Transforming Neuromuscular Diagnosis and Treatment by Virtual Muscle Biopsy (VBx)

通过虚拟肌肉活检 (VBx) 改变神经肌肉诊断和治疗

• 批准号: 9911192
• 负责人: Richard L. Lieber
• 金额: $ 47.15万
• 依托单位: REHABILITATION INSTITUTE OF CHICAGO D/B/A SHIRLEY RYAN ABILITYLAB
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-20 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9911192
• 关键词: Affect; American; Antibodies; Biological; Biopsy; Cerebral Palsy; Child; Contracture; Data; Denervation; Development; Device or Instrument Development; Devices; Diagnosis; Diagnostic; Disease Progression; Emerging Technologies; Fiber; Fibrosis; Genetic; Genomics; Geometry; Goals; Gold; Grant; Hour; Human; Image; Injury; Knowledge; Laboratories; Lasers; Length; Magnetic Resonance Imaging; Manuals; Measurement; Measures; Mission; Modeling; Molecular; Monitor; Muscle; Muscle function; Muscular Dystrophies; Musculoskeletal Diseases; Myopathy; National Institute of Arthritis and Musculoskeletal and Skin Diseases; Neuromuscular Diseases; Noise; Operative Surgical Procedures; Optics; Pain; Patients; Phase; Physicians; Property; Rattus; Research; Resolution; Sampling; Sarcomeres; Science; Scientific Inquiry; Scientist; Signal Transduction; Skeletal Muscle; Skin; Source; Stroke; Structure; System; Technology; Therapeutic Intervention; Therapy Evaluation; Three-Dimensional Image; Time; Tissues; Treatment Efficacy; United States; Work; Wrist; base; experimental study; frequency comb; innovation; instrument; lens; motor impairment; muscular structure; neuromuscular; neuromuscular function; new technology; novel; optical imaging; photonics; prototype; response; signal processing; theories; therapeutic evaluation; tissue processing; treatment response; virtual; virtual biopsy

PROJECT ABSTRACT: This project is driven by the urgent need for new technology that can diagnose and follow the treatment of human skeletal muscles at the cellular level. Movement impairments due to neuromuscular disease or injury are a major cause of debility in the United States. But while muscle biopsies are the gold standard that scientists use to understand neuromuscular function and that, in addition to genomic sequence, physicians use to diagnose neuromuscular diseases, biopsies are highly invasive, painful, expensive, and relatively unavailable, and a tremendous amount of laboratory tissue processing is required to adequately understand the results. Further, biopsies can typically only be obtained at a single time point, making it difficult if not impossible to quantify disease progression or to determine therapeutic efficacy. It would be revolutionary to diagnose and treat neuromuscular disease using a device that rapidly and noninvasively measures muscle properties at the cellular level—in other words, that functions as a virtual muscle biopsy (VBx). In response to RFA-AR-19-013 (Research Innovations for Scientific Knowledge (RISK) for Musculoskeletal Diseases) we propose development of an instrument platform that exploits recent advances in photonics to create a device that noninvasively provides micron spatial resolution and kHz time resolution of skeletal muscle structure and function. To accomplish this goal, we propose the following three aims: Specific Aim 1 (R61): Develop an optical frequency comb (OFC) source with signal-to-noise ratio exceeding 40 dB. An optical frequency comb (OFC) laser source that uses thousands of laser wavelengths simultaneously represents an emerging technology that offers tremendous potential to revolutionize photonics applications inside and outside of biomedical science. Specific Aim 2 (R61): Create and validate the photonic system necessary to interrogate muscle across the skin. An optical bandwidth greater than 350 nm is necessary to accommodate the complexity of muscle structures and perform a VBx. We hypothesize that VBx can noninvasively measure sarcomere length, fiber size, fiber type, and indicators of fibrosis and denervation with high resolution in real time. In a rat model, we will directly compare data obtained noninvasively using VBx with data obtained by invasive manual tissue processing of the same muscles to evaluate the accuracy and fidelity of VBx. Specific Aim 3 (R33): To perform serial transdermal sarcomere length measurement in patients with wrist flexion contractures. As the first proof-of-principal experiment in humans, we will use VBx to measure a known entity, sarcomere length, in children with cerebral palsy who have wrist flexion contractures just prior to surgery and validate these data against the same muscle sampled intraoperatively. We believe that this device can revolutionize our understanding of neuromuscular function, permit objective evaluation of therapy, and provide a real-time three-dimensional image of biological tissue.

项目摘要： 该项目是由对新技术的迫切需求驱动的，该技术可以诊断和跟踪治疗 人类骨骼肌的细胞水平。神经肌肉疾病或损伤导致的运动障碍 是导致美国人衰弱的主要原因虽然肌肉活检是黄金标准， 科学家用来了解神经肌肉功能，除了基因组序列，医生还使用 为了诊断神经肌肉疾病，活组织检查是高度侵入性的，痛苦的，昂贵的，相对昂贵的。 不可用，并且需要大量的实验室组织处理来充分理解 结果。此外，活组织检查通常只能在单个时间点获得，如果没有， 不可能量化疾病进展或确定治疗功效。如果我们能在未来几年内 使用快速非侵入性测量肌肉的设备诊断和治疗神经肌肉疾病 在细胞水平上的属性-换句话说，它的功能就像一个虚拟的肌肉活检（VBx）。响应于 RFA-AR-19-013（肌肉骨骼疾病科学知识（风险）的研究创新）我们 建议开发一种仪器平台，利用光子学的最新进展来创建一种设备 其非侵入性地提供骨骼肌结构的微米空间分辨率和kHz时间分辨率， 功能为了实现这一目标，我们提出了以下三个目标：具体目标1（R61）： 信噪比超过40 dB的光频梳（OFC）光源。光学频率梳 (OFC)同时使用数千个激光波长的激光源代表了一种新兴的 技术，提供了巨大的潜力，彻底改变光子学应用内外 生物医学科学具体目标2（R61）：创建并验证询问所需的光子系统 肌肉穿过皮肤。需要大于350 nm的光学带宽来适应 肌肉结构的复杂性，并执行VBx。我们假设VBx可以无创地测量 肌节长度、纤维大小、纤维类型以及纤维化和去神经支配的指标，具有真实的高分辨率 时间在大鼠模型中，我们将直接比较使用VBx无创获得的数据与通过 对相同肌肉进行侵入性手动组织处理，以评估VBx的准确性和保真度。具体 目的3（R33）：对屈腕患者进行连续经皮肌节长度测量 挛缩作为第一个在人类身上进行的原理验证实验，我们将使用VBx来测量一个已知的实体， 肌节长度，在手术前腕关节屈曲挛缩的脑瘫儿童中， 与术中取样的相同肌肉对比验证这些数据。我们相信这个装置可以 彻底改变我们对神经肌肉功能的理解，允许客观评价治疗，并提供 生物组织的实时三维图像。