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.
Treatment efficacy of generalized neuromuscular disorders (GNMD) is currently assessed via single point measurements using electromyography, quantitative strength testing, or via imaging with MR systems or in-clinic ultrasound (US); unfortunately, these systems are not cost effective and unable to be used in the clinic (MRI) or have a low specificity in terms of assessment information provided (US). We propose to couple a highly specific electrical impedance imaging modality to standard in-clinic ultrasound probes in order to improve therapeutic efficacy assessment metrics currently provided via US imaging; electrical impedance has been shown by our team to be highly sensitive and specific to neuromuscular disease and for the first time we propose to image these properties in tandem with US-based GNMD imaging. This novel technology will provide highly specific spatial information regarding the heterogeneity of neuromuscular function and health in an easy to use bedside device that is directly coupled to standard ultrasound probes. ! !
