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

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.

[1]  a.R.V.,et al.  Human Neuroanatomy , 1954, Neurology.

[2]  J. E. Tanner,et al.  Spin diffusion measurements : spin echoes in the presence of a time-dependent field gradient , 1965 .

[3]  H. Ralston,et al.  The terminations of corticospinal tract axons in the macaque monkey , 1985, The Journal of comparative neurology.

[4]  P. Grenier,et al.  MR imaging of intravoxel incoherent motions: application to diffusion and perfusion in neurologic disorders. , 1986, Radiology.

[5]  P. Narayana,et al.  Magnetic resonance imaging in the diagnosis of the cranio-cervical manifestations of the mucopolysaccharidoses. , 1987, Magnetic resonance imaging.

[6]  Y. Yamashita,et al.  Chronic injuries of the spinal cord: assessment with MR imaging. , 1990, Radiology.

[7]  J. Tsuruda,et al.  Diffusion-weighted MR imaging of anisotropic water diffusion in cat central nervous system. , 1990, Radiology.

[8]  Y. Qiu,et al.  Morphometric study of cervical anterior horn cells and pyramidal tracts in medulla oblongata and the spinal cord in patients with cerebrovascular diseases , 1991, Journal of the Neurological Sciences.

[9]  J. Hogg Magnetic resonance imaging. , 1994, Journal of the Royal Naval Medical Service.

[10]  P. Basser,et al.  MR diffusion tensor spectroscopy and imaging. , 1994, Biophysical journal.

[11]  T. Terashima,et al.  Immunohistochemical detection of calcium/calmodulin‐dependent protein kinase II in the spinal cord of the rat and monkey with special reference to the corticospinal tract , 1994, The Journal of comparative neurology.

[12]  T. Nakada,et al.  Magnetic resonance axonography of the rat spinal cord: postmortem effects. , 1995, Journal of neurosurgery.

[13]  P. Basser,et al.  Microstructural and physiological features of tissues elucidated by quantitative-diffusion-tensor MRI. , 1996, Journal of magnetic resonance. Series B.

[14]  M. Raichle,et al.  Tracking neuronal fiber pathways in the living human brain. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[15]  C. Holder,et al.  Diffusion-weighted MR imaging of the normal human spinal cord in vivo. , 2000, AJNR. American journal of neuroradiology.

[16]  Sinisa Pajevic,et al.  Color schemes to represent the orientation of anisotropic tissues from diffusion tensor data: Application to white matter fiber tract mapping in the human brain , 1999, Magnetic resonance in medicine.

[17]  D. Parker,et al.  Analysis of partial volume effects in diffusion‐tensor MRI , 2001, Magnetic resonance in medicine.

[18]  C. Beaulieu,et al.  The basis of anisotropic water diffusion in the nervous system – a technical review , 2002, NMR in biomedicine.

[19]  Susumu Mori,et al.  Fiber tracking: principles and strategies – a technical review , 2002, NMR in biomedicine.

[20]  M. Oliviera,et al.  Peripheral nerve grafts promoting central nervous system regeneration after spinal cord injury in the primate. , 2002, Journal of neurosurgery.

[21]  M. Tuszynski,et al.  Spontaneous and augmented growth of axons in the primate spinal cord: Effects of local injury and nerve growth factor‐secreting cell grafts , 2002, The Journal of comparative neurology.

[22]  Derek K. Jones,et al.  Diffusion‐tensor MRI: theory, experimental design and data analysis – a technical review , 2002 .

[23]  L. Olson Medicine: Clearing a path for nerve growth , 2002, Nature.

[24]  Susumu Mori,et al.  Diffusion tensor brain imaging and tractography. , 2002, Neuroimaging clinics of North America.

[25]  O. Abe,et al.  MR diffusion tensor imaging: recent advance and new techniques for diffusion tensor visualization. , 2003, European journal of radiology.

[26]  Y. Masutani,et al.  Three-dimensional white matter tractography by diffusion tensor imaging in ischaemic stroke involving the corticospinal tract , 2003, Neuroradiology.

[27]  Osamu Abe,et al.  [Simple visualization of the corticospinal pathway using tractography: one-ROI and two-ROI methods]. , 2003, Nihon Igaku Hoshasen Gakkai zasshi. Nippon acta radiologica.

[28]  Katsumi Nakajima,et al.  Direct and indirect pathways for corticospinal control of upper limb motoneurons in the primate. , 2004, Progress in brain research.

[29]  M. Tuszynski,et al.  Bilateral corticospinal projections arise from each motor cortex in the macaque monkey: A quantitative study , 2004, The Journal of comparative neurology.

[30]  Kensuke Kawai,et al.  Functional Monitoring for Visual Pathway Using Real-time Visual Evoked Potentials and Optic-radiation Tractography , 2005, Neurosurgery.

[31]  Kazuhiro Tsuchiya,et al.  Diffusion tractography of the cervical spinal cord by using parallel imaging. , 2005, AJNR. American journal of neuroradiology.

[32]  P. Fillard,et al.  MR diffusion tensor imaging and fiber tracking in spinal cord compression. , 2005, AJNR. American journal of neuroradiology.

[33]  H. Okano,et al.  Transplantation of human neural stem cells for spinal cord injury in primates , 2005, Journal of neuroscience research.

[34]  Jonas Frisén,et al.  Allodynia limits the usefulness of intraspinal neural stem cell grafts; directed differentiation improves outcome , 2005, Nature Neuroscience.

[35]  Sung Hyun Kim,et al.  Fiber tracking by diffusion tensor imaging in corticospinal tract stroke: Topographical correlation with clinical symptoms , 2005, NeuroImage.

[36]  K. Hasan,et al.  Diffusion tensor imaging of in vivo and excised rat spinal cord at 7 T with an icosahedral encoding scheme , 2005, Magnetic resonance in medicine.

[37]  Stephan E Maier,et al.  Diffusion Tensor Imaging of the Spinal Cord , 2005, Annals of the New York Academy of Sciences.

[38]  Kenji Ino,et al.  Combined use of tractography-integrated functional neuronavigation and direct fiber stimulation. , 2005, Journal of neurosurgery.

[39]  T Nomura,et al.  Establishment of graded spinal cord injury model in a nonhuman primate: The common marmoset , 2005, Journal of neuroscience research.

[40]  S. Mori,et al.  Principles of Diffusion Tensor Imaging and Its Applications to Basic Neuroscience Research , 2006, Neuron.

[41]  A. Anderson,et al.  Effects of cord motion on diffusion imaging of the spinal cord , 2006, Magnetic resonance in medicine.

[42]  H. Okano,et al.  A selective Sema3A inhibitor enhances regenerative responses and functional recovery of the injured spinal cord , 2006, Nature Medicine.

[43]  Toshiki Endo,et al.  Blood Oxygenation Level-Dependent Visualization of Synaptic Relay Stations of Sensory Pathways along the Neuroaxis in Response to Graded Sensory Stimulation of a Limb , 2006, The Journal of Neuroscience.

[44]  Takashi Hanakawa,et al.  Corticospinal tract localization: integration of diffusion-tensor tractography at 3-T MR imaging with intraoperative white matter stimulation mapping--preliminary results. , 2006, Radiology.

[45]  P. Fillard,et al.  MR diffusion tensor imaging and fiber tracking in 5 spinal cord astrocytomas. , 2006, AJNR. American journal of neuroradiology.