The goal of this thesis was to produce an animal model that develops atherosclerotic plaque featuring plaque neovascularization leading to intraplaque hemorrhage and is suitable for noninvasive imaging studies. Several strategies were tested for their effectiveness in producing such plaques in the rabbit aorta, including: a high cholesterol diet, vascular endothelial growth factor injections, therapeutic contrast ultrasound, and balloon catheter injury. It was found that a combination of the high cholesterol diet and balloon injury was able to achieve plaque neovascularization in a manner dependent on circulating plasma cholesterol levels. In addition, a contrast-enhanced magnetic resonance imaging technique implemented in the animal model was able to detect plaque neovascularization and monitor its change over time in a single group of animals. In conclusion, an animal model was created where plaque neovascularization occurs in a predictable fashion and can be studied with non-invasive magnetic resonance imaging.

There is mounting evidence to support combined therapy with radiation (RT) and antiangiogenic agents (AA) for the treatment of brain tumors. However, the therapeutic benefit of this combined treatment hinges on the specific dose, schedule, and duration of each treatment. Early biomarkers that reflect tumor physiological responses provide key information that could guide these aspects of treatment. Pre-clinical tumor models are invaluable tools for identifying potential biomarkers, their optimal timing for measurement and their ability to guide therapy in clinical translation. This thesis demonstrates the feasibility and potential of serial MRI to guide the design, delivery and measure of early response to combined AA and RT in a murine intracranial glioma model. We identified promising biomarker changes reflecting early treatment response that may ultimately facilitate individualized spatio-temporal delivery of radiotherapy (RT) and anti-angiogenic agents (AA) for brain tumors.

This thesis presents a high-resolution volumetric technique to measure the longitudinal relaxation time T1 in the vessel wall using MRI. The method of Variable Flip Angles (VFA) was applied using a new strategy for flip angle selection that allows measurement of T1 with high accuracy (< 10% mean error) and precision (T1-to-noise ratio > 10) over the wide range of anticipated values (300-3000ms) in the vessel wall. This strategy was validated in simulation, phantom and volunteer spinal cord experiments. Initial validation of vessel wall T1 measurements was performed in ex-vivo thoracic aorta samples from cholesterol-fed rabbits. For in-vivo vessel wall T1 mapping, the technique was augmented with spatial saturation bands for flow suppression and applied to the carotid arteries of three volunteers. Preliminary results from volunteers suggest that this approach may be useful in characterizing T1 changes associated with high-risk atherosclerotic disease.

BACKGROUND: MRI is increasingly being used for rectal cancer staging. The purpose of this study was to summarize published evidence to determine the accuracy of MRI for T-category, lymph node (LN) metastases, and circumferential resection margin (CRM) involvement in rectal cancer. METHODS: Sensitivity, specificity, and diagnostic odds ratios (DOR) were estimated using hierarchical summary receiver operating characteristics modeling and bivariate random effects modeling. RESULTS: MRI was more specific for CRM (94%, 95%CI 88-97) than for T-category (75%, 95%CI 68-80) and LN’s (71%, 95%CI 59-81) but was more sensitive for T-category (87%, 95%CI 81-92) than for CRM (77%, 95%CI 57-90) and LN’s (77%, 95%CI 69-84). DOR was higher for CRM (56.1, 95%CI 15.3-205.8) than for LN’s (8.3, 95%CI 4.6-14.7) and T-category (20.4, 95%CI 11.1-37.3). CONCLUSIONS: MRI has good accuracy for both CRM and T-category and should be considered for preoperative rectal cancer staging. In contrast, LN assessment is poor on MRI.

Cerebral small vessel disease (SVD) is highly prevalent in older adults and is a predictor of stroke, dementia, and death. SVD is also associated with cognitive dysfunction, gait problems, and urinary incontinence. SVD is diagnosed based on white matter hyperintensities on T2 weighted scans. This thesis investigates the cardiac frequency component of resting state functional magnetic resonance imaging data in young healthy adults, older healthy adults, and older adults with pronounced SVD. A cardiac pulsatility metric is defined, and a tissue type contrast is observed between white matter, grey matter, and cerebrospinal fluid. Aging and disease effects are observed on cardiac pulsatility in white matter. The increased pulsatility may reflect the pathology of venous collagenosis and draining vein stenosis. Developing a better understanding of the etiology of SVD is an important step towards treating the disease.

The goal of this thesis was to produce an animal model that develops atherosclerotic plaque featuring plaque neovascularization leading to intraplaque hemorrhage and is suitable for noninvasive imaging studies. Several strategies were tested for their effectiveness in producing such plaques in the rabbit aorta, including: a high cholesterol diet, vascular endothelial growth factor injections, therapeutic contrast ultrasound, and balloon catheter injury. It was found that a combination of the high cholesterol diet and balloon injury was able to achieve plaque neovascularization in a manner dependent on circulating plasma cholesterol levels. In addition, a contrast-enhanced magnetic resonance imaging technique implemented in the animal model was able to detect plaque neovascularization and monitor its change over time in a single group of animals. In conclusion, an animal model was created where plaque neovascularization occurs in a predictable fashion and can be studied with non-invasive magnetic resonance imaging.

There is mounting evidence to support combined therapy with radiation (RT) and antiangiogenic agents (AA) for the treatment of brain tumors. However, the therapeutic benefit of this combined treatment hinges on the specific dose, schedule, and duration of each treatment. Early biomarkers that reflect tumor physiological responses provide key information that could guide these aspects of treatment. Pre-clinical tumor models are invaluable tools for identifying potential biomarkers, their optimal timing for measurement and their ability to guide therapy in clinical translation. This thesis demonstrates the feasibility and potential of serial MRI to guide the design, delivery and measure of early response to combined AA and RT in a murine intracranial glioma model. We identified promising biomarker changes reflecting early treatment response that may ultimately facilitate individualized spatio-temporal delivery of radiotherapy (RT) and anti-angiogenic agents (AA) for brain tumors.

This thesis presents a high-resolution volumetric technique to measure the longitudinal relaxation time T1 in the vessel wall using MRI. The method of Variable Flip Angles (VFA) was applied using a new strategy for flip angle selection that allows measurement of T1 with high accuracy (< 10% mean error) and precision (T1-to-noise ratio > 10) over the wide range of anticipated values (300-3000ms) in the vessel wall. This strategy was validated in simulation, phantom and volunteer spinal cord experiments. Initial validation of vessel wall T1 measurements was performed in ex-vivo thoracic aorta samples from cholesterol-fed rabbits. For in-vivo vessel wall T1 mapping, the technique was augmented with spatial saturation bands for flow suppression and applied to the carotid arteries of three volunteers. Preliminary results from volunteers suggest that this approach may be useful in characterizing T1 changes associated with high-risk atherosclerotic disease.

BACKGROUND: MRI is increasingly being used for rectal cancer staging. The purpose of this study was to summarize published evidence to determine the accuracy of MRI for T-category, lymph node (LN) metastases, and circumferential resection margin (CRM) involvement in rectal cancer. METHODS: Sensitivity, specificity, and diagnostic odds ratios (DOR) were estimated using hierarchical summary receiver operating characteristics modeling and bivariate random effects modeling. RESULTS: MRI was more specific for CRM (94%, 95%CI 88-97) than for T-category (75%, 95%CI 68-80) and LN’s (71%, 95%CI 59-81) but was more sensitive for T-category (87%, 95%CI 81-92) than for CRM (77%, 95%CI 57-90) and LN’s (77%, 95%CI 69-84). DOR was higher for CRM (56.1, 95%CI 15.3-205.8) than for LN’s (8.3, 95%CI 4.6-14.7) and T-category (20.4, 95%CI 11.1-37.3). CONCLUSIONS: MRI has good accuracy for both CRM and T-category and should be considered for preoperative rectal cancer staging. In contrast, LN assessment is poor on MRI.

Cerebral small vessel disease (SVD) is highly prevalent in older adults and is a predictor of stroke, dementia, and death. SVD is also associated with cognitive dysfunction, gait problems, and urinary incontinence. SVD is diagnosed based on white matter hyperintensities on T2 weighted scans. This thesis investigates the cardiac frequency component of resting state functional magnetic resonance imaging data in young healthy adults, older healthy adults, and older adults with pronounced SVD. A cardiac pulsatility metric is defined, and a tissue type contrast is observed between white matter, grey matter, and cerebrospinal fluid. Aging and disease effects are observed on cardiac pulsatility in white matter. The increased pulsatility may reflect the pathology of venous collagenosis and draining vein stenosis. Developing a better understanding of the etiology of SVD is an important step towards treating the disease.