Noninvasive Assessment of Neuromuscular Disease using Electrical Impedance

描述(申请人提供)：神经肌肉疾病包括一组广泛的疾病，从相对轻微的局限性问题，如腕管综合征，到严重的全身性疾病，如肌萎缩侧索硬化症(ALS)。目前评估这些疾病的方法仍然局限于各种测试和程序，这些测试和程序要么是侵入性的，要么是非常定性的。一种新的技术，电阻抗肌图(EIM)，提供了无痛和非侵入性地获得肌肉状况的定量数据的前景。然而，目前还没有专门为EIM使用而量身定做的商业设备，几乎所有以前的EIM工作都依赖于现成的生物阻抗设备，这些设备是为“全身”而不是单肌肉评估设计的。在此SBIR的第一阶段，Conversion Medical Devices，Inc.(CMD)开发了一个初始原型系统，以测试电路设计和数据采集方面的原则证明创新概念，以在扩展的频率范围(从10 MHz到10 MHz)和相对于主要肌肉纤维方向的多个角度提供高灵敏度和准确的数据。这项工作之后是补充工作，生产了第一个手持设备，具有强大的电子设备，能够用可拆卸的、可互换的电极阵列进行类似的测量。在这项为期3年的第二阶段SBIR中，CMD建议进一步改进这项技术，以帮助疾病诊断和跟踪疾病进展，特别是肌萎缩侧索硬化症。在拟议拨款的目标1中，将在一组正常受试者和ALS患者身上进行多电极阵列设计的测试，以确定哪些电极阵列设计提供了最大的重复性和区分健康和疾病个体的能力。在《目标2》中，这个装置 AIM 1中确定的3个“最佳”阵列设计将在30名ALS患者、30名具有类似ALS症状(例如，多根神经病和运动性神经病)的患者以及30名疑似/可能患有ALS的受试者中进行测试，以确定用于诊断的单一最佳阵列设计，并确定其敏感性和特异性。这项研究将在CMD和四个外部地点进行，并将由东北ALS试验联合会(NeALS)管理，该联合会是监督ALS临床试验的主要组织。在目标3中，SA2招募的30名疑似/可能的ALS患者和另外30名疑似/可能的ALS患者将每月使用EIM和SA1中确定的3个阵列进行评估。所有受试者还将接受标准的疾病进展测量，包括手持测力仪、ALS功能评定量表和肺活量测定仪。将确定用于评估疾病进展的最佳阵列设计，并将其与传统的疾病进展标记进行比较，以确定EIM对疾病状态的敏感性。因此，在这项研究计划结束时，我们预计已经开发并大力测试了EIM设备和相关的电极设计，这些设备和相关的电极设计将共同成为神经肌肉疾病的强大新诊断和监测工具。

DESCRIPTION (provided by applicant): The neuromuscular disorders include a wide group of conditions ranging from relatively mild focal problems, such as carpal tunnel syndrome, to severe, generalized diseases, such as amyotrophic lateral sclerosis (ALS). Current methods for evaluating these disorders remain limited to a variety of tests and procedures that are either invasive or remarkably qualitative in nature. One newer technique, electrical impedance myography (EIM), offers the prospect of obtaining quantitative data on muscle condition painlessly and non-invasively. However, no commercial devices specifically tailored for EIM use exist, with nearly all previous EIM work relying upon off-the-shelf bioimpedance devices designed for "whole-body" rather than single-muscle assessment. In Phase 1 of this SBIR, Convergence Medical Devices, Inc (CMD) developed an initial prototype system to test proof-of-principle innovative concepts in circuit design and data acquisition to provide highly sensitive and accurate data at an extended frequency range (out to 10 MHz) and over multiple angles relative to the major muscle fiber direction. This work was followed by supplemental work that produced the first hand-held device with robust electronics capable of similar measurements with a detachable, interchangeable electrode array. In this 3-year Phase 2 SBIR, CMD proposes to further refine that technology so as to assist in disease diagnosis and for following disease progression, with a specific focus on amyotrophic lateral sclerosis. In Aim 1 of the proposed grant, testing of multiple electrode array designs will be performed on a group of normal subjects and those with ALS to determine which electrode array designs offer the greatest reproducibility and ability to discriminate healthy from diseased individuals. In Aim 2, the device and the 3 "best" array designs identified in Aim 1 will be tested in 30 ALS patients, 30 patients with syndromes mimicking ALS (e.g., polyradiculopathy and motor-predominant neuropathy), and 30 subjects with suspected/possible ALS to determine the single best array design for diagnosis and to determine its sensitivity and specificity. This study will take place at CMD and four external sites and will be managed by the Northeast ALS trials Consortium (NEALS), the premier organization for overseeing clinical trials in ALS. In Aim 3, the 30 suspected/possible ALS patients recruited in SA2 and 30 additional suspected/possible ALS patients will be assessed monthly using EIM and the 3 arrays identified in SA1. All subjects will also undergo standard measurements of disease progression including handheld dynamometry, ALS Functional Rating Scale, and spirometry. The best array design for assessing disease progression will be identified and compared to conventional markers of disease progression to determine EIM's sensitivity to disease status. Thus, at the conclusion of this research program, we anticipate having developed and vigorously tested an EIM device and associated electrode designs that together will serve as a powerful new diagnostic and monitoring tool for neuromuscular disease.