Browsing by Author "Song, Allen W"

Diffusion-weighted MRI (DWI) is an essential tool in clinical applications such as detecting ischemic stroke, and in research applications studying neuronal connectivity in the brain. Diffusion-weighted imaging with multi-shot echo-planar acquisition (DWEPI) offers several advantages over single-shot EPI, including improved spatial resolution and reduced off-resonance and susceptibility artifacts. However a major limitation of multi-shot DWEPI is its sensitivity to patient motion during the application of diffusion gradients; the motion generates phase errors which vary from shot to shot, resulting in artifacts in the reconstructed image.

Most current methods for correcting motion-induced artifacts involve the use of navigator echoes to estimate the shot-to-shot phase errors. Accurate navigator information comes at the expense of increased scan times however, which is generally undesirable. The aim of this study is to therefore develop and demonstrate the use of an alternative phase estimation technique, iterative phase-cycling, as a new method to correct motion artifacts in DWI without the use of navigators. The developed method involves an iterative column by column estimation of phase errors in the aliased image and reconstruction of an artifact free image using the estimated errors.

In this study the technique was applied to correct artifacts in simulated images, hybrid-simulated images, and true four-shot DWEPI images. Accuracy of the phase-cycling method was evaluated by computing residual image errors and ghost-to-noise ratios after correction. The efficiency of phase-cycling was evaluated by recording computation times of the correction process. Multiple optimization techniques were developed and used in the experiments, and the accuracy/efficiency of these techniques were also assessed.

Results of the experiments demonstrated the ability of phase-cycling to greatly reduce motion-induced artifacts in multi-shot DWEPI at reasonable computation times. The phase-cycling model used in this study accurately estimated linear and nonlinear errors along the frequency encoding direction and linear errors along the phase encoding direction. An additional mathematical framework is presented illustrating the potential of phase-cycling to correct nonlinear errors along the phase encoding direction in future work.

The study establishes the developed technique as a unique and effective method for correcting motion artifacts in DWEPI without the cost of increased scan times.

Cerebral palsy (CP) is a non-progressive sensory-motor disorder and is one of the most costly and debilitating chronic pediatric conditions, affecting 2-3 out of 1000 children in the United States. To better understand the underlying mechanisms that result in the devastating motor deficits in CP patients, quantitative assessment of brain regions and connectivity with respect to the severity of injury is critical. It is generally known that motor control can be largely influenced by the integrity of the corticospinal tract (CST) connecting the primary motor cortex (pre-central gyrus) to the brainstem and the spinal cord. Thus, we further sought to establish CST volume as a sensitive and reliable biomarker that can reveal functional deficit in individual patients through comprehensive quantitative analyses in 29 consented human subjects (1-6 years of age, mean 2.67±1.36 years) diagnosed with hemiplegic, diplegic, or quadriplegic CP. The proportional reduction of bilateral CST volume with increased disease severity was observed for diplegic and quadriplegic patients (i.e. with bilateral motor deficits). Furthermore, CST volume with respect to disease severity in hemiplegic patients (i.e. with unilateral motor deficits) exhibited more complex patterns of asymmetry, revealing evidence for alternative neuromechanisms of motor control, such as compensation and neuronal plasticity by the unaffected hemisphere. In all cases, other diffusion metrics such as fractional anisotropy (FA) and mean diffusivity (MD) within the CST did not display significant correlation with disease severity. It is thus concluded that individual CST volume, accurately derived from DTI tractography, is one of the strongest non-invasive imaging biomarkers which could potentially help understand the differential causes for motor deficits and compensation in bilateral CP. It could also be further adopted to assess the underlying mechanism for functional recovery in individual patients undergoing cellular therapies. In addition to motor disability, numerous other neurodevelopmental differences are associated with CP and contribute greatly to the disease morbidity. Therefore, we further examined global changes in WM connectivity with respect to CP disease severity with a whole brain connectome analysis in a cohort of 18 pediatric patients with bilateral CP. As expected, reduction in overall and mutual connectivities throughout the motor regions, including the primary and supplemental motor areas, basal ganglia, and brainstem, was associated with the extent of primary motor disability. In addition, our results show diffuse and significant reduction in global inter-regional connectivity, measured as fiber volume, throughout the entire brain in relation to disease severity. This novel finding has not been previously reported in the CP literature and brings CP into line with multiple other pediatric neuropsychiatric disorders that are thought to involve network-level structural and/or functional disruptions early in development.

In recent years, the emergence of diffusion tensor imaging (DTI) has provided a unique means via water diffusional characteristics to investigate the white matter integrity in the human brain, and its impact on neuronal functions. However, since the characterization of white matter integrity using DTI often lacks tissue specificity, most research studies report changes in anisotropy that are not explicitly correlated with particular cellular origins. To improve the utility of DTI in translational neuroimaging, it is critical to develop DTI acquisition techniques that are quantitative and tissue specific.

There are, nevertheless, existing methods for tissue specificity. For example, myelin water images can be generated using multiple echo time (TE) or magnetization transfer techniques. These techniques can detect changes in the concentration of myelin associated markers, but not in their spatial organization. Most white matter pathologies however start with early microstructural changes in the myelin sheaths during which the tissue contents remain similar and are thus not differentiable on a conventional MR image. Thus, the ability to construct a diffusion tensor that is myelin specific can have an immediate impact on our better understanding myelin physiology and pathophysiology during brain development.

Unfortunately, the myelin water signal decays rapidly because of its short transverse relaxation time constant (T2 < 50 ms), especially in DTI experiments where the echo time (TE) can be as large as 100ms. Even in special cases where the TE is shorter, the lack of myelin selectivity in conventional DTI techniques makes assessment of myelin microstructure extremely challenging. Thus we need to develop a DTI methodology that will greatly shorten the TE and allow myelin selectivity.

To address these challenges we have developed innovative DTI acquisition methodologies that can specifically assess myelin microstructural changes in white matter. To preserve more signal from myelin water we used a stimulated echo DTI implementation. In our initial approach we integrated this sequence with a magnetization transfer preparation to achieve additional differentiating sensitization to myelin water and derive a myelin water weighted (MWW) diffusion tensor. Our results indicate that, compared to the conventional DTI, myelin water diffuses along the axis of the fiber, but has the same has larger fractional anisotropy (FA) due to significantly smaller radial diffusivity. The limited specificity of MT and high radio frequency power deposition of MT-DTI restrict its applicability in clinical studies.

To obtain increased myelin specificity we implemented a robust stimulated echo DTI sequence with segmented spiral-out readout trajectory for achieving minimal TE on clinical MRI scanners. To ensure high spatial accuracy throughout the DTI scan we further develop a methodology for inherently and dynamically correcting both motion induced phase errors and off-resonance effects due to magnetic field inhomogeneities (including eddy currents) in the reconstructed image. We the used this technique to conduct an unprecedented experiment in which we collected DTI images at multiple echo times (as short as 18ms) and characterized the dependence of anisotropy on the T2 components including myelin water. The results confirmed the anisotropy characteristics of myelin water found with our initial previous approach.

Building on this new information, we designed a MWW-DTI method based on the simultaneous acquisition of DTI images at two different echo times within clinical practical durations. It is hoped that this new DTI technique sensitized myelin microanatomy will find wide applications in monitoring healthy brain development in pediatric populations, as many developmental brain disorders start with microstructural changes in white matter.

Diffusion tensor imaging (DTI) has emerged as a unique method to characterize brain tissue microstructure non-invasively. DTI typically provides the ability to study white matter structure with a standard voxel resolution of 8μL over imaging field-of-views of the extent of the human brain. As such, it has long been recognized as a promising tool not only in clinical research for the diagnostic and monitoring of white matter diseases, but also for investigating the fundamental biological principles underlying the organization of long and short-range cortical networks. However, the complexity of brain structure within an MRI voxel makes it difficult to dissociate the tissue origins of the measured anisotropy. The tensor characterization is a composite result of proton pools in different tissue and cell structures with diverse diffusion properties. As such, partial volume effects introduce a strong bias which can lead to spurious measurements, especially in regions with a complex tissue structure such as interdigitating crossing fibers or in convoluted cortical folds near the grey/white matter interface.

This dissertation focuses on the design and development of acquisition and image reconstruction strategies to improve the spatial resolution of diffusion imaging. After a brief review of the theory of diffusion MRI and of the basic principles of streamline tractography in the human brain, the main challenges to increasing the spatial resolution are discussed. A comprehensive characterization of artifacts due to motion and field inhomogeneities is provided and novel corrective methods are proposed to enable the acquisition of diffusion weighted data with 2D mulitslice imaging techniques with full brain coverage, increased SNR and high spatial resolutions of 1.25×1.25×1.25 mm3 within an acceptable scan time. The method is extended to a multishot k_{_z}-encoded 3D multislab spiral DTI and evaluated in normal human volunteers.

To demonstrate the increased SNR and enhanced resolution capability of the proposed methods and more generally to assess the value of high-spatial resolution in diffusion imaging, a study of cortical depth-dependence of fractional anisotropy was performed at an unprecedented in-vivo inplane resolution of 0.390×0.390μm2 and an investigation of the trade-offs between spatial resolution and cortical specificity was conducted within the connectome framework.

Magnetic Resonance Imaging (MRI) image quality is strongly dependent on the homogeneity of the main magnetic field, B0. Inhomogeneities in this magnetic field lead to image artifacts such as: blurring, signal loss, and gross distortions of the imaged anatomy of the brain, degrading the images effectiveness to provide diagnostic information. A new radio-frequency (RF) head coil design with integrated direct-current (DC) shim coils to provide localized B0 shimming of the brain and simultaneously provide parallel excitation of reception is presented in this thesis. This design optimizes both the RF and DC shim coils proximity to the subject thereby maximizing both the signal-to-noise ratio and the shimming efficiency. This coil architecture is termed iPRES (integrated parallel receive, excitation and shimming).

An existing 32 channel receive-only head coil array was modified into an iPRES coil architecture. The coils of the array were modified using RF components to enable the simultaneous flow of both RF and DC currents on the same structure. The RF and DC currents provide concurrent signal reception and localized B0 shimming to the brain, respectively. In this thesis, the techniques, measurements and quality-metrics used to facilitate the iPRES coil array modification will be discussed.

The localized B0 shimming performance is evaluated in the frontal region of the brain which suffers from large susceptibility artifacts at the air/tissue boundary of the brain and the sinus. Axial B0 maps and echo-planar images (EPI) are acquired in vivo with optimized DC shim currents demonstrating a reduction in B0 inhomogeneities in the frontal lobe resulting in improved image EPI image quality. The coils quality factor and signal-to-noise ratio did not suffer as a result of the coil modification. The shimming performance and RF quality metrics are compared to standard whole-body spherical harmonic shimming and are discussed at length in the following chapters.

Finally, initial phantom results from the next-generation iPRES coil array will be presented. This architecture again uses an existing RF head coil array to simultaneously drive RF currents for reception and DC currents for local shimming. However, the shimming is further enhanced by providing additional RF-isolated shim coils which increases the shimming degrees of freedom. This design is useful when fast-changing, asymmetric B0 inhomogeneities are present in the imaged anatomy.