The Place of Elastography for Liver Tumors Assessment

*Ana-Maria Ghiuchici and Mirela Dănilă*

### **Abstract**

Elastography is an ultrasound (US) based method widely used in the field of hepatology, particularly for liver stiffness assessment in patients with chronic liver disease. Elastography brings valuable information regarding tissue stiffness and could be considered a virtual biopsy. In the last years, the incidence of focal liver lesions (FLLs) has increased due to frequent detection during a routine abdominal US. The differential diagnosis of FLLs can be challenging, and it is important in terms of treatment options and prognosis. Currently, most FLLs require for diagnosis workup imaging methods with contrast (radiation exposure, potentially nephrotoxic contrast agents) and/or biopsy that are considered invasive procedures and could be contraindicated in particular cases. Avoidance of these invasive methods could be the main reason to perform elastography for FLLs evaluation as they are commonly first detected on US examination. Several studies showed that elastography could bring additional information regarding the stiffness of FLLs in order to predict their nature.

**Keywords:** strain elastography, shear-wave elastography, focal liver lesions, hepatocellular carcinoma, tissue stiffness

#### **1. Introduction**

In clinical practice, standard abdominal US is probably the most widely used imaging technique for liver examination due to the advantages of this method: non-invasive, availability, safe, low-cost. FLLs are often detected incidentally during routine US examinations [1–3]. The characterization and differential diagnosis of these lesions constitute a daily challenge for the practitioner. The continuous development of US tools (i.e., Color-Doppler; Tissue Harmonic Imaging; Contrast-Enhanced Ultrasound - CEUS, elastography) improved FLL characterization [4] and offered a new perspective for the clinician that led to a more complete evaluation of diffuse and focal liver disease.

US elastography is being widely used for liver stiffness assessment as a noninvasive marker of fibrosis useful for the management of patients with diffuse liver disease. Other clinical applications for liver elastography include diagnosing clinically significant portal hypertension and predicting high-risk varices, characterization of FLLs, and the prognosis of the clinical outcomes for chronic liver disease [5–9].

FLLs have different stiffness as the result of different histological structures. They can be classified as benign or malignant. The most frequent solid benign FLLs are

hepatic hemangioma (HH), focal nodular hyperplasia (FNH), and hepatocellular adenoma (HA) [10]. Malignant FLLs can be primary liver tumors (hepatocellular carcinoma, HCC; cholangiocarcinoma, CC) or secondary lesions (metastases).

After detecting an FLL on the abdominal US, we must determine whether the tumor is benign or malignant; this is important for future follow-up, therapeutic management, and prognosis. In many cases, a second-line imaging method with contrast (CT/MRI) and/or biopsy is needed for a definite diagnosis. The need to develop less invasive methods to diagnose and characterize FLLs arises from the limitations of these currently used techniques that involve radiation exposure, potentially nephrotoxic contrast agents, limited availability, expensive and invasive methods.

Elastography can be added to a standard US and CEUS examination of an FLL, providing information regarding tissue stiffness and could be considered a virtual biopsy [11]. Several studies reported the possible role of different elastographic techniques to characterize diverse types of FLLs. They focused on the accuracy in discriminating between benign and malignant primary or secondary (metastases) liver tumors. The ability of US elastography to diagnose FLLs, including HCC, is still undergoing validation [12, 13]. In this chapter, we outline the recent advances regarding US elastography to evaluate FLLs.

### **2. Elastography for the evaluation of focal liver lesions in clinical practice**

Currently, liver cancer is the sixth most common cancer and the fourth cause of cancer-related death worldwide [14]. Therefore, the clinical interest to rule out malignancy of FLLs is to diagnose liver cancer early and to allow prompt therapeutic intervention that can improve the prognosis of these patients. Starting from the premise that neoplastic disease can change the tissue structure/composition, elastography could help assess elasticity differences and predict the nature of an FLL [15, 16].

Elastographic assessment of an FLL must be performed knowing the clinical context and history of the patient (liver disease, previous cancer, medication, comorbidities, infections) [17, 18]. It is also essential to evaluate the liver parenchyma for steatosis or fibrosis, knowing the fact that some tumors are more common in particular clinical settings (i.e., cirrhosis represents the common underlying condition for HCC development).

US elastography is a noninvasive, noncontrast, rapid, cost-effective, easy to perform a method that can complete a standard US examination due to numerous elastographic techniques that are now available in different US machines.

According to elastography guidelines [13, 19–21], elastography techniques can be classified as qualitative (Strain elastography, SE) or quantitative (Shear Wave Elastography, SWE). **Figure 1** shows the types of US-based elastography used in clinical practice. Both SE and SWE techniques can assess tissue stiffness but use different principles. Measurement of minimal displacements in the tissue caused by mechanical compression or an enforced acoustic impulse that acts as a wavefront represents the fundamental principle of US elastography techniques [21].

#### **2.1 Strain elastography for FLLs evaluation**

Strain imaging is a qualitative technique that allows the measurement of physical tissue displacement parallel to the normally applied stress. The applied force can be: (a) mechanically induced by either active displacement of tissue surface

*The Place of Elastography for Liver Tumors Assessment DOI: http://dx.doi.org/10.5772/intechopen.103777*

#### **Figure 1.**

*Scheme of US-based elastography types in clinical practice.*

(strain elastography, SE) or passive internal physiological induced (strain-rate imaging, SRI); (b) ultrasound induced by using acoustic radiation force impulse (ARFI) [21]. SE can provide information about the relative stiffness value between one tissue and another. This technique is limited by interobserver variability and can be challenging to apply in particular situations (i.e., patients with ascites; deep localization of the lesion). Although SE is the least used method for liver examination, studies show the utility of strain techniques in FLL evaluation by characterizing the lesion as either soft or hard.

In a recent study [22], benign FLL had a low strain ratio (mean ratio 1.08 ± 0.40) compared to malignant lesions with a high strain ratio (mean ratio 4.14 ± 1.25). The cut-off value for malignant lesions was 1.7 with a sensitivity of 100% and specificity of 93.10. The highest strain index was for CC (6.25 ± 0.44), followed by hepatoblastoma, HCC, and liver metastases [22].

The utility of semiquantitative strain elastography for FLL characterization was also evaluated in a previous study by Onur et al. [23] that obtained a different cut-off to discriminate between benign and malignant FLL. The cut-off value of the strain index for FLL differentiation was 1.28, with a sensitivity of 78% and a specificity of 65%. No difference in strain values between malignant FLLs was found.

A comprehensive evaluation of FLLs on qualitative and quantitative ARFI techniques was assessed in a study by Nagula et al. showing that malignant lesions were stiffer and larger, while benign lesions were softer and similar in size (P < 0.05) [24]. Also, using ARFI strain imaging, another study found that 83.8% malignant and 55% benign FLLs appeared stiffer as compared with the surrounding liver parenchyma having statistically significant differences (P < 0.05) [25].

The intra-operative (IO) application of SE was also studied [26–28]. In one study that compared the diagnostic accuracy of IO-SE to IO-CEUS for the differentiation between malignant and benign FLLs, the authors concluded that IO-CEUS is useful for localization and characterization of FLLs prior to surgical resection. In contrast, IO-SE provided correct characterization only for a limited number of lesions. The calculated sensitivity of the SE was 70.5%, specificity 60%, PPV 94%, NPV 18.75%, and accuracy 69% [28].

Because SE is a qualitative method, we can obtain the relative stiffness of a lesion compared with the surrounding liver parenchyma. The stiffness of the background liver can be variable depending on the degree of fibrosis and could be considered a limitation of SE for FLL examination. Another confounding factor could be that both benign and malignant lesions can be soft or hard compared to normal liver.
