Biomedical Engineering, Columbia University, New York, NY, USA.
Departments of Medicine and Pathology & Cell Biology, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY, USA.
Med Phys. 2018 Nov;45(11):5244-5250. doi: 10.1002/mp.13170. Epub 2018 Oct 1.
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 50 s 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 11.7 dB 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 2.1 kPa while after 45 s of sonication it was found to be approximately three times stiffer (6.7 kPa).
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 in vivo and during HIFU were thus reported here for the first time.
高强度聚焦超声（HIFU）消融过程中对凝固组织进行无创定量评估是肿瘤治疗的关键步骤之一，特别是在胰腺癌（PDA）等情况下，该病在早期诊断的可能性较低，而在晚期形成对化疗治疗有抵抗力的实体癌的可能性较高。
谐波运动弹性成像（HME）是一种用于局部估计肿瘤硬度的技术。这种基于谐波运动成像（HMI）的技术旨在无创地绘制组织杨氏模量或硬度图。聚焦超声（FUS）换能器在其焦点区域产生振荡声辐射力。通过跟踪以高帧率获取的射频（RF）信号，生成二维（2D）剪切波速度，从而生成杨氏模量图。通过使用相同的方法延长超声时间超过 50s，在应用 HIFU 形成 PDA 鼠肿瘤消融的同时重建 2D 杨氏模量图。
首先在组织模拟体模中评估了该技术测量局部杨氏模量的可行性。发现每个 2D 重建杨氏模量图的对比噪声比（CNR）均高于 11.7dB。在这项验证研究中，平均误差被发现等于小于 19%。然后将 HME 应用于两只患有胰腺导管腺癌肿瘤的转基因小鼠。在开始应用 HIFU 时，该肿瘤的杨氏模量中位数值等于 2.1kPa，而在 45s 超声处理后，发现其刚度增加了大约三倍（6.7kPa）。
本文描述了 HME，并通过测量组织内剪切波速度的传播来证明其无创测量组织硬度的能力，并重建 2D 杨氏模量图。本文首次报道了该方法在体内和 HIFU 期间的应用。
