Electrical Impedance Myography in an Animal Model

描述(申请人提供)：电阻抗肌图(EIM)是我们实验室在过去几年中开发的一种新的、安全的、非侵入性的、快速应用的肌肉评估技术。在EIM中，频率不同的低强度交流电通过肌肉组织，并评估由此产生的表面电压模式。这项技术有望帮助诊断和评估许多导致肌肉萎缩和虚弱的情况，包括肌肉营养不良、神经原性疾病(如肌萎缩侧索硬化症)、炎症性肌病、废用状态和老年人的肌肉萎缩。我们目前在正常人和患有各种神经肌肉疾病的受试者中的工作证实了这种方法的潜在价值。然而，关于测量的性质及其与肌肉病理学的具体关系，仍有许多问题。在这项建议中，我们通过在神经肌肉疾病的大鼠模型中进行详细的EIM测量并获得肌肉组织的定量组织形态计量学来解决这些问题。我们的第一个目标将集中在进一步改进该技术用于大鼠身上，确认其重复性，并确定EIM参数的变化与正常的大鼠生长和衰老。第二个目标将通过跟踪肌肉病理和EIM测量的变化来研究神经源性疾病模型，这些变化伴随着神经挤压损伤的变性和恢复。第三个目的是在炎症性肌炎模型中评估EIM测量之间的相关性。第四个目标将利用后肢悬吊模型研究由于停用而导致的肌肉病理和阻抗变化。有了这些数据，我们目前的EIM理论网络模型将进一步完善，目的是能够根据EIM数据准确地预测肌肉病理。这项工作的其他成果包括：1.了解EIM参数如何随着生长和衰老而变化；2.提高我们处理小肌肉的能力，以便EIM可以更有效地用于患有肌肉营养不良和其他疾病的儿童；以及3.为在神经肌肉疾病动物模型中使用EIM筛选药物和治疗方法铺平道路。

DESCRIPTION (provided by applicant): Electrical impedance myography (EIM) is a new, safe, non-invasive, and rapidly applied technique for muscle assessment that we have been developing in our laboratory for the past several years. In EIM, low- intensity alternating current of varying frequencies is passed through muscle tissue and the consequent surface voltage patterns assessed. The technique holds the promise of assisting with the diagnosis and assessment of many conditions that produce muscle atrophy and weakness, including muscular dystrophies, neurogenic illnesses (such as amyotrophic lateral sclerosis), inflammatory myopathies, disuse states, and muscle wasting of the elderly. Our current work in normal human subjects and those with a variety of neuromuscular disorders is confirming the potential value of this methodology. However, many questions remain regarding the nature of the measurements and their specific relationship with muscle pathology. In this proposal, we address these questions by performing detailed EIM measurements in rat models of neuromuscular disease and obtaining quantitative histomorphometry on the muscle tissue. Our first aim will focus on further refining the technique for use in rats, confirming its reproducibility and identifying changes in EIM parameters with normal rat growth and aging. The second aim will study a neurogenic disease model by following changes in muscle pathology and EIM measurements with degeneration and recovery from a nerve crush injury. The third aim will evaluate the correlation between EIM measures in a model of inflammatory myositis. The fourth aim will study muscle pathology and impedance change due to disuse using a hind limb suspension model. With these data, our current network models of underlying EIM theory will be further refined with the aim of being able to predict accurately muscle pathology from the EIM data. Additional outcomes of this work include: 1. learning how EIM parameters change with growth and aging; 2. improving our ability to work with small muscles such that EIM can be used more effectively in children with muscular dystrophy and other disorders, and 3. to prepare the way for the use of EIM in screening of drugs and therapies in animals models of neuromuscular disease.