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

我之前在实验室所做的工作，使用连续两次NSERC发现基金的资金，专注于使用磁共振成像(MRI)评估微循环。我之前发表的工作表明，动态对比增强磁共振成像(DceMRI)的药代动力学模型过于简单：在兔体内，磁共振造影剂内化于内皮细胞内，血管外和血管内间隙之间假设的对比平衡在组织之间有所不同，在时间上比之前假设的更复杂。这促使我研究了基于非造影剂的方法，使用MRI血氧水平依赖(BOLD)成像，这是脑功能MRI(FMRI)的基础。粗体图像的对比度由于氧合和脱氧血红蛋白比例的调节而不同。如果组织代谢能够以某种方式改变，无论是通过正常的生理机制，还是通过药物扰动，它是一个候选的评估使用BOLD成像。拟议项目的首要目的是继续使用非侵入性磁共振成像方法研究微血管。然而，目前的方向是关注人体成像，在某种形式的生理扰动之前和之后，使用信号处理方法(例如，傅立叶和小波方法)、数据驱动方法(例如，原理和独立分量分析，即PCA和ICA)，以及时间分维(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、各种形式的癌症(乳腺癌、直肠癌、前列腺癌)和阿尔茨海默病中的可行性。拟议的项目将涉及对健康人体肾脏、肝脏和骨骼肌的一些正常生理操作的评估。此外，对BOLD信号改变的生理机制(S)的研究将通过使用磁共振技术动脉自旋标记(ASL)的血流量测量来提供(S)。

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).