Ultrasound Elastography and MR Elastography for Assessing Liver Fibrosis: Part 1, Principles and Techniques

Abstract

Objective

The purpose of this article is to provide an overview of ultrasound and magnetic resonance elastography, including a glossary of relevant terminology, a classification of elastography techniques, and a discussion of their respective strengths and limitations.

Conclusion

Elastography is an emerging technique for the non-invasive assessment of mechanical tissue properties. These techniques report metrics related to tissue stiffness such as shear wave speed, magnitude of the complex shear modulus, and Young’s modulus.

Introduction

Imaging-based elastography is an emerging technology that utilizes imaging to non-invasively assess mechanical tissue properties. Elastography techniques have evolved significantly over the last two decades, and have now been implemented on clinical ultrasound and magnetic resonance (MR) systems [1–4]. These techniques provide the capability to examine by imaging what once could be examined only by direct palpation, which is likely to open new opportunities to non-invasively diagnose disease, guide management, and improve outcomes.

In this first article of a two-part series we provide a brief overview of elastography, including a glossary of commonly used terms (Table 1), a classification of techniques, a description of the basic principles, definitions of mechanical properties, examples of ultrasound and MR elastography, and a discussion of their respective strengths and limitations.

Table 1.

A glossary of commonly used terms in elastography

Acoustic radiation force impulse (ARFI): Ultrasonic compression waves focused on a spot to create shear waves perpendicular to the ultrasound beam axis. pSWE and SWE use acoustic radiation force impulses (also called acoustic push pulses) to generate shear waves. ARFI may also refer to a particular technique commercialized by Siemens that includes both the wave generation method described above and a proprietary wave tracking method.

Attenuation: The loss in amplitude of waves through viscous tissue.

Compression wave: A type of wave in which oscillation motion is parallel to the direction of wave propagation; it is also known as P, primary, or longitudinal wave.

Complex shear modulus (G*): A measure of the overall resistance of a material to an applied shear stress; it has two components: an elastic component called the storage modulus, which is the real part of the complex shear modulus, and a viscous component called the loss viscous modulus, which is the imaginary part of the complex shear modulus.

Dynamic (shear) elastography: A type of elastography technique that relies on the production of shear waves and measurement of shear wave speed propagation.

Effective shear modulus (μ): A term used in the MR elastography literature to describe the resistance to deformation upon application of a shear stress; it is related to the shear wave speed by the following equation: μ = ρ c2, where μ is the effective shear modulus, ρ is the density of the tissue and c is the shear wave speed.

Elastic (Young’s) modulus (E): A measure of elasticity (spring-like behavior); it indicates the ability of a material to resist normal (perpendicular) deformation.

Elasticity: A characteristic of materials that tend to return to their initial shape after a deformation.

Elastogram: A graphical display (parametric map) indicating the spatial distribution of stiffness or stiffness-related parameter.

Elastography: A field of medical imaging that displays or measures the mechanical properties of soft tissues.

Inversion algorithm: Mathematical algorithms that allow calculation of mechanical properties from wave images.

Kilopascals (kPa): A unit of pressure (force per unit area); it is a measure of tissue stiffness in ultrasound elastography and MR elastography.

Loss (viscous) modulus (G″): The imaginary part of the complex shear modulus; it describes the dashpot-like, energy-absorbing and -damping behavior.

Point shear wave elastography (pSWE): An elastography technique that measures regional values of shear wave speed using acoustic radiation force impulse; the prototype is ARFI quantification.

Quasi-static elastography: A type of elastography technique that relies on measurement of tissue deformation that arise from cardiac or respiratory motion.

Shear stiffness: A term commonly used in the literature to describe the magnitude (absolute value) of the complex shear modulus.

Shear wave: A type of wave in which oscillation motion is perpendicular to the direction of wave propagation; it is also known as S, secondary, or transverse waves.

Shear wave elastography (SWE): A term used to describe elastography techniques that generate images of shear wave speed using excitations by acoustic radiation force; the prototype is supersonic shear imaging (SSI).

Static elastography: A type of elastography technique that relies on measurement of tissue deformation before and after manual compression with a transducer.

Stiffness: A qualitative property that has traditionally been assessed through palpation. The concept of “stiffness” refers to resistance to deformation in response to an applied force; it is defined mathematically by numerous moduli (elastic, shear, bulk) each one describing the resistance to deformation of a material in response to different types of stresses or applied pressures: tensile forces, shear forces, and volumetric compressive forces, respectively.

Storage (shear) modulus (G′): The real part of the complex shear modulus; it describes elasticity (spring-like, energy-storing behavior), i.e. the ability of a medium to resist shear (parallel to the surface) deformation without energy loss.

Transient elastography: A term used to designate techniques that rely on shear waves of short duration; the prototype is Fibroscan.

Viscoelasticity: A characteristic of materials that exhibit both viscous and elastic behavior when undergoing deformation.

Viscosity: A characteristic of materials that resists movement or deformation. It applies to both viscous fluid or viscous tissues.

Wave amplitude images: A graphic display of shear wave propagation often represented as a cine-loop.

Classification

As summarized in Figure 1, elastography techniques may be classified according to the source (static, quasi-static, or dynamic) and duration (transient or continuous) of tissue deformation and the modality used for tracking (ultrasound or MR imaging). Techniques also may be classified according to the device type (stand alone or adjunct to an imaging scanner), wave generation method (external vibrator or internally focused acoustic radiation force), inversion algorithm (one-dimensional [1D], two-dimensional [2D], or three-dimensional [3D]), reported parameter(s) (shear wave speed, magnitude of complex shear modulus, Young’s modulus), or output display (purely numerical, M-mode image, or parametric imaging map).

Figure 1.

Classification of elastographic techniques with a focus on current commercial techniques.

Static or Quasi-static Elastography

Static and quasi-static elastography assess stiffness by measuring the deformation (i.e., strain) in response to an applied force (i.e., stress) [5]. In static elastography, the stress is produced by manual compression of the tissue, whereas in quasi-static elastography time-dependent stresses are produced by physiological vibrations (e.g., the heart [6] or blood vessels [7]).

The assessment is qualitative, as opposed to quantitative, because the applied force cannot be known with certainty: manual compression in static elastography is operator dependent and stresses caused by physiologic motion in quasi-static elastography are uncontrolled. Current static and quasi-static elastography techniques are ultrasound based.

Static and quasi-static elastography will not be further discussed because of limited applications for liver fibrosis.

Dynamic Elastography

Dynamic elastography, also known as “shear wave imaging”, techniques assess stiffness and stiffness-related parameters by tracking shear waves propagating through media.

Shear wave speed is related to tissue stiffness: for instance, shear waves travel faster in stiff (inflamed, fibrotic, or cirrhotic) liver and slower in soft (normal or fatty) liver [8]. By measuring shear wave speed, the stiffness may be inferred. For most biological tissues, the shear wave speed and hence the inferred stiffness are frequency dependent: all other things being equal, shear wave speed and inferred stiffness are greater if the shear waves are applied at higher frequency. Since the shear wave frequencies utilized by different techniques differ, the stiffness-related values obtained with various techniques are not directly comparable.

Basic Principles

Types of Waves

Body waves, which travel inside organs, include compression and shear waves. With compression waves, tissue moves back and forth in a direction parallel to wave propagation. In contrast, shear waves produce tissue (particle) motion in a direction perpendicular to wave propagation [9]. Compression waves travel orders of magnitude faster than shear waves: in human soft tissues, compression waves propagate at around 1500 m/s while shear waves propagate at around 1–10 m/s. Because compression waves propagate so rapidly through tissues, their speed and related properties cannot be reliably assessed by current imaging techniques. For this reason, all current imaging elastography techniques are based on tracking shear waves, not compression waves.

Wave Generation

Shear waves may be generated either by applying external mechanical vibration to the surface of the body or by focusing acoustic radiation force impulses inside the tissue of interest. Some ultrasound-based techniques use the former method of shear wave generation while others the latter. MR-based techniques use only mechanical vibration.

With ultrasound- and MR-based external mechanical vibration techniques, the vibrator typically oscillates perpendicular to the body surface at a precisely controlled frequency. Compression waves are applied to the body surface; some of the energy in these compression waves is converted to shear waves through a process called mode conversion [10]. With external vibration, the shear wave frequency can be controlled precisely and the associated energy absorption by tissue is minimal, but wave delivery into the tissue of interest may be inefficient.

With ultrasound-based acoustic radiation force techniques, acoustic compression pulses are focused inside the liver; some of the acoustic energy is absorbed and released in the form of shear waves [11]. Thus, shear waves are generated locally within the liver, which improves the efficiency of wave delivery into the area of interest. Compared to external vibration-induced waves, however, internally focused acoustic radiation forces are associated with higher power output and greater energy absorption, and the shear wave frequency is more difficult to control.

Key Concepts of Dynamic Elastographic Examination

Regardless of the technique, dynamic elastography generally requires the following steps: (1) baseline imaging, (2) generation of shear waves, (3) tracking of shear waves, and (4) measurement of shear wave speed or other mechanical parameter of interest.

Mechanical Properties and Parameters

Current clinically available techniques either report shear wave speed, magnitude of the complex shear modulus, or Young’s modulus. The modulus parameters are often referred to as “stiffness” in the medical elastography literature, but strictly speaking do not have exactly the same meaning as stiffness, which is a qualitative property assessed through palpation. The term stiffness is permanently embedded in the medical elastography literature, however, and to maintain consistency with that literature we also use the term to describe elastography measurements that approximate tissue response to palpation. Two such elastograpy parameters are elasticity and viscosity. Elasticity is the characteristic of a material that tends to return to its initial shape after a deformation. Viscosity is the characteristic of a material that resists rapid movement or deformation. Biological tissues are considered to be viscoelastic, meaning that they have both viscous and elastic properties.

Investigational techniques may also calculate other parameters, but these additional measures are currently not reported in clinical settings. A full discussion of the numerous parameters is beyond the scope of this review. A brief summary is provided in the Supplementary Table available online.

Elastography Techniques

Current elastography techniques are compared in Table 2 and illustrated in Figure 2.

Table 2.

Dynamic elastography techniques. Table adapted from [14].

Modality	Implementations	Commercial name (Manufacturer)	Shear wave				Parameter (units)
			Generation	Duration	Frequency	Imaging
Ultrasound	1D Transient elastography (TE)	Fibroscan (Echosens)	Mechanical	Transient	50 Hz	No anatomic image	Young’s elastic modulus (kPa)
	Point shear-wave elastography (pSWE)	Virtual Touch Quantification (Siemens)	Ultrasound (acoustic radiation force impulse)	Transient	Variable and difficult to precisely control	Location of ROI overlain on 2D B-mode image	Shear wave speed (m/s)
	Shear Wave Elastography (SWE)	Shear Wave Elastography (Supersonic Imagine)	Ultrasound (multipoint focalization of acoustic radiation force impulse)	Transient	Variable and difficult ot precisely control	Quantitative elastogram within 2D image, with possibility to superimpose ROI	Young’s elastic modulus (kPa)
Magnetic resonance imaging	Magnetic resonance elastography (MRE)	MR Elastography (GE, Philips, Siemens)	Mechanical	Continuous	60 Hz	Quantitative elastogram of one or more 2D slicesa	Magnitude of complex shear modulus (kPa)

Note—ROI = region of interest.

^aNot all stiffness data are valid on the 2D elastogram. Valid data is data considered reliable based on confidence map and with good wave propagation.

Figure 2.

Collage illustrating probe location, source of shear wave generation, direction of shear wave propagation, and field of view (first column) with companion images (second column) produced by each elastography technique: (a–b) 1D transient elastography (image courtesy of Echosens), (c–d) point shear wave elastography, (e–f) shear wave elastography, and (g–h) magnetic resonance elastography.

Ultrasound-based Dynamic Elastography

All current ultrasound-based dynamic elastography techniques utilize transient shear wave excitations at a frequency ranging from 50 Hz to 400 Hz depending on the technique [2, 12, 13]. Numerous ultrasound-based techniques have become commercially available. To describe these techniques, we have adopted the terminology proposed by the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) [14], as summarized in Table 3.

Table 3.

Terminology proposed European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) to describe ultrasound-based dynamic elastography techniques [14].

1D transient elastography (TE) refers to methods that use a single element ultrasound transducer to track shear waves generated externally by a vibrating probe placed on the body surface. The prototype is Fibroscan® developed by Echosens [16]. This is a stand-alone device without anatomic imaging capability. Some investigators refer to it as vibration-controlled transient elastography (VCTE).

Point shear-wave elastography (pSWE) refers to methods that measure shear wave speed (or derived stiffness-related parameter) in a user-defined small region of interest. Although a parametric map is not generated, the location of the region of interest is captured on a conventional B-mode image. The prototype is Virtual Touch™ Quantification, using acoustic radiation force impulse (ARFI) technology commercialized by Siemens [11].

Shear wave elastography (SWE) refers to methods that generate quantitative parametric maps displaying the shear wave speed (or derived stiffness-related parameter). The prototype is “supersonic shear imaging (SSI)” developed by SuperSonic Imagine [33].

1D Transient Elastography

The first ultrasound-based shear wave measurement technique based on the concept of transient elastography was commercialized as Fibroscan® (Echosens, Paris, France). A single-element piston-like ultrasound transducer mounted on a vibrating actuator generates a transient vibration (“punch”) of short duration (< 30 ms) [15] at a frequency of 50 Hz. The mechanical impulse generates a shear wave that propagates symmetrically with respect to the axis of the single-element transducer [2, 16–19]. The displacements induced by the shear wave are tracked using ultrasonic waves emitted and received at very high frequency (6 kHz) by the single-element ultrasound transducer. A compression wave is also produced by the mechanical impulse but because of its high speed, it moves beyond the location at which the shear waves are tracked and does not interfere with the shear wave measurements. Ultrasound transducers are available targeted for pediatric (S1 and S2), non-obese adult (M), and obese adult (XL) patients. The S probes (S1, S2) use a pulse tracking frequency of 5 MHz at window depths of 15 to 40 mm and 20 to 50 mm respectively [20]. The M probe uses a pulse tracking frequency of 3.5 MHz at a window depth from 20 to 60 mm, and the XL probe uses a lower pulse tracking frequency of 2.5 MHz at a window depth from 35 to 75 mm [18, 21]. The TE device does not provide an anatomic image, but instead provides M-mode and A-mode graphs to locate the optimal measurement point. The shear wave propagation graph (Figures 2a and 2b) is displayed after each acquisition. The acquired data are used to measure the shear wave speed in the interrogated area. The results are converted to Young’s modulus and reported in kPa. The M probe was the first to be available commercially and there is more extensive experience with this probe than the others.

Advantages

The technique is relatively inexpensive, highly portable, and widely available, and it has been independently validated in numerous centers worldwide. The instrument is easy to learn and the measurement highly standardized and rapid to perform. For these reasons, it can be used by clinicians at point of service, a major advantage [22]. Young’s modulus thresholds using the M-probe have been proposed for different causes of chronic liver disease, which facilitates interpretation of results [23]. The shear wave frequency is controlled at 50 Hz which ensures comparable measurements. The power output is low since the shear wave is generated mechanically, and there is little energy absorption by tissues.

Limitations

The technique may be limited in patients with obesity, narrow intercostal space, and ascites. Failure rate is lower with the XL probe than the M probe (1.1% vs. 16%) and reliability is higher (73% vs. 50%) [24]. However, the performance of 1D TE with the XL probe in obese subjects is controversial, with some studies reporting unreliability/failure rates as high as 23% [25, 26] and others as low as 6% [27]. This is problematic because obesity-associated fatty liver disease is emerging as the most common cause of chronic liver disease in Western nations. Yet, other elastography techniques also can be challenging in obesity [28]. Further research is required to better understand the performance of all elastographic techniques in the obese population. Although the various probes produce similar results in phantoms, the XL probe provides lower stiffness estimates than the M probe in humans [24, 29]. A plausible explanation is that different regions of interest (window depths) are being measured and that, in obese patients, the region interrogated by the M mode may include subcutaneous tissues, which causes the stiffness to be overestimated. Regardless, stiffness thresholds for staging liver fibrosis reported with the M probe may not be directly applicable to the XL probe [29]. Since anatomic images are not captured, the exact measurement location is not recorded, which may introduce sampling variability for monitoring changes in stiffness over time. Without imaging capability, the device has narrow applications outside of liver examination.

Point shear-wave elastography (pSWE)

Point shear-wave elastography relies on a high-frequency spherical compression wave (acoustic radiation force impulse or acoustic push pulse) focused on a spot [11] which is then absorbed as acoustic energy. The absorbed acoustic energy causes the tissue to expand [30], which creates shear waves perpendicular to the ultrasound beam axis [1]. The shear wave displacement created by the push pulse is recorded by a 2D ultrasound probe using a series of tracking pulses. From this data, the shear wave speed can be derived. There are several implementations of pSWE. These can be integrated onto existing ultrasound imaging scanners by adding the needed hardware (appropriate transducers and electronic components) and software (shear wave tracking algorithms).

On the commercial Acuson S2000 and S3000 systems (Siemens AG, Erlangen, Germany), acoustic radiation force impulses are implemented for qualitative (not further discussed) and quantitative applications. With the quantitative technique (Virtual Touch Quantification), a rectangular region of interest (10 × 6 mm) is placed on a B-mode anatomic image (Figures 2c and 2d). A transient shear wave is generated within the region. The shear wave is tracked and its speed measured. Results are reported as shear wave speed in m/s in a range from 0.5 – 5 m/s in abdominal applications [31].

Advantages

This technique permits selection by the operator of a region of interest in a representative area of the liver. The region of interest is saved and in principle a region of interest in a similar location could be selected in follow-up studies to permit more reliable monitoring. pSWE techniques are more robust than 1D TE because shear waves are produced locally inside the liver and can be transmitted even in patients with a large body habitus or ascites. Although an entire ultrasound scanner may be more expensive than a 1D TE device, the incremental cost of adding the required software to an existing scanner is low.

Limitations

More expertise is needed than with 1D TE. A radiologist or sonographer usually is required, and the technique is less suitable for point of service. pSWE is less validated than 1D TE and currently is available on fewer scanners. Nevertheless, there are sufficient publications for a pooled meta-analysis on the diagnostic performance of pSWE for staging of liver fibrosis [32]. The shear wave frequency is difficult to control precisely, which may introduce variability in measurements between different probes and manufacturers. Compared to 1D TE, there is greater energy absorption by tissue.

Shear Wave Elastography (SWE)

The Supersonic Shear Imaging technique (Aixplorer, Aix-en-Provence, France) combines a cone-shaped quasi-planar wavefront and an ultrafast imaging technique to track shear wave displacements across an entire imaging plane [33]. An acoustic radiation force is focused at successively greater depths on an axial line to produce multiple sequential spherical wavefronts. These interfere constructively to create a Mach cone with greater displacement magnitudes than those produced by the individual wavefronts. By analogy with supersonic planes, the Mach cone is produced because the rate of sequential wavefront production is greater than the speed of the resulting shear waves. In the commercial implementation of SWE, several Mach cones are produced at different lateral positions of the image. An ultra-high frame rate (up to 15000 images per second) is used to scan the entire imaging plane in one acquisition with high temporal resolution [12]. The combination of Mach cone generation and fast imaging allows real-time generation of elastograms. The results are reported as m/s or converted to Young’s modulus in kPa.

Advantages

This technique, which also relies on acoustic radiation force to generate shear waves, has similar strengths as pSWE. Fast imaging permits generation of quantitative elastograms. Multiple regions of interest then can be positioned on the elastograms, thereby reducing some of the sampling variability that can occur with 1D TE and pSWE [34].

Limitations

SWE has the same limitations as pSWE with regard to use of acoustic radiation force impulses. Compared to TE and pSWE, SWE has restricted product availability and currently there are fewer studies on its diagnostic performance for assessment of liver fibrosis [12, 35, 36].

Newer Ultrasound-based Systems

GE Healthcare and Philips just released commercial shear wave elastography packages for some of their imaging systems. These utilize acoustic radiation force to generate transient shear waves. Other manufacturers are following suit.

Magnetic Resonance Elastography

MR elastography has been implemented on 1.5 and 3.0T clinical scanners. The measured stiffness does not depend on field strength [37] but, as discussed earlier, does depend on mechanical excitation frequency [38]. Hence, mechanical properties acquired at different field strengths should be comparable as long as they are obtained with the same mechanical excitation frequency.

Because the spatial encoding of the shear wave data is done over multiple wave cycles, MR elastography usually cannot measure transient shear waves. Instead, MR elastography techniques utilize continuous waves.

MR elastography requires 5 components: (1) a driver system to generate oscillatory mechanical waves continuously at a fixed frequency, (2) a phase-contrast multi-phase pulse sequence with motion encoding gradients (MEG) that are synchronized to the mechanical waves, (3) processing of phase-sensitive MR images to depict wave amplitudes (shear wave displacement images or, simply, wave images), (4) further post-processing (using an inversion algorithm) to generate elastograms (Figure 3), (5) analysis of the elastograms.

Figure 3.

The MRE “experiment” works on (a) clinical MR scanners and requires 5 components: (b) a driver system to generate mechanical waves, (c) a phase-contrast multiphase pulse sequence with motion encoding gradients (MEG) that are synchronized to the mechanical waves, (d) acquisition of phase-sensitive MR images which contain raw data on wave motion and can also provide anatomical images, (e) post-processing to generate wave images and stiffness maps, also known as elastograms, and (f) ROI analysis to produce a single stiffness value.

Driver System

Several driver systems have been designed to produce shear waves for MR elastography [39], including pneumatic, electromagnetic, piezoelectric, and focused ultrasound systems. The current commercial system is an acoustic driver that has two components: an active driver in the equipment room that generates compression waves that are transmitted through a flexible tube to a passive driver positioned against the right anterior chest wall of the subject in the scan room and secured using an elastic band. The passive drive usually is made of plastic and contains a flexible membrane that transmits the compression waves into the patient. The active driver does not need to be MR-compatible. These compression waves are then converted inside the patient’s body to shear waves by mode conversion.

In MR elastography, compression waves are generated continuously throughout the entire pulse sequence. The frequency used is typically around 60 Hz, as this low-frequency range results in waves with better propagation than higher-frequency waves while still yielding measurable shear wavelengths ranging from millimeters to centimeters [40].

Pulse Sequence

Various motion-sensitized MRI sequences – including gradient-recalled echo [4], spin echo [41], echo planar imaging [38, 42], steady state free precession [43] – may be used to track the shear waves traversing the tissue of interest.

A trigger pulse keeps the motion-encoding gradient synchronized with the compression waves generated by the driver. In most implementations, the frequency of the motion encoding gradients matches the frequency of the waves. In the commercial 2D MR elastography sequence, the motion-encoding gradient is only applied in the Z direction (orthogonal to the patient axial plane), which suffices for 2D inversion of the wave component propagating along the XY plane. In investigational 3D MR elastography sequences, motion-encoding gradients are successively applied in the X, Y and Z directions. A generic MR elastography pulse sequence diagram designed to detect the propagation of shear waves is illustrated in Figure 4.

Figure 4.

Generic MR elastography sequence. A trigger pulse synchronizes the mechanical vibration and the motion encoding gradient (MEG). In this diagram, the MEG is applied using the slice-select gradient. The MEG are applied successively in the X, Y and Z directions (when generating data for 3D inversion) and switched in polarity. In this diagram, the frequency of the MEG matches the frequency of the cyclical mechanical vibrations. Varying the trigger delay shifts the phase of the mechanical wave relative to the pulse sequence (MEG) allowing generation of data that captures the propagation of the wave displacements and which can be played as a cine loop. Typically, four phase offsets are applied. Interpolation is applied to double the number of phase offsets, from 4 to 8 wave images to generate a fluid cine-loop.

Image Acquisition

Images are acquired with a modified phase contrast technique that generates both magnitude and phase images. Because the motion-encoding gradients are synchronized with the frequency of the shear waves (phase locked), tiny particle displacements caused by the shear waves can be detected on the phase image. To acquire snapshots of the shear wave propagation, phase images are acquired at different time offsets between the motion sensitization gradients and the shear waves (called phase offsets). Typically four phase offsets are acquired (although 3D inversion techniques in development and described later use three phase offsets) to sample different spatial displacements of the wave cycle. Images at each phase offset are acquired through the liver at several slice locations to sample different portions of the liver. The total acquisition time is about one minute, typically divided into four separate ~15-second breatholds (one for each slice location), acquired in end expiration if possible.

Post-processing

The source phase images are post-processed to produce wave displacement images. A mathematical filter called the curl filter separates the compression from the shear wave components. In the clinical implementation adopted by MR vendors, four additional phase offsets are interpolated to double the number of phase offset steps at each level to produce a fluid cine-loop with 8 wave images. Color maps are typically applied to these wave images in which red and blue hues indicate opposite wave polarity and color saturation indicates wave amplitude.

These wave images are further processed to create elastograms which depict the magnitude of the complex shear modulus. Waves propagate in three dimensions. The conversion from shear wave displacement images to parametric maps requires solving an inverse problem: i.e., what distribution of stiffness (or related parameter) explains the observed wave patterns. With 2D inversion algorithms, only two directional components within a slice of the 3D wave propagation are analyzed. With 3D inversion algorithms, a more complete analysis of the full wave motion is possible. Mathematical inversion algorithms currently require simplifying assumptions about tissue properties [44], including that it has a uniform density of 1 gm/cm³ and that it is purely viscoelastic with locally (microscopically) homogeneous, isotropic, and linear mechanical properties. The color elastograms represent the shear modulus with scales from 0 to 8 kPa and from 0 to 20 kPa. In an advanced implementation, an elastogram confidence mask is automatically created that displays the portions of the elastogram in which the wave data is considered reliable.

Image Analysis

To obtain a single reportable value from the multi-slice parametric maps, the MRE-generated magnitude images, wave images, and elastogram confidence masks are viewed together. Geographic regions of interest are drawn manually on portions of the liver parenchyma with reliable data, while avoiding edges of liver, large blood vessels, and regions with multi-path wave interference. Since regions of interest are drawn manually, some subjectivity (operator dependence) is unavoidable. Automated analysis techniques are in development; these are expected to reduce operator dependence.

Parameters Reported

In most publications using a now commercially available implementation of MRE, quantitative results have been reported as “shear stiffness” in kPa. This is taken to mean the magnitude of the complex modulus, also in kPa [45–48]. See example elastograms in Figure 5. Publications using investigational implementations have reported additional parameters such as storage (G′) and loss modulus (G″) [38] or elasticity and viscosity by assuming a Kelvin-Voigt model [49].

Figure 5.

MR elastography in different subjects correlated with biopsy-documented fibrosis stages. (a–e) Axial wave cine-loops and (f–j) corresponding axial elastogram images in subjects with fibrosis stages 0 to 4. The color elastogram represents the magnitude of the complex shear modulus with a scale from 0 to 8 kilopascals (kPa).

Advantages

While numerous investigative teams have developed different MR elastography techniques, utilizing different hardware and software, only one technique is being adopted for clinical implementation by the major MR scanner manufacturers, which potentially will enable reproducibility of results. The hadware and software for this technique are produced by Resoundant Inc (Rochester, MN) and made available by the scanner manufacturers as commercial elastography packages. MR elastography provides a high diagnostic accuracy for advanced fibrosis. This technique is robust, as it is feasible in larger patients or even those with ascites. Compared to ultrasound-based techniques, MR elastography assesses a larger proportion of the liver, which may potentially reduce sampling variability for longitudinal monitoring. The incremental cost of hardware and software is less than cost of a new 1D TE device but higher than the cost of purchasing shear wave elastography software for an existing ultrasound system. Power output and energy absorption by tissues are minimal, as the shear waves are generated externally.

Limitations

Due to reliance on gradient-recalled-echo sequences, quality in the current commercial implementation may be degraded in patients with iron deposition. Investigational sequences may permit MR elastography measurements even in patients with significant iron deposition. MR elastography requires post-processing and offline analysis to obtain valid average stiffness measurements. The calculation involves some subjectivity inherent to the selection of the regions of interest. MR elastography has limited availability outside of academic centers. Additional time is required for positioning the passive transducer, and the tension with which the transducer is secured is not yet standardized. The transducer causes discomfort in some patients, which may be alleviated by flexible traducers in development. Liver MR elastography is acquired with different breatholds; if breatholds are not consistent, this may potentially introduce errors which are not yet well characterized. Finally, shear waves tend to attenuate in normal (soft) livers; consequently wave propagation may be poor in patients with normal livers, and large regions of interest are not always obtainable.

Comparison of Techniques

The relative strengths and limitations of ultrasound-based and MR-based techniques for staging of liver fibrosis are summarized in Table 4.

Table 4.

Strengths and limitations of US elastography and MR elastography techniques for staging of liver fibrosis

Modality	Implementations	Strengths	Limitations
Ultrasound	1D Transient elastography (TE)	Relatively inexpensive Highly portable Widely available Independently validated worldwide Used by clinicians at point of service Shear wave frequency controlled at 50 Hz Little energy absorption by tissues	Failure and unreliable results due to obesity, narrow intercostal space, ascites Potential classification discrepancies between M, XL, and S probes No anatomic images captured No recording of exact measurement location Narrow applications outside of liver investigation
	Point shear-wave elastography (pSWE)	Permits selection of a ROI on B-mode ultrasound images ROI is saved and may be selected in follow-up studies to permit reliable monitoring pSWE more robust than 1D TE Generates shear waves inside the liver (more robust) Diagnostic performance similar to that of 1D TE Low incremental cost of adding required software to an existing scanner	More expertise required than 1D TE (requires a radiologist or sonographer) Not suitable for point of service Less validated than 1D TE Greater energy absorption by tissue than 1D TE
	Shear Wave Elastography (SWE)	Same strengths as pSWE techniques Fast imaging permits generation of quantitative elastograms Numerous ROIs may be positioned on the elastograms May reduce sampling variability that can occur with 1D TE and pSWE	Same limitations as pSWE Limited availability of this ultrasound system Fewer studies on its diagnostic performance for staging liver fibrosis than 1D TE and pSWE
Magnetic resonance imaging	Magnitude of complex shear modulus	Same hardware and software adopted across MR vendors, which potentially will provide reproducible results High diagnostic accuracy for advanced fibrosis Robust (feasible in larger patients or with ascites) Images a larger proportion of the liver, potentially reducing sampling variability for longitudinal monitoring Incremental cost of hardware and software lower than cost of new 1D TE device Low power output and energy absorption by tissues	Quality may be degraded in patients with marked iron deposition Requires post-processing and offline analysis Limited availability outside of academic centers Some subjectivity in selecting regions of interest Additional time required for positioning the transducer Acquisition with different breatholds Large ROIs not always obtainable due to shear wave attenuation in normal liver
	Complex (G′, G″)	Multifrequency approach permits calculation of elasticity and viscosity	Currently in research domain

Note—G′ = storage modulus. G″ = loss modulus. ROI = region of interest.

Conclusion

Over the past two decades, elastography techniques have evolved significantly from investigational prototypes to clinical tools used for patient care. Depending on the indication (screening, diagnosis, or monitoring of liver fibrosis), different modalities may be preferred according to their respective strengths and limitations.

Ultrasound elastography techniques are relatively inexpensive, portable, and increasingly available while providing good diagnostic accuracy, but may be unreliable in obese patients and those with narrow intercostal spaces. MR elastography offers excellent diagnostic accuracy that probably slightly exceeds that of ultrasound-based techniques, but quality may be degraded in patients with marked iron deposition and availability remains comparatively limited. In a research setting, MR elastography may become a surrogate reference standard when liver biopsy is either not feasible or acceptable.

Key Learning Points.

1. Imaging-based elastography techniques have been developed to measure stiffness and other mechanical properties non-invasively for both research and clinical indications.

   In general, these techniques cannot measure stiffness directly; instead, they assess stiffness indirectly by measuring the speed of shear waves propagating in the tissue of interest. The underlying concept is that shear wave speed is related to tissue stiffness: shear waves travel faster in stiff tissues and slower in soft tissues.

2. By measuring shear wave speed, ultrasound elastography and magnetic resonance (MR) elastography techniques estimate tissue stiffness. Depending on the technique, various stiffness-related parameters may be reported.

   1. The most commonly reported parameters and corresponding units are shear wave speed in meters/second, magnitude of complex shear modulus in kPa (commonly described in the literature as “shear stiffness”), and Young’s elastic modulus in kilopascal (kPa) (commonly described in the medical literature as “elasticity”). The lack of uniformity in reported parameters complicates comparisons across techniques.

   2. These elastography techniques may also measure parameters other than stiffness, including shear wave attenuation and tissue viscosity, although these additional parameters are considered investigational and not yet reported clinically.

3. Shear waves may be generated by applying a mechanical vibration to the surface of the body or by focusing an acoustic radiation force (acoustic push pulse) inside the tissue of interest.

   1. Some ultrasound-based techniques use mechanical vibration for shear wave generation while others use acoustic radiation force.

   2. Commercial MR-based techniques use only the former.

   3. The duration of the shear waves also is variable. Shear waves are generated transiently for ultrasound elastography and continuously for MR elastography.

4. Ultrasound elastography techniques track shear waves by using ultrasound tracking beams. Some ultrasound-based techniques display parametric maps called “elastograms” that display the spatial distribution of the stiffness-related parameter of interest; others provide only numerical results.

5. MR elastography tracks shear waves by acquiring images with wave motion-sensitized phase-contrast sequences. Tissue motion caused by the shear waves during the scan are encoded into the phase of the MR signal. This phase information is further processed to generate “wave images” depicting shear wave displacements within the liver. Subsequent processing of the wave images produces “elastograms”.

Abbreviations

1D

one-dimensional

2D

two-dimensional

3D

three-dimensional

ARFI

acoustic radiation force impulse

EFSUMB

European Federation of Societies for Ultrasound in Medicine and Biology

Hz

Hertz frequency unit

kPa

kilopascal

MEG

motion encoding gradient

MR

magnetic resonance

pSWE

point shear-wave elastography

SSI

Supersonic Shear Imaging

SWE

shear wave elastography

TE

transient elastography

VCTE

vibration-controlled transient elastography