Technical Note: In vivo Young's modulus mapping of pancreatic ductal adenocarcinoma during HIFU ablation using harmonic motion elastography (HME).

Abstract

Noninvasive quantitative assessment of coagulated tissue during high-intensity focused ultrasound (HIFU) ablation is one of the essential steps for tumor treatment, especially in such cases as the Pancreatic Ductal Adenocarcinoma (PDA) that has low probability of diagnosis at the early stages and high probability of forming solid carcinomas resistant to chemotherapy treatment at the late stages. Harmonic motion elastography (HME) is a technique for the localized estimation of tumor stiffness. This harmonic motion imaging (HMI)-based technique is designed to map the tissue Young's modulus or stiffness noninvasively. A focused ultrasound (FUS) transducer generates an oscillating, acoustic radiation force in its focal region. The two-dimensional (2D) shear wave speed, and consequently the Young's modulus maps, is generated by tracking the radio frequency (RF) signals acquired at high frame rates. By prolonging the sonication for more than 50s using the same methodology, the 2D Young's modulus maps are reconstructed while HIFU is applied and ablation is formed on PDA murine tumors. The feasibility of this technique in measuring the regional Young's modulus was first assessed in tissue-mimicking phantoms. The contrast-to-noise ratio (CNR) was found to be higher than 11.7dB for each 2D reconstructed Young's modulus map. The mean error in this validation study was found to be equal to less than 19%. Then HME was applied on two transgenic mice with pancreatic ductal adenocarcinoma tumors. The Young's modulus median value of this tumor at the start of the HIFU application was equal to 2.1kPa while after 45s of sonication it was found to be approximately three times stiffer (6.7kPa). The HME was described herein and showed its capability of measuring tissue stiffness noninvasively by measuring the shear wave speed propagation inside the tissue and reconstructing a 2D Young's modulus map. Application of the methodology invivo and during HIFU were thus reported here for the first time.