TY - JOUR
T1 - Pig lumbar spine anatomy and imaging-guided lateral lumbar puncture
T2 - A new large animal model for intrathecal drug delivery
AU - Pleticha, Josef
AU - Maus, Timothy P.
AU - Jeng-Singh, Christian
AU - Marsh, Michael P.
AU - Al-Saiegh, Fadi
AU - Christner, Jodie A.
AU - Lee, Kendall H.
AU - Beutler, Andreas S.
N1 - Funding Information:
The study was supported by funds from the Schulze Family Foundation (A.S.B.) and by the NIH grants K08NS 52232-3 (K.H.L.) and RR018898 (construction grant for the CT facility).
PY - 2013/5
Y1 - 2013/5
N2 - The development of a novel method for intrathecal drug administration in the pig. CT-anatomy demonstrates constraints underlying the failure of human LP techniques. A lateral lumbar puncture approach targets the lateral thecal recess. This new large animal model offers unique strengths when compared with its alternatives. Intrathecal (IT) administration is an important route of drug delivery, and its modelling in a large animal species is of critical value. Although domestic swine is the preferred species for preclinical pharmacology, no minimally invasive method has been established to deliver agents into the 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 for this irregularity. The pig spinal cord was visualised terminating at the S2-S3 level. The lumbar region contained only small amounts of CSF found in the lateral recess. Additional anatomical constraints included ossification of the midline ligaments, overlapping lamina with small interlaminar spaces, and a large bulk of epidural adipose tissue. Accommodating the the pig CT anatomy, we developed a lateral LP (LLP) injection technique that employs advanced planning of the needle path and monitoring of the IT injection progress. The key features of the LLP procedure involved 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 the injection of contrast media to obtain 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. Therefore, LLP is an attractive large animal model for preclinical studies of IT therapies.
AB - The development of a novel method for intrathecal drug administration in the pig. CT-anatomy demonstrates constraints underlying the failure of human LP techniques. A lateral lumbar puncture approach targets the lateral thecal recess. This new large animal model offers unique strengths when compared with its alternatives. Intrathecal (IT) administration is an important route of drug delivery, and its modelling in a large animal species is of critical value. Although domestic swine is the preferred species for preclinical pharmacology, no minimally invasive method has been established to deliver agents into the 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 for this irregularity. The pig spinal cord was visualised terminating at the S2-S3 level. The lumbar region contained only small amounts of CSF found in the lateral recess. Additional anatomical constraints included ossification of the midline ligaments, overlapping lamina with small interlaminar spaces, and a large bulk of epidural adipose tissue. Accommodating the the pig CT anatomy, we developed a lateral LP (LLP) injection technique that employs advanced planning of the needle path and monitoring of the IT injection progress. The key features of the LLP procedure involved 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 the injection of contrast media to obtain 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. Therefore, LLP is an attractive large animal model for preclinical studies of IT therapies.
KW - Computed tomography
KW - Intrathecal
KW - Lumbar puncture
KW - Pig
KW - Swine
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U2 - 10.1016/j.jneumeth.2013.03.006
DO - 10.1016/j.jneumeth.2013.03.006
M3 - Article
C2 - 23518340
AN - SCOPUS:84877128464
SN - 0165-0270
VL - 216
SP - 10
EP - 15
JO - Journal of Neuroscience Methods
JF - Journal of Neuroscience Methods
IS - 1
ER -