Biophysical Basis of Muscle Functional MRI

描述（由申请人提供）： 识别用于不同功能活动的肌肉并评估对该活动的代谢和血液动力学反应是神经肌肉功能的基础和临床研究的重要组成部分。最近的一种解决这些问题的方法是“肌肉功能性磁共振成像”（mfMRI），其中活动肌肉在某些MR图像中显示出比不活动肌肉更高的信号强度（SI）。这些SI变化是由肌肉水的横向弛豫时间常数（T2）和血氧水平依赖性（BOLD）对比度的增加引起的。促成这些现象的生理事件联合收割机产生复杂的SI时间过程，其特征在于：1）初始上升，持续通过最初的一个或两个图像; 2）早期下降，从初始上升的末端延伸通过最初的大约60秒;最后3）长潜伏期增加，约2分钟后达到平台期。我们认为，这一时间过程是由代谢和血液动力学事件的复杂叠加产生的，其通过诸如化学和扩散交换以及血液磁化率的变化的机制来影响横向弛豫。因此，拟议的实验的总体目标是定量描述的生物物理基础的mfMRI SI时间过程，目的是这样的理解将澄清MR成像和感兴趣的生理参数之间的关系，从而加快发展mfMRI到实际应用。我们将：1）检查生理变量对游离细胞内水和细胞内蛋白质之间质子交换的影响; 2）检查体内运动期间膜通透性的改变; 3）量化BOLD效应对mtMRI SI变化的贡献;以及4）开发一个全面的模型，该模型定量描述了运动期间改变的生理和生化变量如何确定mfMRI SI。这些实验的结果将是一个全面的和定量的描述在体内骨骼肌的横向松弛的生理和生物物理的影响，以及如何实验变量（如图像类型和时间）可以改变，以提高特定的生理现象的灵敏度mfMRI。这些知识的未来应用可能包括健康和疾病中肌肉对运动的代谢和血液动力学反应的研究，功能相关多关节动作的改进生物力学模型的开发，以及脊髓损伤患者功能性电刺激方案的评估。

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.