Development of Ultrasound Imaging Phantoms Appropriate for Quantification of Muscle Fascicle Architecture and Mechanical Properties

由于其低成本和易用性，超声波被广泛采用为一种 肌肉骨骼系统。例如，传统的二维亮度模式(B模式)超声 目前正在实施的量化肌肉形态适应在体内广泛和不同的 应用范围广泛。超声弹性成像作为一种较新的成像手段，正越来越多地被应用于 人体肌肉组织力学性能的量化。在临床上，肌肉骨骼超声已经被 被推广为72种临床适应症的“一线影像检查手段”。尽管艾滋病的流行率越来越高 肌肉骨骼超声，其实施和解释仍然存在严重的限制 所产生的数据。临床上，培训的可靠性和标准化被认为是限制 临床超声评估的质量。同样，还有一个关键的、未得到满足的需求，那就是改进验证 超声成像的研究应用方法。例如，对文献的系统回顾 描述了B型超声测量肌肉形态参数的实现 结论是，虽然证据支持其有效性，但证据极其有限，而且有 对这一结论提出了实质性的警告。肌肉力学的研究也有类似的局限性。 通过超声成像的特性。 我们建议开发肌肉样幻影作为解决共同问题的第一步 超声成像培训的可靠性、有效性和标准化，将研究和 诊所。在医学成像中，模特儿是感兴趣的组织的模型，合成来模仿关键特征， 已知的几何组织或相关材料组成；它们通常用于建立 一种“黄金标准”的绩效衡量标准。没有商业上可用的幻影可适用 为了确定肌肉结构或力学特性通过以下方法量化的准确性和可靠性 超音波。因此，这些被广泛采用的成像方法的真正效用并没有实现。 本申请描述了一项临床前研究，重点是原型设备的开发。长期的 这项工作的目标是开发一系列类似肌肉的幻影，使不同肌肉的研究成为可能 建筑，包括与生理相关的材料特性。在这两年的尖顶资金期内，我们 将(1)开发模仿人类肌肉的机械性能并适合超声波的材料 成像，以及(2)使用这些材料来3D打印肌肉状的幻影。我们将评估我们的幻影 根据它们复制通常评估的肌肉的结构和材料特性的程度来产生 通过超声波成像。这项研究的第一个目标是开发可打印的水凝胶，模拟被动和 肌肉的主动机械性能。这一目标的成果包括：(1)量化 杨氏模数可通过使用新的第三代立体光刻方法对水凝胶进行3D打印来实现， (Ii)证明这些材料适合于横波成像，(Iii)表征最大值 强调所产生的材料可以维持，以及(Iv)确定最能复制 骨骼肌所需的特性。第二个目标是创造能够研究肌肉的幻影 建筑和机械与超声波。使用目标1中开发的材料范围，我们将打印 一种人造肌肉，可以复制成人的各种大小、形状和机械性能 手臂。体模将根据使用B型超声区分单个神经束的能力进行评估 成像，以维持相当于人类肌肉的负荷，并具有负荷依赖的材料特性 在报告的肌肉范围内。最终，这里提出的工作将描述潜在的 哪种3D打印可以满足肌肉样成像幻影的需求，为两者的未来奠定基础 审查这一领域的价值，并评估这种产品在商业翻译中的可行性。

Because of its low cost and ease of use, there is widespread adoption of ultrasound as an imaging modality for the musculoskeletal system. For example, traditional, two-dimensional, brightness mode (B-mode) ultrasound is currently being implemented to quantify muscle morphological adaptations in vivo for a broad and disparate range of applications. Ultrasound elastography, a newer modality, is increasingly being applied to the quantification of human muscle tissue mechanical properties. Clinically, musculoskeletal ultrasound has been promoted as a “first-line imaging modality” for 72 clinical indications. Despite the increasing prevalence of musculoskeletal ultrasound, there remain critical limitations for its implementation and for interpretation of the data that results. Clinically, reliability and standardization of training are considered significant obstacles limiting the quality of clinical ultrasound assessments. Similarly, there is a critical, unmet need to improve validation methods for the research application of ultrasound imaging. For example, a systematic review of the literature describing the implementation of B-mode ultrasound for measurement of muscle morphometric parameters concludes that, while the evidence supports its validity, the evidence is extremely limited and there are substantial caveats on this conclusion. There are similar limitations relevant to the study of muscle mechanical properties via ultrasound imaging. We propose the development of muscle-like phantoms as a first step toward addressing common issues of reliability, validation, and standardization of training for ultrasound imaging, that connect research and the clinic. In medical imaging, phantoms are mockups of the tissue of interest, synthesized to mimic critical features, known geometric organization, or relevant material composition; they are commonly implemented to establish a type of “gold-standard” performance measure. There are no commercially available phantoms that are applicable to establish how accurately and reliably either muscle structure or mechanical properties can be quantified via ultrasound. As a result, the true utility of these widely adopted imaging methods is not being achieved. This application describes a preclinical study, focused on prototype device development. The long-term goal for this work is to develop a range of muscle-like phantoms that will enable the study of different muscle architectures and include physiologically relevant material properties. In this two-year SPiRE funding period, we will (1) develop materials that mimic the mechanical properties of human muscle and are suitable for ultrasound imaging, and (2) use these materials to 3D print muscle-like phantoms. We will evaluate the phantoms we produce relative to how well they replicate structural and material properties of muscles commonly assessed with ultrasound imaging. The first aim of this study is to develop printable hydrogels that mimic the passive and active mechanical properties of muscle. The deliverables of this aim include: (i) quantification of the range of Young’s moduli achievable via 3D printing of hydrogels using a novel third generation stereolithography method, (ii) demonstration that these materials are suitable for shear wave imaging, (iii) characterization of the maximum stresses the resulting materials can sustain, and (iv) identification of the formulations that best replicate the desired properties of skeletal muscle. The second aim will create phantoms that enable the study of muscle architecture and mechanics with ultrasound. Using the range of materials developed in Aim 1, we will print artificial muscles that replicate the range of sizes, shapes, and mechanical properties present in the adult human arm. Phantoms will be evaluated on the ability to distinguish individual fascicles using B-mode ultrasound imaging, to sustain loads comparable to human muscle, and to have load-dependent material properties spanning the range reported for muscle. Ultimately, the work proposed here will characterize the potential with which 3D printing can address the need for muscle-like imaging phantoms, setting the stage for both a future Merit Review in this area and an assessment of the viability of such a product for commercial translation.