Diffusion tensor imaging of somatosensory tract in cervical spondylotic myelopathy and its link with electrophysiological evaluation

Background and context Abnormal somatosensory evoked potential (SEP) (ie, prolonged latency) has been associated with poor surgical prognosis of cervical spondylotic myelopathy (CSM). Purpose To further characterize the extent of microstructural damage to the somatosensory tract in CSM patients using diffusion tensor imaging (DTI). Study design/setting Retrospective study. Patient sample A total of 40 volunteers (25 healthy subjects and 15 CSM patients). Outcome measures Clinical, electrophysiological, and radiological evaluations were performed using the modified Japanese Orthopedic Association (mJOA) scoring system, SEP, and cord compression ratio in anatomic magnetic resonance (MR) images, respectively. Axial diffusion MR images were taken using a pulsed gradient, spin-echo-echo-planar imaging sequence with a 3-T MR system. The diffusion indices in different regions of the spinal cord were measured. Methods Comparison of diffusion indices among healthy and myelopathic spinal cord with intact and impaired SEP responses were performed using one-way analysis of variance. Results In healthy subjects, fractional anisotropy (FA) values were higher in the dorsal (0.73±0.11) and lateral columns (0.72±0.13) than in the ventral column of white matter (0.58±0.10) (eg, at C4/5) (p<.05). FA was dramatically dropped in the dorsal (0.54±0.16) and lateral columns (0.51±0.13) with little change in the ventral column (0.48±0.15) at the compressive lesions in CSM patients. There were no significant differences in the mJOA scores or cord compression ratios between CSM patients with or without abnormal SEP. However, patients with abnormal SEP showed an FA decrease in the dorsal column cephalic to the lesion (0.56±0.06) (ie, at C1/2, compared with healthy subjects [0.66±0.02]), but the same decrease was not observed for those without a SEP abnormality (0.67±0.02). Conclusion Spinal tracts were not uniformly affected in the myelopathic cervical cord. Changes in diffusion indices could delineate focal or extensive myelopathic lesions in CSM, which could account for abnormal SEP. DTI analysis of spinal tracts might provide additional information not available from conventional diagnostic tools for prognosis of CSM. © 2014 Elsevier Inc. All rights reserved.postprin

Quantitative analysis of fiber tractography in cervical spondylotic myelopathy

Background context: Diffusion tensor fiber tractography is an emerging tool for the visualization of spinal cord microstructure. However, there are few quantitative analyses of the damage in the nerve fiber tracts of the myelopathic spinal cord. Purpose: The aim of this study was to develop a quantitative approach for fiber tractography analysis in cervical spondylotic myelopathy (CSM). Study design/setting: Prospective study on a series of patients. Materials and methods: A total of 22 volunteers were recruited with informed consent, including 15 healthy subjects and 7 CSM patients. The clinical severity of CSM was evaluated using modified Japanese Orthopedic Association (JOA) score. The microstructure of myelopathic cervical cord was analyzed using diffusion tensor imaging. Diffusion tensor imaging was performed with a 3.0-T magnetic resonance imaging scanner using pulsed gradient, spin-echo, echo-planar imaging sequence. Fiber tractography was generated via TrackVis with fractional anisotropy threshold set at 0.2 and angle threshold at 40. Region of interest (ROI) was defined to cover C4 level only or the whole-length cervical spinal cord from C1 to C7 for analysis. The length and density of tracked nerve bundles were measured for comparison between healthy subjects and CSM patients. Results: The length of tracked nerve bundles significantly shortened in CSM patients compared with healthy subjects (healthy: 6.85-77.90 mm, CSM: 0.68-62.53 mm). The density of the tracked nerve bundles was also lower in CSM patients (healthy: 086±0.03, CSM: 0.80±0.06, p<.05). Although the definition of ROI covering C4 only or whole cervical cord appeared not to affect the trend of the disparity between healthy and myelopathic cervical cords, the density of the tracked nerve bundle through whole myelopathic cords was in an association with the modified JOA score in CSM cases (r=0.949, p=.015), yet not found with ROI at C4 only (r=0.316, p=.684). Conclusions: The quantitative analysis of fiber tractography is a reliable approach to detect cervical spondylotic myelopathic lesions compared with healthy spinal cords. It could be employed to delineate the severity of CSM. © 2013 Published by Elsevier Inc. All rights reserved.postprin

Potential use of diffusion tensor imaging in level diagnosis of multilevel cervical spondylotic myelopathy

STUDY DESIGN.: A prospective study on a series of consecutive patients. OBJECTIVE.: To investigate the use of diffusion tensor imaging (DTI) and orientation entropy in level localization in patients diagnosed with multilevel cervical spondylotic myelopathy (CSM). SUMMARY OF BACKGROUND DATA.: Multilevel CSM presents complex neurological signs that make level localization difficult. DTI is recently found to be able to assess the microstructural changes of the white matter caused by cord compression. METHODS.: Sixteen patients with CSM with multilevel compression were recruited. The level(s) responsible for the clinical symptoms were determined by detailed neurological examination, T2-weighted (T2W) magnetic resonance imaging (MRI), and DTI. On T2W MRI, anterior-posterior compression ratio and increased signal intensities were used to determine the affected level(s). The level diagnosis results from T2W MRI, increased signal intensities, DTI, and combination method were correlated to that of neurological examination on a level-to-level basis, respectively. The accuracy, sensitivity, and specificity were calculated. RESULTS.: When correlated with the clinical level determination, the weighted orientation entropy-based DTI analysis was found to have higher accuracy (82.76% vs. 75.86%) and sensitivity (84.62% vs. 76.92%) than those of the anterior-posterior compression ratio. The increased signal intensities have the highest specificity (100.00%) but the lowest accuracy (58.62%) and sensitivity (53.85%). When combined with the level diagnosis result of wOE with that of anterior-posterior compression ratio, it demonstrated the highest accuracy and sensitivity that were 93.10% and 96.15%, respectively, and equal specificity (66.67%) with using them individually. CONCLUSION.: DTI can be a useful tool to determine the pathological spinal cord levels in multilevel CSM. This information from orientation entropy-based DTI analysis, in addition to conventional MRI and clinical neurological assessment, should help spine surgeons in deciding the optimal surgical strategy. Copyright © 2014 Lippincott Williams & Wilkins.postprin

Quantitative assessment of column-specific degeneration in cervical spondylotic myelopathy based on diffusion tensor tractography

Purpose Cervical spondylotic myelopathy (CSM) is a common spinal cord disorder in the elderly. Diffusion tensor imaging (DTI) has been shown to be of great value for evaluating the microstructure of nerve tracts in the spinal cord. Currently, the quantitative assessment of the degeneration on the specific tracts in CSM is still rare. The aim of the present study was to use tractography-based quantification to investigate the column-specific degeneration in CSM. Methods A total of 43 volunteers were recruited with written informed consent, including 20 healthy subjects and 23 CSM patients. Diffusion MRI was taken by 3T MRI scanner. Fiber tractography was performed using TrackVis to reconstruct the white matter tracts of the anterior, lateral and posterior column on the bilateral sides. The DTI metrics acquired from tractography, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD), were compared between healthy subjects and CSM patients. Results Compared to healthy subjects, FA was found significantly lower in the lateral (Healthy 0.64 ± 0.07 vs. CSM 0.53 ± 0.08) and posterior column (Healthy 0.67 ± 0.08 vs. CSM 0.47 ± 0.08) (p < 0.001), while MD, AD and RD were significantly higher in the anterior, lateral and posterior column in CSM (p < 0.05). Conclusion Loss of microstructural integrity was detected in the lateral and posterior column in CSM. Tractography-based quantification was capable of evaluating the subtle pathological insult within white matter on a column-specific basis, which exhibited potential clinical value for in vivo evaluation of the severity of CSM. © 2014 Springer-Verlag Berlin Heidelberg.postprin

Region-specific analysis of diffusion tensor imaging for cervical spondylotic myelopathy

Cervical Spondylotic Myelopathy (CSM) is a common type of spinal cord dysfunction in the elderly. The natural history of CSM is associated with disc degeneration and spondylosis, leading to the static and dynamic compression of the spinal cord, tissue ischemia, tissue damage, and ultimately neurological function deficit. However, the severity of the spinal cord compression does not necessarily correlate with the signs and symptoms of CSM in patients. Until now, the pathomechanism of CSM was not well understood. Establishing an evaluation technique is, therefore, criticalfor the pathophysiological investigation of CSM. Magnetic resonance imaging (MRI) has been widely used for evaluating the spinal cord parenchyma. However, conventional MRI is limited in detecting macroscopic changes, e.g. spinal cord compression, edema or hemorrhage etc. Recently, there has been increasing interest in diffusion tensor imaging (DTI), which permitting detects tissue water molecule diffusion at the microscopic level. The conventional DTI analysis for CSM relies on hand-drawn regions of interest (ROIs), so called ROI-based measurements. The ROIs are drawn on the sagittal image or on the axial image to cover the whole cord, which are insufficient to describe the precise diffusion pattern. In particular, the deformation and degeneration of the myelopathic cord poses a big challenge for the ROI-based analysis. The most commonly used parameter, fractional anisotropy (FA) has difficulty in determining the level diagnosis due to its relatively large variance along the cord. Furthermore, the functional activation following microstructural damage remains underexplored. In this dissertation, several novel methods for region-specific analysis were proposed for the investigation of microstructural changes in the CSM. In Chapter 2, ROI-based analysis was employed to detect the regional diffusion characteristics in CSM. In Chapter 3, an auto-template was developed that segments the cord and measures the DTI parameters automatically. We found that our auto-template outperforms hand-drawn ROI-based methods in terms of efficiency and reproducibility. In Chapter 4, entropy-based analysis was proposed to characterize the loss of complexity of microstructure in the myelopathic cord. It was demonstrated that FA entropy was an objective and quantitative evaluation parameter that was superior to conventional methods for separating CSM patients from healthy subjects. In Chapter 5, orientation entropy was used to detect the disordered orientational distribution of the nerve tracts in CSM, which could be used as a good index for the pathogenic level estimation. In Chapter 6, a diffusion tensor tractography-based method was proposed to overcome the difficulties in column-specific ROI drawing on the deformed and degenerated spinal cords. In Chapter 7, the structure-function relationship in the cervical spinal cord was explored by a combination of DTI and functional MRI. A significant correlation was found between enhanced functional responses and the loss of microstructural integrity in CSM. In this study, several novel post-processing methods were proposed and demonstrated, which were shown to have extraordinary capabilitiesfor the investigation and assessment of CSM. It is expected that these methods can be used as valuable tools for clinical diagnosis and for the selection of the most appropriate treatment strategy for CSM.published_or_final_versionOrthopaedics and TraumatologyDoctoralDoctor of Philosoph

Is diffusion anisotropy a biomarker for disease severity and surgical prognosis of cervical spondylotic myelopathy

Purpose: To explore the value of diffusion-tensor (DT) imaging in addressing the severity of cervical spondylotic myelopathy (CSM) and predicting the outcome of surgical treatment. Materials and Methods: From July 2009 to May 2012, 65 volunteers were recruited for this institutional review board-approved study, and all gave informed consent; 20 volunteers were healthy subjects (age range, 41-62 years), and 45 were patients with CSM (age range, 43-86 years). Anatomic and DT 3.0-T magnetic resonance images were obtained. Surgical decompression was performed in 22 patients with CSM, and patients were followed up for 6 months to 2 years. The clinical severity of myelopathy and postoperative recovery were assessed by using the modified Japanese Orthopaedic Association (mJOA) score. A recovery ratio (comparison of postoperative with preoperative mJOA score) of more than 50% indicated a good clinical outcome of surgery. DT findings, patient age, T2 high signal intensity (HSI), and somatosensory evoked potential (SEP) were analyzed by using a logistic regression model to predict the surgical outcome of patients with CSM. Results: A significant difference in cervical cord mean fractional anisotropy (FA) was found between healthy subjects and patients with CSM (0.65 ± 0.05 [standard deviation] vs 0.52 ± 0.13, P < .001). FA values were significantly correlated with the severity of neurologic dysfunction indicated by mJOA score (r2 = 0.327, P = .016). Logistic regression analysis showed that mean FA (P = .030) and FA at the C2 vertebra (P = .035) enabled prediction of good surgical outcome; however, preoperative mJOA (P = .927), T2 HSI (P = .176), SEP amplitude (P = .154), and latency (P = .260) did not. Conclusion: FA is a biomarker for the severity of myelopathy and for subsequent surgical outcome. © RSNA, 2013.link_to_subscribed_fulltex