Magnetic Resonance Elastography of Liver Sudhakar Kundapur Venkatesh, MD, FRCR*, Richard L. Ehman, MD KEYWORDS  MR elastography  Diffuse liver diseases  Chronic liver diseases  Liver fibrosis  Cirrhosis  Focal lesions

KEY POINTS  Magnetic resonance elastography (MRE) is the most accurate currently available technique for noninvasive detection of liver fibrosis.  MRE can accurately differentiate simple steatosis from nonalcoholic steatohepatitis with or without fibrosis.  MRE is a promising technique for characterization of focal liver lesions.  MRE may be useful for during follow-up of chronic liver diseases and assessment of treatment response.

Chronic liver disease (CLD) with cirrhosis is one of the leading causes of death in the United States and its incidence has an upward trend.1 With the recent epidemic of obesity and nonalcoholic fatty liver disease (NAFLD), the prevalence of CLD is likely to increase further. CLD from any cause, if untreated, leads to liver fibrosis and progresses to cirrhosis with its associated complications, namely portal hypertension and hepatocellular carcinoma (HCC). Liver fibrosis is the single most important factor determining the prognosis in CLD. Detection of earlier stages of liver fibrosis may be helpful in prevention of progression of fibrosis and may even result in complete regression if the appropriate treatment is instituted.2–4 Patients with advanced fibrosis and cirrhosis are generally recommended to undergo clinical surveillance for complications.5,6 Staging of liver fibrosis is therefore important in the management of CLD. Liver biopsy, the current gold standard for evaluation of liver fibrosis, is invasive, with a small but

definite risk of complication, and is limited by sampling errors and interobserver variability7–10; these considerations have motivated the search for noninvasive evaluation methods. Laboratory tests such as serum liver enzyme levels and fibrosis score panels are attractive but are not accurate for distinguishing intermediate stages of liver fibrosis and are not specific for liver fibrosis.11–13 With conventional imaging methods like ultrasonography (US), computed tomography (CT), and magnetic resonance (MR) imaging, morphologic changes of surface nodularity and volumetric changes in liver architecture can be detected, but these changes are usually seen only in advanced cirrhosis and are not sensitive enough to accurately detect early fibrosis. MR imaging– based techniques such as diffusion-weighted imaging (DWI) and perfusion MR imaging have also been evaluated for CLD and are discussed in other articles in this issue by Taouli and Koh. Elastography-based techniques are of great interest because they have shown high sensitivity

Disclosure: R.L. Ehman receives royalties and has stock options for the development of MRE technology. R.L. Ehman serves as uncompensated chief executive officer and Board member of Resoundant, Inc, a company established by Mayo Clinic to make MRE technology available. Department of Radiology, Mayo Clinic College of Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA * Corresponding author. E-mail address: [email protected] Magn Reson Imaging Clin N Am 22 (2014) 433–446 http://dx.doi.org/10.1016/j.mric.2014.05.001 1064-9689/14/$ – see front matter Ó 2014 Elsevier Inc. All rights reserved.

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Venkatesh & Ehman and specificity in detection and staging of liver fibrosis.13–16 Elastography can be performed with US or MR imaging. At present, US-based techniques are widely available in Europe and Asia but are limited by high technical failure rates and the influence of confounding factors.14,17,18 MR elastography (MRE)19 is now available in many leading institutions around the world. MRE is the most accurate noninvasive technique available for detection and staging of liver fibrosis.20,21 Clinical experience with MRE is growing and new applications are emerging. This review article focuses on liver MRE. The principles and technique of performing clinical liver MRE are discussed, and clinical applications and emerging applications of liver MRE are described.

ELASTOGRAPHY Elastography and elasticity imaging are terms used to describe imaging techniques for evaluating mechanical (viscoelastic) properties of tissues. The tissue property evaluated is referred to as tissue elasticity, viscoelasticity, or simply tissue stiffness. Several elastography techniques using US and MR imaging exist. Common to all these techniques is the principle of applying a force, namely stress (static, quasistatic, or dynamic), to the tissue and measuring the resulting strain (response), which gives an assessment of tissue stiffness. Most techniques provide quantitative values of stiffness, but some yield qualitative data. Because accurate determination of complex mechanical properties is difficult in vivo, several assumptions are made to simplify the understanding and measurement of tissue stiffness. The tissue is considered to be linearly elastic, homogeneous or isotropic, and made of viscoelastic material that responds equally to stresses in any direction.22,23 The Poisson ratio for soft tissues (the ratio of transverse contraction per unit breadth divided by longitudinal extension per unit length) is close to the value of liquids (v 5 0.500). This ratio simplifies understanding of the complex mechanical behavior of soft tissues. With these assumptions, the Young modulus (E) and shear modulus (m) can be calculated for most soft tissues. Young modulus and shear modulus are related by the equation E 5 3m for most soft tissues.24 Both are expressed in units of kilopascals (kPa). The stiffness in vivo depends on several factors, including tissue components, structural organization, and perfusion (blood flow). Pathologic tissues are expected to have different stiffness from normal tissues because of changes in tissue content and/ or organization. The shear modulus differs significantly between normal and pathologic tissues25–27

and therefore has been the focus of investigation with both US and MR imaging. US-based elastography techniques include transient elastography,28 acoustic radiation force impulse29 imaging, and shear wave elastography,30 as well as several other emerging techniques.31 US-based elastography techniques typically assess a small region of liver, although a significantly larger region than a biopsy. These techniques are accurate enough for broad categorization of liver fibrosis and are excellent for distinguishing cirrhosis from lesser degrees of fibrosis, but are generally limited by the distance of liver from skin, high technical failure rates, and confounding factors including obesity and hepatic inflammation.13,14,17 MRE has high technical success and is more accurate than current US techniques. More details on MRE are discussed later. Readers interested in understanding elasticity and tissue mechanical properties in more detail are referred to the excellent reviews on elasticity theory and elastography in Refs.24,25,27,32–34

MAGNETIC RESONANCE ELASTOGRAPHY Principle of MRE Propagating mechanical shear waves travel faster in stiffer tissues and more slowly in softer tissues. If the waves are continuously propagated in a tissue, the speed of the waves is reflected in the wavelength: the wavelength of the shear waves is longer in stiffer tissue and shorter in softer tissues. The shear waves are captured in a wave image and an inversion algorithm processes the information to give tissue stiffness.24 MRE uses dynamic low-frequency shear waves in the range of 20 to 200 Hz35 because their wavelengths in tissue are in the measurable range of millimeters to tens of millimeters and they undergo less attenuation compared with high-frequency waves.24,25,27 MRE technique has 3 important steps (Fig. 1): (1) propagation of the mechanical shear waves within the liver using a source of vibration, (2) imaging the propagating shear waves in the liver using a dynamic MR sequence sensitive to motion, and (3) processing the spatial information in the propagating shear waves with an inversion algorithm to generate quantitative maps of shear stiffness.

Technique of Liver MRE The MRE technique can be readily be implemented on conventional 1.5-T or 3-T clinical scanners with added hardware to generate the shear waves and dedicated software for processing. The measured mechanical properties do not depend on magnetic field strength; that is, the

Magnetic Resonance Elastography of Liver

Fig. 1. Principles of MRE. Basic 3 steps of liver MRE. (A) A passive abdominal driver transmits vibrations from the active driver and generates mechanical shear waves (yellow dotted lines). (B) An MRE sequence with motionencoding gradients (MEGs) synchronized with the mechanical driver is used to image the displacement caused by the propagating waves (wave image from two-dimensional gradient recalled echo [2D-GRE] MRE sequence shown here). (C) An inversion algorithm automatically processes the information in the wave image and produces a stiffness map (elastogram).

stiffness measured with MRE on 3 T and 1.5 T are same provided they are performed at the same mechanical frequency, because the measured stiffness depends on frequency. The mechanical shear wave frequency typically used is 60 Hz. Liver MRE is generally performed with the subject in supine position. MRE is a breath-hold sequence and is typically performed with breath held at the end of expiration. End expiration is preferred because it reproduces the position of the liver consistently; however, it can also be performed with the breath held in deep inspiration or midinspiration as long as the breath holds are consistent. MRE is performed in the fasting state similar to other liver MR protocols. Generating mechanical shear waves in liver Several systems have been used for producing shear waves, including passive pneumatic drum drivers,15,36,37 piezoelectric bending elements,38 electromechanical voice coils,39,40 and passive rigid rod drivers.41,42 The most commonly used technique (Fig. 2) uses an active audio device located outside the scanner room. This device is connected to a passive pneumatic drum driver

via a 7.5-m (25-foot) plastic tube made of polyvinyl chloride. The passive drum driver is a 19-cm plastic disc with a flexible membrane that is kept in contact with the body (Fig. 3) at the level of the xiphisternum and on the right lower chest and upper abdomen so that it lies over the largest part of the liver (the right lobe). The flexible membrane transmits the vibrations into the body. This passive driver is kept in close contact with the body using an elastic strap, which ensures continuous contact with skin and also prevents the driver from moving during the scan. The disc can be applied in any orientation and placed adjacent to receiver surface coils. The acoustic driver typically produces a continuous vibration at 60 Hz, which then induces mechanical shear waves in the body through the passive driver. These low-energy vibrations are within the European Union directive limits43 and are well tolerated. Imaging the propagating shear waves (MRE sequence) In order to visualize tissue motion caused by shear waves, a pair of motion-encoding gradients

Fig. 2. Setup for performing liver MRE. Subject in supine position with passive driver placed over the liver. The passive driver is connected to the active driver placed outside the magnet room with a 7.6 m plastic tube.

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Fig. 3. Positioning of the passive driver. The driver is placed at the level of the xiphisternum at the midclavicular line, over the right lobe of the liver.

(MEGs) oscillating at the same frequency as the mechanical shear waves is applied with a conventional MR imaging sequence (Fig. 4). Conventional sequences that can be used for MRE include gradient recalled echo (GRE),19,44 spin echo,45 balanced steady state free precession,46 and echo planar imaging.47 The MEGs are applied along a specific direction or in all 3 (x, y, and z) directions and switched in polarity at an adjustable

frequency. Trigger pulses synchronize the acoustic driver with the MRE sequence. The transmitted continuous shear waves in the tissues result in tissue displacement that induces cyclical motion of the spins, which produces a measurable phase shift in the presence of MEGs. The phase offset between mechanical motion and the oscillating MEGs can be adjusted to obtain wave images at various time points. The MR signal thus obtained contains phase shift information at each voxel level, giving a snapshot of shear waves propagating in the cross section of the abdomen.35 Altering relative timing or phase offsets, typically 4 to 8 over varying time points between the mechanical waves and the oscillating MEGs, allows derivation of the harmonic component at the mechanical frequency. The MR images obtained contain the phase information of the propagating wave (wave image). The sequence typically produces a magnitude image and a phase image for each phase offset. Generation of stiffness map (elastogram) Inversion algorithms are applied to the wave images that contain the information on the propagating shear waves.24 The algorithms assume tissue as a linear, isotropic, homogeneous, viscoelastic medium that allows calculation of the shear modulus. The maps produced are called stiffness maps or elastograms. The inversion algorithms can also be configured to report confidence maps based on the correlation coefficients of polynomial fits. To differentiate between regions of reliable and less reliable stiffness data, a threshold of 0.95 is applied in the confidence maps. The algorithm takes about 2 minutes to process a stiffness map after completion of an MRE sequence. The most commonly used clinical MRE sequence is described in Table 1.

Calculating Liver Stiffness

Fig. 4. MRE sequence. A 2D-GRE-MRE sequence. This sequence is a modification of a conventional GRE sequence by adding an MEG applied along the sliceselection direction to detect cyclic motion in the through-plane direction. MEGs can also be placed in the other 2 encoding directions as well. The MEG was designed to minimize zeroth and first gradient moments. The MEG and the acoustic driver are synchronized using trigger pulses provided by the imager. The phase offset (q) between the two can be adjusted to acquire wave images at different phases of the cyclic motion. Four phase offsets are typically obtained in this sequence. ACQ, acquisition; RF, radio frequency pulse.

Depending on the application/vendor, a GRE-MRE sequence typically produces several images (Fig. 5): magnitude and phase images, stiffness maps in gray scale, color stiffness maps (0–8 kPa scale and 0–20 kPa), confidence maps, and color wave images. The gray-scale stiffness map depicts shear stiffness in units of kilopascals. On the magnitude images, regions of interest (ROIs) can be drawn avoiding the liver edges, vessels greater than 3 mm, normal liver fissures, gallbladder fossa, pulsation artifacts from large vessels and heart, and areas of wave interference. These ROIs can then be copied onto the gray-scale maps to give stiffness values in kilopascals (Fig. 6). Placement of ROIs over the left lobe of the liver is generally avoided because cardiac pulsations frequently

Magnetic Resonance Elastography of Liver

Table 1 Liver MRE technique Preparation (h) Field strength (T) Position Passive driver Hardware Passive driver Mechanical frequency (Hz) Acoustic power output (%) Sequence TR/TE (ms) FOV (cm) Fractional phase FOV Matrix Slice thickness (mm) Number of slices Number of excitations ASSET acceleration factor Flip angle ( ) Bandwidth (kHz) MEG frequency/period (Hz/ms) Number of MEGs MEG amplitude (Gauss/cm) MEG direction Number of phase offsets Placement of slices Breath hold Breath hold duration (s) Total MRE acquisition time (min)

Fasting 4–6 1.5 or 3 Supine 19-cm disc (passive driver) with a membrane Active driver placed outside the scanner room 19-cm disc with a membrane 60 50 is optimal and adequate for most cases Two-dimensional GRE-MRE 50/20–26 30–42 (patient specific) 0.7–1.0 (patient specific) 256  128 6–10 4 1 2 30 31.25 60/16.7 1 1.76 (machine dependent) Slice direction 4 Largest cross section of the liver End expiration preferred to reproduce slice position 11–16 depending on size of patient 1–2

Abbreviations: FOV, field of view; TR/TE, time to repeat/time to echo.

cause motion artifacts. The ROIs can be circular, oval, or geographic in shape. Large geographic ROIs are preferred to ensure a large area of liver being sampled. MRE of the liver is performed with 4 slices through the largest cross section of the liver and the liver stiffness is reported as a mean of the stiffness values obtained from placing ROIs in these slices. Automated algorithms that can segment a large geographic ROI on the stiffness maps (see Fig. 6) are also available.48 The color maps give an overview of the stiffness within the liver. The distribution of stiffness across the cross section of the liver can be well appreciated on these color maps. In general, a scale color map of 0 to 8 kPa suffices for routine clinical use. The wide-scale (0–20 kPa) color map is useful in stiff livers and in evaluation of very stiff focal lesions. The color wave images, when run with cine mode, show the propagation of the shear

waves. These images are useful to identify areas of wave interference, which should be avoided when drawing ROIs. The confidence maps display crosshatched areas representing regions with less valid measurement, which ROIs should avoid. Several studies have established that MRE of liver has high repeatability and excellent reproducibility with high interobserver agreement.49–54

CLINICAL APPLICATIONS OF LIVER MRE Liver MRE can be performed in most patients, including obese patients, those with anatomic variants, and those with ascites. The technique can be successfully performed in posttransplant recipients and pediatric patients. MRE should ideally be performed after 4 to 6 hours fasting and, if repeated during follow-up, should be also done with fasting to ensure valid comparisons

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Fig. 5. Typical set of images from MRE of liver. A single-slice MRE acquisition with a 2D-GRE-MRE sequence produces (A) magnitude (B) phase images. Postprocessing of the magnitude and phase images produces several sets of images including (C) a gray-scale stiffness map, (D) a color stiffness map with a scale of 0 to 8 kPa, (E) a 95% confidence map, and (F) a color wave image. In addition, a color scale map with a scale of 0 to 20 kPa, its corresponding confidence map, and a gray-scale phase (wave) image are also generated (not shown).

and to avoid the effect of postprandial status on stiffness. Postprandial status does not significantly change the stiffness of normal liver but may cause increased liver stiffness in chronic liver diseases50,55 because of an impaired autoregulatory response to increased portal venous flow after meals. MRE can be performed before or after intravenous gadolinium injections used routinely for liver studies, including gadoxetate.56,57 The normal liver is a soft organ and, at 60 Hz, the

mean stiffness ranges from 1.54 to 2.87 kPa.15,52,54,58 The wide range of stiffness is probably due to various populations studied. No systematic effect of age, sex, body mass index, diet, or ethnicity on liver stiffness has been established. Most normal livers have stiffness value less than 2.5 kPa. This stiffness is similar to that of subcutaneous fat. Simple steatosis (isolated fatty liver) also does not result in any significant increase in stiffness.15,52,54,58

Fig. 6. Measuring liver stiffness. (A) A manual region of interest drawn by an independent observer on the magnitude image is (B) copied on to the stiffness map with 95% confidence map. (C) Geographic region of interest by automated segmentation algorithm. Note that the mean values with both ROIs are similar.

Magnetic Resonance Elastography of Liver Detection and Staging of Liver Fibrosis Untreated CLD from any cause leads to liver fibrosis and, if progressive, to cirrhosis and its associated complications. In liver fibrosis there is accumulation of extracellular matrix mainly from increase in collagen content. Liver biopsy is the current gold standard for detection and staging of liver fibrosis but is limited by sampling errors59 and interobserver variability.60 Various histologic staging systems are available for different causes. One of the most commonly used liver fibrosis staging system is the METAVIR system: F0, no fibrosis; F1, portal fibrosis without septa; F2, portal fibrosis with rare septa; F3, portal fibrosis with numerous septa and bridging; F4, cirrhosis. The staging systems are qualitative and do not precisely measure the degree or amount of fibrosis and hence are thought not to be suitable for monitoring therapies.61 Morphometric evaluation of fibrosis in biopsy samples provides quantitative estimation of degree of fibrosis61–63 and is considered better than histologic staging for assessing mild fibrosis64,65; however, these techniques also require liver biopsy and have the same limitation of sampling error. Liver fibrosis results in increased stiffness of the liver, which can be detected by elastography techniques (Box 1). A preliminary study recently showed that liver stiffness with MRE correlates with fibrosis in biopsy samples.66 MRE is accurate for the detection of liver fibrosis and for differentiating normal livers from fibrotic liver.15,67 (Box 2) MRE can detect increased liver stiffness caused by fibrosis in morphologically normal-appearing liver on conventional MR imaging. Liver stiffness increases systematically with increasing stages of fibrosis (Fig. 7). MRE can differentiate liver fibrosis from normal and/or F0 (livers with inflammation but no fibrosis) with an accuracy ranging from 89% to 99%.15,16,67–69 The cutoff stiffness value for detection of liver fibrosis is greater than 2.4 kPa in published series.15,67–70 Clinically significant fibrosis (defined as at least F2) can be diagnosed with accuracy exceeding 95%.15,16,68–71 Differentiation of cirrhosis from lesser degrees of fibrosis has an accuracy

Box 1 Common causes of increased liver stiffness  Fibrosis  Acute inflammation or acute flare  Portal hypertension  Passive congestion  Acute biliary obstruction

Box 2 Clinical indications for liver MRE  Detection of liver fibrosis  Staging of liver fibrosis  Differentiation of simple steatosis from nonalcoholic steatohepatitis  Longitudinal disease

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 Assessment of treatment response Potential use in characterization of focal liver lesions based on stiffness values.

exceeding 98%. MRE is therefore able to stage liver fibrosis with excellent accuracy and is suitable for clinical decisions (Box 3). Patients with clinically significant fibrosis are candidates for antifibrotic treatment provided they satisfy other requirements, whereas those with cirrhosis generally undergo surveillance for complications. Accuracy of MRE is significantly better than routine serum liver enzymes or tests16,68,69 and transient (ie, ultrasonography) elastography.70 Liver stiffness may be affected by acute inflammation of the liver, acute flares in chronic viral hepatitis, acute biliary obstruction, or passive congestion from increased central venous pressure from any cause, such as congestive cardiac failure (see Box 1). Performing MRE of liver when these conditions are already known to be present is best avoided. The presence of these confounding factors should also be excluded before interpretation of liver stiffness, especially when mildly increased stiffness is detected in patients with no known risk factors for CLD. When clinical features, laboratory tests, and liver stiffness do not correspond, a liver biopsy may be performed.

Differentiation of Simple Steatosis from Nonalcoholic Steatohepatitis Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the United States.72 The clinicopathologic spectrum of NAFLD ranges from simple steatosis to nonalcoholic steatohepatitis (NASH) (steatohepatitis with or without fibrosis) that may progress to cirrhosis and its associated complications. Therefore distinguishing simple steatosis and NASH with and without fibrosis has important implications for management.73 MRE can be performed in obese patients and the degree of fatty change in the liver or amount of subcutaneous fat does not affect the technique. Simple steatosis does not cause increase in stiffness and is similar to

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Fig. 7. MRE in livers with various stages of fibrosis. The stiffness of the liver increases with increasing stages of liver fibrosis. Shown here are examples of biopsy-proven liver fibrosis stages from F0 to F4 from different causes. The top row shows T2-weighted images and the bottom row shows stiffness maps at corresponding levels. The mean stiffness of the liver is shown below the stiffness map.

normal liver.15,52,54,58 Livers with NASH have increased liver stiffness (Fig. 8).74,75 Simple steatosis can be differentiated from NASH with an accuracy of 93% using a cutoff value of 2.74 kPa.74 NASH with advanced fibrosis can similarly be detected with 95.4% accuracy using a cutoff value of 4.15 kPa.75 MRE is probably the best available technique to accurately differentiate simple steatosis from NASH.

Other Applications Evaluation of focal lesions MRE may be useful in the evaluation of focal liver lesions (Fig. 9). Preliminary studies have shown that malignant tumors have higher stiffness than benign tumors and normal liver.37,76 In one study, malignant tumors could be differentiated from benign tumors with 100% accuracy using a cutoff value of 5 kPa.37 MRE is promising for characterization of focal lesions and further studies in this direction are awaited.

Box 3 Suggested guidelines for interpretation of liver stiffness with MRE at 60 Hz 5 kPa: stage 4 fibrosis or cirrhosis

Clinical follow-up and treatment response assessment Liver MRE is probably the most promising available technique for the clinical follow-up of CLD (Fig. 10) and for assessment of response to antifibrotic treatment (Fig. 11). Studies establishing the role of MRE for follow-up and response assessment are required. Emerging applications Several applications are emerging for MRE in the assessment of liver diseases. Preliminary studies have shown utility of MRE in the detection of liver fibrosis secondary to methotrexate, a hepatotoxic drug used in the treatment of psoriasis and other conditions.77 In another study, MRE was shown to be useful in the evaluation of liver fibrosis in patients after Fontan surgery who are at risk of fibrosis caused by increased right atrial pressures.78 MRE showed high accuracy in detecting significant fibrosis in liver transplants (Fig. 12).79–81 MRE of the spleen may be useful as a noninvasive method to assess portal hypertension and to predict esophageal varices.82

LIMITATIONS OF MRE The most common reason for failure of liver MRE is iron overload in livers. The standard MRE sequence is GRE based and is therefore sensitive to the presence of iron in liver. The propagation of waves is not affected, but the signal from liver is poor, resulting in failed MREs. Modified MRE sequences with low echo times are available to increase the signal from liver.83 MRE is also a breath-hold sequence and is therefore susceptible to motion artifacts. At present, a single slice

Magnetic Resonance Elastography of Liver

Fig. 8. MRE can differentiate simple steatosis from steatohepatitis and steatohepatitis with fibrosis. Mean liver stiffness values are displayed on the stiffness maps. Simple steatosis has normal liver stiffness, whereas stiffness is increased in steatohepatitis both with and without cirrhosis.

Fig. 9. MRE of focal liver lesions. Examples of (A) HCC, (B) hemangioma, and (C) focal nodular hyperplasia. The regions of the focal lesions are outlined on the stiffness maps.

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Fig. 10. Usefulness of MRE in longitudinal clinical follow-up of liver fibrosis. A case of primary biliary cirrhosis shows progressively increasing liver stiffness on annual follow-up over a 2-year period. Note that there are no changes in liver surface contour or gross architecture.

Fig. 11. Assessment of treatment response in a patient with chronic hepatitis B. Initial baseline assessment (A) showed moderately increased liver stiffness. The patient was started on antiviral therapy. Two years later, MRE (B) shows significant increase in liver stiffness consistent with progression of cirrhosis and no response to treatment. The region of the liver has been outlined in the stiffness maps.

Fig. 12. MRE of a liver transplant. (A) Contrast-enhanced axial image, (B) wave image, and (C) stiffness map showing normal stiffness of the transplant, ruling out significant fibrosis.

Magnetic Resonance Elastography of Liver through liver can be obtained in 12 seconds or less, greatly improving image acquisition.

FUTURE DIRECTIONS MRE as a technique is evolving and there are opportunities to improve resolution. It may be possible to differentiate different pathologic processes such as inflammation, edema, and passive congestion from fibrosis using additional parameters such as anisotropy and wave attenuation, and different mechanical models. Volumetric assessment of livers may be possible with threedimensional acquisitions, which may provide an opportunity to assess overall liver fibrosis burden, a parameter that could predict outcomes in CLD with higher accuracy.

SUMMARY MRE of the liver is the most accurate current technique for detection and staging of liver fibrosis. Liver MRE is promising and future refinements in the technique and new applications continue to emerge.

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