Pig Lumbar Spine Anatomy and Imaging Guided Lateral Lumbar Puncture: A New Large Animal Model for Intrathecal Drug Delivery

摘要

Intrathecal (IT) administration is an important route of drug delivery. Its modeling in a large animal species is a critical step. Although domestic swine is presently a preferred species in preclinical pharmacology, no proven minimally invasive method has been established to deliver agents into the pig IT space. While a “blind” lumbar puncture (LP) can sample cerebrospinal fluid (CSF), it is unreliable for drug delivery in pigs. Using computed tomography (CT) we determined the underlying anatomical reasons. The pig spinal cord was visualized terminating at the S2-S3 level. The lumbar region contained only small amounts of CSF visualized in the lateral recesses. Additional anatomical constraints identified were ossification of the midline ligaments; overlapping lamina with small interlaminar spaces; and a large bulk of epidural adipose tissue. Accommodating the pig CT anatomy, we developed an injection technique termed lateral LP (LLP) that employs advance planning of the needle path and monitoring of the IT injection progress. Key features of the LLP procedure were choosing a vertebral level without overlapping lamina or spinal ligament ossification; a needle trajectory crossing the midline; and entering the IT space in its lateral recess. Effective IT delivery was validated by injection of contrast media thereby obtaining a CT myelogram. LLP represents a safe and reliable method to deliver agents to the lumbar pig IT space, which can be implemented in a straightforward way by any laboratory with access to CT equipment and is therefore an attractive large animal model for preclinical studies of IT therapies.