Sunday, November 27, 2011

Magnetic Resonance Elastography: Accurately identify the presence and progression of hepatic fibrosis

What Is Magnetic Resonance Elastography (MRE) ?

Today on the blog we have a small update on Magnetic Resonance Elastography (MRE) this entry will include abstracts from 2011, and an article written this month by By Benjamin E. Tubb, M.D., Ph.D.

A few years back we read at Mayo about a new technology called Magnetic Resonance Elastography (MRE) - the latest form of elastography to detect tissue elasticity. MRE provides an early warning in detecting hardening of the liver, and can detect liver fibrosis before it turns into cirrhosis. The technique uses sound waves to see if a patient's liver is harder than it should be - or if it's developing fibrosis.

Hepatitis C and B can lead to long-term liver damage including fibrosis and cirrhosis. Because viral hepatitis causes chronic liver inflammation the formation of scar tissue or fibrosis may occur overtime.

How Does MRE Work?

The Texture Or Stiffness Of The Liver Is Measured By Color Coded Images

During a physical examination of the liver a physician may push or feel for the liver, referred to as palpation. If the liver is healthy it will feel soft. A liver that has fibrosis or scar tissue will feel a bit firmer, and a liver that has progressed to cirrhosis is extremely hard.

With this technology (MRE), the texture of the liver, or stiffness can be measured by images of the liver coded with different colors.

The stiffest areas of the liver show up as red on the elastogram. The softest most flexible parts of the liver show up as purple.

The top picture is Elastograms of a normal liver, the bottom picture is a liver with grade 3 fibrosis, validated by biopsy.

Comparing the two slides we notice the top *soft- healthy liver is coded in purple. The texture or *stiffness of the liver with fibrosis is coded in red .

Thus far early results have shown that MRE is highly accurate in detecting moderate to severe liver fibrosis in many different types of liver disease. This technique may offer a noninvasive alternative to liver biopsy.

November Article

From Intrinsic Imaging

By Benjamin E. Tubb, M.D., Ph.D., Board Certified Radiologist, Intrinsic Imaging

Nov 21 2011

San Antonio (TX), Boston (MA)

Magnetic resonance elastography is an emerging MRI technology that provides sensitive and semi-quantitative assessment of tissue stiffness. The most promising clinical application for MR Elastography is the assessment of liver stiffness as a surrogate marker of liver disease and fibrosis. Liver fibrosis is the primary pathologic process in cirrhosis which affects millions of Americans and causes significant morbidity and mortality. The incidence of liver disease and cirrhosis is increasing, especially cirrhosis related to chronic viral hepatitis and nonalcoholic fatty liver disease (NAFLD). When incorporated into a comprehensive liver MRI exam, elastography provides a sensitive assessment for early diffuse liver disease and a semi-quantitative assessment for stage and progression of fibrosis.

Management of patients with liver disease such as chronic viral hepatitis or NAFLD involves careful monitoring for the development and progression of liver inflammation, fibrosis, and cirrhosis. This is usually achieved through a combination of physical exam, laboratory testing, and imaging. Imaging may include abdominal ultrasound, CT, or MRI exams. However, all of these tests may remain normal during the early stages of liver disease. The liver does not demonstrate gross morphological abnormalities such as nodular contour or segmental atrophy until advanced stages of fibrosis; complications of cirrhosis such as portal venous hypertension, splenomegaly, and ascites also indicate advanced disease. Therefore, in patients with potential early disease, liver biopsy is often used to assess for presence of active liver inflammation and fibrosis. Liver biopsy is an expensive and invasive procedure with associated risks. Also, liver biopsy suffers from sampling error, sometimes underestimating or overestimating the actual degree of liver disease.

MR Elastography has been developed by Dr. Richard Ehman and colleagues at the Mayo Clinic as a noninvasive mechanism of evaluating tissue stiffness. Dr. Ehman's group and others have demonstrated that patients with liver disease have progressively increased stiffness of their liver tissue which can be detected and quantified with MR Elastography, years before the development of gross anatomic abnormalities of liver size and shape that are detectable by other imaging modalities.

MR Elastography requires specialized equipment and software, which are included with some new MRI scanners and can be added to many installed scanners. The necessary equipment is relatively simple: a small disc-shaped transducer is placed over the patient's upper abdomen by the technologist at the start of the exam, and the transducer is connected through a flexible plastic tube to a speaker-like device, which creates low frequency sound waves at a fixed frequency of approximately 40-90 Hertz. These sound waves pass through the transducer and cause small vibrations within the patient's abdomen, without discomfort to the patient. These vibrations create pressure waves within the liver which are detectable through sensitive MR sequences. Specifically, MR Elastography employs phase contrast MR sequences which are sensitive to the direction and amplitude of tissue motion. In patients with chronic liver disease, as the liver tissue becomes stiffer, the wavelength of the pressure waves becomes longer. This can be visualized in color-coded images, and specialized image analysis software can measure the wavelengths and provide quantitative estimates of tissue stiffness, throughout the liver or within a specific region of interest. Tissue elasticity results are reported in kilopascals (kPa). The entire MR Elastography acquisition can be performed in 1 minute, with negligible increase in overall length of the MRI exam.

Studies have demonstrated that MR Elastography provides highly reliable measurements, with little test-retest variation. Normal subjects demonstrate consistent liver stiffness measurements with mean of 2.2 kPa and standard deviation of 0.3 kPa, corresponding to normal soft liver tissue. Patients with increasing degrees of liver fibrosis demonstrate a direct correlation between elastography measurements and stage of fibrosis defined in liver biopsy specimens. Importantly, patients with early liver disease and stage 0 or stage 1 fibrosis demonstrate elevated liver stiffness measurements of approximately 3.5-4.0 kPa. Using a cut-off value of 2.93 kPa, Yin et al. achieved remarkable sensitivity of 98% and a specificity of more than 99% for differentiating any stage of liver fibrosis from normal liver tissue (reference below). Using a cut-off value of 4.89 kPa, these researchers were able to differentiate early disease with stages 0-1 fibrosis from more advanced disease with stages 2-4 fibrosis, with 86% sensitivity and 85% specificity. These results represent a marked improvement over other available tests for early liver disease and will enable greatly improved detection of early liver fibrosis in patients at risk.

MR elastography will allow clinicians to more sensitively and accurately identify the presence and progression of hepatic fibrosis in patients with chronic liver disease, especially the large number of patients with viral hepatitis (5 million Americans) and nonalcoholic fatty liver disease (31 million Americans). MR elastography results will potentially help guide clinicians' decisions about when to perform invasive liver biopsy and how and when to adjust patient therapy. As improved therapies become available, including therapies targeted at slowing, preventing, or even reversing hepatic fibrosis, the highly repeatable and quantitative measurements obtained by MR Elastography will provide accurate assessment of treatment responses.

Some therapies are already in use for treatment of chronic viral hepatitis, such as *Blog Note-(new protease inhibitors) Interferon and Ribavirin, and clinicians may begin to use elastography results to assess the necessity and efficacy of these treatments. Within the larger number of patients with NAFLD, approximately 10-20% will develop active liver inflammation and fibrosis, termed nonalcoholic steatohepatitis (NASH), with significant risk of progression to cirrhosis. Currently there are no specific therapies for NASH, but there is tremendous research interest in this direction. Experimental treatments for NASH include trials of newer antidiabetic medications that increase insulin sensitivity and may reduce liver injury. NIH-sponsored studies of these medications in patients with NASH are underway, including trials of rosiglitazone, pioglitazone, and metformin. There are many other pharmaceutical agents in development for the prevention and treatment of liver fibrosis. MR elastography will play an important role in future trials of these agents, providing noninvasive and quantitative measurements of liver fibrosis, potentially complementing or partially replacing liver biopsy in assessment of patients’ stage and progression of liver disease.

About the Author

Dr. Tubb is a Board Certified Radiologist at Intrinsic Imaging. He obtained his radiology residency training at Johns Hopkins Hospital after completing the combined MD-PhD program at Baylor College of Medicine in Houston, TX. His PhD research was in Molecular and Cellular Biology, with multiple peer-reviewed publications and experience in experiment design and data analysis. During his radiology residency, Dr. Tubb received a one year RSNA Resident Research Award and designed a research project involving targeted MRI contrast agents and high resolution pancreatic imaging. He served as chief resident at Johns Hopkins and also served on the admissions committee. Following residency, Dr. Tubb completed a one year MRI fellowship at the University of Pennsylvania, with broad experience in body/oncologic, breast, spine, and musculoskeletal imaging. Dr. Tubb is actively involved with the design and implementation of the imaging components of clinical trials, as well as application of new imaging technology such as MRI elastography for evaluation of liver disease.

MR elastography (MRE) Abstracts 2011-2010


September 2011

MR elastography for noninvasive assessment of hepatic fibrosis: Experience from a tertiary center in asia
Kim BH, Lee JM, Lee YJ, Lee KB, Suh KS, Han JK, Choi BI; Journal of Magnetic Resonance Imaging (Sep 2011)


To determine the sensitivity and specificity of MR elastography (MRE) in the staging of hepatic fibrosis (HF) using histopathology as the reference standard in an Asian population.


MRE was performed on 55 patients with chronic liver diseases or biliary diseases and on 5 living related liver donors (48 men and 12 women; mean age, 55.7 years). MRE was performed with modified, phase-contrast, gradient-echo sequences, and the mean stiffness values were measured on the elastograms in kilopascals(kPa). Receiver operating characteristic curve analysis was performed to determine the cutoff value and accuracy of MRE for staging HF. Histopathologic staging of HF according to the METAVIR scoring system served as the reference.


Liver stiffness increased systematically along with the fibrosis stage. With a shear stiffness cutoff value of 3.05 kPa, the predicted sensitivity and specificity for differentiating significant liver fibrosis (≥ F2) from mild fibrosis (F1) were 89.7% and 87.1%, respectively. In addition, MRE was able to discriminate between patients with severe fibrosis (F3) and those with liver cirrhosis (sensitivity, 100%; specificity, 92.2%), with a shear stiffness cutoff value of 5.32 kPa.


MRE could be a promising, noninvasive technique with excellent diagnostic accuracy for detecting significant HF and liver cirrhosis. J. Magn. Reson. Imaging 2011. © 2011 Wiley-Liss, Inc.

Magnetic resonance elastography and biomarkers to assess fibrosis from recurrent hepatitis C in liver transplant recipients.

Division of Hepatology, Northwestern University Feinberg School of Medicine, 676 N. Street Clair, Chicago, IL 60611, USA.


Imaging techniques evaluating liver stiffness (magnetic resonance elastography [MRE]) and biomarkers may be useful indicators of fibrosis stage in hepatitis C virus (HCV)+patients. Our aim was to compare the accuracy of MRE and biomarkers in staging fibrosis because of recurrent HCV in liver transplant (LT) recipients with hepatocellular carcinoma.


Liver magnetic resonance imaging and MRE, FIBROSpectII, aspartate aminotransferase-to-platelet ratio index (aspartate aminotransferase [AST]: platelet index), AST:alanine aminotransferase ratio, and magnetic resonance imaging/MRE-guided biopsies targeting the stiffest regions (right and left lobes) were performed in HCV+LT recipients. Sensitivity, specificity, positive predictive value (PPV)/negative predictive value (NPV), and likelihood ratios were calculated for the best cutoff by receiver operating characteristic analysis.


Thirty-two recipients were included: 28 men, age 60 (±6.4) years, and time since LT 3.25 (±1.68) years. Both MRE (P=0.0001) and FIBROSpectII (P=0.009) were significantly different between no fibrosis and more than or equal to stage 1 groups, whereas aspartate aminotransferase-to-platelet ratio index and AST:alanine aminotransferase ratio were not different.

Areas under the receiver operating characteristic curve were 0.87 for MRE and 0.84 for FIBROSpectII. MRE cutoff of 3.81 kPa had 87.5% sensitivity, 79.2% specificity, 58.3% PPV, and 95.0% NPV; FIBROSpectII cutoff of 42 had 87.5% sensitivity, 70.0% specificity, 53.8% PPV, and 93.3% NPV for detection of more than or equal to stage 1 fibrosis. Two patients had high MRE values because of unexpected acute rejection and portal vein thrombosis.


MRE and FIBROSpectII are highly sensitive in detecting fibrosis due to recurrent HCV. Both are limited by the low specificity/PPV and confounding because of other graft complications. Values below the MRE and FIBROSpectII cutoffs, however, strongly suggest the absence of fibrosis and may avert the need for protocol biopsy staging.

July 2011

Test-retest repeatability of MR elastography for noninvasive liver fibrosis assessment in hepatitis C;

Shire NJ, Yin M, Chen J, Railkar RA, Fox-Bosetti S, Johnson SM, Beals CR, Dardzinski BJ, Sanderson SO, Talwalkar JA, Ehman RL; Journal of Magnetic Resonance Imaging (Jul 2011)


To conduct a rigorous evaluation of the repeatability of liver stiffness assessed by MR elastography (MRE) in healthy and hepatitis-C-infected subjects.


A biopsy-correlated repeatability study using four-slice MRE was conducted in five healthy and four HCV-infected subjects. Subjects were scanned twice on day 1 and after 7-14 days. Each slice was acquired during a 14-s breath-hold with a commercially available acquisition technique (MR-Touch, GE Healthcare).

Results were analyzed by two independent analysts.


The intraclass correlation coefficient (ICC) was 0.85 (90% confidence interval [CI]: 0.71 to 0.98) for the between-scan average of maximum stiffness within each slice and 0.88 (90% CI: 0.78 to 0.99) for the average of mean stiffness within each slice for the primary analyst. For both analysts, the average of the mean liver stiffness within each slice was highly reproducible with ICC of 0.93 and 0.94. Within-subject coefficients of variation ranged from 6.07% to 10.78% for HCV+ and healthy subjects.


MRE is a highly reproducible modality for assessing liver stiffness in HCV patients and healthy subjects and can discriminate between moderate fibrosis and healthy liver. MRE is a promising modality for noninvasive assessment of liver fibrosis

( identifier: NCT00896233). J. Magn. Reson. Imaging 2011;. © 2011 Wiley-Liss, Inc.

Dynamic Postprandial Hepatic Stiffness Augmentation Assessed With MR Elastography in Patients With Chronic Liver Disease;

Yin M, Talwalkar JA, Glaser KJ, Venkatesh SK, Chen J, Manduca A, Ehman RL; American Journal of Roentgenology 197 (1), 64-70 (Jul 2011)


MR elastography (MRE) is an MRI-based technique for quantitatively assessing tissue stiffness by studying shear wave propagation through tissue. The goal of this study was to test the hypothesis that hepatic MRE performed before and after a meal will result in a postprandial increase in hepatic stiffness among patients with hepatic fibrosis because of transiently increased portal pressure.


Twenty healthy volunteers and 25 patients with biopsyproven hepatic fibrosis were evaluated. Preprandial MRE measurements were performed after overnight fasting. A liquid test meal was administered, and 30 minutes later a postprandial MRE acquisition was performed. Identical imaging parameters and analysis regions of interest were used for pre- and postprandial acquisitions.


The results in the 20 subjects without liver disease showed a mean stiffness change of 0.16 ± 0.20 kPa (range, -0.12 to 0.78 kPa) or 8.08% ± 10.33% (range, -5.36% to 41.7%). The hepatic stiffness obtained in the 25 patients with hepatic fibrosis showed a statistically significant increase in postprandial liver stiffness, with mean augmentation of 0.89 ± 0.96 kPa (range, 0.17-4.15 kPa) or 21.24% ± 14.98% (range, 7.69%-63.3%).


MRE-assessed hepatic stiffness elevation in patients with chronic liver disease has two major components: a static component reflecting structural change or fibrosis and a dynamic component reflecting portal pressure that can increase after a meal. These findings will provide motivation for further studies to determine the potential value of assessing postprandial hepatic stiffness augmentation for predicting the progression of fibrotic disease and the development of portal hypertension. The technique may also provide new insights into the natural history and pathophysiology of chronic liver disease.


Magnetic Resonance Elastography Holds Promise for Detecting, Staging Liver Fibrosis

By Cheryl Lathrop

BOSTON -- November 5, 2010 -- Magnetic resonance elastography (MRE) shows a combination of high sensitivity and specificity, and holds promise as a noninvasive imaging procedure for detecting and staging liver fibrosis, researchers said here at the 61st Annual Meeting of the American Association for the Study of Liver Diseases (AASLD).

Yi Wang, MD, Northwestern University, Chicago, Illinois, and colleagues reported findings from their study at a poster session here on November 1.

Accurate determination of the extent of hepatic fibrosis is essential in patients with chronic liver disease, as it determines disease progression and selection of therapy. Liver biopsy has been the gold standard for the diagnosis of fibrosis, although it is invasive and associated with sampling errors, risks, and low patient acceptance.

In MRE, mechanical waves are transmitted through the abdomen, and the speed of the propagation of these waves through the liver is evaluated to assess the liver’s elasticity. The prototype system was developed at the Mayo Clinic, Rochester, Minnesota, and consists of an acoustic driver, a gradient-echo MRE pulse sequence, and software for data analysis.

Between October 2008 and November 2009, 127 consecutive patients with suspected cirrhosis or portal hypertension were prospectively evaluated, of which 42 didn’t have a documented histopathology, leaving a final cohort of 76 patients. Four transaxial slices were acquired, and quantitative images displaying shear stiffness were generated by processing the acquired images with a direct inversion algorithm.

The predictive value was determined by constructing a receiver operator characteristic curve of the sensitivity versus 1-sensitivity, and calculating area under the curve. Liver biopsy was obtained within 1 year of the MRE acquisition.

Liver stiffness values measured on MRE increased in parallel with the degree of fibrosis. Liver tissues without fibrosis (F0) had lower median shear stiffness than tissues with any degree of fibrosis (P less then .0001). A positive linear correlation between shear stiffness values and stage of fibrosis was seen (P less then .0001).

The MRE showed a great ability to identify fibrosis stage >=2 and demonstrated a combination of high sensitivity (91%) and specificity (97%).

The study had 2 limitations: The small number of F2-F3 patients may lead to bias; and the fibrosis stage may have changed in the period of time between the liver biopsy and the MRE.

However, MRE is an excellent option to characterise liver fibrosis, concluded Dr. Wang.

[Presentation title: Detection of Hepatic Fibrosis by Magnetic Resonance Elastography. Abstract 1317]

1 comment:

  1. Does anybody perform MRE besides at Mayo clinic? If so, hot can I found MRE providers (I live in Connecticut)?

    Thank you.