The nature of the blood oxygen level dependent signal in functional magnetic resonance imaging: Influences and intrinsic functional information

The blood oxygen level dependent (BOLD) contrast is the most utilized method in functional magnetic resonance imaging (fMRI). While the technique is widely used, the factors affecting the signal are incompletely understood. The source and impact of the physiological noise fMRI, the effects of subject motion and the methods to correct it, and the biological information of the intrinsic BOLD signal have not been elucidated. In this dissertation, the influence of physiological noise in BOLD fMRI was assessed with spin-echo and gradient-echo imaging sequences, apparent diffusion coefficient maps, and principal-component analysis. The choice of the reference image in image realignment was analyzed to assess the effectiveness of the image realignment algorithm in correcting subject motion. The BOLD signal time course in response to stimuli activating the magnocellular and parvocellular pathways of the visual system was assessed for the possibility of differentiating the responses of the two pathways in a common region of the brain. It was discovered that physiological noise in fMRI was dependent on imaging sequence, and that the magnitude of the noise was correlated with vessel size. Functional activation sensitivity was optimized by reference image selection for the realignment algorithm in cases where subject motion was large. Lastly, the BOLD signal hemodynamic response function was found to be intrinsically useful in differentiating regional brain response to different stimuli as well as provide information regarding the metabolic requirements of different pathways within a brain region. These new understandings of the nature of the BOLD signal in fMRI allow for the selection of the optimal imaging sequence and realignment procedure for future fMRI experiments, and the analysis of the BOLD signal time course opens new possibilities for experimental design to discern brain function