Noninvasive assessment of neuromuscular diseases using electrical impedance

描述（由申请人提供）：神经肌肉疾病，从严重的全身性疾病（如肌营养不良和肌萎缩性侧索硬化症（ALS））到局部疾病（包括神经损伤和神经根病），影响着美国和世界各地数百万人的生活。今天，诊断工具和一般结果的措施仍然主要是定性和不准确的。此外，经常使用的针肌电图的侵入性技术不仅是主观的，而且是痛苦的，通常耐受性差。此外，这些诊断工具通常需要相当多的患者合作，这也可能导致数据质量的变化，特别是在儿童接受测试时。缺乏准确的非侵入性技术不仅影响了患者的诊断和治疗，还限制了在临床试验期间衡量新疗法疗效的能力。因此，一种能够以最少的患者合作快速、定量、可靠和非侵入性地评估神经肌肉疾病状态的技术，不仅作为诊断工具，而且作为诊断后定制患者护理和简化临床药物试验的手段，将得到广泛的应用。在这方面已经显示出巨大前景的一种技术是电阻抗肌描记术（EIM）。在过去的十年中，EIM技术已经在各种神经肌肉疾病的人类受试者中进行了广泛的研究，并且这些研究已经提供了非常有希望的结果，包括证明这些技术不仅可以将疾病彼此区分开，而且还可以帮助准确地评估疾病随时间的进展或缓解。然而，几乎所有这些研究都是使用市售阻抗设备进行的，这些设备并没有专门针对肌肉健康评估进行优化。因此，第一阶段SBIR应用的目标是为这种设备的初始开发和测试提供资金，包括采用新型机械传感器技术和电子技术，以在更宽的频率范围内实现比现成系统更好的精度。因此，该项目的具体目标是：1）开发一套强大的，可重新配置的机械传感器，可以与各种商业阻抗测量设备接口; 2）开发一种具有新颖电路拓扑结构的电子阻抗测量系统，专门针对快速，准确和宽带EIM测量进行优化;以及3）在各种测试介质中评估所开发的系统。随着这三个目标的成功完成，我们将有能力在临床试验中测试该设备，作为计划的第二阶段SBIR赠款的一部分。 公共卫生相关性：神经肌肉疾病影响着美国和国外数百万人的生活。用于评估肌肉和神经功能障碍的诊断工具在很大程度上仍然是定性的、不准确的和痛苦的，并且特别难以用于儿童。电阻抗肌电图（EIM）技术在克服这些局限性方面显示出巨大的前景。因此，该项目的总体目标是开发一种手持式，非侵入性电阻抗设备，可以对肌肉健康进行准确，快速的评估。

DESCRIPTION (provided by applicant): Neuromuscular disorders, ranging from severe generalized diseases such as muscular dystrophy and amyotrophic lateral sclerosis (ALS) to localized conditions, including nerve injuries and radiculopathy, impact the lives of millions of people in the US and around the world. Today, diagnostic tools and general outcome measures remain largely qualitative and imprecise. Moreover, the frequently used invasive technique of needle electromyography is not only subjective, but is also painful and generally poorly tolerated. Furthermore, these diagnostic tools often require considerable patient cooperation, which can also lead to variability in data quality, especially when children are being tested. The lack of an accurate, noninvasive technology not only affects the diagnosis and treatment of patients, it also limits the ability to gauge the efficacy of new treatments during clinical trials. Thus, a technology that can rapidly, quantitatively, reliably, and noninvasively evaluate neuromuscular disease status with minimal patient cooperation, would find wide application not only as a diagnostic tool, but also as a means of tailoring patient care after diagnosis and for streamlining clinical drug trials. One technology that has shown great promise in this regard is electrical impedance myography (EIM). Over the past decade, EIM techniques have been studied extensively in human subjects in a variety of neuro- muscular disorders, and these studies have provided very promising results, including demonstrating that these techniques cannot only differentiate diseases from one another but also can assist in accurately assessing disease progression or remission over time. Almost all of these studies, however, have been made with commercially available impedance devices that are not optimized specifically for muscle health assessment. Thus, the goal of this Phase I SBIR application is to fund the initial development and testing of such a device, including the employment of novel mechanical sensor techniques and electronics to achieve better accuracy over a wider frequency range than possible with off-the-shelf systems. The specific aims of this project thus are: 1) to develop a set of robust, reconfigurable mechanical sensors that can interface with a variety of commercial impedance measurement devices; 2) to develop an electronic impedance-measuring system with novel circuit topology, specifically optimized for fast, accurate, and wide-bandwidth EIM measurements; and 3) to evaluate the developed system in a variety of test media. With the successful completion of these three aims, we will be well-positioned to test this device in clinical trials as part of a planned Phase II SBIR grant. PUBLIC HEALTH RELEVANCE: Neuromuscular disorders impact the lives of millions of people in the US and abroad. Diagnostic tools used for assessing muscle and nerve dysfunction remain largely qualitative, inaccurate, and painful, and are particularly difficult to use with children. The technique of electrical impedance myography (EIM) has shown great promise in overcoming these limitations. Thus, the overall goal of this project is to develop a handheld, noninvasive electrical impedance device that can perform accurate, rapid assessments of muscle health.