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The Journal of Neuroscience, October 31, 2007, 27(44):11991-11998; doi:10.1523/JNEUROSCI.3354-07.2007

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Development/Plasticity/Repair
In Vivo Tracing of Neural Tracts in the Intact and Injured Spinal Cord of Marmosets by Diffusion Tensor Tractography

Kanehiro Fujiyoshi,^1,2 * Masayuki Yamada,^4,5 * Masaya Nakamura,¹ Junichi Yamane,^1,2 Hiroyuki Katoh,¹ Kazuya Kitamura,^1,2 Kenji Kawai,⁴ Seiji Okada,⁶ Suketaka Momoshima,³ Yoshiaki Toyama,¹ and Hideyuki Okano²

Department of ¹Orthopaedic Surgery, ²Physiology, and ³Radiology and ⁴Center for Integrated of Medical Research, Keio University School of Medicine, Shinjuku, Tokyo 160-8582, Japan, ⁵Central Institute for Experimental Animals, Miyamae-ku, Kawasaki, Kanagawa 216-0001, Japan, and ⁶Department of Research Superstar Program Stem Cell Unit, Graduate School of Medical Science, Kyushu University, Fukuoka 812-8582, Japan

Correspondence should be addressed to Hideyuki Okano, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. Email: hidokano{at}sc.itc.keio.ac.jp

In spinal cord injury, axonal disruption results in motor and sensory function impairment. The evaluation of axonal fibers is essential to assess the severity of injury and efficacy of any treatment protocol, but conventional methods such as tracer injection in brain parenchyma are highly invasive and require histological evaluation, precluding clinical applications. Previous advances in magnetic resonance imaging technology have led to the development of diffusion tensor tractography (DTT) as a potential modality to perform in vivo tracing of axonal fibers. The properties and clinical applications of DTT in the brain have been reported, but technical difficulties have limited DTT studies of the spinal cord. In this study, we report the effective use of DTT to visualize both intact and surgically disrupted spinal long tracts in adult common marmosets. To verify the feasibility of spinal cord DTT, we first performed DTT of postmortem marmosets. DTT clearly illustrated spinal projections such as the corticospinal tract and afferent fibers in control animals, and depicted the severed long tracts in the injured animals. Histology of the spinal cords in both control and injured groups were consistent with DTT findings, verifying the accuracy of DTT. We also conducted DTT in live marmosets and demonstrated that DTT can be performed in live animals to reveal in vivo nerve fiber tracing images, providing an essential tool to evaluate axonal conditions in the injured spinal cord. Taken together, these findings demonstrate the feasibility of applying DTT to preclinical and clinical studies of spinal cord injury.

Key words: spinal cord injury; corticospinal tract; diffusion tensor tractography; magnetic resonance imaging; common marmoset; calmodulin-dependent protein kinase II-; pathway-specific DTT; in vivo tracing

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Received July 24, 2007; accepted Sept. 4, 2007.

Correspondence should be addressed to Hideyuki Okano, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. Email: hidokano{at}sc.itc.keio.ac.jp

This article has been cited by other articles:

				M. Dubois-Dalcq, A. Williams, C. Stadelmann, B. Stankoff, B. Zalc, and C. Lubetzki From fish to man: understanding endogenous remyelination in central nervous system demyelinating diseases Brain, July 1, 2008; 131(7): 1686 - 1700. [Abstract] [Full Text] [PDF]

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