Construction and MRI testing of a 3D model of the spinal subarachnoid space
If you would like to help with this study as a master's or bachelor's thesis project, please send Bryn Martin an email with your resume and research interests.
Delivery of drugs to the spinal cord through the cerebrospinal fluid can provide a direct and effective route for management of pain in patients with chronic neurological disorders (Rainov and Heidecke 2007; Shoichet, Tator et al. 2007; Dickson 2009). However, design and optimization of drug delivery technology (e.g. infusion pumps) is difficult since in vivo studies are expensive to conduct on large animals that have similar size as humans. At present there is no in vitro hydrodynamic model of the spinal canal that can be used to help develop such devices. 3D computational fluid dynamics models have been developed for the intracranial space, but these computational models do not enable direct testing of drug delivery prototypes (Gupta, Soellinger et al. 2009). A physical spine model would include the complex 3D geometry of the spinal subarachnoid space including nerve roots and have realistic and controllable pulsation of cerebrospinal fluid throughout the system.
Hypothesis and research objectives
The goal of this project is to construct and validate the first 3D anatomically and hydrodynamically accurate model of the healthy spinal subarachnoid space.
Methods and study outline
- In vivo MR measurements. Obtain high resolution MRI images of the entire spine from the C1 to sacrum level.
- Model construction. MR geometry scan will be manually segmented using the freely available software Segment version 1.8 R1145 (http://segment.heiberg.se) to obtain a 3D representation of the SSS. The voxel-based segmented structures will be converted to non-uniform rational B-spline surfaces in order to allow for generation of a high-quality structural model (Gupta, Soellinger et al. 2009). A 3D model will be constructed with a 3D printer made with a flexible polymer with similar elastic properties of the spinal subarachnoid space with spinal cord present (Martin, Kalata et al. 2005; Martin, Labuda et al. 2009; Martin and Loth 2009).
- Model testing. MRI flow and geometry measurements will be obtained from the model to quantify the hydrodynamic and geometric properties of the model. 2D thru-plane pcMRI images will be acquired to quantify flow at various axial locations along the model (Martin, Kalata et al. 2005). 4DMRI measurements will also be conducted on the model to obtain flow in 3D (Santini, Wetzel et al. 2009; Bunck, Kroger et al. 2011). CSF pulse wave velocity will be assessed from the model using the methodology of Kalata et al. (Kalata, Martin et al. 2009). Pressure will be obtained throughout the spinal subarachnoid space at the same location as flow measurements (Martin and Loth 2009).
- Comparison of model to computational fluid dynamics simulations. The MRI measurements will be compared to a computational fluid dynamics simulation based on the geometric and flow boundary conditions used for the in vitro model.
Expected results and potential impact
We expect to develop the first validated 3D model of the spinal subarachnoid space with similar hydrodynamic and geometric conditions to that present in vivo. This model will have impact to help improve development of intrathecal drug delivery devices and validate existing 4D MRI flow measurement techniques. This model also has potential to be used for teaching students about spinal neurohydrodynamic physiology.
To be posted.
Bunck, A. C., J. R. Kroger, et al. (2011). "Magnetic resonance 4D flow characteristics of cerebrospinal fluid at the craniocervical junction and the cervical spinal canal." European radiology 21(8): 1788-1796.
Dickson, P. I. (2009). "Novel treatments and future perspectives: outcomes of intrathecal drug delivery." Int J Clin Pharmacol Ther 47 Suppl 1: S124-127.
Gupta, S., M. Soellinger, et al. (2009). "Three-dimensional computational modeling of subject-specific cerebrospinal fluid flow in the subarachnoid space." J Biomech Eng 131(2): 021010.
Kalata, W., B. A. Martin, et al. (2009). "MR measurement of cerebrospinal fluid velocity wave speed in the spinal canal." IEEE Trans Biomed Eng 56(6): 1765-1768.
Martin, B. A., W. Kalata, et al. (2005). "Syringomyelia hydrodynamics: an in vitro study based on in vivo measurements." J Biomech Eng 127(7): 1110-1120.
Martin, B. A., R. Labuda, et al. (2009). "Spinal Canal Pressure Measurements in an In Vitro Spinal Stenosis Model: Implications on Syringomyelia Theories." J Biomech Eng In Press(June 2009).
Martin, B. A. and F. Loth (2009). "The influence of coughing on cerebrospinal fluid pressure in an in vitro syringomyelia model with spinal subarachnoid space stenosis." Cerebrospinal Fluid Res 6(1): 17.
Rainov, N. G. and V. Heidecke (2007). "Management of chronic back and leg pain by intrathecal drug delivery." Acta Neurochir Suppl 97(Pt 1): 49-56.
Santini, F., S. G. Wetzel, et al. (2009). "Time-resolved three-dimensional (3D) phase-contrast (PC) balanced steady-state free precession (bSSFP)." Magn Reson Med.
Shoichet, M. S., C. H. Tator, et al. (2007). "Intrathecal drug delivery strategy is safe and efficacious for localized delivery to the spinal cord." Prog Brain Res 161: 385-392.