Care, Milano,
Italy
We performed microdialysis and diffusion tensor imaging in the same
cohort of 15 severe traumatic brain injury patients to assess axonal
injury with 2 complementary approaches. 100 kDa cut-off micro-
dialysis catheters were implanted at a median time of 17 h (13–29
hours) after injury in normal appearing (on CT scan) frontal white
matter in all patients. Diffusion tensor MRI scans at 3T were per-
formed 2–9 weeks after injury in 11 patients. Stability of diffusion
tensor imaging findings was verified by repeat scans 1–3 years later in
7 patients. An additional 4 patients were scanned only at 1–3 years
after injury. Imaging abnormalities were assessed based on compari-
sons with 5 controls (healthy subjects) for each patient, matched by
age and sex (32 controls in total).
We found that acute microdialysis measurements of the axonal
cytoskeletal protein tau in the brain extracellular space correlated
well with diffusion tensor MRI-based measurements of reduced
brain white matter integrity in the 1 cm radius white matter-masked
region near the microdialysis catheter insertion sites. Specifically,
we found a significant inverse correlation between microdialysis
measured levels of tau 13–36 hours after injury and anisotropy re-
ductions in comparison with healthy controls (Spearman r
= -
0.64,
p
=
0.006). Anisotropy reductions near microdialysis catheter inser-
tion sites were highly correlated with reductions in multiple addi-
tional white matter regions. We interpret this result to mean that
both microdialysis and diffusion tensor MRI accurately reflect the
same pathophysiological process: traumatic axonal injury. This
cross-validation increases confidence in both methods for the clini-
cal assessment of axonal injury. Future work will be required to
determine the prognostic significance of these assessments of trau-
matic axonal injury when combined with other clinical and radio-
logical measures.
Keywords: microdialysis, diffusion tensor imaging, tau
A-15