Mid-lumbar (L3) epidural stimulation effects on bladder and external urethral sphincter in non-injured and chronically transected urethane-anesthetized rats.

Recent pre-clinical and clinical spinal cord epidural stimulation (scES) experiments specifically targeting the thoracolumbar and lumbosacral circuitries mediating lower urinary tract (LUT) function have shown improvements in storage, detrusor pressure, and emptying. With the existence of a lumbar spinal coordinating center in rats that is involved with external urethral sphincter (EUS) functionality during micturition, the mid-lumbar spinal cord (specifically L3) was targeted in the current study with scES to determine if the EUS and thus the void pattern could be modulated, using both intact and chronic complete spinal cord injured female rats under urethane anesthesia. L3 scES at select frequencies and intensities of stimulation produced a reduction in void volumes and EUS burst duration in intact rats. After chronic transection, three different subgroups of LUT dysfunction were identified and the response to L3 scES promoted different cystometry outcomes, including changes in EUS bursting. The current findings suggest that scES at the L3 level can generate functional neuromodulation of both the urinary bladder and the EUS in intact and SCI rats to enhance voiding in a variety of clinical scenarios.

Relationships between spinal cord blood flow measured with flow-sensitive alternating inversion recovery (FAIR) and neurobehavioral outcomes in rat spinal cord injury.

In the traumatically injured spinal cord, decreased perfusion is believed to contribute to secondary tissue damage beyond the primary mechanical impact, and restoration of perfusion is believed to be a promising therapeutic target. However, methods to monitor spinal cord perfusion non-invasively are limited. Perfusion magnetic resonance imaging (MRI) techniques established for the brain have not been routinely adopted to the spinal cord. The purpose of this study was to examine the relationship between spinal cord blood flow (SCBF) and injury severity in a rat thoracic spinal cord contusion injury (SCI) model using flow-sensitive alternating inversion recovery (FAIR) with two variants of the label position. SCBF as a marker of severity was compared to T1 mapping and to spinal cord-optimized diffusion weighted imaging (DWI) with filtered parallel apparent diffusion coefficient. Thirty-eight rats underwent a T10 contusion injury with varying severities (8 sham; 10 mild; 10 moderate; 10 severe) with MRI performed at 1 day post injury at the lesion site and follow-up neurological assessments using the Basso, Beattie, Bresnahan (BBB) locomotor scoring up to 28 days post injury. Using whole-cord regions of interest at the lesion epicenter, SCBF was decreased with injury severity and had a significant correlation with BBB scores at 28 days post injury. Importantly, estimates of arterial transit times (ATT) in the injured spinal cord were not altered after injury, which suggests that FAIR protocols optimized to measure SCBF provide more value in the context of acute traumatic injury to the cord. T1-relaxation time constants were strongly related to injury severity and had a larger extent of changes than either SCBF or DWI measures. These findings suggest that perfusion decreases in the spinal cord can be monitored non-invasively after injury, and multi-parametric MRI assessments of perfusion, diffusion, and relaxation capture unique features of the pathophysiology of preclinical injury.

Evolution of Magnetic Resonance Imaging as Predictors and Correlates of Functional Outcome after Spinal Cord Contusion Injury in the Rat.

Clinical methods for determining the severity of traumatic spinal cord injury (SCI) and long-term functional outcome in the acute setting are limited in their prognostic accuracy because of the heterogeneity of injury and dynamic injury progression. The aim of this study was to evaluate the time course and sensitivity of advanced magnetic resonance imaging (MRI) methods to neurological function after SCI in a rat contusion model. Rats received a graded contusion injury at T10 using a weight-drop apparatus. MRI consisted of morphological measures from T2-weighted imaging, quantitative T2 imaging, and diffusion-weighted imaging (DWI) at 1, 30, and 90 days post-injury (dpi). The derived metrics were compared with neurological function assessed using weekly Basso, Beattie, and Bresnahan (BBB) locomotor scoring and return of reflexive micturition function. At the acute time point (1 dpi), diffusion metrics sensitive to axonal injury at the injury epicenter had the strongest correlation with time-matched BBB scores and best predicted 90-dpi BBB scores. At 30 dpi, axonal water fraction derived from DWI and T2 values were both correlated with time-matched locomotor scores. At the chronic time point (90 dpi), cross-sectional area was most closely correlated to BBB. Overall, the results demonstrate differential sensitivity of MRI metrics at different time points after injury, but the metrics follow the expected pathology of acute axonal injury followed by continued degeneration and finally a terminal level of atrophy. Specificity of DWI in the acute setting may make it impactful as a prognostic tool while T2 imaging provided the most information about injury severity in chronic injury.

Longitudinal In Vivo Diffusion Magnetic Resonance Imaging Remote from the Lesion Site in Rat Spinal Cord Injury.

Diffusion tensor imaging (DTI) has demonstrated success as a biomarker of spinal cord injury (SCI) severity as shown from numerous pre-clinical studies. However, artifacts from stabilization hardware at the lesion have precluded its use for longitudinal assessments. Previous research has documented ex vivo diffusion changes in the spinal cord both caudal and cranial to the injury epicenter. The aim of this study was to use a rat contusion model of SCI to evaluate the utility of in vivo cervical DTI after a thoracic injury. Forty Sprague-Dawley rats underwent a thoracic contusion (T8) of mild, moderate, severe, or sham severity. Magnetic resonance imaging (MRI) of the cervical cord was performed at 2, 30, and 90 days post-injury, and locomotor performance was assessed weekly using the Basso, Bresnahan, and Beattie (BBB) scoring scale. The relationships between BBB scores and MRI were assessed using region of interest analysis and voxel-wise linear regression of DTI, and free water elimination (FWE) modeling to reduce partial volume effects. At 90 days, axial diffusivity (ADFWE), mean diffusivity (MDFWE), and free water fraction (FWFFWE) using the FWE model were found to be significantly correlated with BBB score. FWE was found to be more predictive of injury severity than conventional DTI, specifically at later time-points. This study validated the use of FWE technique in spinal cord and demonstrated its sensitivity to injury remotely.

Characterization of Lumbar Spine Annular Disruption in PMHS Using MRI, Cryomicrotomy and Histology Techniques.

Internal intervertebral disc disruption is involved in the onset of a wide range of spinal dysfunction, ultimately affecting not only the disc itself but the surrounding osseous and neural structures as well. The ability of disc to withstand and effectively distribute axial load is dependent upon whether peripherally located annular fibers provide the support necessary to contain and corral the pressure sensitive nucleus. Any alteration in the structures immediate to the nucleus jeopardize this ability. While annular tears and fissures have been thoroughly investigated, one form of internal disc disruption is less well-understood. A network of elastin cross-bridges provides resistance to delamination of the collagenous sheets that comprise the annulus. The current investigation utilized a Nitrogen gas-induced pressure mechanism to disrupt elastin cross links that exist between annular lamellae. Twenty five cadaveric lumbar spine motion segments (mean age: 52±12 yr.) were subjected to the annular disruption protocol. Damage to the annulus was assessed using MRI, cryomicrotome and histological staining procedures. MRI images were compared to cryomicrotome images to determine the ability of standard clinical MRI scans to determine annular damage. In many cases MRI was moderately revealing in terms of damage. Future studies will quantify biomechanical consequences of these low level annular disruptions relative to segmental stability.