Stroke is the most prevalent neurological disease facing our nation today. Treatments, however, are few and insufficient at reducing the impact of this neurological condition. Experimental animal models are important to improving our understanding of stroke, and for developing new therapies to counter the pathology of stroke. Magnetic Resonance Imaging is the leading tool for the non-invasive investigation of stroke pathophysiology. While most MRI work in animals is conducted under anesthesia, anesthesia has profound effects on cerebral circulation and metabolism, and can affect stroke outcome. Several novel methods were combined with MRI compatible physiologic monitoring equipment to conduct stroke studies in conscious animals. Stress was studied as a factor in these studies and conditioning was utilized to reduce the impact of stress on the animals' physiology. Models of both occlusive and hemorrhagic strokes were successfully implemented within the MRI apparatus. Lastly, experiments using a macrosphere model showed evidence of a pathophysiologic difference between awake and anesthetized animals that undergo stroke.

Magnetic Resonance Imaging (MRI) is a widely used soft tissue imaging technique that has gained considerable success because of its sensitivity to several tissue parameters. However, commercially available whole-body imaging systems with large encircling radio frequency (RF) and gradient coils are less efficient when the goal is to obtain detailed, high-resolution images with high specificity and sensitivity from localized regions of the body such as the female breast. This research addresses these problems by proposing a new design in RF coil development for breast cancer screening in a conventional 1.5T MRI system. The new design provides two resonant receiving modes that operate in a quadrature configuration, and a region of interest (ROI) that closely conforms to the shape of the female breast. We adopted an optimum design strategy that combined the analytic Biot-Savart intergral equation with the Method of Moment formulation in the development of electromagnetic models and simulation tools. These models were used to analyze the magnetic field distribution and the spatial field coverage, as well as the magnetic field uniformity in the ROI. Results from our analysis were employed in the construction of a highly scalable prototype. The validation of our design strategy is confirmed by comparisons with the commercial Ansoft HFSS v8.5 finite element package.

"Manganese (Mn2+) has recently gained acceptance as a magnetic resonance imaging (MRI) contrast agent useful for generating contrast in the functioning brain. The paramagnetic properties of Mn2+, combined with the cell's affinity for Mn2+ via voltage-gated calcium channels, makes Mn2+ sensitive to cellular activity in the brain. Compared with indirect measures of brain function, such as blood oxygenation level dependent (BOLD) functional MRI, manganese-enhanced MRI (MEMRI) can provide a direct means to visualize brain activity. MEMRI of the brain typically involves osmotic opening of the blood-brain barrier (BBB) to deliver Mn2+ into the interstitial space prior to initiation of a specific neuronal stimulus. This method assumes that the BBB-disruption process itself does not induce any apparent stimuli or cause tissue damage that might obscure any subsequent experimental observations. However, this assumption is often incorrect and can lead to misleading results for particular types of MRI applications. One aspect of these studies focused on characterizing the confounding effects of the BBB-opening process on MRI measurements typically employed to characterize functional activity or disease in the brain (Chapters 4 and 5). The apparent diffusion coefficient (ADC) of tissue water was found to decrease (relative to the undisrupted contralateral hemisphere) following BBB opening, obscuring similar ADC changes associated with ischemic brain tissue following stroke. Brain regions exhibiting reduced ADC values following osmotic BBB disruption also experienced permanent tissue damage, as validated by histological measures in the same vicinity of the brain. Non-specific MEMRI-signal enhancement was also observed under similar conditions and was found to be correlated to regions with BBB opening as verified by Evans Blue histological staining. In this case, MEMRI may prove to be a useful alternative for monitoring BBB-permeability changes in vivo. MEMRI was also investigated as a method for visualizing regions of BBB damage following ischemic brain injury (Chapter 6). BBB disruption following stroke has been investigated using gadolinium-based MRI contrast agents (e.g., Gd-DTPA). However, as an extracellular MRI contrast agent, Gd-DTPA is not expected to provide information regarding cell viability or function as part of MR image contrast enhancement. By comparison, brain regions with ischemia-induced BBB damage, and blood-flow levels sufficient to deliver Mn2+, show MEMRI-signal enhancement that correlates to regions with tissue damage as verified by histological staining. This approach should allow us to better understand the factors responsible for ischemia-induced BBB damage. Furthermore, MEMRI should be a useful tool for monitoring therapeutic interventions that might mitigate the damage associated with BBB disruption following stroke. "

Image segmentation is a process to identify regions of interest from digital images. Image segmentation plays an important role in medical image processing which enables a variety of clinical applications. It is also a tool to facilitate the detection of abnormalities such as cancerous lesions in the brain. Although numerous efforts in recent years have advanced this technique, no single approach solves the problem of segmentation for the large variety of image modalities existing today. Consequently, brain MRI segmentation remains a challenging task. The purpose of this thesis is to demonstrate brain MRI segmentation for delineation of tumors, ventricles and other anatomical structures using Insight Segmentation and Registration Toolkit (ITK) routines as the foundation. ITK is an open-source software system to support the Visible Human Project. Visible Human Project is the creation of complete, anatomically detailed, three-dimensional representations of the normal male and female human bodies. Currently under active development, ITK employs leading-edge segmentation and registration algorithms in two, three, and more dimensions. A goal of this thesis is to implement those algorithms to facilitate brain segmentation for a brain cancer research scientist.