Biophysical attributes of an in vitro spinal cord surrogate for use in developing an intradural neuromodulation system

The goal of this study was to validate a simple, inexpensive, and robust model system to be used as an in vitro surrogate for in vivo brain tissues in preclinical and exploratory studies of infusion-based intraparenchymal drug and cell delivery. Agarose gels of varying concentrations and porcine brain were tested to determine the infusion characteristics of several different catheters at flow rates of 0.5 and 1 microl per minute by using bromophenol blue (BPB) dye (molecular weight [MW] approximately 690) and gadodiamide (MW approximately 573). Magnetic resonance (MR) imaging and videomicroscopy were used to measure the distribution of these infusates, with a simultaneous measurement of infusion pressures. In addition, the forces of catheter penetration and movement through gel and brain were measured. Agarose gel at a 0.6% concentration closely resembles in vivo brain with respect to several critical physical characteristics. The ratio of distribution volume to infusion volume of agarose was 10 compared with 7.1 for brain. The infusion pressure of the gel demonstrated profiles similar in configuration and magnitude to those of the brain (plateau pressures 10-20 mm Hg). Gadodiamide infusion in agarose closely resembled that in the brain, as documented using T1-weighted MR imaging. Gadodiamide distribution in agarose gel was virtually identical to that of BPB dye, as documented by MR imaging and videomicroscopy. The force profile for insertion of a silastic catheter into agarose gel was similar in magnitude and configuration to the force profile for insertion into the brain. Careful insertion of the cannula using a stereotactic guide is critical to minimize irregularity and backflow of infusate distribution. Agarose gel (0.6%) is a useful surrogate for in vivo brain in exploratory studies of convection-enhanced delivery.

Anatomical measurement. To obtain quantitative anatomical data on each spinal cord segment in human, and determine the presence of correlations between the measures. Department of Rehabilitation Medicine, Pusan National University Hospital, Pusan, Korea. A total of 15 embalmed Korean adult human cadavers (13 males, two females; mean age 57.3 years) were used. The length of each cord segment was defined as the root attachment length plus the upper inter-root length. After performing a total vertebrectomy, a transverse cut was made at the approximate proximal and distal point of each segment from segment C3 to S5. Sagittal and transverse diameters at the proximal end of each segment, and cross-sectional area, height, and volume of the segment were measured. The transverse diameter was largest at segment C5, and decreased progressively to segment T8. However, the sagittal diameter of each segment did not change distinctly with the segment. The cervical and lumbar enlargements were determined by the transverse diameters of the segments. Segment C5 had the largest cross-sectional area, at 75.0 mm(2). Segment T6 was the longest, averaging 22.4 mm in length. The longest segment in the cervical spinal cord was segment C5, at 15.5 mm, and segment L1 in the lumbar spinal cord. The volume was largest at segment C5, with a value of 1173.9 mm(3). We found characteristic quantitative differences in the values of the parameters measured in the thoracic spinal cord compared to those measured in the cervical and lumbar or lumbosacral spinal cords. These measurements of spinal cord segments appear to provide valuable and practical standard quantitative features and may provide basic data for understanding the morphometric characteristics relevant to pathophysiologic conditions of the spinal cord.