Magnetic resonance elastography (MRE) is a noninvasive technique capable of quantifying tissue mechanical properties in vivo. The most established clinical application of MRE in the abdomen is in chronic liver disease, this technique represents the most accurate noninvasive technique for the detection and staging of liver fibrosis. Increasing experience and ongoing research is also leading to exploration of applications in other abdominal organs, including pancreas, spleen, kidneys, uterus and prostate. The current research progress of MRE technologies and its potential applications of this technology in these abdominal organs are surveyed. Abdominal MRE may be seamlessly incorporated into a standard multi-parametric MRI examination to provide a rapid, reliable and comprehensive imaging evaluation for solving complex problems at a single patient appointment in the future.
MR Elastography in abdominal applications：Liver, Pancreas, Spleen, kidneys, Uterus and Prostate
Magnetic Resonance Elastography(MRE) has been used to measure tissue stiffness by imaging the propagation of shear waves in tissue in vivo since the 1990’s[1]. The most established clinical application of MRE in the abdomen is in chronic liver disease, this technique represents the most accurate noninvasive technique for the detection and staging of liver fibrosis and has the potential to be an alternative to liver biopsy[2, 3].Increasing experience and ongoing research is also leading to exploration of applications in other abdominal organs. In this outline, the current research progress of abdominal MRE technologies, including patient preparation, modified technical approach (developed passive drivers, MRE sequences, and reconstruction), and its potential applications of this technology in liver, pancreas, spleen, kidneys, uterus and prostate of the abdomen are surveyed. In an era of increasing adoption of multi-parametric MR imaging approaches for solving complex abdominal problems, Abdominal MRE as a biomarker may be seamlessly incorporated into a standard MRI examination to provide a rapid, reliable and comprehensive imaging evaluation at a single patient appointment in the future.1.Liver
Chronic liver disease (CLD) with cirrhosis is one of the leading causes of death around the world, and with a tendency to lead liver fibrosis and progresses to cirrhosis with its associated complications, namely portal hypertension and hepatocellular carcinoma(HCC)[3]. Assessment of fibrosis or HCC is important not only for diagnosis but also for management, prognostic evaluation, and follow-up of patients with chronic liver disease. Liver biopsy, although current gold standard is not a preferred technique by both patients and attending physicians due to its invasive nature, sampling error and low interobserver agreement for staging fibrosis[4].With the rising prevalence of chronic liver disease, interest is increasing in the development of noninvasive methods of estimation of liver fibrosis. In 1995, Muthupillai et al[1] paved the way for the development of MR elastography by inducing harmonic vibrations of acoustic-range frequencies and imaging the propagation of these vibrations with an MR-based sequence to calculate quantitative values for tissue mechanical parameters. MRE calculates stiffness by measuring sub-millimeter (microns) displacements of tissue induced by a low frequency vibration, including 3 basic steps:(1) Generate shear waves in tissue; (2) Create a visual image of the propagating shear waves; (3) Process the wave images to measure tissue stiffness. MRE has been used to noninvasively quantify the mechanical properties of abdominal organs,including liver, spleen, kidneys, pancreas, uterus, and other non-abdominal organs over the past years[5]. The most established clinical application of MRE in the abdomen is in chronic liver disease. Liver MRE technique can be readily be implemented on conventional 1.5-T or 3-T clinical scanners. MRE of the liver are performed after 4-6 hours of fasting similar to a clinical liver MRI study. Liver MRE is generally performed with the subject in supine position.The mechanical shear wave frequency typically used is 60 Hz. MRE is a breath-hold sequence and is typically performed with breath held at the end of expiration[3].The MRE acquisition is a modified phase contrast sequence, MRE sequences can be based on gradient recalled echo (GRE), spin echo (SE), balanced steady state free precision (SSFP), or echo planar imaging (EPI) techniques[6]. The EPI acquisition with 3D vector MRE processing may also reduce the artifacts that arise due to through-plane wave propagation and wave scattering or diffraction effects that cause problems in 2D GRE MRE analysis. Currently, 2D gradient-echo (GRE) MRE is the most commonly used technique for liver fibrosis assessment and it has been shown to have a high degree of accuracy and a high success rate[7, 8]. Althought the degree, extent, pattern, and distribution of fibrosis and cirrhosis may be different in chronic liver diseases with various etiologies, this technique represents the most accurate noninvasive technique for the detection and staging of liver fibrosis from varied etiologies and has the potential to be an alternative to liver biopsy[9-11], and noninvasive hepatic venous pressure gradient(HVPG), and esophageal varices assessment can be performed with liver and spleen MR elastography[12-14]. MRE can also be used to longitudinal follow-up of chronic liver disease, and assess the treatment response[12, 15-19], liver stiffness measured by MRE is an independent risk factor for HCC in patients with chronic liver disease, and can serve as a postoperative predictor of liver regeneration in patients with liver cirrhosis and HCC. MRE with 3D-SE-EPI is a newly emerging noninvasive method for assessing liver fibrosis[20]. With respect to 2D-GRE, 3D-SE-EPI has the advantage of lower failure rate with equivalent high diagnostic performance for staging liver fibrosis in chronic liver disease patients, and thus more helpful for those challenging cases in 2D-GRE [20, 21].In addition to, liver stiffness and damping ratio measurements by Multifrequency 3D MR elastography can extend hepatic MR elastography to potentially enable assessment of necroinflammatory, congestive, and fibrotic processes of chronic liver diseases[22]. Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths around the world[23]. MRE is also a promising technique for characterization of focal liver lesions, preliminary studies have shown that malignant tumors,such as HCC, have higher stiffness than benign tumors and normal liver[24, 25]. Recently, HCC stiffness may be able to differentiate HCC tumor grade, also has promise for the preoperative prediction of tumor capsule formation, thus providing motivation for further evaluation of HCC characteristics with MRE. it [26]. And furthermore, tumor stiffness by MRE show a significant correlation with tumor enhancement and necrosis, especially in HCCs treated with radioembolization(RE)[27].2.Pancreas
Chronic pancreatitis or the pancreatic cancer are associated with the stiffness of the pancreas and hence increased the interest in exploring the technique of MRE for evaluation of the pancreas. Each participant was instructed to fast for at least 6 hours before the MRE examination to avoid compression by a full stomach. To reduce motion artifact from bowel peristalsis or air/stool, the use of an antispasmodic agent or cleaning enema may be beneficial in some patients. 3D MRE in pancreas has been performed successfully with liver driver, a modified ergonomic soft driver and pelvic wall driver to induce low frequency shear waves (40 and 60 Hz)[28], 3D MRE is a highly reproducible method for assessing pancreatic stiffness[29]. The mean stiffness of a normal pancreas at 40Hz was 1.15± 0.17kPa, and at 60Hz the stiffness was similar to a normal liver parenchyma, The effect of water uptake on normal pancreatic stiffness became significant in the frequency range from 50 to 60 Hz[30]. MRE might be a promising method to detect, stage, and monitor the treatment for chronic pancreatitis, or differentiate benign from malignant masses in the pancreas[31]. The further experimental design with a higher frequency will need to be evaluated to determine if the spatial resolution is adequate to resolve small regions of increased stiffness in the pancreatic tumor.3.Spleen
Measurements of the stiffness value of the spleen led to an intriguing and potentially important observation about the correlation between spleen and liver mechanics in patients with chronic liver disease. Generally MRE of the spleen is also performed at the same acoustic frequency of 60Hz similar to liver(single driver on the liver, single driver on the spleen and dual driver acoustic excitation)[30, 32], which provides platform- and observer-independent spleen stiffness measurements[33], but water uptake has an effect on spleen stiffness[30]. A significant difference of splenic stiffness was observed using different driver positions. In earlier studies, splenic stiffness is not significantly correlated with BMI, arterial mean blood pressure, spleen volume, or liver stiffness in healthy volunteers, but correlate with splenic size, platelet count, liver stiffness and presence of esophageal varices, a splenic stiffness greater than 10.5 kPa is predictive of esophageal varices in patients with chronic liver disease, and compared with liver stiffness and spleen volume, spleen stiffness is more strongly associated with severe gastroesophageal varices[34-36]. In patients with liver fibrosis, spleen stiffness increases in parallel with increasing liver stiffness, It also can predict the presence of severe portal hypertension, esophageal varices and high-risk varices in patients with advanced hepatic fibrosis or cirrhosis [13, 34], the spleen loss modulus appears to be the best parameter for identifying patients with severe portal hypertension or high-risk varices[12]. More studies suggest a promising role for noninvasive 3D MRE of the spleen in the evaluation of portal hypertension and significant esophageal varices, which is a frequent clinical condition caused by cirrhosis of the liver and is responsible for the development of many lethal complications [35, 37-39].4. Kidneys
Chronic kidney disease(CKD) is a global public health concern that is increasing in incidence and prevalence[40]. The progression of chronic kidney disease is related to renal hypoxia and fibrosis, which threaten the viability of the kidney by diminishing blood flow leading to irreversible tissue fibrosis and ultimately kidney failure. Early characterization and monitoring of pathologies are crucial to allow effective treatments and to improve the chance of a successful outcome. The assessment of these pathologies is difficult and relies heavily on invasive biopsies. MRE allows noninvasive assessment of tissue stiffness, each participant was instructed to have a light meal 2–3h and stop drinking 1h before MRE examination. The pattern of wave propagation in kidney is extremely complex, Some modified prototype passive drivers( or with Y-type) were used to successfully perform kidney 2D/3D MRE in humans with low frequency shear waves (60, 90, and120Hz), or in small animals with higher frequency shear waves(120Hz and 300Hz)[41]. Elastograms of the kidney in coronal view clearly depicted higher stiffness in cortex than in medulla[30]. There was a trend toward higher mean stiffness in renal transplant patients with moderate fibrosis in comparison to those with mild fibrosis, although this difference did not reach statistical significance[42]. But MRE-derived medullary, not cortical, stiffness might be a useful index of renal fibrosis in renal artery stenosis(RAS), acute RAS[43]. MRE also shows promise in the detection of significantly lower renal stiffness in patients with hepatorenal syndrome compared with those with normal renal function[44]. These studies therefore support MRE as a promising novel imaging technique is capable of noninvasively detecting damaged renal tissue and monitoring kidney disease progression longitudinally in-vivo. However, in the kidney tissue stiffness can drastically decline in conditions that decrease its arterial blood flow or perfusion pressure, may represent a marker of renal hypoperfusion[45], it means that renal elasticity is also strongly dependent upon hemodynamic variables or other factors. The use of MRE to assess changes in renal mechanics associated with the dynamic perfusion of renal may also provide insights into pathophysiology of renal diseases. Further studies are needed to examine the utility of this approach in humans.5.Uterus
Knowledge of mechanical properties of uterus and cervix may be useful and important to evaluate physiological fluctuations of the uterus, detect benign or malignant lesions of the uterus and monitor the therapeutic outcome. The presence of air and/or stool in the rectum may induce artifactual distortion that can compromise uterus MRE quality. Thus, some type of minimal preparation enema administered by the patient in the hours prior to the exam may be beneficial, The patient should evacuate the rectum or empty bladder, if possible, just prior to the MRE exam. MRE was performed successfully using a 19 cm passive driver positioned over the lower abdomen to induce shear waves at a frequency of 60 Hz in the uterus[46], 3D MRE sequence will be superior to 2D MRE to evaluate tiny focal lesions in uterus[47]. Uterus is a fibromuscular solid organ under the effect of the hormones and is composed of three layers: the endometrial, the junctional and the myometrial zones. 3D MRE of the uterus in healthy female volunteers showed that the uterine corpus had a higher elasticity but similar viscosity compared to cervix[48], and stiffness of both endometrium and myometrium decreased during the menstrual cycle. The average range of elasticity of fibroid is from 3.95 to 6.68 kPa, variability in the elasticity of fibrosis may have clinical significance for differentiating fibroids from rare uterine sarcomas[46]. Fibroids became stiffer after hi-frequency ultrasound (HiFU)[49], evaluation of the stiffness of the fibroids may give insights into their growth and possibly predict treatment outcomes. Further investigation may support the use of MRE for the diagnosis and characterization of uterine neoplasms.I greatly acknowledge Dr. Richard L. Ehman and MRE team(Mayo Clinic). Funding support for this work were provided by the National Institute of Health Grant EB001981(to Richard L. Ehman), National Natural Science Foundation of China No. 81271562, and Scinece and Technology Foundation of Guangzhou No. 201704020016(to Jin Wang).
Potential competing interests: The Mayo Clinic, Richard L. Ehman, has intellectual property rights and a financial interest in MRE technology.
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