At RSNA 2021, Canon Medical announced the partnership with Resoundant to incorporate MR Elastography on the Canon MRI platforms^*. This MR technique can detect and stage liver fibrosis. Liver fibrosis is the formation of scar tissue and affects the functioning of the liver. With the increasing incidence of obesity and type 2 diabetes, also the prevalence of liver fibrosis is growing. Before the onset of fibrosis, the patient often has a fatty liver. If there is no inflammation or tissue damage yet, this fat buildup in the liver can be reversed with lifestyle changes. Therefore, it is important to quantify the fat content of the liver and intervene in a timely matter. Canon Medical’s Fat Fraction Quantification Application can provide this information of the liver in a single breath-hold. MR Elastography and Fat Fraction Quantification have become two essential techniques is the management of liver disease.

In this article written by Michael Kalutkiewicz, MA, Vice President Global Policy & Communications at Resoundant, Rochester, MN, USA, which is a an article from the free digital book of Olea Medical ‘Spin to the Limit: MRI Physical and Principles Challenges’, you will learn about these two MR techniques.

For centuries, physicians have used a physical examination technique known as palpation as an essential tool in clinical medicine. This enduring diagnostic method is remarkably effective because many disease processes cause large changes in tissue stiffness that can be readily easily perceptible through simple touch.

Despite its traditional place in medicine, palpation is a subjective technique, applicable only to regions of the body that are accessible to touch and limited in its ability to reveal small changes that may signal early disease. Although advanced medical imaging technologies like MRI and CT have revolutionized diagnostic medicine, traditional imaging protocols unfortunately are not capable of revealing the underlying properties of palpation: the mechanical stiffness of tissue.

To address this need, a team led by Richard Ehman, MD at Mayo Clinic, invented a technology called Magnetic Resonance Elastography (MRE)¹. Their goal was to enhance the medical standard of palpation with the diagnostic power of medical imaging by developing a practical technology capable of sensitively and quantitatively assessing the mechanical properties of soft tissue in any area of the body.

The team focused on using mechanical vibrations as a probe to measure tissue stiffness. When a shear wave propagates in a medium, its wavelength is determined by the viscoelastic properties of the material. Dr Ehman and his team set out to find a way to visualize propagating mechanical waves inside the body using MRI.

This goal was extremely challenging, because such waves only displace tissue by a few nanometers. After extensive research, the team succeeded in developing MRE – a novel MRI technique capable of reliably imaging mechanical waves inside the body with extraordinary sensitivity¹.

Results demonstrated that by synchronizing motion-sensitizing gradients with applied waves, cyclic motions as small as the wavelength of light could be selectively imaged in vivo, even in the presence of physiologic motion¹.

The Mayo Clinic team further developed novel mathematical techniques to process the wave images in order to create cross-sectional maps quantitatively displaying the stiffness of tissues and organs in the body. They first reported these discoveries in the Science journal in 1995¹. After more than 10 years of further research and development involving talented teams from all over the world, MRE was validated and the technology successfully translated into clinical practice. In 2009, MRE was cleared by the US FDA and, since then, the technology has been installed on more than 1500 MRI systems around the world.

MRE technology is now provided by MRI manufacturers as an option that can be installed on virtually any conventional MRI system. The installation includes unique acquisition and processing software, as well as specialized hardware to apply vibrations to the body. In order to ensure standardization of MRE technology, the Mayo Clinic founded Resoundant, Inc. to assist MRI manufacturers in implementing their versions of MRE. The specialized hardware used in all current regulatory approved MRE systems is designed and manufactured by Resoundant.

Click HERE if you want to read more about the history, physics, applications and future of MRI in the book: ‘Spin to the Limit: MRI Physical and Principles Challenges’ (free of charge) of Olea Medical.

An MRE examination is accomplished in several steps, with a specific protocol depending on the purpose of the exam. The most frequent current indication for MRE is to evaluate liver disease – MRE has been established in the literature as the most accurate non-invasive approach for detecting and staging liver fibrosis.

In an MRE exam of the liver, a small plastic device is positioned over the patient’s right chest wall to deliver gentle low frequency vibrations during the scan, creating propagating mechanical waves in the liver. The vibrations are not uncomfortable, and the exam is well tolerated in routine clinical practice.

A specialized MRE pulse sequence is used to acquire images showing the propagation characteristics of the applied shear waves in the liver. The imaging time is very brief, typically requiring 1 to 4 acquisitions of about 15 seconds. Most scans are complete in under 2 minutes.

In the final step, the scanner automatically analyzes the wave images, using advanced mathematical algorithms to create cross-sectional images that quantitatively display tissue stiffness, using a standardized color scale. The images are sometimes called “elastograms” (Figure 1). In more formal engineering terms, the images display the magnitude of the complex shear modulus of the tissue.

In the final step of the examination, stiffness values are analyzed and interpreted by a radiologist.

The advent of a way to noninvasively assess the mechanical properties of tissue has proven timely, as chronic liver disease has burgeoned into a major health problem worldwide². While many conditions lead to chronic liver disease, the leading cause of end-stage liver disease is nonalcoholic fatty liver disease (NAFLD), which is now thought to affect 25% of the global population². This condition is characterized by elevated liver fat content. About 12% of people with NAFLD will progress to develop chronic liver cell injury and inflammation, known as non alcoholic steatohepatitis (NASH). Many patients with NASH will develop liver fibrosis in response to chronic liver injury and, as a result, approximately 1-2% of people with NAFLD will progress to develop cirrhosis (end-stage liver disease)².

This progression of hepatic fibrosis is often clinically silent until it progresses to high-mortality end-stage cirrhosis. The early, subtle changes in liver stiffness are undetectable to traditional palpation, while blood-based markers lack the needed specificity³. This is unfortunate, since if fibrosis is diagnosed early, lifestyle interventions are highly successful in halting⁴ and in some cases even reversing the condition.

When advanced fibrosis or cirrhosis is suspected, liver biopsy is the standard diagnostic method for detecting liver fibrosis. But liver biopsy is expensive and invasive. Moreover, biopsy’s approach of sampling just 0.002% of the liver is greatly affected by sampling error, as fibrosis progression is heterogeneous in nature. In addition, liver specimens are evaluated using a subjective grading system which is affected by substantial inter-observer variability. Given these challenges, it has been estimated that upwards of 30% of biopsies may lead to an inaccurate diagnosis⁵.

To fill this diagnostic gap between early disease and end-stage cirrhosis, two MRI techniques have emerged as new Gold Standards. Multiple studies have established that MRE has the highest diagnostic performance among non-invasive techniques⁶ for detecting and staging liver fibrosis. In parallel with the advent of MRE, significant improvements have been made in longstanding MRI-based methods for quantitatively assessing liver fat, often represented as “proton density fat fraction” (PDFF)⁷. It is now possible to acquire data that can be processed to generate quantitative PDFF images in a single MRI acquisition lasting less than 20 seconds. Like MRE, PDFF techniques have been well-validated in dozens of studies against paired biopsies⁷, with high degrees of inter-reader agreement and repeatability.

Both techniques have also been standardized across various vendor platforms and field strengths, facilitating their use as drug development tools in clinical trials⁸ and in clinical practice. Neither technique is significantly affected by common co-morbidities that can cause failure in complementary ultrasound-based techniques, such as obesity or ascites.

Together, MRE and PDFF have already been recognized in professional clinical guidelines^9-10 as front-line tools for liver assessment in patients with suspected chronic liver disease – particularly NAFLD, and the more severe NASH. Those that progress to increased liver inflammation and fibrosis represent 25% of these patients, putting them at significantly increased risk for liver-related events as fibrosis progresses. An accurate assessment of steatosis and fibrosis using PDFF and MRE, respectively, will be an essential part of patient management.

Perhaps most interestingly, their rapid acquisition time allows practices to experiment with them as a fast, low-cost exam for liver assessment. Both PDFF and MRE sequences can be done in just a few breath-holds, making the total exam time well under 10 minutes in most circumstances. In the US, the Centers for Medicare and Medicaid Services (CMS) issued a reimbursement option for standalone MRE (not as part of a full abdominal MRI workup). The cost is just $240 – representing perhaps the first low-cost, rapid MR exam that can be deployed to address a specific global health need. At the Mayo Clinic, this protocol is being called the Hepatogram¹¹ and is largely replacing the need for liver biopsies – resulting in further systemic savings and an improved patient experience.

The advent of tools such as MRE could represent a new era in MR imaging, where rapid, low-cost protocols are utilized to answer very specific clinical questions. Just as the idea of exploratory surgery has been replaced by advanced imaging, general MRI exams to search for diffuse answers may be needed less frequently. As acceptance and adoption of these specific approaches grow, it will no doubt usher in an exciting and innovative era of MRI. //

References
¹ Muthupillai R, Lomas DJ, Rossman PJ, Greenleaf JF, Manduca A, Ehman RL. Magnetic resonance elastography by direct visualization of propagating acoustic strain waves. Science. 1995;269(5232):1854-7.
² Shetty A, Syn WK. Health and Economic Burden of Nonalcoholic Fatty Liver Disease in the United States and Its Impact on Veterans. Fed Pract. 2019;36(1):14-19.
³ Neuman MG, Cohen LB, Nanau RM. Biomarkers in nonalcoholic fatty liver disease. Can J Gastroenterol Hepatol. 2014;28(11):607-618.
⁴ Kwak MS, Kim D. Non-alcoholic fatty liver disease and lifestyle modifications, focusing on physical activity. Korean J Intern Med. 2018;33(1):64-74.
⁵ Davison BA, Harrison SA, Cotter G, Alkhouri N, Sanyal A, Edwards C, Colca JR, Iwashita J, Koch GG, Dittrich HC. Suboptimal reliability of liver biopsy evaluation has implications for randomized clinical trials. J Hepatol. 2020;73(6):1322-1332.
⁶ Liang Y, Li D. Magnetic resonance elastography in staging liver fibrosis in non-alcoholic fatty liver disease: a pooled analysis of the diagnostic accuracy. BMC Gastroenterol. 2020;20(1):89.
⁷ Park CC, Nguyen P, Hernandez C, Bettencourt R, Ramirez K, Fortney L, Loomba R. Magnetic Resonance Elastography vs Transient Elastography in Detection of Fibrosis and Noninvasive Measurement of Steatosis in Patients With Biopsy-Proven Nonalcoholic Fatty Liver Disease. Gastroenterology. 2017;152(3):598-607.e2.
⁸ Dulai PS, Sirlin CB, Loomba R. MRI and MRE for non-invasive quantitative assessment of hepatic steatosis and fibrosis in NAFLD and NASH: Clinical trials to clinical practice. J Hepatol. 2016;65(5):1006-1016.
⁹ Lim JK, Flamm SL, Singh S, Falck-Ytter YT. American Gastroenterological Association Institute Guideline on the Role of Elastography in the Evaluation of Liver Fibrosis. Gastroenterology. 2017;152(6):1536-1543.
¹⁰ Chalasani N, Younossi Z, Lavine JE, Charlton M, Cusi K, Rinella M, Sanyal AJ. The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2018;67(1):328-357.
¹¹ Allen AM, Yin M, Venkatesh SK, Mounajjed T, Kellogg TA, Kendrick ML, Ehman RL. SAT-464-Novel multiparametric magnetic resonance elastography (MRE) protocol accurately predicts NAS score for NASH diagnosis. Journal of Hepatology. 2017;66:S659.

You can also read this piece as the original published article in VISIONS 38#. Click to download it here.