Table 1.
Cynomolgus monkey case information.
Fig 1.
This study involved a total of four MRI scans collected over a period of 45 days. MRIPRE-1 and MRIPRE-2 were performed prior to catheter implantation to confirm scan consistency (see results published in Khani et al. [21]). An intrathecal catheter was implanted within the cervical SAS (C5, n = 4) and lumbar SAS (L1, n = 4). Catheter patency was confirmed on day 24 and 28. MRIPOST-1 was collected to determine the acute impact of catheter implantation compared to MRIPRE-2. MRIPOST-2 was collected to determine if the impact persisted two weeks after implantation.
Fig 2.
Manual segmentation of the spinal SAS using a T2-weighted MR image.
Axial PC-MRI and CSF velocity profiles are indicated at corresponding vertebral levels for a representative cynomolgus monkey analyzed in this study. (A) Visualization of SAS area manually selected around the spinal cord at multiple axial levels. (B) Mid-sagittal high-resolution T2-weighted MRI and 3D visualization of entire SAS geometry. (C) 3D visualization of peak systolic CSF velocity profiles based on in vivo PC-MRI measurements at FM, C2-C3, C5-C6, T4-T5, T11-T12, and L3-L4. Arrows represent the location of catheter placement at the cervical (C5) or lumbar (L1) implantation groups (N = 4 NHPs in each group).
Table 2.
Cynomolgus monkey geometric and hydrodynamic parameter results at each measurement time point and for the cervical and lumbar implantation groups.
Table 3.
Statistical comparison of parameters across measurement time points for baseline vs. follow-up MRIs and cervical vs. lumbar catheter insertion.
P values are obtained from linear mixed effects model (see “Statistical analysis” section for details).
Fig 3.
Axial distribution of geometric parameters computed along the spine for cynomolgus monkeys with cervical catheter implantation (MRI #C) or lumbar catheter implantation (MRI #L) was measured prior to catheter implantation (MRIPRE-2), 17 days after catheter implantation (MRIPOST-1), and 31 days after catheter implantation (MRIPOST-2).
(A) Area of dura, Ad, (B) Area of spinal cord, Ac, (C) Area of SAS, Asas, (D) Perimeter of dura, Pd, (E) Perimeter of spinal cord, Pc, (F) Perimeter of SAS, Psas. Each line corresponds to mean value of each NHPs group with catheter located in the lumbar (L) or cervical (c) spine before (MRIPRE-2) or after catheter placement (MRIPOST-1 and MRIPOST-2).
Fig 4.
Average CSF flow waveforms for each MRI time point (4 NHPs at each point) measured at six axial locations along the spine (FM, C2-C3, C5-C6, T4-T5, T10-T11, L3-L4).
Note: Peak systolic, CSF flow is in the caudal direction (negative values).
Fig 5.
Mean CSF flow waveforms and Spatial-temporal distribution of CSF flow rate.
Spatial-temporal distribution of the interpolated CSF flow rate along the spine for all cases measured by PC-MRI. Dashed line indicates peak CSF flow rate at each axial level and dotted line indicates linear fit on top of those values used to compute CSF pulse wave velocity (PWV).
Fig 6.
Hydrodynamic parameter axial distribution computed along the spine for cynomolgus monkeys.
(A) Reynolds number, Re, (B) Flow rate amplitude, Qa, (C) Stroke Volume, SV, (D) left axis, Hydraulic diameter, Dh, right axis, Womersley number, α, (E) mean peak systolic, , and diastolic,
, CSF velocity. Each line corresponds to mean value of each NHPs group with catheter located in the lumbar or cervical spine before or after catheter placement.