3D Shearwave Elasticity Biomarker Development for Neuromuscular Disease

神经肌肉疾病，包括杜氏肌营养不良症和庞贝病，是进行性的和 通常会导致明显的fi残疾，有时甚至死亡。令人鼓舞的是，新的酶替代和基因工程-- 磁疗正在变得可行，但它们与有害的副作用有关，并评估它们的 EFfiCacy仍然是一个挑战。目前用于评估肌肉健康的方法是主观的、非定量的、 关注肌肉数量和力量；然而，测量肌肉数量可能会高估肌肉数量 功能肌肉和肌肉力量测试受到患者合作、疼痛和合并症的影响。 临床上迫切需要一种低成本、非侵入性的生物标记物来准确评估 肌肉健康，监测疾病进展，并确定治疗反应。超声横波 弹性成像(SWE)方法评估软组织的生物力学特性，这些方法 在描述健康和患病的肌肉方面表现出了希望；然而，在商业上- 可用的SWE方法仅限于从2D成像平面估计材料参数，并测量- fi的可变性和BER对齐的挑战限制了临床应用。我们已经开发出一种3D- SWE成像系统和先进的重建算法，我们已经获得了初步的 活体数据，这是fi第一次展示了SWE产生的复杂3D横波行为 在骨骼肌中的活体兴奋，并观察到fi在患者之间的显著差异 与临床力量指标一致的肌病。我们已经开发了重建算法 利用这些数据的3D性质来估计多种独立的材料属性，包括： 纵向和横向剪切模数、剪切各向异性、拉伸各向异性和粘度 和横跨肌肉的fi小腿。我们假设，更完整的材料表征 这些测量将提供更好的肌肉健康生物标记物。我们现在建议优化Se- 查询并最大限度地减少3D数据采集时间；自动化和验证我们的参数重建方法 算法；并量化校准弹性体模中的参数测量准确度和精密度。 最后，我们提出了一项试验性的临床研究，我们将量化和比较3D-SWE肌肉参数 在肌病和肌营养不良症患者和健康对照组中，评估 这些测量，并评估它们与肌肉健康的临床测量的相关性。成功的COM- 该项目的完成将以低成本提供肌肉健康的非侵入性定量生物标志物 便携式平台，实现对疾病进展的频繁测量和纵向监控 和治疗反应，将促进个性化和优化的神经肌肉疾病人- 管理人员。

Neuromuscular disorders, including Duchenne's Muscular Dystrophy and Pompe disease, are progressive and often result in significant disability and sometimes death. Encouragingly, novel enzyme replacement and ge- netic therapies are becoming available, but they are associated with detrimental side effects and assessing their efficacy remains a challenge. Current methods used to assess muscle health are subjective, non-quantitative, and focus on muscle quantity and strength; however, measuring muscle quantity can over-estimate the amount of functional muscle, and muscle strength tests are affected by patient cooperation, pain, and co-morbidities. There is an urgent and unmet clinical need for a low-cost, non-invasive biomarker to accurately assess muscle health, monitor disease progression, and determine treatment response. Ultrasonic shear wave elasticity (SWE) imaging methods estimate the biomechanical properties of soft tissues, and these methods have demonstrated promise in the characterization of healthy and diseased muscle; however, commercially- available SWE methods are limited to estimating material parameters from a 2D imaging plane, and measure- ment variability and challenges with fiber alignment have limited clinical adoption. We have developed a 3D- SWE imaging system and advanced reconstruction algorithms with which we have obtained preliminary in vivo data that demonstrate, for the first time, the complex 3D shearwave behaviors generated by SWE excitations in vivo in skeletal muscles, and have observed significant differences between patients with myopathy that are consistent with clinical strength metrics. We have developed reconstruction algorithms that leverage the 3D-nature of these data to estimate multiple independent material properties, including: the longitudinal and transverse shear moduli, the shear anisotropy, the tensile anisotropy, and the viscosity along and across the muscle fibers. We hypothesize that the more complete material characterization afforded by these measurements will provide improved biomarkers of muscle health. We now propose to optimize the se- quencing and minimize the 3D data acquisition time; to automate and validate our parameter reconstruction al- gorithms; and to quantify the parameter measurement accuracy and precision in calibrated elasticity phantoms. Finally, we propose a pilot clinical study in which we will quantify and compare 3D-SWE muscle parameters in vivo in patients with myopathy and muscular dystrophy and in healthy controls, evaluate the repeatability of these measurements, and assess their correlation with clinical measures of muscle health. Successful com- pletion of this project will provide non-invasive quantitative biomarkers of muscle health on a low-cost portable platform, enabling frequent measurement and longitudinal monitoring of disease progression and treatment response which will facilitate personalized and optimized neuromuscular disease man- agement.