Devon M. Middleton

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.

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.

Diffusion Tensor Imaging of the Normal Cervical and Thoracic Pediatric Spinal Cord

BACKGROUND AND PURPOSE: DTI data of the normal healthy spinal cord in children are limited compared with adults and are typically focused on the cervical spinal cord. The purpose of this study was the following: to investigate the feasibility of obtaining repeatable DTI parameters along the entire cervical and thoracic spinal cord as a function of age in typically developing pediatric subjects; to analyze the DTI parameters among different transverse levels of the cervical and thoracic spinal cord; and to examine the sex differences in DTI parameters along the cervical and thoracic spinal cord. MATERIALS AND METHODS: Twenty-two subjects underwent 2 identical scans by using a 3T MR imaging scanner. Axial diffusion tensor images were acquired by using 2 overlapping slabs to cover the cervical and thoracic spinal cord. After postprocessing, DTI parameters were calculated by using ROIs drawn on the whole cord along the entire spinal cord for both scans. RESULTS: An increase in fractional anisotropy and a decrease in mean diffusivity, axial diffusivity, and radial diffusivity were observed with age along the entire spinal cord. Significantly lower fractional anisotropy and higher mean diffusivity values were observed in the lower cervical cord compared with the upper cervical cord. Axial diffusivity values in the cervical cord were higher compared with the thoracic cord. No statistically significant sex differences were observed for all DTI parameters. There was a moderate-to-strong repeatability for all DTI parameters. CONCLUSIONS: This study provides an initial understanding of DTI values of the spinal cord relevant to age and sex and shows that obtaining repeatable DTI values of the entire cord in children is feasible.

Reduced FOV diffusion tensor MR imaging and fiber tractography of pediatric cervical spinal cord injury

Study design:Quantitative study.Objectives:To evaluate the effectiveness of pediatric spinal cord diffusion tensor tractography (DTT) generated from reduced field of view diffusion tensor imaging (DTI) data and investigate whether there are differences in these values between typically developing (TD) subjects and patients with spinal cord injury (SCI).Setting:Temple University Hospital and Shriners Hospitals for Children-Philadelphia, USA.Methods:A total of 20 pediatric subjects including 10 healthy subjects (age 15.13±3.51 years (mean±s.d.) and age range 11–21 years) and 10 subjects with SCI in the cervical area (age 13.8±3.26 years and age range 8–20 years) were recruited, and scanned using a 3.0T MR scanner. Quantitative parameters of DTI and fiber tracking, such as mean fractional anisotropy (FA), apparent diffusion coefficient (ADC), mean length of fiber tracts and tract density, were calculated for each subject.Results:Subjects with SCI showed reduced FA and tract density, and increased ADC values and length of fiber tracts, compared with controls. Statistically significant differences were seen in FA (P=0.0238) and tract density (P=0.0005) between controls and subjects with SCI, whereas there were no significant differences in ADC values and length of fiber tracts. The tractography visually showed that the white matter tracts (blue color) of the SCI patients were overall less abundant and less organized compared with control cases.Conclusion:The results show that DTI and DTT could be used as surrogate markers for quantification and visualization of the injured spinal cord.

Inter- and intra-rater reliability of diffusion tensor imaging parameters in the normal pediatric spinal cord.

AIM To assess inter- and intra-rater reliability (agreement) between two region of interest (ROI) methods in pediatric spinal cord diffusion tensor imaging (DTI). METHODS Inner-Field-of-View DTI data previously acquired from ten pediatric healthy subjects (mean age = 12.10 years) was used to assess for reliability. ROIs were drawn by two neuroradiologists on each subject data twice within a 3-mo interval. ROIs were placed on axial B0 maps along the cervical spine using free-hand and fixed-size ROIs. Agreement analyses for fractional anisotropy (FA), axial diffusivity, radial diffusivity and mean diffusivity were performed using intra-class-correlation (ICC) and Cronbachs alpha statistical methods. RESULTS Inter- and intra-rater agreement between the two ROI methods showed moderate (ICC = 0.5) to strong (ICC = 0.84). There were significant differences between raters in the number of pixels selected using free-hand ROIs (P < 0.05). However, no significant differences were observed in DTI parameter values. FA showed highest variability in ICC values (0.10-0.87). Cronbachs alpha showed moderate-high values for raters and ROI methods. CONCLUSION The study showed that high reproducibility in spinal cord DTI can be achieved, and demonstrated the importance of setting detailed methodology for post-processing DTI data, specifically the placement of ROIs.

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.

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.

Intensity inhomogeneity correction in clinical pediatric spinal cord MRI images

Intensity inhomogeneity correction is one of the challenges in Magnetic Resonance Imaging (MRI). Correction of intensity inhomogeneity for spinal cord images is more difficult than brain images because of the small size of homogeneous regions such as gray and white matter structures in a spinal cord. In this paper we present a pixel based correction method called Improved Adaptive Gamma Correction Method (IAGCM). Several qualitative and quantitative evaluations were tested on spinal cord images on seven healthy and three subjects with spinal cord injury. Contrast to Noise Ratio (CNR) and Signal to Noise Ratio (SNR) for different parameters of “p” were considered as quantitative evaluation. Qualitative evaluations were performed by scoring of images by an independent board certified neuroradiologist on images applied with pseudo color transformation. Overall the results showed improvement in the CNR of the corrected images. In conclusion, the proposed IAGCM method is a simple method to implement and performed well in improving the image quality of spinal cord images.

Segmentation of spinal cord in the pediatric spinal Diffusion Tensor MR Imaging

Classification and segmentation of small structures such as spinal cord is extremely challenging. In this paper, a multi stage segmentation algorithm is proposed and tested to accurately and reliably segment the spinal canal and spinal cord from the background in the pediatric spinal Diffusion Tensor MR images. First, median filter and image compression methods were applied to mitigate the amplitude of the noise and improve the homogeneity of the image. Next, mathematical morphological processing was applied to segment and label the regions attributed to the spinal canal. These segmented regions were classified into the spinal canal and background using a Euclidean metric obtained by centroid coordinates of segmented regions in the volumetric DTI data. Finally, Otsu thresholding technique was applied to extract cord region from spinal canal. Segmentation accuracy, sensitivity, specificity and spatial overlap index were examined as performance measurements. The quantitative measurements represent the effectiveness of the proposed method.

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

Study designRetrospective study.ObjectivesTo 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.SettingUSA.Methods26 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.ResultsIn 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.ConclusionsThis 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.