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

点击翻译按钮获取中文摘要

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.