Benjamin M. Ellingson and Langston T. Holly
Lesion growth and degeneration patterns measured using diffusion tensor 9.4-T magnetic resonance imaging in rat spinal cord injury
Presented at the 2009 Joint Spine Section Meeting
Benjamin M. Ellingson, Brian D. Schmit, and Shekar N. Kurpad
Using diffusion tensor MR imaging, the authors conducted a study to explore lesion growth and degeneration patterns, from the acute through chronic stages of spinal cord injury (SCI), in an experimental animal model.
In vivo and ex vivo diffusion tensor imaging was performed using a 9.4-T MR imaging system in rats allowed to recover from traumatic contusion SCI from 2 weeks through 25 weeks postinjury, mimicking progression of human SCI from the acute through chronic stages.
Results showed significant growth of the traumatic lesion up to 15 weeks postinjury, where both the size and mean diffusivity (MD) reached a maximum that was maintained through the remainder of recovery. Mean diffusivity was sensitive to overall spinal cord integrity, whereas fractional anisotropy showed specificity to sites of cavity formation. The use of an MD contour map for in vivo data and a 3D surface map for ex vivo data, showing MD as a function of rostral-caudal distance and recovery time, allowed documentation of rostral and caudal spreading of the lesion.
Results from this study demonstrate changes in both lesion morphology and diffusivity beyond previously reported time points and provide a unique perspective on the process of cavity formation and degeneration following traumatic SCI. Additionally, results suggest that MD more accurately defines regions of histological damage than do regions of T2 signal hyperintensity. This could have significant clinical implications in the detection and potential treatment of posttraumatic syringes in SCI.
Benjamin M. Ellingson, Noriko Salamon, Davis C. Woodworth, Hajime Yokota, and Langston T. Holly
The purpose of this study was to quantify the reproducibility, temporal stability, and functional correlation of diffusion MR characteristics in the spinal cord in patients with cervical stenosis with or without myelopathy. The association between longitudinal diffusion tensor imaging (DTI) measurements and serial neurological function assessment was explored at both the group and individual level.
Sixty-six nonoperatively treated patients with cervical stenosis were prospectively followed (3 months to > 5 years) using synchronous serial MRI and functional outcome assessment. A total of 183 separate MRI examinations were performed, separated by at least 3 months, and each patient had a minimum of 2 MRI scans (range 2–5 scans). Anatomical and DTI measurements were performed within the spinal cord at the C1–2 region as well as at the area of highest compression. Coefficients of variance (COVs) were compared across measurements in both reference tissue and areas of compression for anatomical measurements, fractional anisotropy (FA), and mean diffusivity (MD). The correlation between diffusion MR measures at the site of compression and evaluations of neurological function assessed using the modified Japanese Orthopaedic Association (mJOA) scale at multiple time points was evaluated.
The COVs for anatomical measurements (Torg ratio and canal diameter) were between 7% and 10%. The median COV for FA measurements at the site of compression was 9%, and for reference tissue at C1–2 it was 6%. The median COV for MD at the site of compression was approximately 12%, and for reference tissue at C1–2 it was 10%. The FA and MD measurements of C1–2 averaged 0.61 and 0.91 μm2/msec, respectively, whereas the FA and MD measurements at the site of compression averaged 0.51 and 1.26 μm2/msec, respectively. Both FA (slope = 0.037; R2 = 0.3281, p < 0.0001) and MD (slope = −0.074; R2 = 0.1101, p = 0.0084) were significantly correlated with the mJOA score. The FA decreased by approximately 0.032 units per mJOA unit decrease (R2 = 0.2037, p < 0.0001), whereas the MD was increased by approximately 0.084 μm2/msec for every mJOA unit decrease (R2 = 0.1016, p < 0.0001).
Quantitative DTI measurements of the spinal cord in patients with cervical stenosis with or without myelopathy have a median COV of 5%–10%, similar to anatomical measurements. The reproducibility of these measurements and significant correlation with functional outcome status suggest a potential role in the evaluation and longitudinal surveillance of nonoperatively treated patients. With respect to the specific DTI measurements, FA within the spinal cord appears slightly more sensitive to neurological function and more stable than measures of MD. Therefore, DTI of the spinal cord may be a clinically feasible imaging technique for longitudinally monitoring patients with cervical spondylotic myelopathy.
Benjamin M. Ellingson, Noriko Salamon, Davis C. Woodworth, and Langston T. Holly
The purpose of this study was to explore the use of super-resolution tract density images derived from probabilistic diffusion tensor imaging (DTI) tractography of the spinal cord as an imaging surrogate for microstructural integrity and functional impairment in patients with cervical spondylosis.
Structural MRI and DTI images were collected for 27 patients with cervical spondylosis with (n= 21) and without (n= 6) functional impairment as defined by the modified Japanese Orthopaedic Association Scale (mJOA). DTI was performed axially through the site of compression in a total of 20 directions with 10 averages. Probabilistic tractography was performed at 0.5-mm isotropic spatial resolution using the streamline technique combined with constrained spherical deconvolution. The following measurements were calculated for each patient: maximum tract density at the site of compression, average tract density in rostral normal-appearing spinal cord, and the ratio of maximum density to normal density.
Compared with normal tissue, the site of compression exhibited elevated fiber tract density in all patients, and a higher fiber tract density was also noted in focal areas at the site of compression in patients with functional impairment. There was a strong negative correlation between maximum tract density and mJOA score (R2= 0.6324, p < 0.0001) and the ratio of maximum tract density to normal tract density (R2= 0.6647, p < 0.0001). When grouped according to severity of neurological impairment (asymptomatic, mJOA score of 18; mild, mJOA score of 15–17; moderate, mJOA score of 11–14; and severe, mJOA score < 11), the results showed a significant difference in the ratio between severe and both no impairment (p= 0.0009) and any impairment (p= 0.036). A ratio of maximum fiber tract density at the site of compression to fiber tract density at C-2 greater than 1.45 had 82% sensitivity and 70% specificity for identifying patients with moderate to severe impairment (ROC AUC= 0.8882, p= 0.0009).
These results support the use of DTI as a surrogate for determining spinal cord integrity in patients with cervical spondylosis. Probabilistic tractography provides spinal cord microstructural information that can help discern clinical status in cervical spondylosis patients with varying degrees of neurological impairment.
Chencai Wang, Benjamin M. Ellingson, Sabah Islam, Azim Laiwalla, Noriko Salamon, and Langston T. Holly
The aim of this study was to investigate cerebral reorganization, both structurally and functionally, occurring in patients with degenerative cervical myelopathy (DCM) after surgical decompression.
In the current observational study of 19 patients, high-resolution T1-weighted structural MRI and resting-state functional MRI scans were obtained pre- and postoperatively in patients with DCM and healthy controls (HCs). The resting-state functional MRI data were utilized to perform region-of-interest (ROI)–to-ROI and ROI-to-voxel functional connectivity (FC) analysis and were similarly compared between and within cohorts. Macroscopic structural plasticity was evaluated by assessing for changes in cortical thickness within the DCM cohort after decompression surgery.
Prior to surgery, FC patterns were significantly different between DCM patients and HCs in cerebral areas responsible for postural control, motor regulation, and perception and integration of sensory information. Significantly stronger FC between the cerebellum and frontal lobes was identified in DCM patients postoperatively compared with DCM patients preoperatively. Additionally, increased FC between the cerebellum and primary sensorimotor areas was found to be positively associated with neurological improvement in patients with DCM. No macroscopic structural changes were observed in the DCM patients after surgery.
These results support the authors’ hypothesis that functional changes within the brain are associated with effective postoperative recovery, particularly in regions associated with motor regulation and with perception and integration of sensory information. In particular, increased FC between the cerebellum and the primary sensorimotor after surgery appears to be associated with neurological improvement. Macroscopic morphological changes may be too subtle to be detected within 3 months after surgery.
Ryan M. Martin, Matthew J. Wright, Evan S. Lutkenhoff, Benjamin M. Ellingson, John D. Van Horn, Meral Tubi, Jeffry R. Alger, David L. McArthur, and Paul M. Vespa
Hemorrhagic contusions are often the most visible lesions following traumatic brain injury. However, the incidence, location, and natural history of traumatic parenchymal hemorrhage and its impact on neurological outcome have been understudied. The authors sought to examine the location and longitudinal evolution of traumatic parenchymal hemorrhage and its association with cognitive outcome.
Sixteen patients with hemorrhagic contusions due to acceleration-deceleration injuries underwent MRI in the acute (mean 6.3 days postinjury) and chronic (mean 192.9 days postinjury) phases. ImageJ was used to generate GRE and FLAIR volumes. To account for the effect of head-size variability across individuals, the authors calculated each patient's total brain tissue volume using SIENAX. GRE and FLAIR volumes were normalized to the total brain tissue volume, and values for absolute and percent lesion volume and total brain volume change were generated. Spearman's rank correlations were computed to determine associations between neuroimaging and 6-month postinjury neuropsychological testing of attention (Symbol Digit Modalities Test [SDMT], oral [O] and written [W] versions), memory (Selective Reminding Test, total learning and delayed recall), and executive function (Trail Making Test Part B [TMT-B]).
The patients' mean age was 31.4 ± 14.0 years and their mean Glasgow Coma Scale score at admission was 7.9 ± 2.8. Lesions were predominantly localized to the frontal (11 lesions) and temporal (9 lesions) lobes. The average percent reductions in GRE and FLAIR volumes were 44.2% ± 46.1% and 80.5% ± 26.3%, respectively. While total brain and frontal lesion volumes did not correlate with brain atrophy, larger temporal lobe GRE and FLAIR volumes were associated with larger volumes of atrophy (GRE: acute, −0.87, p < 0.01, chronic, −0.78, p < 0.01; FLAIR: acute, −0.81, p < 0.01, chronic, −0.88, p < 0.01). Total percent volume change of GRE lesions correlated with TMT-B (0.53, p < 0.05) and SDMT-O (0.62, p < 0.05) scores. Frontal lobe lesion volume did not correlate with neuropsychological outcome. However, robust relationships were seen in the temporal lobe, with larger acute temporal lobe GRE volumes were associated with worse scores on both oral and written versions of the SDMT (SDMT-W, −0.85, p < 0.01; SDMT-O, −0.73, p < 0.05). Larger absolute change in temporal GRE volume was strongly associated with worse SDMT scores (SDMT-W, 0.88, p < 0.01; SDMT-O, 0.75, p < 0.05). The same relationships were also seen between temporal FLAIR lesion volumes and neuropsychological outcome.
Traumatic parenchymal hemorrhages are largely clustered in the frontal and temporal lobes, and significant residual blood products are present at 6 months postinjury, a potential source of ongoing secondary brain injury. Neuropsychological outcome is closely tied to lesion volume size, particularly in the temporal lobe, where larger GRE and FLAIR volumes are associated with more brain atrophy and worse SDMT scores. Interestingly, larger volumes of hemorrhage resorption were associated with worse SDMT and TMT-B scores, suggesting that the initial tissue damage had a lasting impact on attention and executive function.