\u3cem\u3eEx Vivo\u3c/em\u3e Diffusion Tensor Imaging of Spinal Cord Injury in Rats of Varying Degrees of Severity

The aim of this study was to characterize magnetic resonance diffusion tensor imaging (DTI) in proximal regions of the spinal cord following a thoracic spinal cord injury (SCI). Sprague–Dawley rats (n = 40) were administered a control, mild, moderate, or severe contusion injury at the T8 vertebral level. Six direction diffusion weighted images (DWIs) were collected ex vivo along the length of the spinal cord, with an echo/repetition time of 31.6 ms/14 sec and b = 500 sec/mm2. Diffusion metrics were correlated to hindlimb motor function. Significant differences were found for whole cord region of interest (ROI) drawings for fractional anisotropy (FA), mean diffusivity (MD), longitudinal diffusion coefficient (LD), and radial diffusion coefficient (RD) at each of the cervical levels ( p \u3c 0.01). Motor function correlated with MD in the cervical segments of the spinal cord (r2 = 0.80). The diffusivity of water significantly decreased throughout ‘‘uninjured’’ portions of the spinal cord following a contusion injury ( p \u3c 0.05). Diffusivity metrics were found to be altered following SCI in both white and gray matter regions. Injury severity was associated with diffusion changes over the entire length of the cord. This study demonstrates that DTI is sensitive to SCI in regions remote from injury, suggesting that the diffusion metrics may be used as a biomarker for severity of injury

Diffusion Imaging in the Rat Cervical Spinal Cord

Magnetic resonance imaging (MRI) is the state of the art approach for assessing the status of the spinal cord noninvasively, and can be used as a diagnostic and prognostic tool in cases of disease or injury. Diffusion weighted imaging (DWI), is sensitive to the thermal motion of water molecules and allows for inferences of tissue microstructure. This report describes a protocol to acquire and analyze DWI of the rat cervical spinal cord on a small-bore animal system. It demonstrates an imaging setup for the live anesthetized animal and recommends a DWI acquisition protocol for high-quality imaging, which includes stabilization of the cord and control of respiratory motion. Measurements with diffusion weighting along different directions and magnitudes (b-values) are used. Finally, several mathematical models of the resulting signal are used to derive maps of the diffusion processes within the spinal cord tissue that provide insight into the normal cord and can be used to monitor injury or disease processes noninvasively. The video component of this article can be found at http://www.jove.com/video/52390/ Introduction Magneti

Severity of Spinal Cord Injury Influences Diffusion Tensor Imaging of the Brain

Background: The purpose of this study was to determine whether DTI changes in the brain induced by a thoracic spinal cord injury are sensitive to varying severity of spinal contusion in rats. Methods: A control, mild, moderate, or severe contusion injury was administered over the eighth thoracic vertebral level in 32 Sprague-Dawley rats. At 11 weeks postinjury, ex vivo DTI of the brain was performed on a 9.4T Bruker scanner using a pulsed gradient spin-echo sequence. Results: Mean water diffusion in the internal capsule regions of the brain and pyramid locations of the brainstem were correlated with motor function (r2 = 0.55). Additionally, there were significant differences between injury severity groups for mean diffusivity and fractional anisotropy at regions associated with the corticospinal tract (P = 0.05). Conclusion: These results indicate that DTI is sensitive to changes in brain tissue as a consequence of thoracic SCI

Clinical Correlates of High Cervical Fractional Anisotropy in Acute Cervical Spinal Cord Injury

Objective: Fractional anisotropy (FA) of the high cervical cord (C1-C2), rostral to the injury site, correlates with upper limb function in patients with chronic cervical spinal cord injury (SCI). In acute cervical SCI, this relationship has not been investigated. The objective of this study was to identify functional correlates of FA of the high cervical cord in a series of patients with acute cervical SCI. Methods: Traumatic cervical SCI patients who underwent presurgical cervical spine diffusion tensor imaging at our institution were reviewed for this study. FA of the whole cord as well as the lateralcorticospinal tracts (CSTs) was calculated on axial images from C1-C2. Upper limb motor (C5-T1) and sensory (C2-T1) function scores were extracted from the admission American Spinal Injury Association (ASIA) examinations. Correlation analysis for FA with ASIA examinations was performed using a Pearson correlation. Results: Twelve subjects (9 men, 3 women; mean age 54.7 ± 4.0 years) underwent cervical spine diffusion tensor imaging at a mean duration of 3.6 ± 0.9 days postinjury. No patient had cord compression or intramedullary T2-weighted hyperintensities within the C1-C2 segments. FA correlated with upper limb motor score (whole cord: r = 0.59, P = .04; CST: 0.67, P = .01) and the ASIA grade (whole cord: r = 0.61, P = .03; CST: r = 0.71, P = .009). No correlation was found between FA and sensory scores. Conclusions: FA of the whole cervical cord as well as the CST, rostral to the injury site, is associated with preserved upper limb motor function as well as superior ASIA grades after acute cervical SCI. FA of the high cervical cord is a potential biomarker of neural injury after acute cervical SCI

Optimizing Filter-Probe Diffusion Weighting in the Rat Spinal Cord for Human Translation

Diffusion tensor imaging (DTI) is a promising biomarker of spinal cord injury (SCI). In the acute aftermath, DTI in SCI animal models consistently demonstrates high sensitivity and prognostic performance, yet translation of DTI to acute human SCI has been limited. In addition to technical challenges, interpretation of the resulting metrics is ambiguous, with contributions in the acute setting from both axonal injury and edema. Novel diffusion MRI acquisition strategies such as double diffusion encoding (DDE) have recently enabled detection of features not available with DTI or similar methods. In this work, we perform a systematic optimization of DDE using simulations and an in vivo rat model of SCI and subsequently implement the protocol to the healthy human spinal cord. First, two complementary DDE approaches were evaluated using an orientationally invariant or a filter-probe diffusion encoding approach. While the two methods were similar in their ability to detect acute SCI, the filter-probe DDE approach had greater predictive power for functional outcomes. Next, the filter-probe DDE was compared to an analogous single diffusion encoding (SDE) approach, with the results indicating that in the spinal cord, SDE provides similar contrast with improved signal to noise. In the SCI rat model, the filter-probe SDE scheme was coupled with a reduced field of view (rFOV) excitation, and the results demonstrate high quality maps of the spinal cord without contamination from edema and cerebrospinal fluid, thereby providing high sensitivity to injury severity. The optimized protocol was demonstrated in the healthy human spinal cord using the commercially-available diffusion MRI sequence with modifications only to the diffusion encoding directions. Maps of axial diffusivity devoid of CSF partial volume effects were obtained in a clinically feasible imaging time with a straightforward analysis and variability comparable to axial diffusivity derived from DTI. Overall, the results and optimizations describe a protocol that mitigates several difficulties with DTI of the spinal cord. Detection of acute axonal damage in the injured or diseased spinal cord will benefit the optimized filter-probe diffusion MRI protocol outlined here

Diffusion Tensor Imaging Correlates with Short-Term Myelopathy Outcome in Patients with Cervical Spondylotic Myelopathy

Objective To determine if spinal cord diffusion tensor imaging indexes correlate with short-term clinical outcome in patients undergoing elective cervical spine surgery for cervical spondylotic myelopathy (CSM). Methods A prospective consecutive cohort study was performed in patients undergoing elective cervical spine surgery for CSM. After obtaining informed consent, patients with CSM underwent preoperative T2-weighted magnetic resonance imaging and diffusion tensor imaging of the cervical spine. Fractional anisotropy (FA) values at the level of maximum cord compression and at the noncompressed C1-2 level were calculated on axial images. We recorded the modified Japanese Orthopaedic Association (mJOA) scale, Neck Disability Index, and Short Form-36 physical functioning subscale scores for all patients preoperatively and 3 months postoperatively. Statistical analysis was performed to identify correlations between FA and clinical outcome scores. Results The study included 27 patients (mean age 54.5 years ± 1.9, 12 men). The mean postoperative changes in mJOA scale, Neck Disability Index, and Short Form-36 physical functioning subscale scores were 0.9 ± 0.3, −6.0 ± 1.9, and 3.4 ± 1.9. The mean FA at the level of maximum compression was significantly lower than the mean FA at the C1-2 level (0.5 vs. 0.55, P = 0.01). FA was significantly correlated with change in mJOA scale score (Pearson r = −0.42, P = 0.02). FA was significantly correlated with the preoperative mJOA scale score (Pearson r = 0.65, P \u3c 0.001). Conclusions Preoperative FA at the level of maximum cord compression significantly correlates with the 3-month change in mJOA scale score among patients with CSM. FA was also significantly associated with preoperative mJOA scale score and is a potential biomarker for spinal cord dysfunction in CSM

Diffusion Tensor Imaging in a Large Longitudinal Series of Patients With Cervical Spondylotic Myelopathy Correlated With Long-Term Functional Outcome

BACKGROUND Fractional anisotropy (FA) of the high cervical cord correlates with upper limb function in acute cervical cord injury. We investigated the correlation between preoperative FA at the level of maximal compression and functional recovery in a group of patients after decompressive surgery for cervical spondylotic myelopathy (CSM). OBJECTIVE To determine the usefulness of FA as a biomarker for severity of CSM and as a prognostic biomarker for improvement after surgery. METHODS Patients received diffusion tensor imaging (DTI) scans preoperatively. FA values of the whole cord cross-section at the level of maximal compression and upper cervical cord (C1-2) were calculated. Functional status was measured using the modified Japanese Orthopedic Association (mJOA) scale preoperatively and at follow-up up to 2 yr. Regression analysis between FA and mJOA was performed. DTI at C4-7 was obtained in controls. RESULTS Forty-four CSM patients enrolled prior to decompression were compared with 24 controls. FA at the level of maximal compression correlated positively with preoperative mJOA score. Preoperative FA correlated inversely with recovery throughout the postoperative period. This was statistically significant at 12 mo postoperation and nearly so at 6 and 24 mo. Patients with preoperative FA0.55. CONCLUSION In the largest longitudinal study of this kind, FA promises a valid biomarker for severity of CSM and postoperative improvement. FA is an objective measure of function and could provide a basis for prognosis. FA is particularly useful if preoperative values are less than 0.55

Diffusion Tensor Imaging of the Spinal Cord: Insights From Animal and Human Studies

Diffusion tensor imaging (DTI) provides a measure of the directional diffusion of water molecules in tissues. The measurement of DTI indexes within the spinal cord provides a quantitative assessment of neural damage in various spinal cord pathologies. DTI studies in animal models of spinal cord injury indicate that DTI is a reliable imaging technique with important histological and functional correlates. These studies demonstrate that DTI is a noninvasive marker of microstructural change within the spinal cord. In human studies, spinal cord DTI shows definite changes in subjects with acute and chronic spinal cord injury, as well as cervical spondylotic myelopathy. Interestingly, changes in DTI indexes are visualized in regions of the cord, which appear normal on conventional magnetic resonance imaging and are remote from the site of cord compression. Spinal cord DTI provides data that can help us understand underlying microstructural changes within the cord and assist in prognostication and planning of therapies. In this article, we review the use of DTI to investigate spinal cord pathology in animals and humans and describe advances in this technique that establish DTI as a promising biomarker for spinal cord disorders

Alterations in Cortical Sensorimotor Connectivity following Complete Cervical Spinal Cord Injury: A Prospective Resting-State fMRI Study

Functional magnetic resonance imaging (fMRI) studies have demonstrated alterations during task-induced brain activation in spinal cord injury (SCI) patients. The interruption to structural integrity of the spinal cord and the resultant disrupted flow of bidirectional communication between the brain and the spinal cord might contribute to the observed dynamic reorganization (neural plasticity). However, the effect of SCI on brain resting-state connectivity patterns remains unclear. We undertook a prospective resting-state fMRI (rs-fMRI) study to explore changes to cortical activation patterns following SCI. With institutional review board approval, rs-fMRI data was obtained in eleven patients with complete cervical SCI (\u3e2 years post injury) and nine age-matched controls. The data was processed using the Analysis of Functional Neuroimages software. Region of interest (ROI) based analysis was performed to study changes in the sensorimotor network using pre- and post-central gyri as seed regions. Two-sampled t-test was carried out to check for significant differences between the two groups. SCI patients showed decreased functional connectivity in motor and sensory cortical regions when compared to controls. The decrease was noted in ipsilateral, contralateral, and interhemispheric regions for left and right precentral ROIs. Additionally, the left postcentral ROI demonstrated increased connectivity with the thalamus bilaterally in SCI patients. Our results suggest that cortical activation patterns in the sensorimotor network undergo dynamic reorganization following SCI. The presence of these changes in chronic spinal cord injury patients is suggestive of the inherent neural plasticity within the central nervous system

Evaluation of Whole-Brain Resting-State Functional Connectivity in Spinal Cord Injury - A Large-Scale Network Analysis Using Network Based Statistic

Large-scale network analysis characterizes the brain as a complex network of nodes and edges to evaluate functional connectivity patterns. The utility of graph-based techniques has been demonstrated in an increasing number of restingstate functional MRI (rs-fMRI) studies in the normal and diseased brain. However, to our knowledge, graph theory has not been used to study the reorganization pattern of resting-state brain networks in patients with traumatic complete spinal cord injury (SCI). In the present analysis, we applied a graph-theoretical approach to explore changes to global brain network architecture as a result of SCI. Fifteen subjects with chronic (\u3e 2 years) complete (American Spinal Injury Association [ASIA] A) cervical SCI and 15 neurologically intact controls were scanned using rs-fMRI. The data were preprocessed followed by parcellation of the brain into 116 regions of interest (ROI) or nodes. The average time series was extracted at each node, and correlation analysis was performed between every pair of nodes. A functional connectivity matrix for each subject was then generated. Subsequently, the matrices were averaged across groups, and network changes were evaluated between groups using the network-based statistic (NBS) method. Our results showed decreased connectivity in a subnetwork of the whole brain in SCI compared with control subjects. Upon further examination, increased connectivity was observed in a subnetwork of the sensorimotor cortex and cerebellum network in SCI. In conclusion, our findings emphasize the applicability of NBS to study functional connectivity architecture in diseased brain states. Further, we show reorganization of large-scale resting-state brain networks in traumatic SCI, with potential prognostic and therapeutic implications