Ultrasound-coupled electrical impedance tomography for assessment of neuromuscular disorders

项目摘要/摘要 临床需求：未来几十年有望在治疗方法上发生一场革命 全身性神经肌肉疾病，包括肌营养不良症、肌萎缩侧索硬化症、 脊髓性肌萎缩症、重症肌无力和各种获得性肌病。然而，为了帮助 促进这一点，学术和工业临床研究界需要改进的生物标记物来评估 他们新的潜在疗法的影响。此外，一旦这些疗法获得批准，这些工具将 需要帮助针对个别患者的需要进行量身定做的治疗。限制：当前的方法 对GNMD的评估非常有限，具有适度的敏感性和不确定的可靠性。这些方法通常 包括简单测力、肌电(EMG)或核磁共振或超声成像(US)。为 例如，力的测量需要患者的合作，这使得他们非常依赖于Low 可靠性。肌电是侵入性的，痛苦的，通常只提供定性的结果。核磁共振检查很贵 并且不能在常规的诊所就诊中进行。最后，美国非常方便，因为它可以使用 然而，直接在临床上进行有意义的定量成像是定性的，而且非常具有挑战性。 评估。我们的产品-超声耦合电阻抗断层扫描(US-EIT)是一种 与标准超声探头集成以提供增强US的电特性成像设备 成像。类似于用于血流成像的多普勒成像，我们的设备将能够‘打开’以提供 下层肌肉组织的电学特性图。肌肉的电学特性已经被 通过许多研究表明，它可以区分健康组织和患病组织。事实上，电阻抗 肌肉造影术(EIM)已被广泛用于诊断和评估GNMD；然而，这种方法是一种 单一局部测量，不提供有关肌肉病理生理学的空间信息。我们计划 首次在商业环境中将电阻抗成像与标准US相结合 评估国家导弹防御系统。我们假设该设备将具有足够的灵敏度和特异度，从而提供一种 肌肉健康方面的高度可靠的输出。具体目标：我们特别建议设计一种声学透明剂 与标准US探头无缝集成的电极阵列和外壳。其次，我们将评估我们的 评估肌营养不良症(即区分健康和疾病)的技术的重复性和能力 肌肉)在人体上进行了一项小型的可行性试验。未来方向：RyTek Medical是一家小公司 为各种临床应用开发生物阻抗传感设备。这款设备将补充我们的 现有的努力。在此阶段1工作结束时，我们将展示US-EIT调查是 我们将提供证据表明，这种方法可以区分健康的 来自患病的肌肉。这将使我们获得第二阶段的资金，重点是进行旨在 评估肌营养不良的进展，并准备向FDA申请510(K)或IDE。

PROJECT SUMMARY/ABSTRACT Clinical Need: The coming decades promise a revolution in the therapies available for patients with generalized neuromuscular diseases (GNMDs), including muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy, myasthenia gravis, and a variety of acquired myopathies. However, in order to help facilitate this, the academic and industrial clinical research communities need improved biomarkers to assess the impact of their new potential therapies. In addition, once these therapies become approved, these tools will be needed to help in tailoring therapy to the needs of individual patients. Limitations: Current approaches for evaluating GNMD are very limited, with modest sensitivity and uncertain reliability. These methods typically include simple force measurements, electromyography (EMG), or imaging with MRI or ultrasound (US). For example, force measurements require patient cooperation making them very subject dependent with low reliability. EMG is invasive, painful, and generally only provides qualitative outcomes. MRI is very expensive and not able to be performed in a routine clinic visit. Finally, US is extremely convenient since it can be used directly in the clinic, however, it is qualitative and very challenging to perform meaningful quantitative image assessment. Our Product – Ultrasound-coupled Electrical Impedance Tomography (US-EIT) is an electrical property imaging device that integrates with a standard ultrasound probe to provide augmented US imaging. Similar to Doppler imaging for blood flow mapping, our device will be able to be ‘flipped on’ to provide a map of the electrical properties of the underlying muscle tissue. Electrical properties of muscle have been shown through many studies to discriminate healthy from diseased tissue. In fact, electrical impedance myography (EIM) has been extensively used for diagnosing and assessing GNMD; however, this approach is a single local measurement and provides no spatial information regarding muscle pathophysiology. We plan to combine for the first time ever in a commercial setting, electrical impedance imaging with standard US for assessing NMD. We hypothesize that this device will be sufficiently sensitive and specific so as to provide a highly reliable output on muscle health. Specific Objectives: We specifically propose to design a sonolucent electrode array and housing that seamlessly integrates to a standard US probe. Secondly, we will evaluate our technology’s repeatability and ability to evaluate muscular dystrophy (i.e. distinguish healthy from diseased muscle) in a small feasibility trial in humans. Future Directions: RyTek Medical is a small company developing bioimpedance-sensing devices for a variety of clinical applications. This device will complement our existing efforts. By the end of this Phase 1 effort, we will have demonstrated that the US-EIT probe is functional in a human population and we will have provided evidence that this approach can distinguish healthy from diseased muscle. This will position us for Phase 2 funding focused on conducting a clinical trial aimed at assessing muscular dystrophy progression and preparing for a 510(k) or IDE application to the FDA.