The Impact of Spinal Cord Nerve Roots and Denticulate Ligaments on Cerebrospinal Fluid Dynamics in the Cervical Spine

Cerebrospinal fluid (CSF) dynamics in the spinal subarachnoid space (SSS) have been thought to play an important pathophysiological role in syringomyelia, Chiari I malformation (CM), and a role in intrathecal drug delivery. Yet, the impact that fine anatomical structures, including nerve roots and denticulate ligaments (NRDL), have on SSS CSF dynamics is not clear. In the present study we assessed the impact of NRDL on CSF dynamics in the cervical SSS. The 3D geometry of the cervical SSS was reconstructed based on manual segmentation of MRI images of a healthy volunteer and a patient with CM. Idealized NRDL were designed and added to each of the geometries based on in vivo measurments in the literature and confirmation by a neuroanatomist. CFD simulations were performed for the healthy and patient case with and without NRDL included. Our results showed that the NRDL had an important impact on CSF dynamics in terms of velocity field and flow patterns. However, pressure distribution was not altered greatly although the NRDL cases required a larger pressure gradient to maintain the same flow. Also, the NRDL did not alter CSF dynamics to a great degree in the SSS from the foramen magnum to the C1 level for the healthy subject and CM patient with mild tonsillar herniation (similar to 6 mm). Overall, the NRDL increased fluid mixing phenomena and resulted in a more complex flow field. Comparison of the streamlines of CSF flow revealed that the presence of NRDL lead to the formation of vortical structures and remarkably increased the local mixing of the CSF throughout the SSS

A numerical investigation of intrathecal isobaric drug dispersion within the cervical subarachnoid space

Intrathecal drug and gene vector delivery is a procedure to release a solute within the cerebrospinal fluid. This procedure is currently used in clinical practice and shows promise for treatment of several central nervous system pathologies. However, intrathecal delivery protocols and systems are not yet optimized. The aim of this study was to investigate the effects of injection parameters on solute distribution within the cervical subarachnoid space using a numerical platform. We developed a numerical model based on a patient-specific three dimensional geometry of the cervical subarachnoid space with idealized dorsal and ventral nerve roots and denticulate ligament anatomy. We considered the drug as massless particles within the flow field and with similar properties as the CSF, and we analyzed the effects of anatomy, catheter position, angle and injection flow rate on solute distribution within the cerebrospinal fluid by performing a series of numerical simulations. Results were compared quantitatively in terms of drug peak concentration, spread, accumulation rate and appearance instant over 15 seconds following the injection. Results indicated that solute distribution within the cervical spine was altered by all parameters investigated within the time range analyzed following the injection. The presence of spinal cord nerve roots and denticulate ligaments increased drug spread by 60% compared to simulations without these anatomical features. Catheter position and angle were both found to alter spread rate up to 86%, and catheter flow rate altered drug peak concentration up to 78%. The presented numerical platform fills a first gap towards the realization of a tool to parametrically assess and optimize intrathecal drug and gene vector delivery protocols and systems. Further investigation is needed to analyze drug spread over a longer clinically relevant time frame

Accuracy of 4D Flow Measurement of Cerebrospinal Fluid Dynamics in the Cervical Spine: An In Vitro Verification Against Numerical Simulation

Abnormal alterations in cerebrospinal fluid (CSF) flow are thought to play an important role in pathophysiology of various craniospinal disorders such as hydrocephalus and Chiari malformation. Three directional phase contrast MRI (4D Flow) has been proposed as one method for quantification of the CSF dynamics in healthy and disease states, but prior to further implementation of this technique, its accuracy in measuring CSF velocity magnitude and distribution must be evaluated. In this study, an MR-compatible experimental platform was developed based on an anatomically detailed 3D printed model of the cervical subarachnoid space and subject specific flow boundary conditions. Accuracy of 4D Flow measurements was assessed by comparison of CSF velocities obtained within the in vitro model with the numerically predicted velocities calculated from a spatially averaged computational fluid dynamics (CFD) model based on the same geometry and flow boundary conditions. Good agreement was observed between CFD and 4D Flow in terms of spatial distribution and peak magnitude of through-plane velocities with an average difference of 7.5 and 10.6% for peak systolic and diastolic velocities, respectively. Regression analysis showed lower accuracy of 4D Flow measurement at the timeframes corresponding to low CSF flow rate and poor correlation between CFD and 4D Flow in-plane velocities

Characterization of the discrepancies between four-dimensional phase-contrast magnetic resonance imaging and in-silico simulations of cerebrospinal fluid dynamics

The purpose of the present study was to compare subject-specific magnetic resonance imaging (MRI)-based computational fluid dynamics (CFD) simulations with time-resolved three-directional (3D) velocity-encoded phase-contrast MRI (4D PCMRI) measurements of the cerebrospinal fluid (CSF) velocity field in the cervical spinal subarachnoid space (SSS). Three-dimensional models of the cervical SSS were constructed based on MRI image segmentation and anatomical measurements for a healthy subject and patient with Chiari I malformation. CFD was used to simulate the CSF motion and compared to the 4D PCMRI measurements. Four-dimensional PCMRI measurements had much greater CSF velocities compared to CFD simulations (1.4 to 5.6 x greater). Four-dimensional PCMRI and CFD both showed anterior and anterolateral dominance of CSF velocities, although this flow feature was more pronounced in 4D PCMRI measurements compared to CFD. CSF flow jets were present near the nerve rootlets and denticulate ligaments (NRDL) in the CFD simulation. Flow jets were visible in the 4D PCMRI measurements, although they were not clearly attributable to nerve rootlets. Inclusion of spinal cord NRDL in the cervical SSS does not fully explain the differences between velocities obtained from 4D PCMRI measurements and CFD simulations

Inter-operator Reliability of Magnetic Resonance Image-Based Computational Fluid Dynamics Prediction of Cerebrospinal Fluid Motion in the Cervical Spine

For the first time, inter-operator dependence of MRI based computational fluid dynamics (CFD) modeling of cerebrospinal fluid (CSF) in the cervical spinal subarachnoid space (SSS) is evaluated. In vivo MRI flow measurements and anatomy MRI images were obtained at the cervico-medullary junction of a healthy subject and a Chiari I malformation patient. 3D anatomies of the SSS were reconstructed by manual segmentation by four independent operators for both cases. CFD results were compared at nine axial locations along the SSS in terms of hydrodynamic and geometric parameters. Intraclass correlation (ICC) assessed the inter-operator agreement for each parameter over the axial locations and coefficient of variance (CV) compared the percentage of variance for each parameter between the operators. Greater operator dependence was found for the patient (0.19 0.78). For the healthy subject, hydraulic diameter and Womersley number had the least variance (CV = similar to 2%). For the patient, peak diastolic velocity and Reynolds number had the smallest variance (CV = similar to 3%). These results show a high degree of inter-operator reliability for MRI-based CFD simulations of CSF flow in the cervical spine for healthy subjects and a lower degree of reliability for patients with Type I Chiari malformation

Velocity magnitude contours at different locations along cervical SSS plotted at the time corresponding to the peak systole for the healthy case (A) and patient diagnosed with Chiari I malformation (B).

<p>In each set of contours, the left and right column represent the results for cases without and with NRDL, respectively.</p

CSF flow streamlines at t/T = 4.5.

<p>The reported streamlines are obtained from test cases (a) (without NRDL) and (b) PS₁ (with NRDL).</p

An MRI-Compatible Hydrodynamic Simulator of Cerebrospinal Fluid Motion in the Cervical Spine

Goal: Develop and test an MRI-compatible hydrodynamic simulator of cerebrospinal fluid (CSF) motion in the cervical spinal subarachnoid space. Four anatomically realistic subject-specific models were created based on a 22-year-old healthy volunteer and a five-year-old patient diagnosed with Chiari I malformation. Methods: The in vitro models were based on manual segmentation of high-resolution T2-weighted MRI of the cervical spine. Anatomically realistic dorsal and ventral spinal cord nerve rootlets (NR) were added. Models were three dimensional (3-D) printed by stereolithography with 50-mu m layer thickness. A computer controlled pump system was used to replicate the shape of the subject specific in vivo CSF flow measured by phase-contrast MRI. Each model was then scanned by T2-weighted and 4-D phase contrast MRI (4D flow). Results: Cross-sectional area, wetted perimeter, and hydraulic diameter were quantified for each model. The oscillatory CSF velocity field (flow jets near NR, velocity profile shape, and magnitude) had similar characteristics to previously reported studies in the literature measured by in vivo MRI. Conclusion: This study describes the first MRI-compatible hydrodynamic simulator of CSF motion in the cervical spine with anatomically realistic NR. NR were found to impact CSF velocity profiles to a great degree. Significance: CSF hydrodynamics are thought to be altered in craniospinal disorders such as Chiari I malformation. MRI scanning techniques and protocols can be used to quantify CSF flow alterations in disease states. The provided in vitro models can be used to test the reliability of these protocols across MRI scanner manufacturers and machines