A non-surgical model of cervical spinal cord injury induced with focused ultrasound and microbubbles
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BACKGROUND: The most commonly used animal models of spinal cord injury (SCI) involve surgical exposure of the dorsal spinal cord followed by transection, contusion or compression. This high level of invasiveness often requires significant post-operative care and can limit post-operative imaging, as the surgical incision site can interfere with coil placement for magnetic resonance imaging (MRI) during the acute phase of SCI. While these models are considered to be similar to human SCI, they do not occur in a closed vertebral system as do the majority of human injuries. NEW METHOD: Here we describe a novel, non-surgical model of SCI in the rat using MR-guided focused ultrasound (FUS) in combination with intravenous injection of microbubbles, applied to the cervical spinal cord. RESULTS: The injury was well-tolerated and resulted in cervical spinal cord damage in 60% of the animals. The area of Gd-enhancement immediately post-FUS and area of signal abnormality at 24h were correlated with the degree of injury. The extent of injury was easily visualized with T2-weighted MRI and was confirmed using histology. COMPARISON WITH EXISTING METHOD(S): Pathology was similar to that seen in other rat models of direct spinal cord contusion and compression. Unlike these methods, FUS is non-surgical and has lower mortality than seen in other models of cervical SCI. CONCLUSIONS: We developed a novel model of SCI which was non-surgical, well-tolerated, localized, and replicated the pathology seen in other models of SCI.