Nonlinear Ultrasound Radiation-Force Elastography

Introduction

The elasticity of soft tissues depends, to a large extent, on their molecular building blocks (fat, collagen, etc.), and on the microscopic and macroscopic structural organization of these blocks (Fung, 1981). Pathological changes are generally correlated with local changes in tissue stiffness (Figure 1). Many cancers, such as scirrhous carcinoma of the breast, liver metastases, prostatic carcinoma, and thyroid cancer, appear as extremely hard nodules (Anderson, 1984). Other types of breast cancers (e.g. intraductal and papillary carcinoma) are soft (Ariel, 1987). Other diseases involve fatty and/or collagenous deposits, which increase or decrease tissue elasticity. The standard medical practice of soft tissue palpation is based on qualitative assessment of the low-frequency stiffness of tissue and has been used for centuries by physicians to distinguish between normal and diseased tissues. Palpation is sometimes used to assess organs such as the liver, and it is not uncommon for surgeons at the time of laparotomy to palpate tumors that were not detected preoperatively using conventional imaging methods, such as Ultrasound, Computer Tomography (CT), or Magnetic Resonance Imaging (MRI), since none of these modalities currently provides the type of information elicited by palpation.

Figure 1.

(a) Sonogram and (b) elastogram of an in-vivo benign breast tumour (fibroadenoma) and (c) sonogram and (d) elastogram of an in-vivo malignant breast tumour (invasive ductal carcinoma). Note that black indicates stiff and white indicates soft tissue. Adapted version, reprinted from Ultrasonics, 38, Konofagou (2000), pp. 400-404, ©2000, with permission from Elsevier.

In many cases, despite the difference in stiffness, the small size of a pathological lesion and/or its location deep in the body, preclude its detection and evaluation by palpation. In general, the lesion may or may not possess acoustic backscatter properties, which would make it detectable using ultrasound. For example, tumors of the prostate or the breast could be invisible or barely visible in standard ultrasound examinations, yet be much harder than the embedding tissue. Furthermore, diffuse diseases (e.g. cirrhosis of the liver) are known to significantly increase the stiffness of the liver tissue as a whole (Anderson, 1984). However, they may appear normal in conventional B-mode ultrasound examination. Based on the simple concept of palpation and the observation that echogenicity and the stiffness of tissue are generally uncorrelated (Garra, 1997; Ophir, 2001), tissue elastography or elasticity imaging (Ophir, 1991) seeks to provide non-invasive quantitative systems that can measure or image the local mechanical properties of tissue. Such systems could provide new information related to tissue structure and/or pathology (see Figure 1) and could significantly enhance the accuracy of diagnosis, even at early stages of disease.

In conventional (B-mode) ultrasound imaging, the ability to differentiate between various tissues within the body depends on changes in the acoustic properties, which in turn, depend primarily on the bulk (elastic) modulus (Cobbold, 2007). The range of variation of the bulk modulus is very small, i.e., significantly less than an order of magnitude. On the other hand, the shear modulus μ_l (known as the second Lamé constant), which is defined as the ratio of shear stress to shear strain that is involved in the passage of a transverse wave, may change by many orders of magnitude, depending on the tissue (Cobbold, 2007). This suggests that by imaging one or more characteristics of shear wave propagation, improved sensitivity to localized changes in elastic properties could be achieved, thereby, providing useful diagnostic information (Sarvazyan, 1998).