Mechanical properties are quantitative biomarkers that can be used for monitoring and characterizing pathophysiologic conditions of tissue. Elastography is a noninvasive technique for assessing mechanical properties such as liver stiffness. Liver stiffness now a well-established biomarker for assessing fibrosis in chronic liver disease, as an alternative to biopsy.

MRI-based and ultrasound-based dynamic elastography methods have been introduced for clinical staging of fibrosis. Some of the methods are commercially available. However, each have their inherent strengths and weaknesses. The published literature generally indicates that MR elastography has higher diagnostic performance and fewer technical failures than ultrasound-based elastography in assessing hepatic fibrosis.

There is significant potential to further develop elastography techniques to implement multiparametric methods that have promise for distinguishing between process such as inflammation, fibrosis, venous congestion, etc.

Radiologists, hepatologists, engineers, medical physicists, and basic scientists interested in assessing the mechanical properties of soft tissues.

To provide an overview of the importance and challenges of measuring mechanical properties of soft tissue, in particular the liver.

To summarize the principle strategies for assessing mechanical properties of the liver, with an emphasis on dynamic methods used in commercially available products.

To suggest how ultrasound and MR elastography could be used to improve quantitative assessment of hepatic fibrosis in patients with chronic liver diseases.

To demonstrate examples of liver elastography applications and future directions.

Hepatic fibrosis is the common pathway of progressive hepatic damage resulting from many different causes of liver injury. It can be clinically silent until it progresses to high-mortality end stage of cirrhosis. Liver biopsy is considered the reference standard for fibrosis assessment. However, this invasive method has the following drawbacks: risk of complications, sampling error and subjective scoring system with considerable inter-observer variability. Due to the growing concern about nonalcoholic fatty liver disease (NAFLD), which affects one-third of the adult population in the US, it is critically important for clinical management to employ a safer, more comfortable, and less expensive alternative to liver biopsy for diagnosing hepatic fibrosis.

Many disease processes cause marked changes in tissue mechanical properties. Mechanical properties are therefore promising biomarkers for monitoring and charactering various pathophysiologic conditions of tissues. In patient care, the innovative liver stiffness biomarker is beginning to see widespread clinical use for assessing hepatic fibrosis as an alternative to biopsy. In this very intensive field of research, there are two major imaging methods of noninvasive liver stiffness assessment for hepatic fibrosis: MR and ultrasound-based elastography.

Ultrasound-based elastography methods include transient elastography using an extrinsic vibrating source (40-50Hz) and shear wave elastography (point or 2D) using an acoustic radiation force impulse (ARFI) (100-500Hz). Transient elastography measures liver stiffness in a 1D volume of 10-mm wide and 40-mm long, 25-65 mm (M probe) or 35-75mm (XL probe) below the skin surface. It gives a result of Young’s modulus (E = 3ρC_s², E: Young’s modulus; ρ: tissue density; C_s: velocity of shear wave) in kPa. Shear wave elastography is a 1D or 2D-elastography techniques incorporated into conventional US machines (sonoelastography), based on the measurement of the velocity of shear waves generated from ARFI. They give results of Young’s modulus E in kPa or shear velocity C_s in m/s. Compared with MR elastography, ultrasound methods are inexpensive but have limited accessible sampling size due to circumscribed acoustic window/depth. Technical failures occur in patients with obesity, ascites and narrow intercostal space (failure rate: 6-23%). The difference between machines and observers can vary on the order of 12% (1-3).

MR-based elastography is a phase-contrast technique for estimating the shear stiffness of tissues by imaging propagating shear waves generated from a standardized extrinsic vibrating source (60Hz). It can be 2D or 3D acquisition, generate 2D or 3D maps of shear stiffness (magnitude of complex shear modulus |G*| = |G’+iG’’|, approximate 1/3 of E) in kPa. The advantages of MR elastography include its ability to analyze almost the entire liver, and its applicability to patients with obesity or ascites. Compared with ultrasound-based elastography, it could be comparably inexpensive and fast if performed as a limited MR elastography-only exam. Technical failures occur in patients with iron overloaded liver and claustrophobia (failure rate: 4.7-5.6%). The overall difference between venders, magnetic strength and observers varies on the order of 10% (1-3).

A consensus conference of held by the Society of Radologists in Ultrasound found that among all quantitative elastography methods, MR elastography has the closest performance to properly-performed biopsy in assessing hepatic fibrosis. MR elastography has a significantly higher accuracy than transient elastography (1). These studies also suggest that patients can then be grouped into three categories: those with normal elastography values who have a low likelihood of cirrhosis (stage F0 or F1) and may not require additional follow-up, those with high elastography values who have a high likelihood of cirrhosis (F4), and those in between who have moderate to severe fibrosis (stages F2 and F3) and are at risk for progression of the fibrosis, depending on the origin of the fibrosis (1-3).

Technical repeatability and reproducibility of elastography have also been rigorously evaluated in multiple studies for within-subject variability in a test-retest scenario and within-observer variability. Results suggest that both ultrasound and MR-based elastography are reliable techniques with high repeatability and reproducibility, with a few studies suggesting that MR elastography has superior reliability than ultrasound methods (4-7). To further improve inter-observer reproducibility and relieve time-consuming labor of manual analysis in MR elastography, a fully automated segmentation algorithm has been developed for calculating liver stiffness. This automated method is highly consistent with the measurements manually performed by expert readers (8). Results ensure that the liver MRE technique has the capability to serve as a “ground truth” to evaluate an ultrasound based elastography technique for detecting fibrosis in a patient study (9).

Many investigations have demonstrated that liver stiffness can have a static component that is mainly determined by extracellular matrix composites and structure (e.g., hepatic fibrosis), and a dynamic component that is affected by intrahepatic hemodynamic changes (e.g., inflammation). It has been well-established that the liver stiffness increased progressively with the severity of chronic liver diseases with all four disease factors: inflammation, fibrosis, food intake, and congestion- and fibrosis-induced portal hypertension (10-13). There is a need to establish the relationships between mechanical properties other than shear stiffness in distinguishing different pathophysiologic states of the liver. These quantities include the model-free properties and model-based viscoelastic parameters (14-23). Among them, liver viscosity was found to be correlated with fibrosis but not to steatosis or disease activity (24). The dispersions of shear wave velocity and attenuation were found to be associated with the degree of steatosis (25). The damping ratio and the loss modulus were found to increase significantly at the early onset of liver injury or necroinflammation. This was apparent even with coexisting steatosis or before histologically detectable macrophage transformation or migration, but was not sensitive to the later progressive development of fibrosis. Being able to distinguish how these dynamic components contribute to tissue mechanical properties and how the contributions change with different pathologies, and temporally over the course of disease development, will have important diagnostic and prognostic implications and will direct translational research.

Among dynamic elastography techniques, MR elastography has the strongest performance profile, generally superior to ultrasound-based techniques and with fewer technical failures. The higher diagnostic performance is most likely due to the larger volume of liver tissue that can be assessed with MRE, and basic technical features such as the use of a narrow-band mechanical vibration spectrum, thereby avoiding the dispersion mediated depth dependence that is seen with many ultrasound-based elastography techniques. MRI-based evaluation of liver disease allows ready quantitative assessment of hepatic fat content, perfusion and diffusion.