Abstract
Peripheral nerve injuries are a significant concern in surgical procedures, often leading to chronic pain and functional impairment. Despite advancements in imaging, preoperative and intraoperative visualization of peripheral nerves remains a challenge. This study introduces and evaluates a novel tri-iodinated lidocaine-based contrast agent for computed tomography neurography, aiming to enhance the intraoperative visibility of peripheral nerves in vivo. A tri-iodinated lidocaine analogue was synthesized and characterized for its radiodensity, sodium channel binding and nerve affinity. Sodium channel affinity was performed using molecular docking. In vitro contrast enhancement was assessed by comparing the agent's Hounsfield unit (HU) values with those of Omnipaque, a clinically approved contrast medium. In vivo imaging was conducted on rat sciatic nerves using micro-CT, followed by ex vivo validation. Nerve conduction blockade was assessed via electrical stimulation and histological analysis was performed to evaluate neurotoxicity. Experimental results revealed the tri-iodinated lidocaine analogue to have similar or higher affinity toward voltage-gated sodium channels than the parent lidocaine and a radiodensity comparable to the commercial CT contrast agent Omnipaque in vitro. In vivo, the contrast agent provided CT visualization of the sciatic nerve, with a significant increase in HU values compared to untreated nerves. Electrical stimulation confirmed transient nerve conduction blockade without observable histological damage, supporting its dual role as an imaging and nerve-blocking agent. This study presents a novel tri-iodinated lidocaine-based contrast agent that enables clear CT visualization of peripheral nerves while maintaining reversible nerve inhibition. These findings support its potential application in preoperative planning and intraoperative nerve protection to reduce surgical nerve injuries. Further studies are warranted to optimize imaging conditions and evaluate its clinical feasibility.