Magnetic Resonance Imaging (MRI) is an essential instrument in clinical diag- nosis; however, it is burdened by a slow data acquisition process due to physical limitations. Compressive Sensing (CS) is a recently developed mathematical framework that o ers signi cant bene ts in MRI image speed by reducing the amount of acquired data without degrading the image quality. The process of image reconstruction involves solving a nonlinear constrained optimization problem. The reduction of reconstruction time in MRI is of signi cant bene t. We reformulate sparse MRI reconstruction as a Second Order Cone Program (SOCP).We also explore two alternative techniques to solving the SOCP prob- lem directly: NESTA and speci cally designed SOCP-LB. / UOIT

Diffusion imaging is a relatively recent branch of magnetic resonance imaging that produces images of human physiology through diffusion of water molecules within the body. One difficulty in calculating diffusion coefficients, particularly in the brain, is the multitude of natural barriers to water diffusion, such as cell membranes, myelin sheaths, and fiber tracts. These barriers mean that water diffusion is not a homogeneous random process. Due to the complexity of modeling these structures, a simplifying assumption made in some methods of data analysis is that there are no barriers to water diffusion. We develop tools to simulate the diffusion of water in an inhomogeneous medium, which may then be used to test the accuracy of this assumption. The inherent difficulty (and computational cost) of including barriers (e.g., cell membranes) can be lessened by employing the immersed boundary (IB) method to represent these structures without the need for complicated computational grids. The contribution of this thesis is the implementation and validation of an IB method that allows for diffusion across semi-permeable membranes. The method is tested for a square interface aligned with the computational grid by comparing it to a second numerical scheme that uses standard finite differences. We also calculate the rate of convergence for the IB method to assess the numerical accuracy. To demonstrate the flexibility of the IB method to simulate diffusion with any interface shape, we also present simulations for irregular interfaces. / UOIT

Research suggests that brain growth follows an abnormal trajectory in children with autism spectrum disorders (ASD). A better understanding of when and how patterns of brain development diverge from that seen in typically developing children could yield insight into the etiology of the disorder, and resulting symptomatology. To investigate this hypothesis, three studies examined the relation between structural and functional brain measures and age in a group of children with an ASD, aged 6 to 14 years. Age by group interactions were found in all three studies, providing further evidence that brain development may follow an atypical trajectory in ASD. Study 1: Differences in the relation between structural indices and age were found in grey matter volume, surface area and thickness, as well as in cortical thickness of specific regions in the left inferior frontal gyrus (BA 44) and left precuneus. These measures of grey matter structure generally decreased with age in the ASD children, compared to little or no change with age in the typically developing children. Study 2: Differences in the relation between age and measures of longitudinal, radial and mean diffusivity were found in frontal, long distant, interhemispheric and posterior white matter tracts; diffusivity decreased with age in the typically developing group, but showed little or no change in the ASD group. Study 3: Differences in the relation between BOLD activation on a set-shifting task and age were found in brain regions important for cognitive flexibility, such as areas of prefrontal, right insula and parietal cortex. These effects were mainly due to decreasing activation with age for the ASD group, but increasing or no age-related change in the TD group. The findings of these three studies provide converging evidence in support of an hypothesis of dysregulated brain development in this population, which could have significant, compounding effects on the development of neural connectivity, and contribute to atypical cognitive development in children with ASD.

Rationale: Ng et al. (2008) demonstrated that sub-acute hippocampal atrophy occurred between 4.5 and 24 months following moderate-to-severe traumatic brain injury (TBI); it remains to be determined if atrophy occurred before 24 months. Objectives: (1) to determine if sub-acute hippocampal atrophy occurs by the first year of injury; (2) to determine associated clinical and demographic variables. Methods: Ten moderate-to-severe TBI patients underwent MRI at 5 and 12 months post-injury. Glasgow Coma Scale (GCS) and demographic variables were correlated with change. Results: Significant hippocampal volume decreases were observed for right (P< 0.002, Cohen’s d= 0.34) and left (P< 0.036, Cohen’s d= 0.22) sides. GCS was significantly correlated with right (r= -0.663, P< 0.037), but not left percent hippocampal volume change (r= -0.327, P< 0.356). No significant correlations were observed for demographic variables. Conclusion: Sub-acute hippocampal atrophy occurs between 5 and 12 months post-injury and is associated with injury severity.

Children born prematurely exhibit a broad range of neuroanatomical abnormalities. The aim of this study was to investigate the long-term effects of very preterm birth on brain volume (cortical and subcortical), cortical thickness and surface area. The participants were 25 children born very preterm (<32 weeks gestational age) without significant post-natal medical sequelae and 32 term-born children between 7 and 10 years of age. Neuroanatomical measures were derived from an automated pipeline. The results suggest a pattern of decreased brain volume, surface area and cortical thickness for children born preterm and the relation between subcortical gray volume and total brain volume differed between groups. The cortex was significantly thinner for children born preterm than term-born children in focal regions of the parietal and temporal lobes. Therefore, even without significant postnatal medical sequelae, very preterm children still exhibit structural differences that persist into middle childhood.

Rationale: Ng et al. (2008) demonstrated that sub-acute hippocampal atrophy occurred between 4.5 and 24 months following moderate-to-severe traumatic brain injury (TBI); it remains to be determined if atrophy occurred before 24 months. Objectives: (1) to determine if sub-acute hippocampal atrophy occurs by the first year of injury; (2) to determine associated clinical and demographic variables. Methods: Ten moderate-to-severe TBI patients underwent MRI at 5 and 12 months post-injury. Glasgow Coma Scale (GCS) and demographic variables were correlated with change. Results: Significant hippocampal volume decreases were observed for right (P< 0.002, Cohen’s d= 0.34) and left (P< 0.036, Cohen’s d= 0.22) sides. GCS was significantly correlated with right (r= -0.663, P< 0.037), but not left percent hippocampal volume change (r= -0.327, P< 0.356). No significant correlations were observed for demographic variables. Conclusion: Sub-acute hippocampal atrophy occurs between 5 and 12 months post-injury and is associated with injury severity.

Children born prematurely exhibit a broad range of neuroanatomical abnormalities. The aim of this study was to investigate the long-term effects of very preterm birth on brain volume (cortical and subcortical), cortical thickness and surface area. The participants were 25 children born very preterm (<32 weeks gestational age) without significant post-natal medical sequelae and 32 term-born children between 7 and 10 years of age. Neuroanatomical measures were derived from an automated pipeline. The results suggest a pattern of decreased brain volume, surface area and cortical thickness for children born preterm and the relation between subcortical gray volume and total brain volume differed between groups. The cortex was significantly thinner for children born preterm than term-born children in focal regions of the parietal and temporal lobes. Therefore, even without significant postnatal medical sequelae, very preterm children still exhibit structural differences that persist into middle childhood.

The use of parallel imaging techniques for image acceleration is now common in clinical magnetic resonance imaging (MRI). There has been limited work, however, in translating the parallel imaging techniques to routine animal imaging. This dissertation describes foundational level work to enable parallel imaging of mice on a 4.7 Tesla/40 cm bore research scanner. Reducing the size of the hardware setup associated with typical parallel imaging was an integral part of achieving the work, as animal scanners are typically small-bore systems. To that end, an array element design is described that inherently decouples from a homogenous transmit field, potentially allowing for elimination of typically necessary active detuning switches. The unbalanced feed of this "dual-plane pair" element also eliminates the need for baluns in this case. The use of the element design in a 10-channel adjustable array coil for mouse imaging is presented, styled as a human cardiac top-bottom half-rack design. The design and construction of the homogenous transmit birdcage coil used is also described, one of the necessary components to eliminating the active detuning networks on the array elements. In addition, the design of a compact, modular multi-channel isolation preamplifier board is described, removing the preamplifiers from the elements and saving space in the bore. Several additions/improvements to existing laboratory infrastructure needed for parallel imaging of live mice are also described, including readying an animal preparation area and developing the ability to maintain isoflurane anesthesia delivery during scanning. In addition, the ability to trigger the MRI scanner to the ECG and respiratory signals from the mouse in order to achieve images free from physiological motion artifacts is described. The imaging results from the compact 10-channel mouse array coils are presented, and the challenges associated with the work are described, including difficulty achieving sample-loss dominance and signal-to-noise ratio (SNR) limitations. In conclusion, in vivo imaging of mice with cardiac and respiratory gating has been demonstrated. Compact array coils tailored for mice have been studied and potential future work and design improvements for our lab in this area are discussed.

Research suggests that brain growth follows an abnormal trajectory in children with autism spectrum disorders (ASD). A better understanding of when and how patterns of brain development diverge from that seen in typically developing children could yield insight into the etiology of the disorder, and resulting symptomatology. To investigate this hypothesis, three studies examined the relation between structural and functional brain measures and age in a group of children with an ASD, aged 6 to 14 years. Age by group interactions were found in all three studies, providing further evidence that brain development may follow an atypical trajectory in ASD. Study 1: Differences in the relation between structural indices and age were found in grey matter volume, surface area and thickness, as well as in cortical thickness of specific regions in the left inferior frontal gyrus (BA 44) and left precuneus. These measures of grey matter structure generally decreased with age in the ASD children, compared to little or no change with age in the typically developing children. Study 2: Differences in the relation between age and measures of longitudinal, radial and mean diffusivity were found in frontal, long distant, interhemispheric and posterior white matter tracts; diffusivity decreased with age in the typically developing group, but showed little or no change in the ASD group. Study 3: Differences in the relation between BOLD activation on a set-shifting task and age were found in brain regions important for cognitive flexibility, such as areas of prefrontal, right insula and parietal cortex. These effects were mainly due to decreasing activation with age for the ASD group, but increasing or no age-related change in the TD group. The findings of these three studies provide converging evidence in support of an hypothesis of dysregulated brain development in this population, which could have significant, compounding effects on the development of neural connectivity, and contribute to atypical cognitive development in children with ASD.

In these days, nanomaterials are applied in a variety of biomedical applications including magnetic resonance imaging (MRI), cell imaging, drug delivery, and cell separation. Most MRI contrast agents affect the longitudinal relaxation time (T1) and transverse relaxation time (T2) of water protons in the tissue and result in increased positive or negative contrast. Here, we report the optimization of r1 (1/T1) or r2 (1/T2) relaxivity dynamics with diameter controlled gadolinium oxide nanocrystals (2~22 nm) and iron based magnetic nanocrystals (4 ~33 nm). The r1 and r2 MR relaxivity values of hydrated nanocrystals were optimized and examined depending on their core diameter, surface coating, and compositions; the high r1 value of gadolinium oxide was 40-60 S-1mM-1, which is 10-15 fold higher than that of commercial Gd (III) chelates (4.3~4.6 S-1mM-1). Moreover, in vitro toxicological studies revealed that polymer coated nanocrystals suspensions had no significant effect on human dermal fibroblast (HDF) cells even at high concentration. Towards multimodal imaging or multifunctional ability, we developed the iron oxide/QDs complexes, which consist of cores of iron oxide that act as nucleation sites for fluorescent QDs. The choice of variable QDs helped to visualize and remove large iron oxide materials in a magnetic separation. Additionally, diluted materials concentrated on the magnet could be fluorescently detected even at very low concentration. The designed MRI or multifunctional nanomaterials will give great and powerful uses in biomedical applications.