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.

Considerations and recommendations for selection and utilization of upper extremity clinical outcome assessments in human spinal cord injury trials.

STUDY DESIGN: This is a focused review article. OBJECTIVES: This review presents important features of clinical outcomes assessments (COAs) in human spinal cord injury research. Considerations for COAs by trial phase and International Classification of Functioning, Disability and Health are presented as well as strengths and recommendations for upper extremity COAs for research. Clinical trial tools and designs to address recruitment challenges are identified. METHODS: The methods include a summary of topics discussed during a two-day workshop, conceptual discussion of upper extremity COAs and additional focused literature review. RESULTS: COAs must be appropriate to trial phase and particularly in mid-late-phase trials, should reflect recovery vs. compensation, as well as being clinically meaningful. The impact and extent of upper vs. lower motoneuron disease should be considered, as this may affect how an individual may respond to a given therapeutic. For trials with broad inclusion criteria, the content of COAs should cover all severities and levels of SCI. Specific measures to assess upper extremity function as well as more comprehensive COAs are under development. In addition to appropriate use of COAs, methods to increase recruitment, such as adaptive trial designs and prognostic modeling to prospectively stratify heterogeneous populations into appropriate cohorts should be considered. CONCLUSIONS: With an increasing number of clinical trials focusing on improving upper extremity function, it is essential to consider a range of factors when choosing a COA. SPONSORS: Craig H. Neilsen Foundation, Spinal Cord Outcomes Partnership Endeavor.

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).

The implications of injury in the developing nervous system on upper extremity function.

STUDY DESIGN: Literature review. PURPOSE: The corticospinal system (CS) and peripheral nervous system (PNS) are common sites of damage during the early stages of life. The prenatal or immediately prenatal period is the most common time for damage to occur. Here we briefly review the basic features of the development of the CS and the PNS and the clinical consequences of injury to or improper development of these systems on upper extremity (UE) function. RESULTS: The proper development of both the CS and PNS is necessary to achieve adequate function of the (UE). Injury or improper development of these systems can lead to upper extremity dysfunction and limit participation in activities of daily living. CONCLUSIONS: Both the PNS and CS play major roles in the proper functioning of the UE. A better understanding of their roles and common developmental disorders is needed to move rehabilitation of motor impairments forward.

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.

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.

Using a limited number of dermatomes as a predictor of the 56-dermatome test of the international standards for neurological classification of spinal cord injury in the pediatric population.

BACKGROUND: For young children with spinal cord injury (SCI), the sensory exam of the International Standards for the Neurological Classification of Spinal Cord Injury (ISNCSCI) is long and arduous, often making it impossible to complete. OBJECTIVES: In this study, we determine whether an abbreviated sensory exam provides comparable information to the full 56-dermatome exam. METHOD: A total of 726 56-dermatome sensory exams were completed with 190 children and youth with SCI ranging in age from 3 to 21 years. The cohort was randomly split into test and validation groups. For the test group, a principal component analysis (PCA) was carried out separately for pin prick (PP) and light touch (LT) scores. From the PCA, a hierarchical cluster analysis was performed to identify the most influential set of 4, 8, 12, and 16 dermatomes. From the sensory exam data obtained from the validation group, a linear regression was performed to compare the limited-dermatome composite scores to the total 56-dermatome scores. RESULTS: For both LT and PP, the 16-dermatome test resulted in the best fit (0.86 and 0.87, respectively) with the 56-dermatome test and was comprised of dermatomes from both the left (7 dermatomes) and right (9 dermatomes) sides and at least 1 dermatome from each vertebral region bilaterally (cervical, thoracic, lumbar, sacral). CONCLUSION: A 16-dermatome sensory exam provided a good correlation to the 56-dermatome exam. The shortened exam may be useful for evaluating children with SCI who cannot tolerate the full examination.

Cerebral activation during the test of spinal cord injury severity in children: an FMRI methodological study.

BACKGROUND: The International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) are internationally accepted to determine and classify the extent of motor and sensory impairment along with severity (ASIA Impairment Scale [AIS]) following spinal cord injury (SCI). The anorectal examination is a component of the ISNCSCI that determines injury severity. There is a void in the health care literature on the validity of the anorectal examination as an indication of SCI severity. OBJECTIVE: To validate the use of functional magnetic resonance imagining (fMRI) for the purpose of classifying the severity of SCI in children. METHODS: Seventeen patients, with the average age of 14.3 years, underwent 1 complete ISNCSCI examination. Subjects also underwent the anorectal portion of this exam while fMRI data were collected using a 3.0 Tesla Siemens Verio Scanner. Cortical areas of activation were analyzed for possible differences of cortical involvement between complete (AIS A) and incomplete (AIS B, C, and D) SCI subjects. Anxiety/anticipation of the test was also assessed. RESULTS: This study established an fMRI imaging protocol that captures the cortical locations and intensity of activation during the test of sacral sparing. In addition to developing the data acquisition protocol, we also established the postacquisition preprocessing and statistical analysis parameters using SPM8. CONCLUSION: Preliminary findings indicate that fMRI is a useful tool in evaluating the validity of the anorectal examination in determining SCI severity. Assessment of which cortical regions are activated during the testing procedure provides an indication of which pathways are transmitting information to the brain.

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.

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.

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.

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.

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.

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.

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.

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.