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Benjamin M. Ellingson, Brian D. Schmit and Shekar N. Kurpad

Object

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.

Methods

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

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.

Conclusions

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.

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Michael B. Jirjis, Chris Valdez, Aditya Vedantam, Brian D. Schmit and Shekar N. Kurpad

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.

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Saman Shabani, Mayank Kaushal, Matthew Budde, Brian Schmit, Marjorie C. Wang and Shekar Kurpad

OBJECTIVE

Cervical spondylotic myelopathy (CSM) is a common cause of spinal cord dysfunction. Recently, it has been shown that diffusion tensor imaging (DTI) may be a better biomarker than T2-weighted signal intensity (T2SI) on MRI for CSM. However, there is very little literature on a comparison between the quantitative measurements of DTI and T2SI in the CSM patient population to determine disease severity and recovery.

METHODS

A prospective analysis of 46 patients with both preoperative DTI and T2-weighted MRI was undertaken. Normalized T2SI (NT2SI), regardless of the presence or absence of T2SI at the level of maximum compression (LMC), was determined by calculating the T2SI at the LMC/T2SI at the level of the foramen magnum. Regression analysis was performed to determine the relationship of fractional anisotropy (FA), a quantitative measure derived from DTI, and NT2SI individually as well their combination with baseline preoperative modified Japanese Orthopaedic Association (mJOA) score and ∆mJOA score at the 3-, 6-, 12-, and 24-month follow-ups. Goodness-of-fit analysis was done using residual diagnostics. In addition, mixed-effects regression analysis was used to evaluate the impact of FA and NT2SI individually. A p value < 0.05 was selected to indicate statistical significance.

RESULTS

Regression analysis showed a significant positive correlation between FA at the LMC and preoperative mJOA score (p = 0.041) but a significant negative correlation between FA at the LMC and the ΔmJOA score at the 12-month follow-up (p = 0.010). All other relationships between FA at the LMC and the baseline preoperative mJOA score or ∆mJOA score at the 3-, 6-, and 24-month follow-ups were not statistically significant. For NT2SI and the combination of FA and NT2SI, no significant relationships with preoperative mJOA score or ∆mJOA at 3, 6, and 24 months were seen on regression analysis. However, there was a significant correlation of combined FA and NT2SI with ∆mJOA score at the 12-month follow-up. Mixed-effects regression revealed that FA measured at the LMC was the only significant predictor of ΔmJOA score (p = 0.03), whereas NT2SI and time were not. Goodness-of-fit analysis did not show any evidence of lack of fit.

CONCLUSIONS

In this large prospective study of CSM patients, FA at LMC appears to be a better biomarker for determining long-term outcomes following surgery in CSM patients than NT2SI or the combination values at LMC.