Diffusion tensor tractography to visualize axonal outgrowth and regeneration in a 4-cm reverse autograft sciatic nerve rabbit injury model

• Published in: Neurological research (New York) Vol. 41; no. 3; pp. 257 - 264
• Main Authors: Farinas, Angel F., Pollins, Alonda C., Stephanides, Michael, O'Neill, Dillon, Al-Kassis, Salam, Esteve, Isaac V. Manzanera, Colazo, Juan M., Keller, Patrick R., Rankin, Timothy, Wormer, Blair A., Kaoutzanis, Christodoulos, Dortch, Richard D., Thayer, Wesley P.
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 04-03-2019
• Subjects: Animals; Axons - pathology; Axons - physiology; Diffusion Tensor Imaging; diffusion tensor tractography; Imaging, Three-Dimensional; magnetic resonance imaging (MRI); Nerve Regeneration; Peripheral Nerve Injuries - diagnostic imaging; Peripheral Nerve Injuries - pathology; Peripheral Nerve Injuries - physiopathology; peripheral nerve regeneration; Rabbits; Reverse autograft; Sciatic Nerve - diagnostic imaging; Sciatic Nerve - physiopathology; sciatic nerve injury; Transplantation, Autologous; magnetic resonance imaging (MRI); Reverse autograft; peripheral nerve regeneration; diffusion tensor tractography; sciatic nerve injury
• ISSN: 0161-6412; 1743-1328
• DOI: 10.1080/01616412.2018.1554284

Background: Diffusion tensor tractography (DTT) has recently been shown to accurately detect nerve injury and regeneration. This study assesses whether 7-tesla (7T) DTT imaging is a viable modality to observe axonal outgrowth in a 4 cm rabbit sciatic nerve injury model fixed by a reverse autograft (RA) surgical technique.
Methods: Transection injury of unilateral sciatic nerve (4 cm long) was performed in 25 rabbits and repaired using a RA surgical technique. Analysis of the nerve autograft was performed at 3, 6, and 11 weeks postoperatively and compared to normal contralateral sciatic nerve, used as control group. High-resolution DTT from ex vivo sciatic nerves were obtained using 3D diffusion-weighted spin-echo acquisitions at 7-T. Total axons and motor and sensory axons were counted at defined lengths along the graft.
Results: At 11 weeks, histologically, the total axon count of the RA group was equivalent to the contralateral uninjured nerve control group. Similarly, by qualitative DTT visualization, the 11-week RA group showed increased fiber tracts compared to the 3 and 6 weeks counterparts. Upon immunohistochemical evaluation, 11-week motor axon counts did not significantly differ between RA and control; but significantly decreased sensory axon counts remained. Nerves explanted at 3 weeks and 6 weeks showed decreased motor and sensory axon counts.
Discussion: 7-T DTT is an effective imaging modality that may be used qualitatively to visualize axonal outgrowth and regeneration. This has implications for the development of technology that non-invasively monitors peripheral nerve regeneration in a variety of clinical settings.