Fujiyoshi Kanehiro, Yamada Masayuki, Nakamura Masaya, Yamane Junichi, Katoh Hiroyuki, Kitamura Kazuya, Kawai Kenji, Okada Seiji, Momoshima Suketaka, Toyama Yoshiaki, Okano Hideyuki
Department of Orthopaedic Surgery, Keio University School of Medicine, Shinjuku, Tokyo 160-8582, Japan.
J Neurosci. 2007 Oct 31;27(44):11991-8. doi: 10.1523/JNEUROSCI.3354-07.2007.
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.
在脊髓损伤中,轴突中断会导致运动和感觉功能受损。评估轴突纤维对于评估损伤的严重程度和任何治疗方案的疗效至关重要,但诸如向脑实质注射示踪剂等传统方法具有高度侵入性,且需要组织学评估,因此无法应用于临床。磁共振成像技术的先前进展促使扩散张量纤维束成像(DTT)的发展,成为一种在体内追踪轴突纤维的潜在方法。DTT在脑部的特性和临床应用已有报道,但技术难题限制了对脊髓的DTT研究。在本研究中,我们报告了有效利用DTT在成年普通狨猴体内可视化完整和手术中断的脊髓长束。为验证脊髓DTT的可行性,我们首先对死后狨猴进行了DTT。DTT清晰地显示了对照动物中的脊髓投射,如皮质脊髓束和传入纤维,并描绘了受伤动物中被切断的长束。对照组和受伤组脊髓的组织学与DTT结果一致,验证了DTT的准确性。我们还对活体狨猴进行了DTT,并证明DTT可在活体动物中进行,以揭示体内神经纤维追踪图像,为评估损伤脊髓中的轴突状况提供了重要工具。综上所述,这些发现证明了将DTT应用于脊髓损伤临床前和临床研究的可行性。