Exploring Functional Connectivity in Chronic Spinal Cord Injury Patients With Neuropathic Pain Versus Without Neuropathic Pain.

The great majority of spinal cord injury (SCI) patients have debilitating chronic pain. Despite decades of research, these pain pathways of neuropathic pain (NP) are unknown. SCI patients have been shown to have abnormal brain pain pathways. We hypothesize that SCI NP patients' pain matrix is altered compared to SCI patients without NP. This study examines the functional connectivity (FC) in SCI patients with moderate-severe chronic NP compared to SCI patients with mild-no NP. These groups were compared to control subjects. The Neuropathic Pain Questionnaire and neurological evaluation based on the International Standard Neurological Classification of SCI were utilized to define the severity and level of injury. Of the 10 SCI patients, 7 (48.6 ± 17.02 years old, 6 male and 1 female) indicated that they had NP and 3 did not have NP (39.33 ± 8.08 years old, 2 male and 1 female). Ten uninjured neurologically intact participants were used as controls (24.8 ± 4.61 years old, 5 male and 5 female). FC metrics were obtained from the comparisons of resting-state functional magnetic resonance imaging among our various groups (controls, SCI with NP, and SCI without NP). For each comparison, a region-of-interest (ROI)-to-ROI connectivity analysis was pursued, encompassing a total of 175 ROIs based on a customized atlas derived from the AAL3 atlas. The analysis accounted for covariates such as age and sex. To correct for multiple comparisons, a strict Bonferroni correction was applied with a significance level of p < 0.05/NROIs. When comparing SCI patients with moderate-to-severe pain to those with mild-to-no pain, specific thalamic nuclei had altered connections. These nuclei included: medial pulvinar; lateral pulvinar; medial geniculate nucleus; lateral geniculate nucleus; and mediodorsal magnocellular nucleus. There was increased FC between the lateral geniculate nucleus and the anteroventral nucleus in NP post-SCI. Our analysis additionally highlights the relationships between the frontal lobe and temporal lobe with pain. This study successfully identifies thalamic neuroplastic changes that occur in patients with SCI who develop NP. It additionally underscores the pain matrix and involvement of the frontal and temporal lobes as well. Our findings complement that the development of NP post-SCI involves cognitive, emotional, and behavioral influences.

Metal artifact reduction around cervical spine implant using diffusion tensor imaging at 3T: A phantom study.

PURPOSE: Diffusion MRI continues to play a key role in non-invasively assessing spinal cord integrity and pre-operative injury evaluation. However, post-operative Diffusion Tensor Imaging (DTI) acquisition of patients with metal implants results in severe geometric distortion. We propose and demonstrate a method to alleviate the technical challenges facing the acquisition of DTI on post-operative cases and longitudinal evaluation of therapeutics. MATERIAL AND METHODS: The described technique is based on the combination of the reduced Field-Of-View (rFOV) strategy and the phase segmented EPI, termed rFOV-PS-EPI. A custom-built phantom based on a cervical spine model with metal implants was used to collect DTI data at 3 Tesla scanner using: rFOV-PS-EPI, reduced Field-Of-View single-shot EPI (rFOV-SS-EPI), and conventional full FOV techniques including SS-EPI, PS-EPI, and readout-segmented EPI (RS-EPI). Geometric distortion, SNR, and signal void were assessed to evaluate images and compare the sequences. A two-sample t-test was performed with p-value of 0.05 or less to indicate statistical significance. RESULTS: The reduced FOV techniques showed better capability to reduce distortions compared to the Full FOV techniques. The rFOV-PS-EPI method provided DTI images of the phantom at the level of the hardware whereas the conventional rFOV-SS-EPI is useful only when the metal is approximately 20 mm away. In addition, compared to the rFOV-SS-EPI technique, the suggested approach produced smaller signal voids area as well as significantly reduced geometric distortion in Circularity (p < 0.005) and Eccentricity (p < 0.005) measurements. No statistically significant differences were found for these geometric distortion measurements between the rFOV-PS-EPI DTI sequence and conventional structural T2 images (p > 0.05). CONCLUSION: The combination of rFOV and a phase-segmented acquisition approach is effective for reducing metal-induced distortions in DTI scan on spinal cord with metal hardware at 3 T.

Connecting Researchers and Clinicians Before Connecting the Injured Spinal Cord.

Background: Translating research findings from animal models of spinal cord injury (SCI) to humans is a challenging enterprise. It is likely that differences in the use of common terms contribute to this. Objectives: The purpose of this study was to identify how scientists and clinicians define terms used across the research and clinical care continuum. Methods: We utilized the Delphi technique to develop consensus on the opinions of experts (defined as researchers and/or clinicians working in the field of SCI) through a series of structured, iterative surveys. A focus group of stakeholders developed the terms on the initial survey. Results were used to create definitions and formulate questions for a second and third survey. Results: Survey 1 yielded one definition for eight terms and multiple definitions for six terms in addition to three new terms that respondents believed should be defined. In Survey 2, definitions for eight terms reached at least 80% agreement: anatomically complete spinal cord injury, functionally complete spinal cord injury, neuromodulation, physical exercise, physical rehabilitation, plasticity, task specificity, and training intensity. Consensus was not reached for six terms. In Survey 3, definitions for seven additional terms reached at least 80% agreement: recovery, repair, compensation, regeneration, physical function, physiological function, and chronic. There were three terms that did not reach agreement after the three rounds: acute, translational research, and sprouting. Conclusion: We found that different terminology contributes to the gap between preclinical and clinical research and clinical application. This suggests that increased communication among different disciplines could be a way to advance the field.

Harmonization of multi-site diffusion tensor imaging data for cervical and thoracic spinal cord at 1.5 T and 3 T using longitudinal ComBat.

MRI scanner hardware, field strengths, and sequence parameters are major variables in diffusion studies of the spinal cord. Reliability between scanners is not well known, particularly for the thoracic cord. DTI data was collected for the entire cervical and thoracic spinal cord in thirty healthy adult subjects with different MR vendors and field strengths. DTI metrics were extracted and averaged for all slices within each vertebral level. Metrics were examined for variability and then harmonized using longitudinal ComBat (longComBat). Four scanners were used: Siemens 3 T Prisma, Siemens 1.5 T Avanto, Philips 3 T Ingenia, Philips 1.5 T Achieva. Average full cord diffusion values/standard deviation for all subjects and scanners were FA: 0.63, σ = 0.10, MD: 1.11, σ = 0.12 × 10-3 mm2/s, AD: 1.98, σ = 0.55 × 10-3 mm2/s, RD: 0.67, σ = 0.31 × 10-3 mm2/s. FA metrics averaged for all subjects by level were relatively consistent across scanners, but large variability was found in diffusivity measures. Coefficients of variation were lowest in the cervical region, and relatively lower for FA than diffusivity measures. Harmonized metrics showed greatly improved agreement between scanners. Variability in DTI of the spinal cord arises from scanner hardware differences, pulse sequence differences, physiological motion, and subject compliance. The use of longComBat resulted in large improvement in agreement of all DTI metrics between scanners. This study shows the importance of harmonization of diffusion data in the spinal cord and potential for longitudinal and multisite clinical research and clinical trials.

Case report: Utilizing diffusion-weighted MRI on a patient with chronic low back pain treated with spinal cord stimulation.

Diffusion-weighted magnetic resonance imaging (dwMRI) has increasingly demonstrated greater utility in analyzing neuronal microstructure. In patients with chronic low back pain (cLBP), using dwMRI to observe neuronal microstructure can lead to non-invasive biomarkers which could provide clinicians with an objective quantitative prognostic tool. In this case report, we investigated dwMRI for the development of non-invasive biomarkers by conducting a region-based analysis of a 55-year-old male patient with failed back surgery syndrome (FBSS) treated with spinal cord stimulation (SCS). We hypothesized that dwMRI could safely generate quantitative data reflecting cerebral microstructural alterations driven by neuromodulation. Neuroimaging was performed at 6- and 12- months post-SCS implantation. The quantitative maps generated included diffusion tensor imaging (DTI) parameters; fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD) computed from whole brain tractography. To examine specific areas of the brain, 44 regions of interest (ROIs), collectively representing the pain NeuroMatrix, were extracted and registered to the patient's diffusion space. Average diffusion indices were calculated from the ROIs at both 6- and 12- months. Regions with >10% relative change in at least 3 of the 4 maps were reported. Using this selection criterion, 8 ROIs demonstrated over 10% relative changes. These ROIs were mainly located in the insular gyri. In addition to the quantitative data, a series of questionnaires were administered during the 6- and 12-month visits to assess pain intensity, functional disability, and quality of life. Overall improvements were observed in these components, with the Pain Catastrophizing Scale (PCS) displaying the greatest change. Lastly, we demonstrated the safety of dwMRI for a patient with SCS. In summary, the results from the case report prompt further investigation in applying dwMRI in a larger cohort to better correlate the influence of SCS with brain microstructural alterations, supporting the utility of dwMRI to generate non-invasive biomarkers for prognostication.

The role of the insula in chronic pain following spinal cord injury: A resting-state fMRI study.

BACKGROUND AND PURPOSE: Spinal cord injury (SCI) results in the loss of motor and sensory function from disconnections between efferent and afferent pathways. Most SCI patients are affected with chronic neuropathic pain, but there is a paucity of data concerning neuroplastic changes following SCI. Chronic pain disrupts default networks and is associated with abnormal insular connectivity. The posterior insula (PI) is associated with the degree of pain and intensity of pain. The anterior insula (AI) is related to signal changes. Comprehension of SCI pain mechanisms is essential to elucidate effective treatment options. METHODS: This study examines the insular gyri functional connectivity (FC) of seven (five male, two female) SCI participants with moderate-severe chronic pain compared to 10 (five male, five female) healthy controls (HC). All subjects had 3-Tesla MRI performed and resting-state functional MRI (fMRI) was acquired. FC metrics were obtained from the comparisons of resting-state fMRI among our various groups. A seed-to-voxel analysis was pursued, encompassing six gyri of the insula. For multiple comparisons, a correction was applied with a significance level of p < .05. RESULTS: There were significant differences in FC of the insula between SCI participants with chronic pain compared with HC. In the SCI participants, there was hyperconnectivity of the AI and PI to the frontal pole. In addition, there was increased FC noted between the PI and the anterior cingulate cortex. Hyperconnectivity was also observed between the AI and the occipital cortex. CONCLUSIONS: These findings illustrate that there is a complex hyperconnectivity and modulation of pain pathways after traumatic SCI.

Metal Artifact Reduction Around Cervical Spine Implant Using Diffusion Tensor Imaging at 3T: A Phantom Study.

Diffusion MRI continues to play a key role in non-invasively assessing spinal cord integrity and pre-operative injury evaluation. However, post-operative Diffusion Tensor Imaging (DTI) acquisition of a patient with a metal implant results in severe geometric image distortion. A method has been proposed here to alleviate the technical challenges facing the acquisition of DTI in post-operative cases and to evaluate longitudinal therapeutics. The described technique is based on the combination of the reduced Field-Of-View (rFOV) strategy and the phase segmented acquisition scheme (rFOV-PS-EPI) for significantly mitigating metal-induced distortions. A custom-built phantom based on spine model with metal implant was used to collect high-resolution DTI data at 3 Tesla scanner using a home-grown diffusion MRI pulse sequence, rFOV-PS-EPI, single-shot (rFOV-SS-EPI), and the conventional full FOV techniques including SS-EPI, PS-EPI, and the readout-segmented (RS-EPI). This newly developed method provides high-resolution images with significant reduced metal-induced artifacts. In contrast to the other techniques, the rFOV-PS-EPI allows DTI measurement at the level of the metal hardware whereas the current rFOV-SS-EPI is useful when the metal is approximately 20 mm away. The developed approach enables high-resolution DTI in patients with metal implant.

Correlations of diffusion tensor imaging and clinical measures with spinal cord cross-sectional area measurements in pediatric spinal cord injury patients.

PURPOSE: The purpose of this work was to employ a semi-automatic method for measuring spinal cord cross-sectional area (SCCSA) and investigate the correlations between diffusion tensor imaging (DTI) metrics and SCCSA for the cervical and thoracic spinal cord for typically developing pediatric subjects and pediatric subject with spinal cord injury. METHODS: Ten typically developing (TD) pediatric subjects and ten pediatric subjects with spinal cord injury (SCI) were imaged using a Siemens Verio 3 T MR scanner to acquire DTI and high-resolution anatomic scans covering the cervical and thoracic spinal cord (C1-T12). SCCSA was measured using a semi-automated edge detection algorithm for the entire spinal cord. DTI metrics were obtained from whole cord axial ROIs at each vertebral level. SCCSA measures were compared to DTI metrics by vertebral level throughout the entire cord, and above and below the injury site. Correlation analysis was performed to compare SCCSA, DTI and clinical measures as determined by the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) examination. RESULTS: In subjects with SCI, FA and SCCSA had a positive correlation (r = 0.81, P < 0.01), while RD and SCCSA had a negative correlation (r = -0.68, P = 0.02) for the full spinal cord. FA and SCCSA were correlated above (r = 0.56, P < 0.01) and below (r = 0.54, P < 0.01) the injury site. TD subjects showed negative correlations between AD and SCCSA (r = -0.73, P = 0.01) and RD and SCCSA (r = -0.79, P < 0.01). CONCLUSION: The ability to quickly and effectively measure SCCSA in subjects with SCI has the potential to allow for a better understanding of the progression of atrophy following a SCI. Correlations between cord cross section and DTI metrics by vertebral level suggest that imaging inferior and superior to lesion may yield useful information for diagnosis and prognosis.

Case report: The promising application of dynamic functional connectivity analysis on an individual with failed back surgery syndrome.

Failed back surgery syndrome (FBSS), a chronic neuropathic pain condition, is a common indication for spinal cord stimulation (SCS). However, the mechanisms of SCS, especially its effects on supraspinal/brain functional connectivity, are still not fully understood. Resting state functional magnetic resonance imaging (rsfMRI) studies have shown characteristics in patients with chronic low back pain (cLBP). In this case study, we performed rsfMRI scanning (3.0 T) on an FBSS patient, who presented with chronic low back and leg pain following her previous lumbar microdiscectomy and had undergone permanent SCS. Appropriate MRI safety measures were undertaken to scan this subject. Seed-based functional connectivity (FC) was performed on the rsfMRI data acquired from the FBSS subject, and then compared to a group of 17 healthy controls. Seeds were identified by an atlas of resting state networks (RSNs), which is composed of 32 regions grouped into 8 networks. Sliding-window method and k-means clustering were used in dynamic FC analysis, which resulted in 4 brain states for each group. Our results demonstrated the safety and feasibility of 3T MRI scanning in a patient with implanted SCS system. Compared to the brain states of healthy controls, the FBSS subject presented very different FC patterns in less frequent brain states. The mean dwell time of brain states showed distinct distributions: the FBSS subject seemed to prefer a single state over the others. Although future studies with large sample sizes are needed to make statistical conclusions, our findings demonstrated the promising application of dynamic FC to provide more granularity with FC changes associated with different brain states in chronic pain.

Clinical Utility of Diffusion Tensor Imaging as a Biomarker to Identify Microstructural Changes in Pediatric Spinal Cord Injury.

Background: Lack of clarity about the neurological consequence of spinal cord injury (SCI) in children causes speculation about diagnoses, recovery potential, and treatment effectiveness. Diffusion tensor imaging (DTI) has shown promising results as a biomarker to evaluate spinal cord integrity at a microstructural level. Objectives: To look at the difference between pediatric participants with and without SCI to determine which DTI metrics best categorize spinal cord tissue damage and to correlate DTI metrics with two clinical measures: Capabilities of the Upper Extremity Test (CUE-T) and Spinal Cord Independence Measure version III (SCIM-III). Methods: This single-site, prospective study included pediatric participants with SCI (n = 26) and typically developed (TD) control subjects (n = 36). All participants underwent two magnetic resonance imaging (MRI) scans on a 3T MR scanner. Participants with SCI also completed the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI), CUE-T, and SCIM-III outcomes measures. Results: This study found significant strength of association between fractional anisotropy (FA) and upper extremity muscle strength (UEMS) in participants with SCI. Most DTI parameters showed a significant difference between participants with SCI and TD participants and a moderate correlation with the CUE-T total score. Regional effects on group differences were found to be significant. Conclusion: This study demonstrates the strength of association between DTI parameters and clinical measures in the pedantic SCI population. It illustrates DTI as a potential biomarker of SCI location and severity in the pediatric SCI population.

DTI of chronic spinal cord injury in children without MRI abnormalities (SCIWOMR) and with pathology on MRI and comparison to severity of motor impairment.

STUDY DESIGN: This investigation was a cohort study that included: 36 typically developing (TD) children and 19 children with spinal cord lesions who underwent spinal cord MRI. OBJECTIVES: To investigate diffusion tensor imaging (DTI) cervical and thoracic spinal cord changes in pediatric patients that have clinically traumatic and non-traumatic spinal cord injury (SCI) without MR (SCIWOMR) abnormalities. SETTING: Thomas Jefferson University, Temple University, Shriners Hospitals for Children all in Philadelphia, USA. METHODS: 36 TD children and 19 children with spinal cord lesions that represent either a chronic traumatic acquired SCI or chronic non-traumatic SCI (≥6 months post injury), age range, 6-16 years who underwent cervical and thoracic spinal cord MRI in 2014-2017. Additionally DTI was correlated to clinical American Spinal Injury Association Impairment Scale (AIS). RESULTS: Both SCIWOMR and MRI positive (+) groups showed abnormal FA and RD DTI values in the adjacent MRI-normal appearing segments of cephalad and caudal spinal cord compared to TD. The FA values demonstrated perilesional abnormal DTI findings in the middle and proximal segments of the cephalad and caudal cord in the SCIWOMR AIS A/B group compared to SCIWOMR AIS C/D group. CONCLUSIONS: We found DTI changes in children with SCIWOMR with different causes of spinal lesions. We also investigated the relationship between DTI and clinical AIS scores. This study further examined the potential diagnostic value of DTI and should be translatable to adults with spinal cord lesions.

Brain White Matter Abnormality Induced by Chronic Spinal Cord Injury in the Pediatric Population: A Preliminary Tract-based Spatial Statistic Study.

Objectives: Tract-based spatial statistics (TBSS) is a diffusion tensor imaging (DTI)-based processing technique that aims to improve the objectivity and interpretability of analysis of multisubject diffusion imaging studies. This study used TBSS to measure quantitative changes in brain white matter structures following spinal cord injury (SCI). Methods: Eighteen SCI subjects aged 8-20 years old (mean age, 16.5 years) were scanned using a conventional single-shot EPI DTI protocol using a 3.0T Siemens MR scanner. All participants underwent a complete International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) examination to determine the level and severity of injury. Five participants were classified as American Spinal Injury Association Impairment Scale (AIS) A, nine as AIS B, and four as AIS C/D. Imaging parameters used for data collection were as follows: 20 directions, b = 1000 s/mm2, voxel size = 1.8 mm x 1.8 mm, slice thickness = 5 mm, TE = 95 ms, TR = 4300 ms, slices = 30, TA = 4:45 min. To generate TBSS, nonparametric permutation tests were used for voxel-wise statistical analysis of the fractional anisotropy (FA) skeletons between AIS groups. A two-tailed t test was applied to extract voxels with significant differences at p < .05. Results: Notable significant changes occurred throughout the corticospinal, spinothalamic, and dorsal column/medial lemniscus tracts. Altered regions in the temporal, occipital, and parietal lobes were also identified. Conclusion: These results suggest that white matter structures are altered differently between people with different AIS classifications. TBSS has the potential to serve as a screening tool to identify white matter changes in regions of interest.

Graph theoretical structural connectome analysis of the brain in patients with chronic spinal cord injury: preliminary investigation.

STUDY DESIGN: Retrospective study. OBJECTIVES: We aimed to characterize the convergent disruptions of the structural connectivity based on network modeling technique (i.e., graph theory) to identify significant changes in network organization/reorganization between uninjured and chronic spinal cord injury (SCI) participants. SETTING: USA. METHODS: Ten adult participants including 4 with chronic SCI and 6 uninjured were scanned using a multi-shell diffusion imaging on a 3.0 T MR scanner. Whole brain structural connectivity matrix was estimated by performing the quantification of the number of white matter fibers (called edges) connecting each possible pair of brain region (called nodes). Brain regions were defined according to Desikan-Killiany cortical atlas. Using connectivity matrix, connectivity strength as well as six different graph theoretical measurements were computed for each participant. They include: (1) global efficiency; (2) local efficiency; (3) degree; (4) betweenness centrality; (5) average shortest length and (6) clustering coefficient. Finally network based statistics was applied to extract nodes/connections with significant differences between groups (uninjured vs SCI). RESULTS: The SCI group showed significant decreases in betweenness centrality in the left precentral gyrus (T-score=2.98, p value=0.02), and the right caudal middle frontal gyrus (score = 2.35, p value=0.047). It also showed significant decrease in left transverse temporal gyrus (T-score=2.36, p value=0.046) in clustering coefficient. In addition, altered regions in the occipital and parietal lobe were also identified. CONCLUSION: These results suggest that not only local but also global alterations of the white matter occur after SCI. The proposed modeling technique has the potential to serve as a screening tool to identify any areas of the brain affected after SCI.

Diffusion Tensor Imaging Assessment of Regional White Matter Changes in the Cervical and Thoracic Spinal Cord in Pediatric Subjects.

There are no studies to date,describing changes in the diffusion tensor imaging (DTI) metrics of the white matter (WM) regions of the entire cervical and thoracic spinal cord (SC) remote from the lesion in pediatric spinal cord injury (SCI) subjects. The purpose of this study was to determine whether DTI at sites cephalad and caudal to a lesion provides measures of cord abnormalities in children with chronic SCI. A retrospective study included 10 typically developing subjects (TD) and 10 subjects with chronic SCI who underwent SC imaging in 2014-2017. Axial diffusion tensor images using an inner field of view DTI sequence were acquired to cover the entire cervical and thoracic SC. Regions of interest were drawn on the SC WM: right and left lateral (motor), ventral (motor), and dorsal (sensory) tracts. To detect differences in DTI metrics between TD and SCI of the cord, a one way analysis of variance with pooled t test was performed. A stepwise regression analysis was performed to assess the correlation between DTI metrics and clinical scores. In motor and sensory tracts, fractional anisotropy (FA) and axial diffusivity (AD) were significantly decreased in the proximal segments of the caudal cord. In motor tracts cephalad to the lesion, FA was significantly decreased whereas AD was significantly increased in the proximal segment; however, AD was decreased in the distal and middle segments. International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) total score was significantly correlated with FA and AD of the motor and sensory tracts cephalad to the lesion. This study demonstrates that FA and AD have the potential to be sensitive biomarkers of the full extent of cord injury and might be useful in detecting remote injuries to the SC and in guiding new treatments.

Translational Challenges of Rat Models of Upper Extremity Dysfunction After Spinal Cord Injury.

There are approximately 17,500 new spinal cord injury (SCI) cases each year in the United States, with the majority of cases resulting from a traumatic injury. Damage to the spinal cord causes either temporary or permanent changes in sensorimotor function. Given that the majority of human SCIs occur in the cervical spinal level, the experimental animal models of forelimb dysfunction play a large role in the ability to translate basic science research to clinical application. However, the variation in the design of clinical and basic science studies of forelimb/upper extremity (UE) function prevents the ease of translation. This review provides an overview of experimental models of forelimb dysfunction used in SCI research with special emphasis on the rat model of SCI. The anatomical location and types of experimental cervical lesions, functional assessments, and rehabilitation strategies used in the basic science laboratory are reviewed. Finally, we discuss the challenges of translating animal models of forelimb dysfunction to the clinical SCI human population.

Characterization of spinal cord diffusion tensor imaging metrics in clinically asymptomatic pediatric subjects with incidental congenital lesions.

STUDY DESIGN: Retrospective study. OBJECTIVES: To perform quantitative DTI measurements of the entire cervical and thoracic spinal cord (SC) in typically developing (TD) pediatric subjects with incidental findings of syringomyelia or hydromyelia on conventional MRI and in a TD population without any abnormalities. SETTING: USA. METHODS: 26 TD recruited as part of large SC DTI study, four of these had incidental findings. Axial DTI images were acquired on 3T MR scanner to cover the cervical and thoracic SC. We performed group analysis of DTI values in the cord above and below the MR-defined lesion. For single-subject analysis, the cord above and below the lesion was compared to average values of TD population. A standard least squares regression model was used to compare DTI parameters fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) between TD population and subjects with hydromyelia and syringomyelia. A p value of 0.05 was used for statistical significance. RESULTS: In group analysis, MD and AD were significantly different in cord above the lesion in subjects with hydromyelia and syringomyelia (n = 4) compared to TD population (n = 22). For single-subject analysis, DTI parameters were significantly different in cord above the syringomyelia and below the syringomyelia; MD, AD, and RD were significantly different. A subject with hydromyelia showed significant difference in FA below the lesion. CONCLUSIONS: This study demonstrates that DTI has the potential to be used as an imaging biomarker to evaluate SC above and below the congenital lesion in syringohydromyelia subjects.

Age related diffusion and tractography changes in typically developing pediatric cervical and thoracic spinal cord.

Background and objective: Diffusion tensor imaging (DTI) and diffusion tensor tractography (DTT) are two techniques that can measure white matter integrity of the spinal cord. Recently, DTI indices have been shown to change with age. The purpose of this study is (a) to evaluate the maturational states of the entire pediatric spinal cord using DTI and DTT indices including fractional anisotropy (FA), mean diffusivity (MD), mean length of white matter fiber tracts and tract density and (b) to analyze the DTI and DTT parameters along the entire spinal cord as a function of spinal cord levels and age. Method: A total of 23 typically developing (TD) pediatric subjects ranging in age from 6 to 16 years old (11.94 ±â€¯3.26 (mean ±â€¯standard deviation), 13 females and 10 males) were recruited, and scanned using 3.0 T MR scanner. Reduced FOV diffusion tensor images were acquired axially in the same anatomical location prescribed for the T2-weighted images to cover the entire spinal cord (C1-mid L1 levels). To mitigate motion induced artifacts, diffusion directional images were aligned with the reference image (b0) using a rigid body registration algorithm performed by in-house software developed in Matlab (MathWorks, Natick, Massachusetts). Diffusion tensor maps (FA and MD) and streamline deterministic tractography were then generated from the motion corrected DTI dataset. DTI and DTT parameters were calculated by using ROIs drawn to encapsulate the whole cord along the entire spinal cord by an independent board certified neuroradiologist. These indices then were compared between two age groups (age group A = 6-11 years (n = 11) and age group B = 12-16 years (n = 12)) based on similar standards and age definitions used for reporting spinal cord injury in the pediatric population. Standard least squared linear regression based on a restricted maximum likelihood (REML) method was used to evaluate the relationship between age and DTI and DTT parameters. Results: An increase in FA (group A = 0.42 ±â€¯0.097, group B = 0.49 ±â€¯0.116), white matter tract density (group A = 368.01 ±â€¯236.88, group B = 440.13 ±â€¯245.24) and mean length of fiber tracts (group A = 48.16 ±â€¯20.48 mm, group B = 60.28 ±â€¯23.87 mm) and a decrease in MD (group A = 1.06 ±â€¯0.23 × 10-3 mm2/s, group B = 0.82 ±â€¯0.24 × 10-3 mm2/s) were observed with age along the entire spinal cord. Statistically significant increases have been shown in FA (p = 0.004, R2 = 0.57), tract density (p = 0.0004, R2 = 0.58), mean length of fiber tracts (p < 0.001, R2 = 0.5) and a significant decrease has been shown in MD (p = 0.002, R2 = 0.59) between group A and group B. Also, it has been shown DTI and DTT parameters vary along the spinal cord as a function of intervertebral disk and mid-vertebral body level. Conclusion: This study provides an initial understanding of age related changes of DTI values as well as DTT metrics of the spinal cord. The results show significant differences in DTI and DTT parameters which may result from decreasing water content, myelination of fiber tracts, and the thickening diameter of fiber tracts during the maturation process. Consequently, when quantitative DTI and DTT of the spinal cord is undertaken in the pediatric population an age and level matched normative dataset should be used to accurately interpret the quantitative results.

Application of Color Transformation Techniques in Pediatric Spinal Cord MR Images: Typically Developing and Spinal Cord Injury Population.

The purpose of this study was to evaluate an improved and reliable visualization method for pediatric spinal cord MR images in healthy subjects and patients with spinal cord injury (SCI). A total of 15 pediatric volunteers (10 healthy subjects and 5 subjects with cervical SCI) with a mean age of 11.41 years (range 8-16 years) were recruited and scanned using a 3.0T Siemens Verio MR scanner. T2-weighted axial images were acquired covering entire cervical spinal cord level C1 to C7. These gray-scale images were then converted to color images by using five different techniques including hue-saturation-value (HSV), rainbow, red-green-blue (RGB), and two enhanced RGB techniques using automated contrast stretching and intensity inhomogeneity correction. Performance of these techniques was scored visually by two neuroradiologists within three selected cervical spinal cord intervertebral disk levels (C2-C3, C4-C5, and C6-C7) and quantified using signal to noise ratio (SNR) and contrast to noise ratio (CNR). Qualitative and quantitative evaluation of the color images shows consistent improvement across all the healthy and SCI subjects over conventional gray-scale T2-weighted gradient echo (GRE) images. Inter-observer reliability test showed moderate to strong intra-class correlation (ICC) coefficients in the proposed techniques (ICC > 0.73). The results suggest that the color images could be used for quantification and enhanced visualization of the spinal cord structures in addition to the conventional gray-scale images. This would immensely help towards improved delineation of the gray/white and CSF structures and further aid towards accurate manual or automatic drawings of region of interests (ROIs).

Reduced Field of View Diffusion Tensor Imaging and Fiber Tractography of the Pediatric Cervical and Thoracic Spinal Cord Injury.

The aim of this study is to assess the utility and effectiveness of diffusion tensor imaging (DTI) and diffusion tensor tractography (DTT) of the entire pediatric cervical and thoracic spinal cord toward discrimination of typically developing (TD) controls and subjects with spinal cord injury (SCI). A total of 43 pediatric subjects, including 23 TD subjects ranging in age from 6 to 16 years old and 20 subjects with SCI ranging in age from 7 to 16 years, were recruited and scanned using a 3.0 Tesla magnetic resonance scanner. Reduced field of view diffusion tensor images were acquired axially to cover the entire spinal cord across two slabs. For DTI analysis, motion correction was performed by coregistration of the diffusion-weighted images to the reference image (b0). Streamline deterministic tractography results were generated from the preprocessed data. DTI and DTT parameters of the whole cord, including fractional anisotropy (FA), mean diffusivity (MD), tract length, and tract density, were calculated, averaged across the whole spinal cord, and compared between the TD and SCI groups. Statistically significant decreases have been shown in FA (TD = 0.46 ± 0.11; SCI = 0.37 ± 0.09; p < 0.0001) and tract density (TD = 405.93 ± 243.84; SCI = 268.90 ± 270.34; p < 0.0001). However, the mean length of tracts and MD did not show significant differences. When investigating differences in DTI and DTT parameters above and below the injury site, it was shown that the FA and tract density in patients with cervical SCI decreased significantly in the thoracic region. An identical trend was observed in the cervical region for patients with thoracic SCI as well. When comparing TD and SCI subjects, FA and tract density were the most sensitive parameters in detecting functional changes of the spinal cord in chronic pediatric SCI. The results show that both DTI and DTT have the potential to be imaging biomarkers in the diagnosis of SCI.

Identification of ghost artifact using texture analysis in pediatric spinal cord diffusion tensor images.

PURPOSE: Ghost artifacts are a major contributor to degradation of spinal cord diffusion tensor images. A multi-stage post-processing pipeline was designed, implemented and validated to automatically remove ghost artifacts arising from reduced field of view diffusion tensor imaging (DTI) of the pediatric spinal cord. METHOD: A total of 12 pediatric subjects including 7 healthy subjects (mean age=11.34years) with no evidence of spinal cord injury or pathology and 5 patients (mean age=10.96years) with cervical spinal cord injury were studied. Ghost/true cords, labeled as region of interests (ROIs), in non-diffusion weighted b0 images were segmented automatically using mathematical morphological processing. Initially, 21 texture features were extracted from each segmented ROI including 5 first-order features based on the histogram of the image (mean, variance, skewness, kurtosis and entropy) and 16s-order feature vector elements, incorporating four statistical measures (contrast, correlation, homogeneity and energy) calculated from co-occurrence matrices in directions of 0°, 45°, 90° and 135°. Next, ten features with a high value of mutual information (MI) relative to the pre-defined target class and within the features were selected as final features which were input to a trained classifier (adaptive neuro-fuzzy interface system) to separate the true cord from the ghost cord. RESULTS: The implemented pipeline was successfully able to separate the ghost artifacts from true cord structures. The results obtained from the classifier showed a sensitivity of 91%, specificity of 79%, and accuracy of 84% in separating the true cord from ghost artifacts. CONCLUSION: The results show that the proposed method is promising for the automatic detection of ghost cords present in DTI images of the spinal cord. This step is crucial towards development of accurate, automatic DTI spinal cord post processing pipelines.