Reproducibility of magnetic resonance imaging measurements of spinal cord atrophy: the role of quality assurance.

A sensitive magnetic resonance imaging (MRI) method to measure spinal cord cross-sectional area with the potential to monitor disease progression has recently been developed. As changes in cord area due to disease are usually small, assessment of the reliability of the methodology is essential in serial studies of spinal cord atrophy. The aim of this study was to institute and evaluate a protocol of quality assurance to determine long-term reproducibility of serial studies. Serial MRI of the spinal cord was carried out in five healthy volunteer controls over 1 year. Cross-sectional spinal cord areas were measured in a total of 46 scans. The mean coefficient of variation of all subjects over one year was 1.35%. The intra-observer coefficient of variation for same scan analysis was 0.63%. This study has confirmed high reliability of our serial data over one year and the on-going quality assurance protocol enables continuing evaluation of the reproducibility of results in serial studies. Quality assurance is an essential and practical component of all serial MRI studies, without which the clinical implications of change cannot be reliably evaluated.     

Characterization of cardiac-related noise in fMRI of the cervical spinal cord

Magnetic resonance imaging (MRI) has recently been applied to study spinal cord function in humans. However, spinal functional MRI (fMRI) encounters major technical challenges with cardiac noise being considered a major source of noise. The present study relied on echo-planar imaging of the cervical cord at short TR (TR=250 ms; TE=40 ms; flip=45 degrees), combined with plethysmographic recordings to characterize the spatiotemporal properties of cardiac-induced signal changes in spinal fMRI. Frequency-based analyses examining signal change at the cardiac frequency confirmed mean fluctuations of about 10% (relative to the mean signal) in the spinal cord and surrounding cerebrospinal fluid (CSF), with maximal responses reaching up to 66% in some voxels. A spatial independent component analysis (sICA) confirmed that cardiac noise is an important source of variance in spinal fMRI with several components showing a response coherent with the cardiac frequency spectrum. The time course of the main cardiac components approximated a sinusoidal function tightly coupled to the cardiac systole with at least one component showing a comparable temporal profile across runs and subjects. Spatially, both the frequency-domain analysis and the sICA demonstrated cardiac noise distributed irregularly along the full rostrocaudal extent of the segments scanned with peaks concentrated in the ventral part of the lateral slices in all scans and subjects, consistent with the major channels of CSF flow. These results confirm that cardiac-induced changes are a significant source of noise likely to affect the detection of spinal Blood Oxygen Level Dependent (BOLD) responses. Most importantly, the complex spatiotemporal structure of cardiac noise is unlikely to be accounted for adequately by ad hoc linear methods, especially in data acquired using long TR (i.e. aliasing the cardiac frequency). However, the reliable spatiotemporal distribution of cardiac noise across scanning runs and within subjects may provide a valid means to identify and extract cardiac noise based on sICA methods.     

Functional MRI of motor and sensory activation in the human spinal cord

MR imaging of the cervical spinal cord was carried out on volunteers during alternated rest and either motor or sensory stimulation of one hand, in order to detect image intensity changes arising concomitant to neuronal activity. We employed both spin-echo and gradient-echo echo-planar imaging, on the right and left hands, with both symmetric and asymmetric temporal patterns of rest and stimulation. Intensity changes correlated with the time course of stimulation were consistently detected, and the magnitude of the intensity changes depended on the duration of stimulation. The activated regions in the spinal cord extended along a column on the side of the body being stimulated and included localized regions on the contralateral side, in agreement with the neural anatomy.     

In vivo diffusion tensor imaging of thoracic and cervical rat spinal cord at 7 T

In vivo diffusion tensor imaging (DTI) of rat cervical and thoracic spinal cord was performed using a three-element phased array coil at 7 T. The magnetic field was shimmed over the spinal cord in real time using an in-house developed automatic algorithm. Echo planar imaging (EPI)-based diffusion-weighted images (DWIs) were acquired with 21 gradient encoding directions. The DWIs were tensor encoded, and diffusion tensor metrics, fractional anisotropy (FA), mean diffusivity (MD), longitudinal diffusivity (λ₀) and transverse diffusivity (λ) were determined for both white matter (WM) and gray matter (GM). The results on six normal rats indicated no significant differences in the diffusion tensor metrics between thoracic and cervical regions. However, the DTI-derived metrics in cervical spinal cord from our study are somewhat different from the published results in rats. The possible reasons for these differences are suggested.     

Signal-to-noise ratio comparison of phased-array vs. implantable coil for rat spinal cord MRI

The signal-to-noise ratio (SNR) performance and practicality issues of a four-element phased-array coil and an implantable coil system were compared for rat spinal cord magnetic resonance imaging (MRI) at 7 T. MRI scans of the rat spinal cord at T10 were acquired from eight rats over a 3 week period using both coil systems, with and without laminectomy. The results demonstrate that both the phased array and the implantable coil systems are feasible options for rat spinal cord imaging at 7 T, with both systems providing adequate SNR for 100-mum spatial resolution at reasonable imaging times. The implantable coils provided significantly higher SNR, as compared to the phased array (average SNR gain of 5.3x between the laminectomy groups and 2.5x between the nonlaminectomy groups). The implantable coil system should be used if maximal SNR is critical, whereas the phased array is a good choice for its ease of use and lesser invasiveness.     

Quantitative evaluation of optimal imaging parameters for single-cell detection in MRI using simulation

Super-paramagnetic iron oxide (SPIO) nanoparticles are actively investigated to enhance disease detection through molecular imaging using magnetic resonance imaging (MRI). Detection of the cells labeled by SPIO depends on the MRI protocols and pulse sequence parameters that can be optimized. To evaluate the sensitivity and specificity of the image acquisition methods and to obtain optimal imaging parameters for single-cell detection, we further developed an MRI simulator. The simulator models an object (tissue) at a microscopic level to evaluate effects of spatial distribution and concentration of nanoparticles on the resulting image. In this study, the simulator was used to evaluate and compare imaging of the labeled cells by the gradient-echo (GE), true-FISP [fast imaging employing steady-state acquisition (FIESTA)] and echo-planar imaging (EPI) pulse sequences. Effects of the imaging and object parameters, such as field strength, imaging protocol and pulse sequence parameters, imaging resolution, cell iron load, position of SPIO within the voxel and cell division within the voxel, were investigated in the work. The results suggest that true-FISP has the highest sensitivity for single-cell detection by MRI.     

Compensation of susceptibility-induced signal loss in echo-planar imaging for functional applications

Functional magnetic resonance imaging favors the use of multi-slice gradient-recalled echo-planar imaging due to its short image acquisition times, whole brain coverage and sensitivity to BOLD contrast. However, despite its advantages, gradient-recalled echo-planar imaging also is sensitive to static magnetic field gradients arising primarily from air-tissue interfaces. This can lead to image artifacts such as voxel shifts and complete signal loss. A method to recover signal loss by adjusting the refocusing gradient amplitude in the slice-select direction, preferably axially, is proposed. This method is implemented as an automated computer algorithm that partitions echo-planar images into regions of recoverable signal intensities using a histogram analysis and determines each region's proper refocusing gradient amplitude. As an example, different refocusing gradient amplitudes are interleaved in a fMRI acquisition to maximize the signal to noise ratio and obtain functional activation in normal and dropout regions. The effectiveness of this method is demonstrated by recovering signal voids in the orbitofrontal cortex, parahippocampal/amygdala region, and inferior visual association cortex near the cerebellum.     

The 3D characteristics of post‐traumatic syringomyelia in a rat model: a propagation‐based synchrotron radiation microtomography study

Many published literature sources have described the histopathological characteristics of post‐traumatic syringomyelia (PTS). However, three‐dimensional (3D) visualization studies of PTS have been limited due to the lack of reliable 3D imaging techniques. In this study, the imaging efficiency of propagation‐based synchrotron radiation microtomography (PB‐SRµCT) was determined to detect the 3D morphology of the cavity and surrounding microvasculature network in a rat model of PTS. The rat model of PTS was established using the infinite horizon impactor to produce spinal cord injury (SCI), followed by a subarachnoid injection of kaolin to produce arachnoiditis. PB‐SRµCT imaging and histological examination, as well as fluorescence staining, were conducted on the animals at the tenth week after SCI. The 3D morphology of the cystic cavity was vividly visualized using PB‐SRµCT imaging. The quantitative parameters analyzed by PB‐SRµCT, including the lesion and spared spinal cord tissue area, the minimum and maximum diameters in the cystic cavity, and cavity volume, were largely consistent with the results of the histological assessment. Moreover, the 3D morphology of the cavity and surrounding angioarchitecture could be simultaneously detected on the PB‐SRµCT images. This study demonstrated that high‐resolution PB‐SRµCT could be used for the 3D visualization of trauma‐induced spinal cord cavities and provides valuable quantitative data for cavity characterization. PB‐SRµCT could be used as a reliable imaging technique and offers a novel platform for tracking cavity formation and morphological changes in an experimental animal model of PTS.     

Cervical spine MR imaging using multislice gradient echo imaging: comparison with cardiac gated spin echo

Forty-one patients with suspected cervical spine disorders were studied using multislice gradient echo imaging (GE) technique, with a 1.5-T system. The images were compared to cardiac-gated spin echo (CGSE) images in the diagnosis of suspected cord and spinal disorders. Images were graded for ability to detect cord lesion, cord-CSF contrast, CSF-bone contrast and contrast between CSF and extradural abnormality. The signal-to-noise ratio and contrast-to-noise ratio were used to compare images. There was 44% decrease in contrast between cord lesion and normal cord on GE when compared to CGSE, except for spinal cord hemorrhage. There was a 40% improvement between bone and CSF contrast on GE compared to CGSE. GE images were significantly better qualitatively as well as quantitatively in the detection of extradural lesions. This effect was more marked in axial plane where CGSE images are extremely suboptimal. CGSE images are better than GE for spinal cord lesions, while GE are superior in the diagnosis of degenerative disease in the cervical spine.     

High-resolution in vivo diffusion tensor imaging of the injured cat spinal cord using self-navigated,interleaved, variable-density spiral acquisition (SNAILS-DTI)

Diffusion tensor magnetic resonance imaging (DTI) is useful for studying the microstructural changes in the spinal cord following traumatic injury; however, image quality is generally poor due to the small size of the spinal cord, physiological motion and susceptibility artifacts. Self-navigated, interleaved, variable-density spiral diffusion tensor imaging (SNAILS-DTI) is a distinctive pulse sequence that bypasses many of the challenges associated with DTI of the spinal cord, particularly if imaging gradient hardware is of conventional quality. In the current study, we have demonstrated the feasibility of implementing SNAILS-DTI on a clinical 3.0-T MR scanner and examined the effect of navigator filter parameters on image quality and reconstruction time. Results demonstrate high-quality, high-resolution (546 μm×546 μm) in vivo DTI images of the cat spinal cord after traumatic spinal cord injury.     

Susceptibility weighted imaging in detecting hemorrhage in acute cervical spinal cord injury

Background and Purpose

Susceptibility weighted imaging (SWI) is sensitive to deoxyhemoglobin and blood products such as hemosiderin in detecting microbleeds in the brain. However, there are no studies on SWI in the spine cord injury so far. The purpose of this study was to evaluate the role of SWI in detecting hemorrhage in acute cervical spinal cord injury (SCI).

Materials and Methods

Twenty-three patients with a history of acute cervical spine trauma were studied. High-resolution SWI, gradient-echo (GRE) T2* weighted-image (T2*WI) and conventional magnetic resonance imaging (MRI) were performed on all patients within 15 days of the onset of injury. On the basis of the MRI findings, the patients were classified into four patterns: normal cord, spinal cord edema, spinal cord contusion and spinal cord hemorrhage. Quantitative analysis was performed by calculating and comparing the signal ratio of the hemorrhage to normal spinal cord on the same slice of T2*WI and SWI. All patients were clinically evaluated in follow-up. Twenty volunteers were also scanned as a control group.

Results

Out of 23 patients with a history of acute cervical spine trauma, 4 patients showed normal spinal cord on both conventional MRI and SWI, 8 had only spinal cord edema and 5 had contusion on conventional MRI, but SWI showed hemorrhage in 2 of the 5 patients with spinal contusion on conventional MRI; the other 6 patients had intraspinal hemorrhage on conventional MRI, and SWI proved hemorrhage in all these 6 patients. There was a significant difference between the signal ratios of hemorrhage to normal tissue on T2*WI and SWI (Z=2.34, P=.02).

Conclusion

Susceptibility weighted imaging is more sensitive than conventional MRI in detecting hemorrhage in acute cervical SCI. This technique could prove to be a useful tool in the routine evaluation of cervical SCI patients.     

Optimization of a transmit/receive surface coil for squirrel monkey spinal cord imaging

MR Imaging the spinal cord of non-human primates (NHP), such as squirrel monkey, is important since the injuries in NHP resemble those that afflict human spinal cords. Our previous studies have reported a multi-parametric MRI protocol, including functional MRI, diffusion tensor imaging, quantitative magnetization transfer and chemical exchange saturation transfer, which allows non-invasive detection and monitoring of injury-associated structural, functional and molecular changes over time. High signal-to-noise ratio (SNR) is critical for obtaining high-resolution images and robust estimates of MRI parameters. In this work, we describe our construction and use of a single channel coil designed to maximize the SNR for imaging the squirrel monkey cervical spinal cord in a 21 cm bore magnet at 9.4 T. We first numerically optimized the coil dimension of a single loop coil and then evaluated the benefits of a quadrature design. We then built an optimized coil based on the simulation results and compared its SNR performance with a non-optimized single coil in both phantoms and in vivo.     

Diffusion anisotropy in excised normal rat spinal cord measured by NMR microscopy

A conventional spin-echo NMR imaging pulse sequence was used to obtain high-resolution images of excised normal rat spinal cord at 7 and 14 T. It was observed that the large pulsed-field gradients necessary for high-resolution imaging caused a diffusion weighting that dominated the image contrast and that could be used to infer microscopic structural organization beyond that defined by the resolution of the image matrix (i.e., fiber orientation could be assigned based on diffusion anisotropy). Anisotropic diffusion coefficients were therefore measured using apparent diffusion tensor (ADT) imaging to assess more accurately fiber orientations in the spinal cord; structural anisotropy information is portrayed in the six unique images of the complete ADT. To reduce the dimensionality of the data, a trace image was generated using a separate color scale for each of the three diagonal element images of the ADT. This new image retains much of the invariance of the trace to the relative orientations of laboratory and sample axes (inherent to a greyscale trace image) but provides, by the use of color, contrast reflecting diffusion anisotropy. The colored trace image yields a pseudo-three-dimensional view of the rat spinal cord, from which it is possible to deduce fiber orientations.     

Diffusion-weighted imaging of the brain at 7 T with echo-planar and turbo spin echo sequences: preliminary results

Ultra-high-field clinical MRI scanners (e.g., 7 T and above) are becoming increasingly prevalent and can potentially enhance diagnostic ability through higher contrast, resolution and/or sensitivity. Diffusion-weighted MRI is a highly valued component in today's radiological exam and may benefit from the enhanced signal-to-noise ratio provided by high field with the appropriate imaging strategy. The most common diffusion pulse sequence readout (echo-planar imaging (EPI)) has been widely employed for in vivo human 7 T diffusion tensor imaging (DTI). In this article, we present results of brain DTI at 7 T with two diffusion-weighted imaging pulse sequence readouts: echo-planar imaging (EPI-DTI) and turbo spin echo (TSE-DTI). Results indicate that analogous coverage, quality and resolution typical of lower field (2 mm) can be obtained by properly processed EPI-DTI at 7 T, and, with some reduction in efficiency and sharpness, TSE-DTI at 7 T. Furthermore, 7 T TSE-DTI shows promise in obtaining higher-resolution results in targeted acquisitions of specific brain areas.     

Visualization of mouse spinal cord intramedullary arteries using phase‐ and attenuation‐contrast tomographic imaging

Many spinal cord circulatory disorders present the substantial involvement of small vessel lesions. The central sulcus arteries supply nutrition to a large part of the spinal cord, and, if not detected early, lesions in the spinal cord will cause irreversible damage to the function of this organ. Thus, early detection of these small vessel lesions could potentially facilitate the effective diagnosis and treatment of these diseases. However, the detection of such small vessels is beyond the capability of current imaging techniques. In this study, an imaging method is proposed and the potential of phase‐contrast imaging (PCI)‐ and attenuation‐contrast imaging (ACI)‐based synchrotron radiation for high‐resolution tomography of intramedullary arteries in mouse spinal cord is validated. The three‐dimensional vessel morphology, particularly that of the central sulcus arteries (CSA), detected with these two imaging models was quantitatively analyzed and compared. It was determined that both PCI‐ and ACI‐based synchrotron radiation can be used to visualize the physiological arrangement of the entire intramedullary artery network in the mouse spinal cord in both two dimensions and three dimensions at a high‐resolution scale. Additionally, the two‐dimensional and three‐dimensional vessel morphometric parameter measurements obtained with PCI are similar to the ACI data. Furthermore, PCI allows efficient and direct discrimination of the same branch level of the CSA without contrast agent injection and is expected to provide reliable biological information regarding the intramedullary artery. Compared with ACI, PCI might be a novel imaging method that offers a powerful imaging platform for evaluating pathological changes in small vessels and may also allow better clarification of their role in neurovascular disorders.     

Phase-aligned multiple spin-echo averaging: a simple way to improve signal-to-noise ratio of in vivo mouse spinal cord diffusion tensor image

Purpose

To improve signal-noise-ratio of in vivo mouse spinal cord diffusion tensor imaging using-phase aligned multiple spin-echo technique.

Material and methods

In vivo mouse spinal cord diffusion tensor imaging maps generated by multiple spin-echo and conventional spin-echo diffusion weighting were examined to demonstrate the efficacy of multiple spin-echo diffusion sequence to improve image quality and throughput. Effects of signal averaging using complex, magnitude and phased images from multiple spin-echo diffusion weighting were also assessed. Bayesian probability theory was used to generate phased images by moving the coherent signals to the real channel to eliminate the effect of phase variation between echoes while preserving the Gaussian noise distribution. Signal averaging of phased multiple spin-echo images potentially solves both the phase incoherence problem and the bias of the elevated Rician noise distribution in magnitude image. The proposed signal averaging with Bayesian phase-aligned multiple spin-echo images approach was compared to the conventional spin-echo data acquired with doubling the scan time. The diffusion tensor imaging parameters were compared in the mouse contusion spinal cord injury. Significance level (p-value) and effect size (Cohen’s d) were reported between the control and contused spinal cord to inspect the sensitivity of each approach in detecting white matter pathology.

Results

Compared to the spin-echo image, the signal-noise-ratio increased to 1.84-fold using the phased image averaging and to 1.30-fold using magnitude image averaging in the spinal cord white matter. Multiple spin-echo phased image averaging showed improved image quality of the mouse spinal cord among the tested methods. Diffusion tensor imaging metrics obtained from multiple spin-echo phased images using three echoes and two averages closely agreed with those derived by spin-echo magnitude data with four averages (two times more in acquisition time). The phased image averaging correctly reflected pathological features in contusion spinal cord injury.

Conclusion

Our in vivo imaging results indicate that averaging the phased multiple spin-echo images yields an 84% signal-noise-ratio increase over the spin-echo images and a 41% gain over the magnitude averaged multiple spin-echo images with equal acquisition time. Current results from the animal model of spinal cord injury suggest that the phased multiple spin-echo images could be used to improve signal-noise-ratio.     

High resolution diffusion weighted magnetic resonance imaging of the pancreas using reduced field of view single-shot echo-planar imaging at 3 T

Diffusion weighted magnetic resonance imaging (DWI) has been mostly acquired using single-shot echo-planar imaging (ss EPI) to minimize motion induced artifacts. The spatial resolution, however, is inherently limited in ss EPI especially for abdominal imaging, even with the advances in parallel imaging. A novel method of reduced Field of View ss EPI (rFOV ss EPI) has achieved high resolution DWI in human carotid artery, spinal cord with reduced blurring and higher spatial resolution than conventional ss EPI, but it has not been used to pancreas imaging. In the work, comparisons between the full FOV ss-DW EPI and rFOV ss-DW EPI in image qualities and ADC values of pancreatic tumors and normal pancreatic tissues were performed to demonstrate the feasibility of pancreatic high resolution rFOV DWI. There were no significant differences in the mean ADC values between full FOV DWI and rFOV DWI for the 17 subjects using b = 600 s/mm² (P = 0.962). However, subjective scores of image quality was significantly higher at rFOV ss DWI (P = 0.008 and 0.000 for b-value = 0 s/mm² and 600 s/mm² respectively). The spatial resolution of DWI for pancreas was increased by a factor of over 2.0 (from almost 3.0 mm/pixel to 1.25 mm/pixel) using rFOV ss EPI technique. Reduced FOV ss EPI can provide good DW images and is promising to benefit applications for pancreatic diseases.     

Use of capillaries in the construction of an MRI phantom for the assessment of diffusion tensor imaging: demonstration of performance

Although diffusion tensor imaging (DTI) shows great potential for the diagnosis of a variety of pathologies, no consensus for an appropriate assessment standard of DTI exists. This study examined the feasibility of using water-filled arrays of glass capillaries to construct a DTI phantom suitable for making repeated and reproducible measurements required in a quality assessment program. Three phantoms were constructed using arrays of capillaries with three inner diameters (23, 48, and 82 μm). Data were acquired using DTI protocols; the fractional anisotropy (FA), mean apparent diffusion coefficient (ADC) and principal eigenvectors of the diffusion tensors were calculated. This study demonstrated four results: (1) echo-planar images show that susceptibility within the capillary arrays does not lead to substantial differences in precessional frequency in regions containing the arrays and neither do the regions show noticeable image distortion; (2) principal eigenvectors of the diffusion tensors agree to within <10.3° of the array orientations; (3) mean FA values (0.18–0.50) and ADC values (1.40–1.93×10−³ mm²/s) within specified regions of interest are in general agreement with simulations after a simple noise correction; and (4) these array performance characteristics are observable using a typical clinical DTI protocol.     

In vivo diffusion tensor imaging of rat spinal cord at 7 T

In vivo diffusion tensor imaging of normal rat spinal cord was performed using a multi-segmented, blipped EPI sequence at 7 T field strength. At high diffusion weighting, the signal exhibited a non-monoexponential decay that was fitted to a biexponential function, associated with the fast and slow components of diffusion in the cord tissue, using a nonlinear regression analysis along with a constrained optimization procedure. From the measured tensors, the eigenvalues and the maps of invariant scalar measures (fractional anisotropy, relative anisotropy, volume ratio, and trace) were calculated and analyzed statistically. The results were combined to quantitatively characterize the anisotropic properties of the fast and slow diffusions in white- and gray matter of live spinal cords.     

Relationships between spinal cord blood flow measured with flow-sensitive alternating inversion recovery (FAIR) and neurobehavioral outcomes in rat spinal cord injury

In the traumatically injured spinal cord, decreased perfusion is believed to contribute to secondary tissue damage beyond the primary mechanical impact, and restoration of perfusion is believed to be a promising therapeutic target. However, methods to monitor spinal cord perfusion non-invasively are limited. Perfusion magnetic resonance imaging (MRI) techniques established for the brain have not been routinely adopted to the spinal cord. The purpose of this study was to examine the relationship between spinal cord blood flow (SCBF) and injury severity in a rat thoracic spinal cord contusion injury (SCI) model using flow-sensitive alternating inversion recovery (FAIR) with two variants of the label position. SCBF as a marker of severity was compared to T₁ mapping and to spinal cord-optimized diffusion weighted imaging (DWI) with filtered parallel apparent diffusion coefficient. Thirty-eight rats underwent a T10 contusion injury with varying severities (8 sham; 10 mild; 10 moderate; 10 severe) with MRI performed at 1 day post injury at the lesion site and follow-up neurological assessments using the Basso, Beattie, Bresnahan (BBB) locomotor scoring up to 28 days post injury. Using whole-cord regions of interest at the lesion epicenter, SCBF was decreased with injury severity and had a significant correlation with BBB scores at 28 days post injury. Importantly, estimates of arterial transit times (ATT) in the injured spinal cord were not altered after injury, which suggests that FAIR protocols optimized to measure SCBF provide more value in the context of acute traumatic injury to the cord. T₁-relaxation time constants were strongly related to injury severity and had a larger extent of changes than either SCBF or DWI measures. These findings suggest that perfusion decreases in the spinal cord can be monitored non-invasively after injury, and multi-parametric MRI assessments of perfusion, diffusion, and relaxation capture unique features of the pathophysiology of preclinical injury.