Advanced Analysis of Functional Magnetic Resonance Imaging (MRI) Data for Evaluation of Tissue Physiology

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Previous work done in my lab, using funding from 2 consecutive NSERC Discovery grants, has focused on the evaluation of microcirculation using magnetic resonance imaging (MRI). My previous published work has shown how pharmacokinetic models of dynamic contrast enhanced MRI (dceMRI) are overly simplistic: In rabbits MRI contrast agents become internalized inside endothelial cells, and supposed 'contrast equilibrium' between the extra and intravascular space varies between tissues and is more temporally complex than previously assumed. This led me to investigate non-contrast agent based approaches using MRI blood-oxygen level dependent (BOLD) imaging, the basis behind brain functional MRI (fMRI). BOLD image contrast varies due to modulation in the ratio of oxy- to deoxyhaemoglobin. If tissue metabolism can somehow be changed, be it through normal physiological mechanisms, or through pharmacological perturbations, it is a candidate for assessment using BOLD imaging. The overlying purpose of the proposed project is to continue study on microvasculature using non-invasive MR imaging methods. However, the current direction is now to focus on human imaging, before and after some form of physiological perturbation, with signal processing approaches (e.g. Fourier and Wavelet methods), data driven methods (e.g. principle and independent component analysis, i.e. PCA and ICA), and temporal fractal dimension (FD) analysis. In my lab we have successfully assessed the feasibility of this method in skeletal muscle, liver, kidney, various forms of cancer (breast, rectum, prostate) and in Alzheimer's disease. The proposed project will involve evaluation of a number of normal physiological manipulations in healthy human kidney, liver, and skeletal muscle. Furthermore, investigation of physiological mechanism(s) underlying the BOLD signal change(s) will be provided through measurement of blood flow using the MRI technique arterial spin labeling (ASL).