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.

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).

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.

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.

Neuromotor prosthetic to treat stroke-related paresis: N-of-1 trial.

Background: Functional recovery of arm movement typically plateaus following a stroke, leaving chronic motor deficits. Brain-computer interfaces (BCI) may be a potential treatment for post-stroke deficits. Methods: In this n-of-1 trial (NCT03913286), a person with chronic subcortical stroke with upper-limb motor impairment used a powered elbow-wrist-hand orthosis that opened and closed the affected hand using cortical activity, recorded from a percutaneous BCI comprised of four microelectrode arrays implanted in the ipsilesional precentral gyrus, based on decoding of spiking patterns and high frequency field potentials generated by imagined hand movements. The system was evaluated in a home setting for 12 weeks. Results: Robust single unit activity, modulating with attempted or imagined movement, was present throughout the precentral gyrus. The participant acquired voluntary control over a hand-orthosis, achieving 10 points on the Action Research Arm Test using the BCI, compared to 0 without any device, and 5 using myoelectric control. Strength, spasticity, the Fugl-Meyer scores improved. Conclusions: We demonstrate in a human being that ensembles of individual neurons in the cortex overlying a chronic supratentorial, subcortical stroke remain active and engaged in motor representation and planning and can be used to electrically bypass the stroke and promote limb function. The participant's ability to rapidly acquire control over otherwise paralyzed hand opening, more than 18 months after a stroke, may justify development of a fully implanted movement restoration system to expand the utility of fully implantable BCI to a clinical population that numbers in the tens of millions worldwide.

Fundamentals of Preoperative Task Functional Brain Mapping.

Blood oxygenation level-dependent (BOLD) imaging is gaining traction in the clinical realm as a measure for quantifying changes in regional blood flow in response to external stimuli. Through the evoked signal changes that are a consequence of hemoglobin's intrinsic paramagnetic properties, this technique allows for the statistical mapping of brain regions associated with a given task, which has broad applications in preneurosurgical planning for tumor resection. From an acquisition perspective, collection of BOLD data most commonly requires the use of echo planar imaging readout schemes. These sequences are currently widely available on most clinical scanners and at various field strengths. However, while the BOLD acquisition protocol is relatively straightforward, additional hardware and rigorous image processing are needed to correlate the time-dependent signal changes associated with a specific and well defined task. This manuscript will provide the necessary information to detail the physiologic underpinning of acquiring BOLD sensitized images and the important technical aspects of processing the data for use in a surgical environment.

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.

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.

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.

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.

Spatially selective 2D RF inner field of view (iFOV) diffusion kurtosis imaging (DKI) of the pediatric spinal cord.

Magnetic resonance based diffusion imaging has been gaining more utility and clinical relevance over the past decade. Using conventional echo planar techniques, it is possible to acquire and characterize water diffusion within the central nervous system (CNS); namely in the form of Diffusion Weighted Imaging (DWI) and Diffusion Tensor Imaging (DTI). While each modality provides valuable clinical information in terms of the presence of diffusion and its directionality, both techniques are limited to assuming an ideal Gaussian distribution for water displacement with no intermolecular interactions. This assumption neglects pathological processes that are not Gaussian therefore reducing the amount of potentially clinically relevant information. Additions to the Gaussian distribution measured by the excess kurtosis, or peakedness, of the probabilistic model provide a better understanding of the underlying cellular structure. The objective of this work is to provide mathematical and experimental evidence that Diffusion Kurtosis Imaging (DKI) can offer additional information about the micromolecular environment of the pediatric spinal cord. This is accomplished by a more thorough characterization of the nature of random water displacement within the cord. A novel DKI imaging sequence based on a tilted 2D spatially selective radio frequency pulse providing reduced field of view (FOV) imaging was developed, implemented, and optimized on a 3 Tesla MRI scanner, and tested on pediatric subjects (healthy subjects: 15; patients with spinal cord injury (SCI):5). Software was developed and validated for post processing of the DKI images and estimation of the tensor parameters. The results show statistically significant differences in mean kurtosis (p < 0.01) and radial kurtosis (p < 0.01) between healthy subjects and subjects with SCI. DKI provides incremental and novel information over conventional diffusion acquisitions when coupled with higher order estimation algorithms.

An investigation of motion correction algorithms for pediatric spinal cord DTI in healthy subjects and patients with spinal cord injury.

Patient and physiological motion can cause artifacts in DTI of the spinal cord which can impact image quality and diffusion indices. The purpose of this investigation was to determine a reliable motion correction method for pediatric spinal cord DTI and show effects of motion correction on DTI parameters in healthy subjects and patients with spinal cord injury. Ten healthy subjects and ten subjects with spinal cord injury were scanned using a 3T scanner. Images were acquired with an inner field-of-view DTI sequence covering cervical spine levels C1 to C7. Images were corrected for motion using two types of transformation (rigid and affine) and three cost functions. Corrected images and transformations were examined qualitatively and quantitatively using in-house developed code. Fractional anisotropy (FA) and mean diffusivity (MD) indices were calculated and tested for statistical significance pre- and post- motion correction. Images corrected using rigid methods showed improvements in image quality, while affine methods frequently showed residual distortions in corrected images. Blinded evaluation of pre and post correction images showed significant improvement in cord homogeneity and edge conspicuity in corrected images (p<0.0001). The average FA changes were statistically significant (p<0.0001) in the spinal cord injury group, while healthy subjects showed less FA change and were not significant. In both healthy subjects and subjects with spinal cord injury, quantitative and qualitative analysis showed the rigid scaled-least-squares registration technique to be the most reliable and effective in improving image quality.