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Identification and Classification of Peripheral Nerve Injuries with Optical Imaging in the Near-infrared
Tiffany P. Gustafson; Ying Yan; Piyaraj Thiranansakul; Walter J. Akers; Susan E. Mackinnon; Philip J. Johnson; Mikhail Y. Berezin
Washington University School of Medicine, Saint Louis, MO, USA
Introduction: The current ability to quickly assess and classify nerve injury, as having a favorable outcome (injuries capable of healing over time, Sunderland grade 1-3), or unfavorable outcome (injuries needing immediate intervention, Sunderland grade 4-5), are inadequate. This has resulted in a wait-and-see approach for diagnosis of peripheral nerve injuries where repair procedures provide a less than desirable result, making one of the most pressing challenges in peripheral nerve repair the development of a technique to noninvasively assess nerve damage. Clinically several diagnostic imaging modalities exist to visualize and evaluate peripheral nerve injuries, including computer tomography, ultrasound and magnetic resonance imaging, but they are dependent upon gross changes to tissue morphology to locate injury, primarily providing information about the state of the peripheral nerve and surrounding tissue. As a result these modalities provide no direct correlation to the extent of injury. Currently, the only accurate method to determine the extent of peripheral nerve injury is by utilizing transgenic rodents producing a fluorescent protein (XFP) in their axons, a model without clinical translation.
Method: We demonstrate the first step towards the development of a clinically translatable optical imaging modality for the diagnosis of peripheral nerve injury. In this work we identified a near infrared (NIR) optical probe for in vivo imaging to locate and classify nerve injuries as having a favorable or unfavorable outcome. The FDA approved hydrophobic NIR dye indocyanine green (ICG) was compared to its modified hydrophilic analog to evaluate the effect of dye hydrophilicity on its ability to migrate along the sciatic nerve of Thy1-GFP rats. Each dye was directly injected into the sciatic nerve and monitored by fluorescence microscopy.
Results: A direct correlation between the hydrophilicity of a probe and its ability to diffuse along the nerve was found. Hydrophobic ICG becomes trapped in neuronal tissue and shows no movement from the point of administration. Alternatively, its hydrophilic analogue moves along the nerve in both the antero- and retro- grade directions with neuronal fluids.
Conclusion: The movement of the hydrophilic dye along the nerve demonstrates the feasibility of utilizing NIR optical imaging to potentially identify the location of and classify nerve injury.
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