Evaluation of Liver Fibrosis Using Shear Wave Elastography: An Overview

*Dong Ho Lee, Jae Young Lee and Byung Ihn Choi*

#### **Abstract**

All kinds of chronic liver disease can progress into liver fibrosis, and the stage of liver fibrosis is an important prognostic factor. Therefore, assessment of liver fibrosis is of importance for the management of the chronic liver disease. Although liver biopsy is considered the standard method, its invasive nature limits clinical use. In this regard, shear wave-based ultrasound elastography has been emerged as a noninvasive method to evaluate liver fibrosis. Among various techniques, transient elastography (TE) has been the most extensively used and validated method. TE provides good diagnostic performance in staging liver fibrosis. In addition to TE, point shear wave elastography (pSWE) and two-dimensional SWE (2D-SWE) have been developed as another noninvasive method, and also reported good diagnostic performance in staging liver fibrosis. Although TE, pSWE, and 2D-SWE show good performance in assessing liver fibrosis, concurrent inflammatory activity and/or hepatic congestion are important limitations in the current elastography technique.

**Keywords:** liver fibrosis, liver cirrhosis, shear wave elastography

#### **1. Introduction**

Chronic liver disease is a major healthcare problem worldwide, and various etiologies including viral hepatitis caused by hepatitis B virus (HBV) or hepatitis C virus (HCV), alcohol abuse, and non-alcoholic fatty liver disease (NAFLD) can induce chronic liver disease [1]. Moreover, chronic liver disease is an evolving and dynamic process, progressing into liver fibrosis [2–4]. When appropriate management is not given, liver injury and fibrosis can continuously progress, eventually leading to the development of liver cirrhosis, portal hypertension, hepatic insufficiency as well as hepatocellular carinoma (HCC) which can increase morbidity and mortality [5, 6]. In addition, the stage of liver fibrosis is associated with the risk of HCC development and liver-related mortality. Therefore, information regarding the stage of liver fibrosis is important for both surveillance and personalized treatment [7–9]. Owing to the dynamic and evolving nature, liver fibrosis would be reversible under the adequate management, especially in early stage of the disease. In contrast, liver cirrhosis is generally considered as an irreversible process [10–13]. Therefore, evaluation, as well as detection of liver fibrosis in the early stage, is of importance for the management of the chronic liver disease.

For the assessment of liver fibrosis, liver biopsy with histopathologic examination has been used as the reference standard method [14]. In addition, histopathologic examination enables the evaluation of concurrent inflammatory activity in the liver, in addition to the assessment of liver fibrosis. However, liver biopsy has several important drawbacks limiting its clinical use. First, liver biopsy is an invasive procedure that can cause potentially lethal complications, such as bleeding. Due to the invasive nature, repeated biopsy for the monitoring of liver fibrosis during the disease course in the same patient can hardly be performed in clinical practice [15]. The small sample volume of liver biopsy, generally 1/50000th of total liver parenchyma, is another important limitation. When the distribution of liver fibrosis is heterogeneous, a small volume with sampling variability of liver biopsy can lead to either overestimation or under-estimation of liver fibrosis [16, 17]. Another important limitation of liver biopsy is considerable inter-reader variability, and the reported kappa value among the different pathologists varies from 0.5 to 0.9 [18, 19]. Therefore, there has been a continuous need for a reliable and noninvasive methods for the evaluation of liver fibrosis in clinical practice, and tremendous effort has been made to develop non-invasive diagnostic methods for the assessment of liver fibrosis [13]. In this regard, shear wave based ultrasound elastography has been developed and introduced as an accurate noninvasive diagnostic method for the evaluation of liver fibrosis. After the introduction of transient elastography (TE) which was the first commercially available liver elastography technique, various ultrasound-based shear wave elastography methods including point shear wave elastography (pSWE) and two-dimensional shear wave elastography (2D-SWE) have been introduced in clinical practice and reported a good diagnostic performance in assessing liver fibrosis [20, 21].

#### **2. Principle of shear wave elastography**

Elastography is an imaging technique measuring a tissue mechanical characteristic such as elasticity, that was firstly described by Ophir et al. [22]. Tissue elasticity is defined as the resistance to the deformation of a certain tissue against applied stress [15], and stiff tissue is more resistant to the deformation than soft tissue in given applied stress. For the superficial organs such as the breast and thyroid, tissue elasticity can be measured by using strain elastography. In strain elastography, stress to tissue is directly applied by manual compression of an ultrasound transducer, and then the degree of tissue deformation after compression is measured by ultrasound imaging [22]. Manual compression works fairly well for superficial organs, and therefore, strain elastography is a useful technique for the evaluation of breast or thyroid lesion, providing information regarding tissue stiffness [23]. However, it is very challenging to induce stress to deeper located organs by manual compression such as the liver, limiting the application of strain elastography to the liver [24]. For deeper located organs such as the liver, the stress can be employed by acoustic radiation force impulse (ARFI) or mechanical push pulse to generate a shear wave within the target tissue [15]. Since shear wave propagation velocity is related to tissue elasticity and the shear wave velocity is faster in stiff tissue than in soft tissue, measurement of shear wave velocity generated by either ARFI or mechanical push pulse leads to the quantitative assessment of tissue elasticity [23]. Given that, the type of ultrasound-based shear wave elastography for the liver can be determined by following two factors: 1) how to generate shear wave within the liver tissue?; and 2) how to measure the velocity of

*Evaluation of Liver Fibrosis Using Shear Wave Elastography: An Overview DOI: http://dx.doi.org/10.5772/intechopen.102853*

generated shear wave within the liver tissue?. Based on these two factors, currently, there are three available ultrasound-based shear wave elastography techniques for the liver: 1) one-dimensional transient elastography (TE); 2) point shear wave elastography (pSWE), and 3) two-dimensional shear wave elastography (2D-SWE) [23]. The characteristics of these three elastography techniques are summarized in **Table 1** and **Figure 1**.

#### **2.1 Transient elastography**

The FibroScan system (Echosens, Paris, France), which is TE system, was the first commercially available ultrasound-based shear wave elastography system for the liver [25]. The FibroScan probe contains both a mechanical vibrating device and an ultrasound transducer [23]. When the mechanical vibrating device part of FibroScan probe employs a 50 Hz mechanical impulse to the skin surface, the shear wave is generated and propagated within the liver tissue [15]. The generated shear wave within the liver tissue by mechanical push pulse applied to the skin surface is traced by an ultrasound transducer for the measurement of shear wave velocity. Then, liver stiffness can be calculated by measured shear wave velocity. The frequency of generated shear wave within liver tissue by mechanical push pulse in TE is 50 Hz. Although TE is an ultrasound-based technique, it is impossible to provide B-mode images of the liver in TE system, and therefore, TE is performed without direct B-mode image guidance [23]. The size of the measurement area of TE is approximately 1 cm width × 4 cm length, which is >100 times larger than the tissue volume assessed by a liver biopsy [26, 27]. There are several available probes for TE, and M probe with an operating center frequency of 3.5 MHz is used for the standard examination [15]. Since TE applies a mechanical push pulse to the skin surface for the generation of shear wave within the liver tissue, the presence of ascites and obesity limiting the


*Note: TE, transient elastography; pSWE, point shear wave elastography; 2D-SWE, two-dimensional shear wave elastography; ARFI, acoustic radiation force impulse; kPa, kilopascal.*

#### **Table 1.**

*Characteristics of currently available ultrasound based shear wave elastography techniques for the liver.*

#### **Figure 1.**

*Currently available ultrasound-based shear wave elastography methods for the liver. (a) Transient elastography (TE). In TE, B-mode images of the liver are not provided, and thus the measurement area cannot be selected. Ten valid measurements were performed for this patient, and the IQR/M value was 6%, indicating reliable measurement result. (b) Point shear wave elastography (pSWE) (Virtual touch quantification, Siemens Acouson S2000). The measurement box is placed within liver parenchyma 2.5 cm apart from liver capsule. Since pSWE provides B-mode images of the liver simultaneously, the placement of measurement box is undertaken under the B-mode image guidance, avoiding large hepatic vessels or areas showing artifact. (c) Two-dimensional shear wave elastography (2D-SWE) (Aixplorer, Supersonic Imagine). The size of measurement box of 2D-SWE is larger than that of pSWE, and placed within liver parenchyma under the B-mode image guidance. 2D-SWE can also provide color-coded elastogram, superimposed on B-mode image of the liver.*

*Evaluation of Liver Fibrosis Using Shear Wave Elastography: An Overview DOI: http://dx.doi.org/10.5772/intechopen.102853*

shear wave generation by mechanical push pulse would be a drawback. In addition, M probe would have a limited ultrasound penetration for obese patients, hampering the accurate measurement of shear wave velocity. To overcome this limitation of M probe, XL probe with a lower operating frequency (2.5 MHz for XL probe vs. 3.5 MHz for M probe) enabling measurement at a greater depth (35–75 mm for XL probe vs. 25–65 mm for M probe) is introduced. Using XL probe, accurate and reliable measurement can be possible for obese patients.

#### **2.2 Point shear wave elastography (pSWE)**

In contrast to TE which uses a mechanical push pulse to generate a shear wave within the liver tissue, pSWE uses ARFI technique to induce stress and to generate a shear wave within the liver tissue. When ARFI is delivered in the liver tissue, the longitudinal waves along with the plane of applied ARFI are generated. At the same time, a portion of longitudinal waves is converted to shear waves within the liver tissue, and propagate perpendicular to the plane of longitudinal waves [28]. The frequency of generated shear wave by applied ARFI is wideband, ranging from 100 to 500 Hz. In pSWE, the velocity of the shear wave generated by ARFI is measured, which is either directly reported in meters per second or changed to Young's modulus E in kilopascal for the estimation of tissue elasticity [27]. Under the assumption of incompressibility, shear wave velocity can be converted to Young's modulus E by the following equation: E (kilopascal) = 3ρc 2 , where c is the measured shear wave velocity in meter per second and ρ is the tissue density, assumed to be 1 of water [15]. Unlike TE, pSWE can be performed using a conventional ultrasound probe equipped with standard diagnostic ultrasound machine [27]. Therefore, pSWE can provide B-mode images of the liver simultaneously during the examination, enabling the selection of a uniform area of liver parenchyma without any large vessels, focal lesions, or artifacts where the shear wave velocity will be measured [23]. Given that, the accuracy and measurement reliability of pSWE are expected to be higher than those of TE. In addition, since the shear wave is generated by ARFI which is introduced inside the liver parenchyma, pSWE would be less affected by the presence of ascites and obesity than TE [9, 29, 30].

#### **2.3 Two-dimensional shear wave elastography (2D-SWE)**

2D-SWE is the newest ultrasound-based shear wave elastography technique, which also utilizes ARFI. In contrast to the pSWE which introduces ARFI in a single focal location, 2D-SWE uses multiple focused ultrasound push pulses to create multiple focal zones interrogated in rapid succession, faster than shear wave speed [23]. Those multiple push pulses in 2D-SWE generate a near cylindrical shear wave cone, allowing the real-time tracing of shear waves in 2D to measure the velocity of induced shear wave or Young's modulus E [23, 31]. The same as the pSWE, the frequency of generated shear wave by multiple push pulses in 2D-SWE is wideband, ranging from 100 to 500 Hz. Since 2D-SWE utilizes the conventional ultrasound probe for standard diagnostic imaging, it can also provide B-mode images of the liver simultaneously, and real-time visualization of a color-coded quantitative elastogram can be superimposed on a B-mide image. This merit of 2D-SWE allows the operator to obtain both anatomical and tissue stiffness information [20]. Currently, most of the major ultrasound vendors provide their own shear wave elastography technique for the liver, either form of pSWE or 2D-SWE.
