NNS 2015 Abstract Book

B3-11

ADVANCED DIFFUSION MRI METHODS TO QUANTITA-

TIVELY DISTINGUISH BETWEEN COMPLEX WHITE

MATTER AND TRAUMATIC AXONAL INJURY

Mihika Gangolli

, Joong Hee Kim

, Laurena Holleran

, Victor

Alvarez

, Thor Stein

, Ann McKee

, David L. Brody

Washington University in St. Louis, School of Medicine, St. Louis, USA

Boston University, CTE Center, Boston, USA

Chronic traumatic encephalopathy (CTE) is a progressive neurode-

generative condition that occurs following repetitive mild traumatic

brain injury. Its distinct neuropathological features, including phos-

phorylated tau tangles and axonal degeneration, can be detected post-

mortem via staining, but remain invisible to current imaging methods.

Diffusion weighted imaging has been proposed as a noninvasive de-

tection method due to its high sensitivity to microstructural changes in

brain tissue integrity. This approach is complicated by the assumption

that diffusion in a voxel can be modeled using a single Gaussian dis-

tribution, leading to ambiguous results when attempting to distinguish

axon degeneration from uninjured regions with complex fiber archi-

tecture. We demonstrate through alternative diffusion imaging methods

and quantitative histology that diffusion imaging can distinguish be-

tween complex fiber architectures and injured axon regions.

Human ex vivo cortical tissue was scanned using an 11.7T Varian

MRI scanner, 202 diffusion weighted gradient directions, and a voxel

size of 250x250x500

m. Diffusion based directionality was calcu-

lated using both diffusion tensor and generalized q-space (GQI)

models. The tissue was then serially sectioned into 50

m slices and

stained for myelinated axons using Black Gold II. Two dimensional

Fourier transforms of Black Gold II stained images were used to

quantify histological fiber directionality of each 250x250x500

region. Registration of the histological data to the diffusion data was

performed by placing landmarks in both data sets and applying a

similarity transform to the histological image.

Using an ROI based analysis, we found that regions with complex

distributions of fiber orientations also had reduced fractional anisot-

ropy in diffusion tensor imaging, while the generalized fractional

anisotropy from GQI was not reduced. These findings demonstrate

that advanced diffusion weighted imaging can account for complex

white matter structures and is likely provide a more specific means of

quantitatively assessing axon directionality and injury.

Keywords: Ex vivo study, Diffusion weighted imaging, Fiber di-

rection, Histological correlation

B3-12

BLAST INDUCED SPATIAL AND TEMPORAL ALTERA-

TIONS IN GLIAL EXPRESSION AND AXONAL INJURY IN

THE RAT SPINAL CORD

Liying Zhang

, Srinivasu Kallakuri, Heena Purkait, Satya Dalavayi,

Karthika Andrew, John Cavanaugh

Wayne State University, Biomedical Engineering, Detroit, USA

Blast induced neurotrauma is a signature wound of veterans returning from

military operations. With much of the research focus being directed at

understanding blast wave induced changes in the brain knowledge related

to blast effect in the spinal cord remains unresolved. Knowledge related to

injury changes in the spinal cord following blast overpressure may help

understand altered sensory problems often reported by veterans. In fact, a

high prevalence of chronic pain, particularly in the back (58%) and head

(55%) in some veterans was also reported. Whether blast overpressure

induces injury changes in the spinal cord and if these changes contribute to

acute or chronic sensory changes is a fundamental question that is yet to be

addressed. We postulate that blast overpressure induces changes in the

spinal cord in the form of glial activation and axonal injury. Anesthetized

male SD rats were subjected to a single insult of blast overpressure (22 psi)

induced by a custom-built shock tube. Rats were divided into groups based

on their survival period: 6 hours, 24 hours, 3 days and 7 days. The spinal

cord segments (cervical, thoracic and lumbar) were cut horizontally into

m thick serial sections. Astrocytic and microglial activation was re-

vealed by Glial fibrillary acidic protein (GFAP) and ionized calcium-

binding adapter molecule 1 (Iba1) immunohistochemistry. Axonal injury

was revealed by neurofilament light chain immunohistochemistry. The

extent of astrocytic and microglial activation was quantified by counting

their number from representative images taken from cervical, thoracic and

lumbar spinal cord sections. Elevated astrocyte and microglial counts were

observed in blast spinal cord compared to sham. Temporally, significantly

high astrocytes were observed in different regions of the spinal cord.

Axonal injury changes were observed in all spinal cord segments at var-

ious time periods after blast. Taken together these findings support that

blast induced injury changes extend into spinal cord and may contribute to

altered neuronal function.

Keywords: Shock tube, Blast induced spinal cord injury, Rats,

Astrocytic and microglial activation

B3-13

OPEN FIELD PRIMARY BLAST EXPOSURE INDUCES NEU-

RONAL AND GLIAL ALTERATIONS IN FRONTAL CORTEX

Liying Zhang

, Srinivasu Kallakuri, Alok Desai, Janine Mathei, Elizabeth

Dawe, Ke Feng, Chaoyang Chen, John Cavanaugh, Albert King

Wayne State University, Biomedical Engineering, Detroit, USA

The wars in Iraq and Afghanistan have highlighted the emergence of

Blast Induced Neurotrauma (BINT) and the associated mild traumatic

brain injury as the signature wound in returning service members.

Several animal studies showed axonal injuries, myelin and cytoskeletal

breakdown, cell death and glial activation as part of efforts in under-

standing the pathological changes in brain after blast. However, detailed

studies aimed at characterizing cellular injury changes in a gyr-

encephalic primary blast exposure model are still limited which forms

the purpose of this study. Anesthetized male Yucatan swine (50–60 kg)

were exposed either to medium (224–332 kPa; n

7) or high over-

pressure (350–403 kPa; n

5) open-field blast. Sham animals (n

were not subjected to blast. After a 3-day survival period, the frontal

cortex of the perfused brain was cut into 5mm blocks which were then

cut into 40

m thick serial sections. Sections were then processed to

assess axonal injury (

-APP-beta amyloid precursor protein), glial

proliferation (glial fibrillary acidic protein; ionized calcium-binding

adapter molecule 1) and cellular injury (cleaved caspase 3 and H&E

staining). Prominent diffuse axonal injury in the form of

-APP im-

munoreactive swollen axons and retraction balls was observed in the

high overpressure group. Also observed were prominent white and grey

matter

-APP reactive zones in the high-overpressure brain sections

compared to medium overpressure and sham brain sections.

-APP

reactive zones were reminiscent of Amyloid

staining in Alzheimer’s.

Also observed was elevated astrocyte counts in both the blast groups. A

significant number of microglia were also observed in medium pressure

compared to sham. Our findings support the presence of prominent

axonal injury and

-APP reactive immunoreactive zones in these frontal

cortical regions following primary blast exposure. Prominent astrocytic

and microglial proliferation also suggests potential inflammatory

changes. These findings suggest a putative role for an altered neuroglial

homeostasis in the etiology of primary blast induced neurotrauma.

Keywords: Swine, Primary blast induced brain injury, Open field

blast,

-APP-beta amyloid precursor protein, Astrocytic and micro-

glial proliferation,

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