3D Shearwave Elasticity Biomarker Development for Neuromuscular Disease

Elasticity imaging techniques generate quantitative measurements of the biomechanical properties of tissue that serve as biomarkers for disease presence as well as enabling the characterization of its progression and response to treatment. Both ultrasonic shearwave elastography (SWE) and magnetic resonance elastogra-

phy (MRE) are currently used clinically to assess liver fibrosis. The availability of standardized, calibrated isotropic liver-mimicking phantoms that provided validation of the quantitative measurements gener- ated by these imaging tools was critical to the success and clinical adoption of MRE and SWE for liver

fibrosis assessment. Although current efforts in elastography research are focused on developing quanti- tative biomarkers for anisotropic tissues, such as skeletal muscle, nerve, and brain, a standard, anisotropic tissue-mimicking phantom does not exist. Given the significant potential impact of imaging biomarkers in such

anisotropic tissues, and the amount of funding dedicated to their development, there clearly exists a criti- cal and unmet need for standardized, reproducible and tunable anisotropic tissue-mimicking elasticity imaging phantoms, the development and dissemination of which is the goal of this supplemental ap-

plication. The Nightingale group has been a pioneer of SWE techniques and a primary contributor to the de- velopment, calibration, and standardization of liver-mimicking SWE phantoms. The Bayly group at Washington University in St. Louis has developed 3D-printed, hydrogel lattice composite anisotropic phantoms that mimic

the mechanical and magnetic properties of brain tissue and can be imaged with MRE. The Bayly group has also validated the mechanical properties of these phantoms using established benchtop dynamic shear testing (DST) procedures. Our teams are collaborating to adapt these anisotropic MRE phantoms to mimic ultrasonic

imaging properties, and we have obtained preliminary data demonstrating the potential for the development of multi-modality standardized calibrated anisotropic phantoms. In this supplement we propose to optimize fabrica- tion processes to demonstrate phantom tunability and robustness, to validate phantom anisotropic mechanical

properties using established DST methods, to compare estimates of biomechanical parameters made with both MRE and SWE, and to develop standard calibration imaging sequences and analysis tools. Upon successful completion of the aims in this supplement, we will provide validated anisotropic multi-modality imag-

ing phantoms, and fabrication and calibration protocols to the elasticity imaging community through the NIST/NIBIB Imaging Phantom Lending Library. Successful completion of this work will provide an accessible, robust, industry-wide standard for testing and validation of anisotropic elasticity imaging

systems.