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

以前在我的实验室完成的工作，使用连续2个NSERC发现赠款的资金，主要集中在使用磁共振成像（MRI）评估微循环。我以前发表的工作表明，动态对比增强MRI（dceMRI）的药代动力学模型是如何过于简单化的：在兔子中，MRI造影剂在内皮细胞内内化，并且在组织之间的额外和血管内空间之间的所谓“对比度平衡”各不相同，并且比以前假设的时间复杂。这促使我使用MRI血氧水平依赖（BOLD）成像研究基于非造影剂的方法，这是脑功能MRI（fMRI）的基础。BOLD图像对比度因氧合血红蛋白与脱氧血红蛋白比例的调制而变化。如果组织代谢可以以某种方式改变，无论是通过正常的生理机制，还是通过药理学扰动，它都是使用BOLD成像进行评估的候选者。拟议项目的主要目的是使用非侵入性MR成像方法继续研究微血管。然而，目前的方向是专注于人类成像，之前和之后的一些形式的生理扰动，与信号处理方法（例如傅立叶和小波方法），数据驱动的方法（例如原理和独立分量分析，即PCA和伊卡），和时间分形维数（FD）分析。在我的实验室里，我们已经成功地评估了这种方法在骨骼肌、肝脏、肾脏、各种癌症（乳腺癌、直肠癌、前列腺癌）和阿尔茨海默病中的可行性。拟议的项目将涉及健康人体肾脏，肝脏和骨骼肌的一些正常生理操作的评价。此外，将通过使用MRI技术动脉自旋标记（ASL）测量血流来研究BOLD信号变化背后的生理机制。

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).