5mm craniotomy filled with 3% gel

CCI piston

skull

 •  TBI was induced in adult Sprague-Dawley rats by CCI as described.  

•  Oscillations and lateral movement of the piston was buffered by application of 1.5-mm thick, sterile 3% agarose gel plug adhered to the brain after craniotomy.

 •  48 hours after injury (with or without agarose gel application) brains were perfused

with 4% paraformaldehyde via a transcardial infusion and post-fixed by immersion.    •  Rat heads then were evaluated using a 500-MHz magnet at 11.75 T with a gradient

recalled echo (3D FLASH) and spin echo Diffusion Tensor Imaging (6 directions)  

Characterization of a CCI Model of Traumatic Brain Injury

•  Traumatic brain injury (TBI) affects 1.7 million in the U.S annually resulting in a myriad of deficits including impaired learning and memory, increased impulsivity, aggression and mood disorders such as depression and anxiety. [REF]

•  Animal models are used to evaluate the effects of TBI and help

develop new treatment and preventative measures. •  One of the most commonly used models is Controlled Cortical

Impact (CCI), which like all current models suffers from variability in the degree of injury delivered.

Piston Impactor Characterization

•  Using the routine metrics of impactor velocity, position and

acceleration to produce a moderately-severe TBI in a rat model, CCI impactor tip movement was filmed by high speed imaging at 10,000 frames per second (FPS).

•  Impact defined by 5-mm tip traveling at 2.25 m/s to a depth of 3.0 mm in the exposed brain following a craniotomy

•  Impactor tip movement was evaluated using Phantom Vision

(PV). Data, processed in MATLAB, were based on PV pixel data verified by a capacitance probe with a detection range of 2 mm.

24 hr 48 hr 1 wk 3 wks Figure X. Magnetic resonance imaging of traumatic brain injury in a rat model. Injury to the frontal cortex was induced bilaterally, under anesthesia, by controlled cortical impact. Images were collected in vivo at the National High Magnetic Field Laboratory, Florida State University using the 900 MHz Magnet with a field strength of 21.1 Tesla between 24 hours and 3 weeks post-injury.

CCI Characterization Introduction Improving CCI

Cote, Jason; Alvi, Farrukh; Kreth, Phil; Patel, Devan; Levenson, Cathy W. Abad, Nastaren; Amouzandeh, Ghoncheh; Boebinger, Scott; Hike, David; Ould Ismail, Abdol Aziz; Grant, Samuel C.

Results

Conclusions •  Gel buffer had little, to no effect on impact, and the injury appears to be greater in severity. •  Control rat image still being acquired, comparison to be made once data has been collected. •  Further work needs to be done to comprehensively characterize the piston impactor: the lateral movement. Gel work will

continue with a greater sample at longer injury times to compare progression and behavioral outcomes between groups to potentially improve the CCI method.

References 1.  Turtzo, L. C., Budde, M. D., Gold, E. M., Lewis, B. K., Janes, L., Yarnell, A., . . . Frank, J. A. (2012). The evolution of traumatic brain injury in a

rat focal contusion model. NMR in Biomedicine NMR Biomed., 26(4), 468-479. doi:10.1002/nbm.2886

2.  Madsen, E. L., Hobson, M. A., Shi, H., Varghese, T., & Frank, G. R. (2005). Tissue-mimicking agar/gelatin materials for use in heterogeneous elastography phantoms. Physics in Medicine and Biology Phys. Med. Biol., 50(23), 5597-5618. doi:10.1088/0031-9155/50/23/013

3.  Mao, H., Guan, F., Han, X., & Yang, K. H. (2011). Strain-Based Regional Traumatic Brain Injury Intensity in Controlled Cortical Impact: A Systematic Numerical Analysis. Journal of Neurotrauma, 28(11), 2263-2276. doi:10.1089/neu.2010.1600

Acknowledgements: This research is sponsored by DMR 1157490. All work has been conducted in accordance with FSU Animal Care and Use Committee (ACUC)

This study was designed to: 1) Characterize CCI through the use of high speed imaging and capacitance probe measurements. 2) Develop methods to reduce injury variability and analyze their effectiveness using MRI

•  Based on the PV and capacitance probe data, the impactor tip strikes Tissue at a velocity consistently higher (mean 2.8m/s±0.028) than the CCI device setting (2.25m/s).

•  The position of the impactor tip does initially penetrate the

desired 3mm, but the post impact oscillations result in the tip penetrating deeper into the brain (mean 3.65± .13). The oscillations and high velocity in its movement could be yielding greater injury severity than desired in this model.

•  In addition to oscillations, high speed camera evaluation revealed a significant amount of lateral movement in the impactor tip at the point of impact. While evaluation of the magnitude and consistency of these lateral movements is still in progress, these movements could contribute to variations in injury and lesion size detected by MRI.

•  In an attempt to mitigate the lateral movement and oscillations of the impactor tip, an agarose gel with a similar density to the rat brain was hypothesized to be a potential solution.

Agarose  Gel  g/100ml   T1  (ms)   T2  (ms)  

0.6   2784.25   111.319  

1   2730.44   92.8502  

2   2157.83   58.1547  

3   2505.4   40.8409