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 (r(2) = 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.

Characterization and limitations of diffusion tensor imaging metrics in the cervical spinal cord in neurologically intact subjects.

PURPOSE: To characterize diffusion tensor imaging (DTI) metrics across all levels of the cervical spinal cord (CSC) and to study the impact of age and signal quality on these metrics. MATERIALS AND METHODS: DTI metrics were calculated for gray matter (GM) and white matter (WM) funiculi throughout the CSC (C1-T1) in 25 healthy subjects (22-85 years old). Signal-to-noise ratios (SNRs) and mean DTI metrics were measured for the upper (C1-3), middle (C4-6) and lower (C7-T1) cervical segments. Age-related changes in DTI metrics were analyzed for the individual segment groups. RESULTS: Fractional anisotropy (FA), mean diffusivity (MD) and transverse apparent diffusion coefficient (tADC) showed significant differences between GM and WM funiculi. Significant age-related changes were observed in FA in upper and middle CSC segments but not in the lower CSC. The median SNR was significantly lower in the middle and lower segment groups as compared to the upper levels, contributing to poor spatial resolution in these regions. CONCLUSION: This study provides DTI data for GM and WM funiculi throughout the CSC. While DTI metrics may be used to define cord pathology, variations in metrics due to age and signal quality need to be accounted for before making definitive conclusions.

Prolonged Electro-muscular Incapacitation in a Porcine Model Causes Spinal Injury.

Conducted electrical weapons are designed to cause temporary electro-muscular incapacitation (EMI) without significant injury. The objective of this study was to assess the risk and cause of spinal injury due to exposure to a benchtop EMI device. Porcine subjects were exposed to 19 and 40 Hz electrical stimuli for a prolonged duration of 30 sec. X-ray imaging, necropsy, and accelerometry found that lumbosacral spinal fractures occurred in at least 89% of all subjects, regardless of the stimulus group, and were likely caused by musculoskeletal fatigue-related stress in the lumbosacral spine. Spinal fractures occurred in the porcine model at an unusually high rate compared to human. This may be due to both the prolonged duration of electrical stimulation and significant musculoskeletal differences between humans and pigs, which suggests that the porcine model is not a good model of EMI-induced spinal fracture in humans.

Increased Hematocrit Due to Electrical-Waveform Exposures in Splenectomized Sus scrofa.

In laboratory studies of the pig Sus scrofa, hematocrit has consistently increased after conducted-electrical-weapon (CEW) exposures, possibly due to contraction of the spleen. Splenectomized animals and intact sham control animals were exposed, each for 30 sec, to a benchtop-produced electrical waveform of net charge levels similar to those of some CEWs. Changes in the blood were compared statistically. Hematocrit increased significantly in both splenectomized and sham animals. There were no significant main-effect differences between values of hematocrit from the two groups. There were, however, significant interactive effects of time and splenectomy for hematocrit, red blood cell count, and hemoglobin. After peak values were reached for these variables, values returned toward baseline levels more slowly in splenectomized animals. This may have been due to the lack of a spleen to sequester red blood cells (thereby resulting in more cells remaining in the general circulation), unlike sham animals with intact spleens.

Diffusion tensor imaging as a biomarker for assessing neuronal stem cell treatments affecting areas distal to the site of spinal cord injury.

OBJECTIVE The aims of this study were to determine if the morphological and functional changes induced by neural stem cell (NSC) grafts after transplantation into the rodent spinal cord can be detected using MR diffusion tensor imaging (DTI) and, furthermore, if the DTI-derived mean diffusivity (MD) metric could be a biomarker for cell transplantation in spinal cord injury (SCI). METHODS A spinal contusion was produced at the T-8 vertebral level in 40 Sprague Dawley rats that were separated into 4 groups, including a sham group (injury without NSC injection), NSC control group (injury with saline injection), co-injection control group (injury with Prograf), and the experimental group (injury with NSC and Prograf injection). The NSC injection was completed 1 week after injury into the site of injury and the rats in the experimental group were compared to the rats from the sham, NSC control, and co-injection groups. The DTI index, MD, was assessed in vivo at 2, 5, and 10 weeks and ex vivo at 10 weeks postinjury on a 9.4-T Bruker scanner using a spin-echo imaging sequence. DTI data of the cervical spinal cord from the sham surgery, injury with saline injection, injury with injection of Prograf only, and injury with C17.2 NSC and Prograf injection were examined to evaluate if cellular proliferation induced by intrathoracic C17.2 engraftment was detectable in a noninvasive manner. RESULTS At 5 weeks after injury, the average fractional anisotropy, longitudinal diffusion (LD) and radial diffusion (RD) coefficients, and MD of water (average of the RD and LD eigenvalues in the stem cell line-treated group) increased to an average of 1.44 × 10-3 sec/mm2 in the cervical segments, while the control groups averaged 0.98 × 10-3 s/mm2. Post hoc Tukey's honest significant difference tests demonstrated that the transplanted stem cells had significantly higher MD values than the other groups (p = 0.032 at 5 weeks). In vivo and ex vivo findings at 10 weeks displayed similar results. This statistical difference between the stem cell line and the other groups was maintained at the 10-week postinjury in vivo and ex vivo time points. CONCLUSIONS These results indicate that the DTI-derived MD metric collected from noninvasive imaging techniques may provide useful biomarker indices for transplantation interventions that produce changes in the spinal cord structure and function. Though promising, the results demonstrated here suggest additional work is needed before implementation in a clinical setting.

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 < 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 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.

Ex vivo 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<0.01). Motor function correlated with MD in the cervical segments of the spinal cord (r(2)=0.80). The diffusivity of water significantly decreased throughout "uninjured" portions of the spinal cord following a contusion injury (p<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.