High-frequency ultrasound-guided intrathecal injections in a young mouse model: Targeting the central nervous system in drug delivery

Background: Intrathecal injections provide important access to the central nervous system for delivery of anes- thetic, analgesic or chemotherapeutic drugs that do not otherwise cross the blood-brain barrier. The adminis- tration of drugs via this route in animal models is challenging due to an inability to visualize the small target space during injection. Successful drug delivery therefore requires expertise in indirectly assessing vertebral and spinal cord anatomy and gaining advanced procedural skills. These factors are especially compounded in small animals such as mice (the most common mammalian model) and in investigations modeling pediatric drug delivery, where the animal is even smaller. New method: To address these issues, we have developed a method in which high-frequency ultrasound imaging is used to visualize and target the lumbar intrathecal space for injections. The technique is demonstrated in mice as young as postnatal day 16. To evaluate the method, a gadolinium-based magnetic resonance imaging (MRI) contrast agent was injected intrathecally, and subsequent brain delivery was verified post-injection by MRI. Results: Successful intrathecal injections of the MRI contrast agent showed distribution to the brain. In this study, we achieved a targeting success rate of 80% in 20 animals. Comparison with existing methods and conclusion: We expect that the new method will be convenient for drug delivery to the central nervous system in rodent research and provide higher reliability than unguided ap- proaches, an essential contribution that will enable intrathecal delivery in pediatric mouse models