Biophysical Basis of Muscle Functional MRI

描述(由申请人提供)： 确定用于不同功能活动的肌肉，并评估对这种活动的代谢和血流动力学反应，是神经肌肉功能基础和临床研究的重要组成部分。最近一种解决这些问题的方法是“肌肉功能磁共振成像”(MfMRI)，在这种方法中，活动肌肉在某些MR图像中的信号强度(SI)比非活动肌肉更高。这些SI变化是由于肌肉水的横向松弛时间常数(T2)的增加和血液氧合水平依赖(BOLD)的对比。导致这些现象的各种生理事件结合在一起形成了一个复杂的SI时间过程，其特征是：1)最初的上升，持续到最初的一到两幅图像；2)早期的下降，从最初的上升的结束延伸到第一个大约60 S；最后，长潜伏期的增加，大约2分钟后达到平台期。我们认为，这一时间过程是代谢和血流动力学事件的复杂叠加，这些事件通过化学和扩散交换以及血液磁化率的变化等机制影响横向松弛。因此，拟议实验的总体目标是定量描述mfMRI SI时间过程的生物物理基础，目的是为了澄清MR成像与感兴趣的生理参数之间的关系，从而加速mfMRI进入实际应用的发展。我们将：1)研究生理变量对细胞内游离水和细胞内蛋白质之间质子交换的影响；2)在活体运动过程中检测细胞膜通透性的变化；3)量化BOLD效应对mtMRI SI变化的贡献；4)建立一个全面的模型，定量描述运动过程中生理和生化变量如何变化确定mfMRI SI。这些实验的结果将是对活体骨骼肌横向松弛的生理和生物物理影响的全面和定量的描述，以及如何改变实验变量(如图像类型和时间)来提高mfMRI对特定生理现象的敏感性。这一知识的未来应用可能包括研究健康和疾病中肌肉对运动的代谢和血流动力学反应，开发功能相关的多关节动作的改进生物力学模型，以及评估脊髓损伤患者的功能性电刺激方案。

DESCRIPTION (provided by applicant): Identifying the muscles used in different functional activities and evaluating the metabolic and hemodynamic responses to this activity are essential components of both basic and clinical studies of neuromuscular function. A recent approach to these questions is "muscle functional Magnetic Resonance Imaging" (mfMRI), in which active muscles appear with higher signal intensity (SI) in certain MR images than do inactive muscles. These SI changes result from an increase in the transverse relaxation time constant (T2) of muscle water and a Blood Oxygenation Level Dependent (BOLD) contrast. The physiological events that contribute to these phenomena combine to produce a complex SI time course that is characterized by 1) an initial rise, lasting through the first one or two images; 2) an early dip, extending from the end of the initial rise through the first approximately 60 s; and finally 3) a long-latency increase, which reaches a plateau after about 2 min. We propose that this time course is produced by a complex superposition of metabolic and hemodynamic events, which affect transverse relaxation through mechanisms such as chemical and diffusive exchange and variations in blood magnetic susceptibility. The overall goal of the proposed experiments is therefore to describe quantitatively the biophysical basis of the mfMRI SI time course, with the aim that such an understanding would clarify the relationships between MR imaging and physiological parameters of interest and thereby accelerate the development of mfMRI into practical applications. We will: 1) examine the effects of physiological variables on proton exchange between free intracellular water and intracellular proteins; 2) examine membrane permeability alterations during exercise in vivo; 3) quantify the BOLD effect's contribution to mtMRI SI changes; and 4) develop a comprehensive model that describes quantitatively how physiological and biochemical variables altered during exercise determine mfMRI SI. The outcome of these experiments will be a comprehensive and quantitative description of the physiological and biophysical influences on transverse relaxation in skeletal muscle in vivo, and how experimental variables (such as image type and timing) can be altered to enhance the sensitivity of mfMRI to particular physiological phenomena. Future applications of this knowledge may include studies of metabolic and hemodynamic responses of muscles to exercise in health and disease, the development of improved biomechanical models of functionally relevant multi-joint actions, and the evaluation of functional electrical stimulation protocols for patients with spinal cord injury.