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Elastography Assessment of Liver Fibrosis: Society of Radiologists in Ultrasound Consensus Conference Statement
Abstract
The Society of Radiologists in Ultrasound convened a panel of specialists from radiology, hepatology, pathology, and basic science and physics to arrive at a consensus regarding the use of elastography in the assessment of liver fibrosis in chronic liver disease. The panel met in Denver, Colo, on October 21-22, 2014, and drafted this consensus statement. The recommendations in this statement are based on analysis of current literature and common practice strategies and are thought to represent a reasonable approach to the noninvasive assessment of diffuse liver fibrosis. (©) RSNA, 2015 Online supplemental material is available for this article.
... Vibration-controlled transient elastography is the first tool with which liver stiffness was measured and studied. It is ultrasound-guided, but without direct image guidance, and a specific device Fibroscan® (Echosens, Paris, France) is needed [12,13]. pSWE and 2D-SWE can both be done as an add-on during liver ultrasonography (using the same probe), can be performed with real-time imaging, so liver capsule, large vessels, bile ducts, and focal masses can be avoided, multiple regions of the liver can be assessed, they are low-cost, easily accessible, repeatable and convenient to use [13]. ...
... It is ultrasound-guided, but without direct image guidance, and a specific device Fibroscan® (Echosens, Paris, France) is needed [12,13]. pSWE and 2D-SWE can both be done as an add-on during liver ultrasonography (using the same probe), can be performed with real-time imaging, so liver capsule, large vessels, bile ducts, and focal masses can be avoided, multiple regions of the liver can be assessed, they are low-cost, easily accessible, repeatable and convenient to use [13]. In 2020, the Society of Radiologists in Ultrasound Liver Elastography proposed a vendor-neutral 'rule of four' (5,9,13,17 kPa) for pSWE and 2D-SWE techniques for viral etiologies and NAFLD [14]. ...
... pSWE and 2D-SWE can both be done as an add-on during liver ultrasonography (using the same probe), can be performed with real-time imaging, so liver capsule, large vessels, bile ducts, and focal masses can be avoided, multiple regions of the liver can be assessed, they are low-cost, easily accessible, repeatable and convenient to use [13]. In 2020, the Society of Radiologists in Ultrasound Liver Elastography proposed a vendor-neutral 'rule of four' (5,9,13,17 kPa) for pSWE and 2D-SWE techniques for viral etiologies and NAFLD [14]. Liver stiffness of 5 kPa or less has a high probability of being normal; liver stiffness less than 9 kPa, in the absence of other known clinical signs, rules out compensated advanced chronic liver disease; values between 9 kPa and 13 kPa are suggestive of compensated advanced chronic liver disease; and values greater than 13 kPa are highly suggestive of compensated advanced chronic liver disease. ...
Nonalcoholic fatty liver disease (NAFLD) and chronic kidney disease are global public health issues associated with high morbidity and mortality. Both diseases are also interlinked. Little is known about the meaning of NAFLD in hemodialysis (HD) patients. Therefore, the aim of our study was to investigate the difference in oxidative stress and inflammation in HD patients with or without advanced NAFLD. Seventy-seven HD patients were included (65.14 ± 12.34 years, 59.2% male) and divided according to abdominal ultrasound and two-dimensional shear wave elastography (2D-SWE) measurements into two groups: 1) no NAFLD or no advanced NAFLD (2D-SWE <9 kPa) and 2) advanced NAFLD (2D-SWE ≥9 kPa). Medical history data and blood results were collected. HD patients with advanced NAFLD had significantly higher levels of 8-hydroxy-2’-deoxyguanosine (8-OHdG; p = 0.025), tumor necrosis factor-alpha (TNF-α; p = 0.023), and intercellular adhesion molecule 1 (ICAM-1; p = 0.015) in comparison to HD patients without advanced NAFLD. Interleukin 6 (IL-6) was higher in the advanced NAFLD group, but the difference was of borderline significance (p = 0.054). There was no significant difference in high-sensitivity C-reactive protein (hs-CRP), and vascular cell adhesion molecule 1 (VCAM-1) between groups. In binary logistic regression analysis, advanced NAFLD was significantly associated with 8-OHdG and ICAM-1. In conclusion, higher oxidative stress and inflammation levels are present in HD patients with advanced NAFLD.
... [4,23] The American Radiological Association and European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) offer several major noninvasive imaging modalities including transient elastography (TE), magnetic resonance elastography (MRE), and shear wave elastography (SWE) [point quantification SWE (PQSWE) and two-dimensional (2D) SWE] for the assessment of hepatic fibrosis. [24,25] TE or FibroScan easily and noninvasively measures the amount of stiffness in the liver tissue. Its cut-off value is 9.9 KpA for advanced fibrosis in adults with NAFLD with 95% sensitivity and 77% specificity. ...
... [11] TE indications for patients with NAFLD include screening and staging of fibrosis and follow-up of diagnosed fibrosis. [25,26] Suspected advanced fibrosis (F3/F4) can also be primarily clarified by elastography. [26] The use of TE in patients with chronic hepatitis B is also useful for the diagnosis of liver cirrhosis. ...
... The area of the liver that is routinely evaluated by MR is the right lobe and therefore shows a much larger volume of liver tissue than that performed with ultrasound elastography. [25] MRE is the most accurate noninvasive method for staging hepatic fibrosis and is more widely used than TE in patients with ascites and obese patients. However, it is only slightly better for F3-F4 fibrosis than other noninvasive tests. ...
Non-alcoholic fatty liver disease (NAFLD) refers to the presence of hepatic steatosis (accumulation of fat in the liver to over 5% of its weight) in the absence of secondary causes of fat accumulation in the liver such as excessive alcohol use. NAFLD is divided into two types: non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH). Therefore, in this clinical guideline, we sought to determine general and important policies for this disease and modify its managment approaches. We adapted this guideline for the management of NAFLD in Isfahan Province. This guideline was developed by clinical appraisal and review of the evidence, available clinical guidelines, and in consultation with members of the Isfahan Chamber of the Iranian Association of Gastroenterology and Hepatology. Biopsy is recommended as the most reliable method (gold standard) to diagnose steatohepatitis and fibrosis in patients with NAFLD. NAFLD fibrosis score (NFS) and fibrosis-4 (FIB-4) are recommended as the test with the highest predictive value for advanced fibrosis in patients with NAFLD compared to other serologic tests. Among the noninvasive methods used to assess liver fibrosis, transient elastography (TE) is preferable to other methods.
... One of the most widely adopted clinical uses of SWE is in the context of liver stiffness change associated with underlying CLD [54,55,[57][58][59]112]. Prior to use of elastography technologies, the only option for assessing liver fibrosis was biopsy and histologic evaluation [57,59,112]. ...
... One of the most widely adopted clinical uses of SWE is in the context of liver stiffness change associated with underlying CLD [54,55,[57][58][59]112]. Prior to use of elastography technologies, the only option for assessing liver fibrosis was biopsy and histologic evaluation [57,59,112]. Transabdominal SWE is a non-invasive, low cost, and low risk tool used to closely monitor disease onset and progression, becoming an important complementary tool for detection, staging and management of CLD caused by viral hepatitis, alcohol-associated fatty liver disease, nonalcoholic fatty liver disease, and autoimmune liver disease (Table 1) [54,55,57,59,60]. ...
... One of the most widely adopted clinical uses of SWE is in the context of liver stiffness change associated with underlying CLD [54,55,[57][58][59]112]. Prior to use of elastography technologies, the only option for assessing liver fibrosis was biopsy and histologic evaluation [57,59,112]. Transabdominal SWE is a non-invasive, low cost, and low risk tool used to closely monitor disease onset and progression, becoming an important complementary tool for detection, staging and management of CLD caused by viral hepatitis, alcohol-associated fatty liver disease, nonalcoholic fatty liver disease, and autoimmune liver disease (Table 1) [54,55,57,59,60]. Studies show that diseased liver has measurable increases in shear wave velocity and hence stiffness even at early fibrotic stages [54]. ...
The ovary is one of the first organs to show overt signs of aging in the human body, and ovarian aging is associated with a loss of gamete quality and quantity. The age-dependent decline in ovarian function contributes to infertility and an altered endocrine milieu, which has ramifications for overall health. The aging ovarian microenvironment becomes fibro-inflammatory and stiff with age, and this has implications for ovarian physiology and pathology, including follicle growth, gamete quality, ovulation dynamics, and ovarian cancer. Thus, developing a non-invasive tool to measure and monitor the stiffness of the human ovary would represent a major advance for female reproductive health and longevity. Shear wave elastography is a quantitative ultrasound imaging method for evaluation of soft tissue stiffness. Shear wave elastography has been used clinically in assessment of liver fibrosis and characterization of tendinopathies and various neoplasms in thyroid, breast, prostate, and lymph nodes as a non-invasive diagnostic and prognostic tool. In this study, we review the underlying principles of shear wave elastography and its current clinical uses outside the reproductive tract as well as its successful application of shear wave elastography to reproductive tissues, including the uterus and cervix. We also describe an emerging use of this technology in evaluation of human ovarian stiffness via transvaginal ultrasound. Establishing ovarian stiffness as a clinical biomarker of ovarian aging may have implications for predicting the ovarian reserve and outcomes of Assisted Reproductive Technologies as well as for the assessment of the efficacy of emerging therapeutics to extend reproductive longevity. This parameter may also have broad relevance in other conditions where ovarian stiffness and fibrosis may be implicated, such as polycystic ovarian syndrome, late off target effects of chemotherapy and radiation, premature ovarian insufficiency, conditions of differences of sexual development, and ovarian cancer.
Summary sentence:
Shear Wave Elastography is a non-invasive technique to study human tissue stiffness, and here we review its clinical applications and implications for reproductive health and disease.
... This wave travels faster through harder tissues and passes through the liver. Adipose tissue can lead to increased attenuation of ultrasound; therefore, by measuring the degree of attenuation of ultrasound (CAP), we can estimate fat content and indicate the degree of hepatic steatosis 16 . The subjects received VCTE. ...
... In addition, we collected liver stiffness measurements (LSMs) to assess liver fibrosis. The extent of fibrosis can be classified into three categories: F2, F3, and F4, with thresholds of 8.2, 9.7, and 13.6 kPa, respectively 16 . ...
Studies have shown that postmenopausal women have more metabolic abnormalities than premenopausal women. No consensus exists on how serum uric acid (sUA) affects metabolism-associated fatty liver disease (MAFLD) in postmenopausal women.This prospective observational study examined this link using National Health and Nutrition Examination Survey (NHANES) 2017 to 2020 data. We divided women’s sUA levels into four quartiles and used logistic regression, subgroup analyses, and restricted triple spline methods to compare the prevalence of MAFLD in postmenopausal and non-menopausal women. We also used histograms to analyze the effect of BMI-based indices. This population-based study involved 4477 women, including 1139 postmenopausal women aged 55–73 years. Multivariate logistic regression showed that, in the fully adjusted model, we found that participants in the highest quartile of sUA had a statistically significant 254% increased risk of MAFLD compared with participants in the lowest quartile (OR: 3.54; 95% CI 3.54 1.47–8.55; P < 0.001). Subgroup analyses showed no significant interaction between sUA levels and specific subgroups P( > 0.05 for all interactions). Additionally, RCS and threshold analysis showed a linear correlation (P = 0.186) and an ideal inflection point of 4.6 (P = 0.818) to the left. Right of the inflection point, the effect size was 1.524 (95% CI 1.291–1.814; P < 0.01). Histograms demonstrated that postmenopausal BMI increased sUA’s influence on MAFLD and higher sUA levels and BMI may enhance the prevalence of MAFLA in US postmenopausal women. The results of this study suggest that monitoring sUA levels in the postmenopausal period is critical in determining the occurrence of and interventions for MAFLD.
... The median time from age at Fontan operation to the liver biopsy was 14 years [9-23]. Patient's median age at liver fibrosis evaluation was 17 years [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27] with a median of 69 days between US elastography and liver biopsy. Hypoplastic left heart syndrome was the primary diagnosis in 41% and a history of arrhythmias and thrombocytopenia was seen in 58.6% and 34.4% patients, respectively (Table 4). ...
... Due to the limitation of some probes being able to assess only certain depth, an insufficient signal in patients who are overweight or obese can also lead to error [23,24]. In addition to elevated central venous pressures higher stiffness can be related to recent ingestion of food, liver steatosis, and inflammation process like acute or chronic hepatitis [25][26][27]. As the studies were done at our center, the protocol and directions regarding fasting were similar for all patients. ...
Fontan-associated liver disease (FALD) is a common complication after the Fontan procedure. A liver biopsy is the gold standard for assessing liver fibrosis. However, ultrasound (US) elastography has increasingly been used as a non-invasive method to diagnose and monitor liver fibrosis. Nonetheless, a clear correlation of severity of fibrosis between US elastography and liver biopsy in this population has not yet been established. In this single-center retrospective study, we included patients with Fontan physiology who had liver fibrosis evaluation between 2008 and 2022 with both US elastography and liver biopsy. Fibrosis was classified by US elastography and liver biopsy based on the METAVIR scoring system and congestive hepatic fibrosis score, respectively. Overall, 29 patients had both US elastography and liver biopsy with a median age of 17 years (IQR 13–27 years). The median time between Fontan operation and liver biopsy was 14 years (IQR 9–23). Nine patients underwent isolated heart transplantation (31%). The median shear wave elastography was 1.97 m/s (IQR 1.66–2.11) with 86% of patient's METAVIR score being > F2. There was no correlation in the severity of fibrosis between US elastography and liver biopsy (polycor = − 0.021). Findings on US elastography had weak correlation with histological fibrosis severity reported in liver biopsy. Further large-scale studies are necessary to assess optimal protocol for using US elastography for surveillance of FALD in Fontan patients.
... In the past few years, the number of liver biopsies has decreased because of the availability of non-invasive methods such as SWE and serum fibrosis indices for estimating liver fibrosis. Serum fibrosis indices such as APRI, FIB-4, and King's score are used for the non- 4,7 invasive assessment of liver fibrosis. A meta-analysis completed by 7,8 Xiao et al. indicated that serum fibrosis indices such as APRI, FIB-4, and King's score have moderate sensitivity and accuracy in identifying fibrosis. ...
... APRI, King's score and FIB4, strongly correlated with SWE. 4. ...
Introduction: Liver fibrosis is a progressive disorder that, if diagnosed early and staged precisely, allows early clinical intervention that may hinder or slow down the progression to end-stage decompensated cirrhosis. Grading of hepatic fibrosis is essential not only for diagnosis but also for prognostic evaluation, planning appropriate therapy, and follow-up of patients with chronic hepatitis. Liver biopsy has been considered the gold standard for grading liver fibrosis. As liver biopsy is invasive and associated with complications, non-invasive serological techniques and Aminotransferase Platelet Ratio Index (APRI), King's Score, and FIB 4 scores have been spotlighted. Aim: To evaluate patients with liver diseases using ultrasonography. To perform shear wave elastography and derive cut-off for patients with liver diseases. To correlate ultrasound and shear wave elastography findings with serological indices in patients with liver disease. Shear wave elast Methods: ography (SWE) was used to assess the liver stiffness. 2D ultrasound was performed to correlate with the findings of the SWE. Serological values were obtained, and serological indices were calculated and correlated with the SWE findings. Results: The study reveals that the younger group (< 45 years) has a higher proportion of liver fibrosis stages, while the older group (> 45 years) has a lower proportion in each stage. Advanced liver fibrosis (ALD) is most prevalent in advanced stages (92.9% in F4), indicating a severe progression. Hepatitis B and C peak at F3 and drop drastically in F4, while NAFLD is more common in the early stages (50.0% in F0-F1). Type of liver disease is statistically significantly associated with stages. Patients without complications were predominant in the early stages but decreased substantially in F4. Patients with complications show a substantial increase in advanced fibrosis stages, comprising 78.6% of F4 cases. Hematemesis is the most common complication, especially in advanced stages (30.0% in F3, 39.3% in F4). Increased echogenicity is more common in advanced stages, rising from 65.0% in F0-F1 to 96.4% in F4. Significant changes in liver size and stiffness with advancing fibrosis are less pronounced. All APRI, FIB 4 and King's scores demonstrate strong correlations with fibrosis progression, making them valuable for assessing liver fibrosis severity and monitoring disease advancement. The SWE test has high AUC values, indicating strong discriminatory power when comparing stages (F0-F1) against F2, F3, and F4. It also demonstrates high accuracy in differentiating between minimal or no fibrosis (F0-F1) and advanced fibrosis (F3), with a sensitivity of 95% and a specificity of 90% at a cut-off value of ≥ 6.60. It also exhibits outstanding discriminatory ability in distinguishing between minimal or no fibrosis (F0-F1) and severe fibrosis/cirrhosis (F4), with a sensitivity of 96.4% and a specificity of 91.4% at a cut-off value of ≥7.50. SWE also shows good discriminatory performance in differentiating between moderate (F2) and advanced fibrosis (F3), with a sensitivity of 95% and a specificity of 77.6% at a cut-off value of ≥ 8.0. It also shows excellent accuracy in distinguishing between moderate fibrosis (F2) and severe fibrosis/cirrhosis (F4), with a sensitivity of 92.9% and a specificity of 79.8% at a cut-off value of ≥ 9.0. However, the diagnostic accuracy decreases when distinguishing between adjacent stages, such as F2 vs. F3 and F3 vs. F4, as indicated by lower AUC values and slightly lower sensitivity and specificity values. The test also has strong positive correlations with APRI and KING, suggesting that as liver size increases, all APRI, FIB 4, and King's scores tend to increase significantly. The study found significant associations between liver disease type, stages, complicat Conclusion: ions, echogenicity, liver texture, liver size, stiffness, portal vein diameter, and spleen size. It also found strong correlations between liver elastography and size, APRI, King's and FIB 4 scores, and SWE, making them valuable tools for assessing liver fibrosis severity and monitoring disease advancement.
... US-derived shear-wave speed (SWS) determined through two-dimensional shear-wave elastography has gained widespread recognition as a valuable diagnostic marker for assessing liver fibrosis (3,4). Notably, SWS can be influenced by various factors, including hepatic necroinflammation, aberrant aminotransferase levels, and hyperbilirubinemia (5)(6)(7). ...
... The primary outcome was the diagnostic performance of DS compared with histologic evaluation of lobular inflammation. Secondary aims included (a) developing a statistical model to predict MASH histologic features using DS, AC, and SWS; (b) evaluating the diagnostic performance of AC for identifying steatosis compared with histologic evaluation; and (c) 3 evaluating the diagnostic performance of SWS for identifying fibrosis compared with histologic evaluation. ...
Background Attenuation coefficient (AC) and shear-wave speed (SWS) are established US markers for assessing patients with metabolic dysfunction-associated steatotic liver disease (MASLD), while shear-wave dispersion slope (DS) is not. Purpose To assess the relationship between the multiparametric US imaging markers DS, AC, and SWS and liver histopathologic necroinflammation in patients with MASLD. Materials and Methods This international multicenter prospective study enrolled consecutive patients with biopsy-proven MASLD between June 2019 and March 2023. Before biopsy, all participants underwent multiparametric US, and measurements of DS, AC, and SWS were obtained. Multivariable linear regression analyses were performed to assess the association of clinical variables and imaging markers with pathologic findings. The diagnostic performance of imaging markers for determining inflammation grade, steatosis grade, and fibrosis stage was assessed using the area under the receiver operating characteristic curve (AUC). Results A total of 124 participants (mean age, 53 years ± 15 [SD]; 62 males) were evaluated. In multivariable regression, lobular inflammation was associated with DS (regression coefficient, 0.06; P = .02), alanine aminotransferase level (regression coefficient, 0.002; P = .002), and Hispanic or Latino ethnicity (regression coefficient, -0.68; P = .047), while steatosis was associated with AC (regression coefficient, 3.66; P < .001) and fibrosis was associated with SWS (regression coefficient, 2.02; P < .001) and body mass index (regression coefficient, 0.05; P = .02). DS achieved an AUC of 0.72 (95% CI: 0.63, 0.82) for identifying participants with inflammation grade A2 or higher (moderate to severe inflammation). AC showed excellent performance for identifying participants with grade S1 (mild) or higher steatosis (AUC, 0.92 [95% CI: 0.87, 0.97]), while SWS showed excellent performance for identifying participants with fibrosis stage F2 or higher (clinically significant fibrosis) (AUC, 0.91 [95% CI: 0.86, 0.96]). Of the three US markers, SWS showed the highest AUC (0.81 [95% CI: 0.74, 0.89]) for the diagnosis of metabolic dysfunction-associated steatohepatitis. Conclusion Of the three US imaging markers (DS, AC, and SWS), DS was most associated with lobular inflammation grade at histologic examination and demonstrated fair diagnostic performance in distinguishing moderate to severe lobular inflammation. ClinicalTrials.gov Identifier: NCT04012242 Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Yin in this issue.
... Elastography techniques are integrated into the image, with the most widely used currently being the one that generates pulses of acoustic radiation force (ARFI) within the probe itself. This includes the measurement of shear wave velocity at a specific point in the organ, referred to as point shear-wave elastography (pSWE), and assessment in an area known as two-dimensional shear-wave elastography (2D-SWE) [4][5][6][7]. Today, several manufacturers implement ARFI technology (both pSWE and 2D SWE) in their ultrasound devices and offer recommendations for technique optimization and data quality assessment [7,8]. ...
Background/Objectives: Liver elastography is increasingly used in neonatal intensive care units (NICUs) as a non-invasive, radiation-free, reproducible technique for assessing liver stiffness. This technique demonstrates substantial advantages over conventional ultrasound in diagnosing diffuse liver diseases by providing quantitative measures of tissue elasticity. This article aims to describe the most critical milestones for performing liver elastography ultrasound point-of-care, a tool increasingly used to complement traditional ultrasound in the study of the liver in intensive care units where the population is very susceptible to manipulation. Methods: Techniques such as point-shear wave elastography (pSWE) and two-dimensional shear wave elastography (2D-SWE) have become key in evaluating conditions such as hypoxic-ischemic liver disease, cholestatic diseases, storage and metabolic disorders, or infectious liver conditions. However, despite its usefulness, performing elastography in neonates, particularly in those weighing less than 1000 g or in high-frequency oscillatory ventilation, presents notable challenges, including the extreme sensitivity of neonates to touch, noise, and temperature changes and the difficulty in obtaining accurate measurements due to limited hepatic depth. Results: Key factors for the success of sonoelastography in this population include minimizing contact time, adjusting mechanical and thermal indices to meet biosecurity guidelines, and ensuring patient comfort and stability during the procedure. Despite these challenges, elastography has proven helpful in routine clinical practice. Conclusions: The growing evidence on elastography has provided standardized reference values, further enhancing its clinical applicability in NICU settings.
... Transient elastography (FibroScan, TE) is a convenient and reproducible method that objectively measures fibrosis and steatosis by assessing liver stiffness (LS) and the controlled attenuation parameter (CAP). It relies on the principles of shear-wave and echo-degeneration, respectively [30]. Numerous studies have demonstrated that FibroScan provides high accuracy in assessing liver fibrosis and steatosis in patients with chronic liver diseases of various causes. ...
Liver transplantation is a critical and evolving field in modern medicine, offering life-saving treatment for patients with end-stage liver disease and other hepatic conditions. Despite its transformative potential, transplantation faces persistent challenges, including a global organ shortage, increasing liver disease prevalence, and significant waitlist mortality rates. Current donor evaluation practices often discard potentially viable livers, underscoring the need for refined graft assessment tools. This review explores advancements in graft evaluation and utilization aimed at expanding the donor pool and optimizing outcomes. Emerging technologies, such as imaging techniques, dynamic functional tests, and biomarkers, are increasingly critical for donor assessment, especially for marginal grafts. Machine learning and artificial intelligence, exemplified by tools like LiverColor, promise to revolutionize donor-recipient matching and liver viability predictions, while bioengineered liver grafts offer a future solution to the organ shortage. Advances in perfusion techniques are improving graft preservation and function, particularly for donation after circulatory death (DCD) grafts. While challenges remain—such as graft rejection, ischemia-reperfusion injury, and recurrence of liver disease—technological and procedural advancements are driving significant improvements in graft allocation, preservation, and post-transplant outcomes. This review highlights the transformative potential of integrating modern technologies and multidisciplinary approaches to expand the donor pool and improve equity and survival rates in liver transplantation.
... Over the last two decades, ultrasound shear wave elastography (SWE) has emerged as a promising imaging technique, offering noninvasive tissue biomarkers with wide-ranging clinical applications (Barr et al., 2015;Cipriano et al., 2022) and enhancing our understanding of skeletal muscle function in vivo (Hug et al., 2015). Specifically, SWE provides real-time quantification of localized tissue shear modulus (an indicator of stiffness) by measuring the velocity of a remotely induced shear wavefront along the ultrasound probe direction (Gennisson et al., 2013). ...
... The liver, the spleen, the pancreas, the salivary glands, the prostate, and the mammary and thyroid glands are among the recent diagnostic applications of SWE [5,7]. It is increasingly being employed in musculoskeletal sonography [8], as well as in dermatology and rheumatology, particularly to evaluate the skin of patients with progressive systemic sclerosis [6]. ...
Objectives: The present study aimed to examine the role of two-dimensional shear wave elastography (SWE) in the assessment of the vascular wall of the carotid arteries and atherosclerotic plaques in patients with rheumatoid arthritis with moderate and low disease activity versus healthy controls. Methods: An observational case–control study was carried out at the University Medical Hospital “Kaspela” in Plovdiv, Bulgaria, from June 2023 to August 2024. This study included 24 patients with rheumatoid arthritis (RA) and 25 healthy controls. We employed two-dimensional SWE (2D-SWE) to examine the vessels around the plaques. The potential links with the degree of stenosis, plaque type, and cardiovascular risk were analyzed. Results: In the RA group, the 2D-SWE values showed significant positive correlations with the severity of the atherosclerotic plaques (rs = 0.461; 95% CI: 0.049 to 0.739; p = 0.023) and the degree of stenosis (rs = 0.920; 95% CI: 0.793 to 0.970; p < 0.001). Based on 2D-SWE, a ROC curve analysis distinguished higher severity plaques from lower severity plaques with an AUC = 0.818, 95% CI: 0.683 to 0.913. The optimal cut-off value of 2D-SWE > 32.40 kPa was associated with a sensitivity of 96%, a specificity of 56%, a positive predictive value (PPV) of 66.70%, and a negative predictive value (NPV) of 92.90%. Conclusion: Elastography can be an effective technique for assessing and stratifying atherosclerotic plaques in patients with RA, as well as for aiding in the early detection and subsequent prevention of future complications.
... To obtain the optimal intercostal acoustic window, the US examination was performed in the supine position with the right arm in maximal abduction and with participants instructed to hold their breath. 26 After B-mode examination of liver parenchyma, combielastography was conducted on the right lobe of the liver through the intercostal space, devoid of large blood vessels and surface nodularity (Fig. 1). Optimal positioning was performed by visualizing both the B-mode and static image superimposed on B-mode in real-time. ...
Background/Aims
Combi-elastography is a B-mode ultrasound-based method in which two elastography modalities are utilized simultaneously to assess metabolic dysfunction-associated steatotic liver disease (MASLD). However, the performance of combi-elastography for diagnosing metabolic dysfunction-associated steatohepatitis (MASH) and determining fibrosis severity is unclear. This study compared the diagnostic performances of combi-elastography and vibration-controlled transient elastography (VCTE) for identifying hepatic steatosis, fibrosis, and high-risk MASH.
Methods
Participants who underwent combi-elastography, VCTE, and liver biopsy were selected from a prospective cohort of patients with clinically suspected MASLD. Combi-elastography-related parameters were acquired, and their performances were evaluated using area under the receiver-operating characteristic curve (AUROC) analysis.
Results
A total of 212 participants were included. The diagnostic performance for hepatic steatosis of the attenuation coefficient adjusted by covariates from combi-elastography was comparable to that of the controlled attenuation parameter measured by VCTE (AUROC, 0.85 vs 0.85; p=0.925). The performance of the combi-elastography-derived fibrosis index adjusted by covariates for diagnosing significant fibrosis was comparable to that of liver stiffness measured by VCTE (AUROC, 0.77 vs 0.80; p=0.573). The activity index from combi-elastography adjusted by covariates was equivalent to the FibroScan-aspartate aminotransferase score in diagnosing high-risk MASH among participants with MASLD (AUROC, 0.72 vs 0.74; p=0.792).
Conclusions
The performance of combi-elastography is similar to that of VCTE when evaluating histology of MASLD.
... According to Barr et al. [22], Dr. Jonathan Ophir first created strain imaging in the 1970s and called it elastography. After his pivotal research, a number of studies for measuring strain and strain elastography (StWE) were commercialized. ...
A class of intricate musculoskeletal diseases known as temporomandibular disorders (TMDs) affects the temporomandibular joint (TMJ) and its supporting structures. The majority of individuals will at some point in their lives experience some degree of TMD symptoms, as these diseases are highly prevalent in the general population. TMDs are multifactorial and are attributed to various physical and biopsychosocial factors. The TMD patients typically experience preauricular pain, tenderness of masticatory muscles, and joint sounds, and these in turn affect their quality of life. To carry out the appropriate course of treatment, it is critical to make an accurate and timely diagnosis. The TMDs are classified as myofascial pain, internal disc derangement, and degenerative disorders of TMJ. Myofascial pain, which is identified by palpating the affected muscles of mastication and tenderness, is one of the most common findings. The muscles in this condition become stiff due to the contraction of myofibrils and are known as trigger bands. The diagnosis of trigger bands involving the masticatory muscles commonly involving the masseter muscle in myofascial pain to date is subjective, and palpation is the only tool used for its diagnosis. An objective assessment of the masticatory muscles is desirable for accurate diagnosis and treatment planning. Various tools like electromyography and hardness meters have been for assessing muscle stiffness, but their application in TMJ muscle disorders has not yielded valuable results. A novel diagnostic method called ultrasound elastography evaluates muscle stiffness both qualitatively and quantitatively using an elastogram and the muscular elasticity index. In this paper, we will review the ultrasound elastographic techniques utilized for the diagnosis and management of TMDs.
... 122,123 A consensus has also been established to standardize the clinical practice of TE and mitigate uncertainties introduced by human factors in measurements. 124 Acoustic radiation force impulse elastography Unlike TE, which operates within a single dimension, ARFI elastography stands out as a technique facilitating the capture of two-dimensional real-time dynamic US representations. As a result, specialized sonographers is necessary to execute the procedure effectively. ...
Liver fibrosis is a reparative response triggered by liver injury. Non‐invasive assessment and staging of liver fibrosis in patients with chronic liver disease are of paramount importance, as treatment strategies and prognoses depend significantly on the degree of fibrosis. Although liver fibrosis has traditionally been staged through invasive liver biopsy, this method is prone to sampling errors, particularly when biopsy sizes are inadequate. Consequently, there is an urgent clinical need for an alternative to biopsy, one that ensures precise, sensitive, and non‐invasive diagnosis and staging of liver fibrosis. Non‐invasive imaging assessments have assumed a pivotal role in clinical practice, enjoying growing popularity and acceptance due to their potential for diagnosing, staging, and monitoring liver fibrosis. In this comprehensive review, we first delved into the current landscape of non‐invasive imaging technologies, assessing their accuracy and the transformative impact they have had on the diagnosis and management of liver fibrosis in both clinical practice and animal models. Additionally, we provided an in‐depth exploration of recent advancements in ultrasound imaging, computed tomography imaging, magnetic resonance imaging, nuclear medicine imaging, radiomics, and artificial intelligence within the field of liver fibrosis research. We summarized the key concepts, advantages, limitations, and diagnostic performance of each technique. Finally, we discussed the challenges associated with clinical implementation and offer our perspective on advancing the field, hoping to provide alternative directions for the future research.
... The colour-coded confidence map is an evaluation of the quality of the acquired signals. The confidence threshold is set at 60%. [17][18] For the purpose of the study, we chose elasticity values <2.1 m/s as early liver fibrosis and values >2.1 m/s as advanced liver fibrosis. ...
Objectives
We performed a single-centre retrospective study comparing the accuracy of non-invasive elastography with liver biopsy in accurate assessment of Fontan-associated liver disease.
Methods
Fontan patients who underwent combined assessment with a percutaneous liver biopsy and non-invasive elastography between January 2015 and December 2023 at our Children’s hospital were included. Liver biopsies were classified using the Congestive Hepatic Fibrosis Score as early Fontan-associated liver disease (scores 1, 2) and advanced Fontan-associated liver disease (score 3/bridging fibrosis and score 4/cirrhosis). Elastography values were categorised as advanced Fontan-associated liver disease for liver elasticity >2.1 m/s by ultrasound and liver stiffness >5 KPa on magnetic resonance elastography.
Results
We included 130 patients (116 children, 89%, mean age at biopsy: 14.6 years ± 3.6) who underwent liver biopsy at a mean duration of 11.1 years (±0.3) following Fontan surgery. Advanced Fontan-associated liver disease was noted in 41 (31.5%) patients with 13 (10%) showing frank cirrhosis. Pre-biopsy ultrasound showed advanced liver fibrosis in 18/125 (14%), with low sensitivity (23%), high specificity (90%), and low accuracy (68%, k = 0.1) in diagnosing advanced Fontan-associated liver disease. Similarly, pre-biopsy magnetic resonance elastography showed advanced fibrosis in 23/86 (27%) of patients, with low sensitivity (30%), fair specificity (75%), and low accuracy (63%, k = 0.1). Interestingly, advanced Fontan-associated liver disease was missed by ultrasound in 29% and by magnetic resonance elastography in 25% of patients. Advanced Fontan-associated liver disease was associated with lower platelet count (p = 0.02) and higher Gamma-glutamyl Transferase levels (p = 0.02).
Conclusion
Advanced hepatic fibrosis is common among paediatric Fontan patients. Non-invasive elastography may overestimate and underestimate the degree of liver fibrosis, and therefore, liver biopsy may be required for confirming disease severity.
... the depth of the lesions makes a difference to the score of the elastic image. Ultrasound beams are usually focused at a depth of around 3 cm to 5 cm, so that the area of maximum radiation force energy is 4 cm to 4.5 cm from the transducer and gradually diminishes as it progresses in the medium (35). If ultrasound beams reach a point beyond reference range, then their intensity is too weak to generate an adequate acoustic radiation force (36). ...
Objective
This study aims to combine ultrasound (US) elastography (USE) and radiomic to predict central cervical lymph node metastasis (CLNM) in patients with papillary thyroid microcarcinoma (PTMC).
Methods
A total of 204 patients with 204 thyroid nodules who were confirmed with PTMC and treated in our hospital were enrolled and randomly assigned to the training set (n = 142) and the validation set (n = 62). US features, USE (gender, shape, echogenic foci, thyroid imaging reporting and data system (TIRADS) category, and elasticity score), and radiomic signature were employed to build three models. A nomogram was plotted for the combined model, and decision curve analysis was applied for clinical use.
Results
The combined model (USE and radiomic) showed optimal diagnostic performance in both training (AUC = 0.868) and validation sets (AUC = 0.857), outperforming other models.
Conclusion
The combined model based on USE and radiomic showed a superior performance in the prediction of CLNM of patients with PTMC, covering the shortage of low specificity of conventional US in detecting CLNM.
... Aside from the diverse advantages provided by the usage of ultrasound as the imaging modality associated with elastography, we have to expect that at some point we will be disrupted by some of the technical difficulties that the modality may possess in light of the sensitivity of the ultrasound image and its susceptibility to change depending on many factors ranging from machine-based artifacts to errors on behalf of the operator [60,61]. ...
Ultrasound is a highly adaptable medical imaging modality that offers several applications and a wide range of uses, both for diagnostic and therapeutic purposes. The principles of sound wave propagation and reflection enable ultrasound imaging to function as a highly secure modality. This technique facilitates the production of real-time visual representations, thereby assisting in the evaluation of various medical conditions such as cardiac, gynecologic, and abdominal diseases, among others. The ultrasound modality encompasses a diverse range of modes and mechanisms that serve to enhance the methodology of pathology and physiology assessment. Doppler imaging and US elastography, in particular, are two such techniques that contribute to this expansion. Elastography-based imaging methods have attracted significant interest in recent years for the non-invasive evaluation of tissue mechanical characteristics. These techniques utilize the changes in soft tissue elasticity in various diseases to generate both qualitative and quantitative data for diagnostic purposes. Specialized imaging techniques collect data by identifying tissue stiffness under mechanical forces such as compression or shear waves. However, in this review paper, we provide a comprehensive examination of the fundamental concepts, underlying physics, and limitations associated with ultrasound elastography. Additionally, we present a concise overview of its present-day clinical utilization and ongoing advancements across many clinical domains.
... According to the actual literature, significant fibrosis and liver cirrhosis were defined as LSM > 8 kPa and > 15 kPa, respectively. In addition, a CAP value > 222 dB/m was defined as significant steatosis [15][16][17][18][19][20][21][22][23][24]. ...
Background and Aims: Chronic hepatitis B virus (HBV) infection is a global public health challenge since more than 250 million individuals are affected worldwide. Since different treatment modalities are available and not all patients are candidates for antiviral treatment, biomarkers that potentially predict the possibility of HBsAg clearance and seroconversion may be useful in clinical practice. Patients and methods: In this retrospective study, we aimed to identify factors positively correlated with HBsAg seroconversion in a large cohort of 371 chronic hepatitis B patients treated at a German tertial center between 2005 and 2020. Results: Seroconversion occurred in 25/371 (6.7%) and HBsAg loss in 29/371 patients (7.8%) with chronic HBV infection. Antiviral therapy was associated with a lower chance of seroconversion (seroconversion antiviral therapy 14/260 (5.4%) vs. therapy-naïve patients 11/111 (9.9%), p = 0.027). Seroconversion rates were higher in patients with (very) low titers of HBV DNA (best cut-off value 357 IU/mL) and quantitative HBsAg. The best cut-off value with regard to seroconversion was 357 IU/mL for HBV DNA (AUC 0.693 (95%-CI 0.063–0.422), sensitivity 0.714, specificity 0.729; p < 0.0005) and 33,55 IU/mL for HBsAg (AUC 0.794 (95%-CI 0.651–0.937), sensitivity 0.714, specificity 0.949; p < 0.0005). However, male gender was positively associated with seroconversion (seroconversion: males 7.6% vs. females 2.7%, p = 0.036). Conclusions: Treatment-naïve male chronic HBV patients with low viral load and inflammatory activity have the best chance to achieve seroconversion. In the absence of cirrhosis, antiviral therapy should therefore not be performed in this patient collective.
... One of the representative applications is ultrasound elastography. [43][44][45] Ultrasound elastography detects the stiffness of the biological tissue noninvasively to analyze abnormal tissue environments such as liver fibrosis, kidney fibrosis, and prostate cancer. Likewise, several researchers have created a medical needle integrated with a mechanical sensor for real-time tissue evaluation during medical treatment. ...
A medical tool is a general instrument intended for use in the prevention, diagnosis, and treatment of diseases in humans or other animals. Nowadays, sensors are widely employed in medical tools to analyze or quantify disease‐related parameters for the diagnosis and monitoring of patients’ diseases. Recent explosive advancements in sensor technologies have extended the integration and application of sensors in medical tools by providing more versatile in vivo sensing capabilities. These unique sensing capabilities, especially for medical tools for surgery or medical treatment, are getting more attention owing to the rapid growth of minimally invasive surgery. In this review, recent advancements in sensor‐integrated medical tools are presented, and their necessity, use, and examples are comprehensively introduced. Specifically, medical tools often utilized for medical surgery or treatment, for example, medical needles, catheters, robotic surgery, sutures, endoscopes, and tubes, are covered, and in‐depth discussions about the working mechanism used for each sensor‐integrated medical tool are provided.
Objective
This study aimed to investigate the association between blood manganese and selenium levels and hepatic steatosis among adolescents, using data from the National Health and Nutrition Examination Survey (NHANES) 2017–2023.
Methods
A cross-sectional analysis was conducted using data from 2,459 adolescents (aged 12–19 years) with complete data on liver ultrasound transient elastography, blood manganese, and selenium levels. Hepatic steatosis was defined as a controlled attenuation parameter (CAP) score of ≥248 dB/m, a measure of liver steatosis, which is a primary characteristic and a less severe stage of hepatic steatosis, assessed by vibration-controlled transient elastography (VCTE). Multivariate logistic regression models were used to assess the associations between blood manganese and selenium levels and hepatic steatosis, while restricted cubic splines (RCS) were employed to examine the dose-response relationships.
Results
The mean age of the participants was 15.37 years, with 52.22% boy. Higher blood manganese and selenium levels were significantly associated with an increased prevalence of hepatic steatosis. In the fully adjusted model, adolescents in the highest quartile of blood manganese had more than twice the odds of hepatic steatosis compared to those in the lowest quartile (OR = 2.41, 95% CI: 1.55–3.75, P < 0.01). Similarly, the highest quartile of blood selenium was associated with a 57% increase in hepatic steatosis prevalence compared to the lowest quartile (OR = 1.57, 95% CI: 1.19–2.08, P < 0.01). RCS analysis confirmed a linear association between both blood manganese and selenium levels and hepatic steatosis prevalence. Subgroup analyses did not reveal statistically significant interactions by age, sex, or obesity status, although associations appeared stronger in younger adolescents.
Conclusion
Elevated blood manganese and selenium levels are associated with a higher prevalence of hepatic steatosis in adolescents. These findings suggest a potential role of trace elements in the development of hepatic steatosis, highlighting the need for further research to better understand the underlying mechanisms involved in liver fat accumulation in this population.
The emergence and integration of nonconventional ultrasound applications into the vascular diagnostic armamentarium offers the opportunity for answering a long-standing question about the morphological makeup of focal carotid atherosclerotic lesions, that is, is this particular plaque vulnerable or not? Vulnerable lesions are those which, based on their histological and morphological features, predispose a patient to an increased risk of a cerebral ischemic event (CIE) secondary to plaque or thrombus embolization. The ability to reliably differentiate plaque types using readily available noninvasive imaging methods facilitates risk stratification in both symptomatic and asymptomatic patients. Improved identification of at-risk lesions makes more targeted patient management and/or interventional decisions possible. Three emerging ultrasound applications that have demonstrated efficacy in offering this enhanced diagnostic capability are point shear wave elastography (pSWE), contrast-enhanced ultrasound (CEUS), and microvascular ultrasound imaging (MUI).
Background: we evaluated regression models based on quantitative ultrasound (QUS) parameters and compared them with a vendor-provided method for calculating the ultrasound fat fraction (USFF) in metabolic dysfunction-associated steatotic liver disease (MASLD). Methods: We measured the attenuation coefficient (AC) and the backscatter-distribution coefficient (BSC-D) and determined the USFF during a liver ultrasound and calculated the magnetic resonance imaging proton-density fat fraction (MRI-PDFF) and steatosis grade (S0–S4) in a combined retrospective–prospective cohort. We trained multiple models using single or various QUS parameters as independent variables to forecast MRI-PDFF. Linear and nonlinear models were trained during five-time repeated three-fold cross-validation in a retrospectively collected dataset of 60 MASLD cases. We calculated the models’ Pearson correlation (r) and the intraclass correlation coefficient (ICC) in a prospectively collected test set of 57 MASLD cases. Results: The linear multivariable model (r = 0.602, ICC = 0.529) and USFF (r = 0.576, ICC = 0.54) were more reliable in S0- and S1-grade steatosis than the nonlinear multivariable model (r = 0.492, ICC = 0.461). In S2 and S3 grades, the nonlinear multivariable (r = 0.377, ICC = 0.32) and AC-only (r = 0.375, ICC = 0.313) models’ approximated correlation and agreement surpassed that of the multivariable linear model (r = 0.394, ICC = 0.265). We searched a QUS parameter grid to find the optimal thresholds (AC ≥ 0.84 dB/cm/MHz, BSC-D ≥ 105), above which switching from a linear (r = 0.752, ICC = 0.715) to a nonlinear multivariable (r = 0.719, ICC = 0.641) model could improve the overall fit (r = 0.775, ICC = 0.718). Conclusions: The USFF and linear multivariable models are robust in diagnosing low-grade steatosis. Switching to a nonlinear model could enhance the fit to MRI-PDFF in advanced steatosis.
Background: Diffuse liver parenchymal disease (LPD) encompasses a wide range of liver disorders characterized by extensive involvement of liver tissue, often resulting in significant morbidity and mortality. Early detection and accurate assessment of these diseases are crucial for effective management and improved patient outcomes. Aims and Objectives: This study aims to evaluate the efficacy of various imaging modalities in the early detection and monitoring of diffuse LPDs, specifically focusing on non-invasive techniques such as ultrasonography (USG), computed tomography (CT), and Fibroscan. Materials and Methods: A prospective observational study was conducted involving 362 patients presenting with clinical signs and symptoms of liver disease at Maharani Laxmi Bai Medical College, Jhansi. Patients underwent standardized imaging protocols, including US, CT, and Fibroscan, along with laboratory tests to confirm liver function abnormalities. Imaging findings were correlated with clinical and laboratory data to assess diagnostic accuracy and efficacy. Results: The study found that ultrasound, elastography, and CT provide a reliable, non-invasive method for assessing diffuse LPD at the early stage ultrasound along with Fibroscan and CT both have comparable diagnostic capabilities in assessing diffuse LPD. Ultrasound and Fibroscan being non-invasive and radiation-free should be used as initial investigations whereas CT further contributes to the detailed characterization of liver parenchyma. Integration of these imaging modalities significantly enhanced early diagnosis and disease monitoring. Conclusion: Integrating advanced imaging modalities, especially elastography, into routine diagnostic protocols for diffuse LPDs enables early detection and effective management. Non-invasive techniques such as US and CT improve patient outcomes by allowing timely intervention and continuous monitoring of disease progression, thus reducing the need for invasive procedures such as liver biopsy.
Este manual destina-se aos profissionais de saúde e busca uniformizar a assistência
prestada aos casos de Obesidade com pacientes candidatos à Cirurgia Bariátrica atendidos neste serviço de saúde, através da consolidação de conceitos e critérios e da definição de exames complementares necessários para este grupo de pacientes, de forma a promover um planejamento terapêutico racional e um algoritmo de fluxo após a admissão.
Obesidade é uma condição clínica definida como o acúmulo excessivo de tecido
adiposo no organismo, estando associada a múltiplas comorbidades, principalmente
doenças cardiovasculares, diabetes, apneia do sono e até mesmo neoplasias malignas.
Pacientes que possuem índice de massa corporal (IMC) superior a 30kg/m2 devido ao
depósito excessivo de tecido adiposo é classificado como um indivíduo obeso.
Doença Hepática Gordurosa Não Alcoólica (DHGNA) é a hepatopatia mais comum
no mundo e sua crescente ocorrência está intimamente relacionada à epidemia de
obesidade. A DHGNA é caracterizada por um amplo espectro de anormalidades histológicas que variam da simples esteatose até fibrose hepática, cirrose e inclusive hepatocarcinoma. Trata-se de uma doença desafiadora, multissistêmica e com alto impacto econômico. Espera-se que, até 2030, a DHGNA se transforme na principal indicação para transplante de fígado.
Disfunção Miocárdica é definida como uma falha no mecanismo de bombeamento
sanguíneo realizado pelo coração aos órgãos. Ocorrendo uma chegada inadequada e
insuficiente do sangue aos órgãos. Ela pode ocorrer por várias razões, as mais comuns são doenças cardíacas propriamente ditas como a doença arterial coronariana e infartos, hipertensão arterial crônica e também conforme estudos recentes a sobrecarga cardíaca em consequência da obesidade severa.
Background: Diffuse liver parenchymal disease (LPD) encompasses a wide range of liver disorders characterized by extensive involvement of liver tissue, often resulting in significant morbidity and mortality. Early detection and accurate assessment of these diseases are crucial for effective management and improved patient outcomes. Aims and Objectives: This study aims to evaluate the efficacy of various imaging modalities in the early detection and monitoring of diffuse LPDs, specifically focusing on non-invasive techniques such as ultrasonography (USG), computed tomography (CT), and Fibroscan. Materials and Methods: A prospective observational study was conducted involving 362 patients presenting with clinical signs and symptoms of liver disease at Maharani Laxmi Bai Medical College, Jhansi. Patients underwent standardized imaging protocols, including US, CT, and Fibroscan, along with laboratory tests to confirm liver function abnormalities. Imaging findings were correlated with clinical and laboratory data to assess diagnostic accuracy and efficacy. Results: The study found that ultrasound, elastography, and CT provide a reliable, non-invasive method for assessing diffuse LPD at the early stage ultrasound along with Fibroscan and CT both have comparable diagnostic capabilities in assessing diffuse LPD. Ultrasound and Fibroscan being non-invasive and radiation-free should be used as initial investigations whereas CT further contributes to the detailed characterization of liver parenchyma. Integration of these imaging modalities significantly enhanced early diagnosis and disease monitoring. Conclusion: Integrating advanced imaging modalities, especially elastography, into routine diagnostic protocols for diffuse LPDs enables early detection and effective management. Non-invasive techniques such as US and CT improve patient outcomes by allowing timely intervention and continuous monitoring of disease progression, thus reducing the need for invasive procedures such as liver biopsy.
Objective Liver evaluation is essential in preterm infants because of exposure to hepatotoxic drugs, the effects of parenteral nutrition, and their organ immaturity. The clinical significance of shear wave elastography (SWE) which measures tissue elasticity, is unclear in preterm infants. For SWE application to liver evaluation in preterm infants, we examined the postnatal course and factors associated with changes.
Study Design We prospectively measured liver SWE values every other week in 37 preterm infants born at 23 to 35 weeks gestation and 12 term infants born after 36 weeks gestation.
Results The median early postnatal liver SWE value was 1.22 (interquartile range, 1.19–1.26) m/s. The correlations of liver SWE values with gestational age and birth weight were r = −0.18 (p = 0.23) and r = −0.21 (p = 0.157), respectively. The median liver SWE values from birth to 36 to 38 postmenopausal weeks were 1.22 (1.17–1.24) m/s at <28 weeks gestation (n = 9), 1.21 (1.18–1.25) m/s at 28 to 29 weeks gestation (n = 11), 1.24 (1.21–1.28) m/s at 30 to 31 weeks gestation (n = 8), and 1.21 (1.20–1.24) m/s at ≥32 weeks gestation (n = 9). There was no change over time in any gestational age group (p = 0.158). The median liver SWE values were 1.22 (1.17–1.25) m/s (n = 10) and 1.22 (1.19–1.25) m/s (n = 27) for small- and appropriate-for-gestational-age infants, respectively (p = 0.93). The correlations of abnormally high serum concentrations of direct bilirubin (>1.0 mg/dL) and alanine aminotransferase (>12 IU/L) with liver SWE values were r = 0.37 (p = 0.041) and r = 0.21 (p = 0.35), respectively.
Conclusion Liver SWE values may be useful for the evaluation of liver damage with cholestasis in preterm infants because they remain constant regardless of gestational age and birth weight and do not change over time or with a deviation of body size.
Key Points
Liver fibrosis refers to the formation of scar tissue in the liver when inflammation persists over a long period. Assessing liver fibrosis is crucial for predicting the prognosis of chronic liver disease and managing patients with these conditions. Although a liver biopsy remains the gold standard for assessing liver fibrosis, it is limited by its invasive nature. Consequently, continuous efforts have been made to develop non-invasive methods for evaluating liver fibrosis, including imaging techniques and serum biomarkers. Vibration-controlled transient elastography (VCTE), a representative non-invasive imaging technique, has been used widely for liver fibrosis assessment since its introduction in 2003. This paper discusses the principles and methods of measurement, the advantages and disadvantages, and the considerations for interpreting VCTE based on the 2024 KASL Clinical Practice Guidelines for Non-invasive Tests to Assess Liver Fibrosis in Chronic Liver Disease. In addition, the diagnostic utility of VCTE in chronic viral hepatitis is reviewed.
Background & Aims
Effective anti-fibrotic drugs and new non-invasive evaluation methods for liver fibrosis (LF) are urgently needed. Our study aimed to evaluate the histological effects of the Qizhu (QZ) formula on LF and to explore a non-invasive Near-infrared photoacoustic imaging (NIR-PAI) kinetic model for liver function detection and pharmacodynamic evaluation.
Methods
C57BL/6 J mice were randomly divided into six groups (n=6). An LF model was induced by CCl4 for 8 weeks, followed by an 8-week treatment period. Histological and serological parameters were assessed, and indocyanine green (ICG) metabolism (maximum peak time [Tmax] and half-life [T1/2]) was monitored by NIR-PAI. Spearman correlation analysis was conducted to evaluate correlations.
Results & Conclusions
Histological and serological results confirmed the anti-fibrotic effects of QZ. NIR-PAI kinetic parameters indicated that QZ shortened the Tmax and T1/2 of ICG. There were good correlations between ICG metabolism and liver histopathology. The non-invasive NIR-PAI kinetic model shows potential in liver function detection and pharmacodynamic evaluation.
Objectives
This study aimed to investigate and compare 2‐dimensional shear wave elastography (2D‐SWE) measurements and influencing factors among 2 different devices and to evaluate the ability and influencing factors of these measurements to assess liver fibrosis.
Methods
From October 2022 to September 2023, 290 hepatocellular carcinoma (HCC) patients and 30 healthy volunteers were prospectively included. The 2D‐SWE measurements were performed using AixPlorer V (SEmean) and APLIO i900 (CEmean). This study compared 2D‐SWE measurements between instruments for evaluating the liver fibrosis stage and analyzed the potential influencing factors.
Results
The 2D‐SWE measurements obtained by the 2 instruments were significantly different ( P < .001), but the differences were significant only for patients with stage F4 liver fibrosis ( P < .001) and not for volunteers or patients with stage F0–F3 liver fibrosis (all P > .050). Multivariate linear regression analysis revealed that the factors independently influencing the SEmean were alanine aminotransferase (ALT) ( P = .034) and liver fibrosis stage ( P < .001), while fibrosis stage ( P = .028) was the only factor influencing the CEmean.
Conclusions
Although 2D‐SWE from the 2 different instruments was capable of detecting liver fibrosis, it yielded varying results in HCC patients. These discrepancies were predominantly observed in patients with F4 liver fibrosis but not in healthy adults or patients with F0–F3 liver fibrosis. One potential contributing factor to the differences between instruments could be ALT levels.
The history of the emerging elastographic technique is presented. Ultrasound imaging of elasticity and tissue strain has gained clinical acceptance as an established technique useful in routine daily clinical practice.
Molecular imaging holds the potential for noninvasive and accurate grading of liver fibrosis. It is limited by the lack of biomarkers that strongly correlate with liver fibrosis grade. Here, we discover the grading potential of fibroblast activation protein alpha (FAPα) for liver fibrosis through transcriptional analysis and biological assays on clinical liver samples. The protein and mRNA expression of FAPα are linearly correlated with fibrosis grade (R² = 0.89 and 0.91, respectively). A FAPα-responsive MRI molecular nanoprobe is prepared for quantitatively grading liver fibrosis. The nanoprobe is composed of superparamagnetic amorphous iron nanoparticles (AFeNPs) and paramagnetic gadoteric acid (Gd-DOTA) connected by FAPα-responsive peptide chains (ASGPAGPA). As liver fibrosis worsens, the increased FAPα cut off more ASGPAGPA, restoring a higher T1-MRI signal of Gd-DOTA. Otherwise, the signal remains quenched due to the distance-dependent magnetic resonance tuning (MRET) effect between AFeNPs and Gd-DOTA. The nanoprobe identifies F1, F2, F3, and F4 fibrosis, with area under the curve of 99.8%, 66.7%, 70.4%, and 96.3% in patients’ samples, respectively. This strategy exhibits potential in utilizing molecular imaging for the early detection and grading of liver fibrosis in the clinic.
Purpose
To evaluate the diagnostic value of ultrasound elastography (USE) for characterizing hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC).
Methods
The protocol was pre-registered a priori at (https://osf.io/namvk/). Using PubMed, Web of Science, Embase, and Cochrane Library, we found studies up to April 20, 2024 by searching HCC, ICC, and USE as keywords. Parameters of USE were directly compared between HCC and ICC patients using random-effects bivariate model on STATA 17.0, MedCalc 20.0, and Psychometrica. Trim & fill method and sensitivity analysis were also performed.
Results
Eighteen studies were included with 1057 patients, consisting of 863 HCC lesions, 188 ICC lesions, and 6 mixed lesions. The pooled Emean values of HCC and ICC were 28.3 (CI = 19.8 to 36.8) and 44.0 (CI = 20.9 to 67.2). HCC tumors were 34.3% softer than ICC while peritumoral tissue in HCC lesions was 75% stiffer than ICC lesions based on Emean. The strain value index (tumoral-to-peritumoral ratio) in HCC patients was 49.4% less than that of ICC patients. USE demonstrated a pool sensitivity of 87% (CI = 73–95%), specificity of 82% (CI = 65–92%), positive likelihood ratio of 4.8 (CI = 2.2 to 10.3), negative likelihood ratio of 0.16 (CI = 0.07 to 0.37), and diagnostic odds ratio of 31 (CI = 7 to 127) in differentiation of ICC from HCC.
Conclusion
By evaluating tumoral and pre-tumoral stiffness, along with strain value index, USE may provide a valuable quantitative diagnostic tool for accurately differentiating HCC and ICC.
Background
Lipid metabolism factors may play a role in the development of arthritis and hepatic steatosis and fibrosis. The aim of this study was to explore the potential association between arthritis and hepatic steatosis and liver fibrosis.
Materials and methods
The nationally representative sample from the National Health and Nutrition Examination Survey was analyzed, with data on arthritis diagnosis, subtype, and liver status obtained. Liver status was assessed using transient elastography. Hepatic steatosis was defined as a Controlled Attenuation Parameter (CAP) score ≥263 dB/m, and liver fibrosis status was defined as F0‒F4. Logistic regression models and subgroup analyses stratified by sex were used to evaluate the associations. Smooth curve fitting was used to describe the associations.
Results
The present study of 6,840 adults aged 20 years or older found a significant positive correlation between arthritis and CAP in multivariate logistic regression analysis (β = 0.003, 95 % CI 0.001 to 0.0041, p < 0.001). Participants with arthritis had a higher risk of hepatic steatosis (OR = 1.248, 95 % CI 1.036 to 1.504, p = 0.020), particularly those with osteoarthritis or degenerative arthritis, but not rheumatoid arthritis (p = 0.847). The positive correlation was maintained in females (β = 0.004, 95 % CI 0.002 to 0.006, p < 0.001), but not in males. There was no significant relationship between arthritis and liver fibrosis (p = 0.508).
Conclusion
This study indicates that there is a positive correlation between arthritis and hepatic steatosis, particularly in females. Nonetheless, there is no significant relationship between arthritis and the risk of liver fibrosis.
Aim
Shear wave (SW) elastography is used to evaluate metabolic dysfunction‐associated steatotic liver disease (MASLD) pathophysiology. Increased elasticity due to fibrosis and increased viscosity due to necrosis and inflammation affect SW. Assessing fibrosis, the most prognostically relevant pathology, is critical. Viscosity is evaluated using the dispersion slope (DS); however, cut‐off values that affect SW values are unclear. We compared the ultrasound imaging parameters (SW for viscoelasticity; DS for viscosity) with pathological findings.
Methods
Patients ( n = 159) who underwent liver biopsy and SW and DS assessments at our hospital were included. Fibrosis stage and inflammation grade cut‐off values were calculated from SW, DS, and liver biopsy results using receiver operating characteristic curves. Cases in which liver biopsy results were inconsistent with SW results were used to determine the effect of viscosity on SW values. DS was examined in the Correct and Incorrect Diagnosis groups, which were categorized based on the concordance between SW and liver biopsy results. Dispersion slope cut‐off values between the two groups were calculated.
Results
Fibrosis stage cut‐off values by SW (m/s) were: ≥F2, 1.62; ≥F3, 1.74; and F4, 1.97. Inflammation grade cut‐off values by DS (m/s/kHz) were: ≥A1, 11.6; ≥A2, 14.5; and A3, 16.1. The Correct/Incorrect Diagnosis groups had 25/70 patients. The DS cut‐off value for both groups was 13.2 m/s/kHz.
Conclusions
Shear wave and DS are useful for evaluating liver fibrosis and inflammation in MASLD. For DS > 13.2 m/s/kHz, SW may be affected by the increased viscosity owing to inflammation. In such patients, caution should be used when determining/interpreting values.
Background and objectives
Non-alcoholic fatty liver disease (NAFLD) and urinary incontinence (UI) are both highly prevalent and age-related diseases. Nevertheless, the link between NAFLD and UI is unclear. Hence, the study was designed to evaluate the association between the NAFLD and UI (including UI types) in a nationally representative sample of United States (US) female adults.
Methods
We conducted this study used data from U.S. female adults in the National Health and Nutrition Examination Survey (NHANES) 2017-March 2020 (pre-pandemic) cycles. The diagnosis of NAFLD is based on Vibration controlled transient elastography (VCTE) and absence of know liver diseases and significant alcohol consumption. The diagnosis and types of UI were assessment using a self-report questionnaire. Multivariable logistic regression models were used to analyze the association between NALFD and UI. Stratified analyses based on age, obesity, race, educational level, married status, PIR, and smoking status were conducted.
Results
Of the 2149 participants, the mean (95% CI) age was 53.9 (52.7–55.0), 686 (61.1%) were Non-Hispanic White. UI was significantly more common in participants with NAFLD [490 (64.7%)] than those without NAFLD [552 (44.9%)]. Adjusted for age, race/ethnicity, marital status, educational level, family poverty income ratio (PIR) status, alanine aminotransferase (ALT), aspartate aminotransferase (AST), smoking status, obesity, type 2 diabetes mellitus (T2DM), hypertension and insulin resistance (IR) in a multivariable logistic regression model, NALFD were associated with UI [OR: 1.93, 95%CI 1.23–3.02, P = 0.01] and urge UI [OR: 1.55, 95%CI 1.03–2.33, P = 0.03], while patients with NAFLD did not show an increased odds in stress UI and mixed UI when compared with those without NAFLD subject (P > 0.05). In the subgroup analyses, NAFLD remained significantly associated with UI, particularly among those participants without obesity (OR: 2.69, 95% CI 1.84-4.00) and aged ≥ 60 years (OR: 2.20, 95% CI 1.38–3.51).
Conclusions
Among US female adults, NAFLD has a strong positive correlation with UI. Given that NAFLD is a modifiable disease, these results may help clinicians to target female patients with NAFLD for treatments and interventions that may help prevent the occurrence of UI and reduce the symptoms of UI.
Background
Non-invasive imaging modalities are warranted for diagnosing and monitoring veno-occlusive disease because early diagnosis and treatment improve the prognosis.
Objective
To evaluate the usefulness of liver shear wave elastography (SWE) and shear wave dispersion (SWD) imaging in diagnosing and monitoring veno-occlusive disease in pediatric patients.
Materials and methods
We conducted a prospective cohort study at a single tertiary hospital from March 2021 to April 2022. The study protocol included four ultrasound (US) sessions: a baseline US and three follow-up US after hematopoietic stem cell transplantation. Clinical criteria, including the European Society for Blood and Marrow Transplantation criteria, were used to diagnose veno-occlusive disease. We compared clinical factors and US parameters between the veno-occlusive disease and non-veno-occlusive disease groups. The diagnostic performance of US parameters for veno-occlusive disease was assessed by plotting receiver operating characteristic (ROC) curves. We describe temporal changes in US parameters before and after veno-occlusive disease diagnosis.
Results
Among the 38 participants (mean age 10.7 years), eight developed veno-occlusive disease occurring 17.0 ± 5.2 days after hematopoietic stem cell transplantation. Liver stiffness, as measured by SWE (15.0 ± 6.2 kPa vs. 5.8 ± 1.8 kPa; P<0.001), and viscosity, as assessed with SWD (17.7 ± 3.1 m/s/kHz vs. 14.3 ± 2.8 m/s/kHz; P=0.015), were significantly higher in the veno-occlusive disease group compared to the non-veno-occlusive disease group at the time of diagnosis. Liver stiffness demonstrated the highest area under the ROC (AUROC) curves at 0.960, with an optimal predictive value of >6.5 kPa, resulting in sensitivity and specificity of 100% and 83.3%, respectively. Viscosity demonstrated an AUROC of 0.783, with an optimal cutoff value of 13.9 m/s/kHz for predicting veno-occlusive disease, with a sensitivity of 100% and specificity of 53.3%, respectively. Liver stiffness increased with disease severity and decreased during post-treatment follow-up.
Conclusion
SWE may be a promising technique for early diagnosis and severity prediction of veno-occlusive disease. Furthermore, liver viscosity assessed by SWD may serve as an additional marker of veno-occlusive disease.
Graphical abstract
Liver fibrosis is a wound-healing response to chronic liver injury, which may lead to cirrhosis and cancer. Early-stage fibrosis is reversible, and it is difficult to precisely diagnose with conventional imaging modalities such as magnetic resonance imaging, positron emission tomography, single-photon emission computed tomography, and ultrasound imaging. In contrast, probe-assisted molecular imaging offers a promising noninvasive approach to visualize early fibrosis changes in vivo, thus facilitating early diagnosis and staging liver fibrosis, and even monitoring of the treatment response. Here, the most recent progress in molecular imaging technologies for liver fibrosis is updated. We start by illustrating pathogenesis for liver fibrosis, which includes capillarization of liver sinusoidal endothelial cells, cellular and molecular processes involved in inflammation and fibrogenesis, as well as processes of collagen synthesis, oxidation, and cross-linking. Furthermore, the biological targets used in molecular imaging of liver fibrosis are summarized, which are composed of receptors on hepatic stellate cells, macrophages, and even liver collagen. Notably, the focus is on insights into the advances in imaging modalities developed for liver fibrosis diagnosis and the update in the corresponding contrast agents. In addition, challenges and opportunities for future research and clinical translation of the molecular imaging modalities and the contrast agents are pointed out. We hope that this review would serve as a guide for scientists and students who are interested in liver fibrosis imaging and treatment, and as well expedite the translation of molecular imaging technologies from bench to bedside.
Background The Society of Radiologists in Ultrasound (SRU) has proposed thresholds for acoustic radiation force impulse techniques to diagnose compensated advanced chronic liver disease (cACLD). However, the diagnostic performance of these thresholds has not been extensively validated. Purpose To validate the SRU thresholds in patients with chronic liver disease who underwent supersonic shear imaging and, if suboptimal diagnostic performance is observed, to identify optimal values for diagnosing cACLD. Materials and Methods This retrospective single-center study included high-risk patients with chronic liver disease who had liver stiffness (LS) measurements and had undergone endoscopy or liver biopsy between January 2018 and December 2021. Patients were randomly allocated to test and validation sets. cACLD was defined as varices at endoscopy and/or severe fibrosis or cirrhosis at liver biopsy. The diagnostic performance of the SRU guidelines was evaluated, and optimal threshold values were identified using receiver operating characteristic (ROC) curve analysis. Results A total of 1180 patients (median age, 57 years [IQR, 50-64 years]; 761 men), of whom 544 (46%) had cACLD, were included. With the SRU recommended thresholds of less than 9 kPa and greater than 13 kPa in the test set (n = 786), the sensitivity and specificity for ruling out and ruling in cACLD were 81% (303 of 374 patients; 95% CI: 77, 85) and 92% (380 of 412 patients; 95% CI: 89, 94), respectively. In ROC curve analysis, the identified optimal threshold values were less than 7 kPa and greater than 12 kPa, showing 91% sensitivity (340 of 374 patients; 95% CI: 88, 93) for ruling out cACLD and 91% specificity (373 of 412 patients; 95% CI: 87, 93) for ruling in cACLD, respectively. In the validation set (n = 394), the optimal thresholds showed 91% sensitivity (155 of 170 patients; 95% CI: 86, 95) and 92% specificity (206 of 224 patients; 95% CI: 88, 95). Conclusion Compared with the SRU guidelines, the dual LS threshold values of less than 7 kPa and greater than 12 kPa were better for diagnosing cACLD. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Barr in this issue.
Introduction
One of the most common complications of cirrhosis is diabetes, which prevalence is strictly related to severity of hepatopathy. Actually, there are no data on the persistence of post-transplant glucose abnormalities and on a potential impact of diabetes on development of fibrosis in the transplanted liver. To this aim, we evaluated liver fibrosis in cirrhotic subjects before and after being transplanted.
Methods
The study included 111 individuals who had liver transplantation. The assessment was performed before and two years after surgery to investigate a potential impact of the persistence of diabetes on developing de novo fibrosis in the transplanted liver. The degree of fibrosis was assessed using the Fibrosis Index Based on 4 Factors (FIB-4) and the Aspartate to Platelet Ratio Index (APRI).
Results
At pre-transplant evaluation, 63 out of 111 (56.8%) subjects were diabetic. Diabetic subjects had higher FIB-4 (Geometric mean, 95% confidence interval: 9.74, 8.32-11.41 vs 5.93, 4.71-7.46, P<0.001) and APRI (2.04, 1.69-2.47 vs 1.18, 0.90-1.55, P<0.001) compared to non-diabetic subjects. Two years after transplantation, 39 out of 111 (35.1%) subjects remained with diabetes and continued to show significantly higher FIB-4 (3.14, 2.57-3.82 vs 1.87, 1.55-2.27, P<0.001) and APRI (0.52, 0.39-0.69 vs 0.26, 0.21-0.32, P<0.001) compared to subjects without diabetes.
Discussion
Thus, persistence of diabetes after surgery is a possible risk factor for an evolution to fibrosis in the transplanted liver, potentially leading to worsened long-term outcomes in this population.
Background and Aims
Transient elastography (TE), shear-wave elastography (SWE), and/or magnetic resonance elastography (MRE), each providing liver stiffness measurement (LSM), are the most studied imaging-based noninvasive liver disease assessment (NILDA) techniques. To support the American Association for the Study of Liver Diseases guidelines on NILDA, we summarized the evidence on the accuracy of these LSM methods to stage liver fibrosis (F).
Approach and Results
A comprehensive search for studies assessing LSM by TE, SWE, or MRE for the identification of significant fibrosis (F2-4), advanced fibrosis (F3-4), or cirrhosis (F4), utilizing histopathology as standard of reference by liver disease etiology in adults or children from inception to April 2022 was performed. We excluded studies with <50 patients with a single disease entity and mixed liver disease etiologies (with the exception of HCV/HIV co-infection). Out of 9447 studies, 240 with 61,193 patients were included in this systematic review. In adults, sensitivities for the identification of F2-4 ranged from 51% to 95%, for F3-4 from 70% to 100%, and for F4 from 60% to 100% across all techniques/diseases, whereas specificities ranged from 36% to 100%, 74% to 100%, and 67% to 99%, respectively. The largest body of evidence available was for TE; MRE appeared to be the most accurate method. Imaging-based NILDA outperformed blood-based NILDA in most comparisons, particularly for the identification of F3-4/F4. In the pediatric population, imaging-based NILDA is likely as accurate as in adults.
Conclusion
LSM from TE, SWE, and MRE show acceptable to outstanding accuracy for the detection of liver fibrosis across various liver disease etiologies. Accuracy increased from F2-4 to F3-4 and was the highest for F4. Further research is needed to better standardize the use of imaging-based NILDA, particularly in pediatric liver diseases.
Transient elastography (TE) and point shear wave elastography (pSWE) are 2 elastographic ultrasound examinations used in liver stiffness (LS) measurement. It was shown that the LS value detected by TE in pediatric β-thalassemia major patients has increased, and there was no LS evaluation obtained with pSWE in literature. Thus, in this study, it was aimed to evaluate LS with pSWE examination in children with thalassemia major and to determine LS-related parameters in these patients. Sixty-three schoolchildren with a diagnosis of β-thalassemia major and 21 healthy controls between the ages of 7 and 18 years were included. In addition to routine anamnesis, physical examination, and laboratory examinations, renal and liver ultrasounds were performed. Liver stiffness values were measured by pSWE examination. Serum levels of urea, aspartate-aminotransferase, alanine-aminotransferase, iron, and ferritin were significantly higher in patients, and serum creatinine, iron binding capacity, and hemoglobin levels were found to be significantly lower ( P < 0.05 for each). Liver stiffness values were significantly higher in patients compared with healthy controls. In linear regression analysis, serum iron and iron binding capacity values were found to be closely related with LS ( P < 0.001 vs. β = 0.482 and P = 0.047 vs. β = 0.237, respectively). Liver stiffness values obtained by pSWE examination increase significantly in patients. According to the results of our study, in addition to the previously known TE method, we think that the LS evaluation obtained by pSWE, a new method that can make more accurate measurements, can be used in the possible early detection of target organ damage in children with thalassemia major.
Objective: We aimed to assess the reliability of quantifying psoas major (PM) and quadratus lumborum (QL) stiffness with ultrasound shear wave elastography (SWE), and to explore the effects of gender and physical activity on muscle stiffness.
Methods: Fifty-two healthy participants (18−32 y) were recruited. To determine reliability, 29 of them underwent repeated SWE measurements of PM and QL stiffness by an operator on the same day. The intra-class correlation coefficients (ICC3,1), standard error of measurement (SEM) and minimal detectable change with 95% confidence interval (MDC95) were calculated. The rest participants underwent a single measurement. Two-way MANCOVA was conducted for the effects of gender and physical activity on muscle stiffness.
Results: The observed reliability for PM (ICC3,1 = 0.89−0.92) and QL (ICC3,1 = 0.79−0.82) were good-to-excellent and good, respectively. The SEM (kPa) was 0.79−1.03 and 1.23−1.28, and the MDC95 (kPa) was 2.20−2.85 and 3.41−3.56 for PM and QL, respectively. After BMI adjustment, both gender (PM: F = 10.15, p = 0.003; QL: F = 18.07, p < 0.001) and activity level (PM: F = 5.90, p = 0.005; QL: F = 6.33, p = 0.004) influenced muscle stiffness. The female and inactive groups exhibited higher stiffness in both muscles.
Conclusion: SWE is reliable for quantifying the stiffness of PM and QL. Female and physical inactivity may elevate PM and QL stiffness, underscoring the importance of accounting for these factors in muscle stiffness investigations. Larger prospective studies are needed to further elucidate their effects.
Aims: Transient elastography [Fibroscan (FS)] is a novel non-invasive tool to assess liver fibrosis/cirrhosis. However, it remains to be determined if other liver diseases such as extrahepatic cholestasis interfere with fibrosis assessment since liver stiffness is indirectly measured by the propagation velocity of an ultrasound wave within the liver.
Methods and Results: In this study we measured liver stiffness immediately before ERCP and 3 to 12 days after successful biliary drainage in patients with extrahepatic cholestasis due to benign or malignant bile duct obstruction. Initially elevated liver stiffness decreased in 13 of 15 patients after intervention, in 10 of them markedly. In 3 patients, liver stiffness was elevated to a degree that suggested advanced liver cirrhosis (mean 15.2 kPa). Successful drainage led to a drop of bilirubin by 2.8 to 9.8mg/dL while liver stiffness almost normalized (mean 7.1 kPa). In all patients with successful biliary drainage, the decrease of liver stiffness highly correlated with decreasing bilirubin (Spearman’ rho=0.67, P<0.05) with a mean decrease of liver stiffness of 1.2±0.56 kPa per 1g/dl bilirubin. Two patients, in whom liver stiffness did not decrease despite successful biliary drainage, had advanced liver cirrhosis and multiple liver metastases, respectively. The relationship between bile duct obstruction and liver stiffness was reproduced in an animal model of bile duct ligation in landrace pigs where liver stiffness increased from 4.6 kPa to 8.8 kPa during 120 min of bile duct ligation and decreased to 6.1 kPa within 30 min after decompression.
Conclusion: Extrahepatic cholestasis increases liver stiffness irrespective of fibrosis. Once extrahepatic cholestasis is excluded e.g. by liver imaging and laboratory parameters, transient elastography is a valuable tool to assess liver fibrosis in chronic liver diseases.
An interlaboratory study of shear wave speed (SWS) estimation was performed. Commercial shear wave elastography systems from Fibroscan, Philips, Siemens and Supersonic Imagine, as well as several custom laboratory systems, were involved. Fifteen sites were included in the study. CIRS manufactured and donated 11 pairs of custom phantoms designed for the purposes of this investigation. Dynamic mechanical tests of equivalent phantom materials were also performed. The results of this study demonstrate that there is very good agreement among SWS estimation systems, but there are several sources of bias and variance that can be addressed to improve consistency of measurement results.
Conventional diagnostic ultrasound images of the anatomy (as opposed to blood flow) reveal differences in the acoustic properties of soft tissues (mainly echogenicity but also, to some extent, attenuation), whereas ultrasound-based elasticity images are able to reveal the differences in the elastic properties of soft tissues (e.g., elasticity and viscosity). The benefit of elasticity imaging lies in the fact that many soft tissues can share similar ultrasonic echogenicities but may have different mechanical properties that can be used to clearly visualize normal anatomy and delineate pathologic lesions. Typically, all elasticity measurement and imaging methods introduce a mechanical excitation and monitor the resulting tissue response. Some of the most widely available commercial elasticity imaging methods are 'quasi-static' and use external tissue compression to generate images of the resulting tissue strain (or deformation). In addition, many manufacturers now provide shear wave imaging and measurement methods, which deliver stiffness images based upon the shear wave propagation speed. The goal of this review is to describe the fundamental physics and the associated terminology underlying these technologies. We have included a questions and answers section, an extensive appendix, and a glossary of terms in this manuscript. We have also endeavored to ensure that the terminology and descriptions, although not identical, are broadly compatible across the WFUMB and EFSUMB sets of guidelines on elastography (Bamber et al. 2013; Cosgrove et al. 2013).
Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.
The breast section of these Guidelines and Recommendations for Elastography produced under the auspices of the World Federation of Ultrasound in Medicine and Biology (WFUMB) assesses the clinically used applications of all forms of elastography used in breast imaging. The literature on various breast elastography techniques is reviewed, and recommendations are made on evidence-based results. Practical advice is given on how to perform and interpret breast elastography for optimal results, with emphasis placed on avoiding pitfalls. Artifacts are reviewed, and the clinical utility of some artifacts is discussed. Both strain and shear wave techniques have been shown to be highly accurate in characterizing breast lesions as benign or malignant. The relationship between the various techniques is discussed, and recommended interpretation based on a BI-RADS-like malignancy probability scale is provided. This document is intended to be used as a reference and to guide clinical users in a practical way.
Copyright © 2015. Published by Elsevier Inc.
Alcoholic liver disease (ALD) is the most common liver disease in the Western world. For many reasons, it is underestimated and underdiagnosed. An early diagnosis is absolutely essential since it (1) helps to identify patients at genetic risk for ALD; (2) can trigger efficient abstinence namely in non-addicted patients; and (3) initiate screening programs to prevent life-threatening complications such as bleeding from varices, spontaneous bacterial peritonitis or hepatocellular cancer. The two major end points of ALD are alcoholic liver cirrhosis and the rare and clinically-defined alcoholic hepatitis (AH). The prediction and early diagnosis of both entities is still insufficiently solved and usually relies on a combination of laboratory, clinical and imaging findings. It is not widely conceived that conventional screening tools for ALD such as ultrasound imaging or routine laboratory testing can easily overlook ca. 40% of manifest alcoholic liver cirrhosis. Non-invasive methods such as transient elastography (Fibroscan), acoustic radiation force impulse imaging or shear wave elastography have significantly improved the early diagnosis of alcoholic cirrhosis. Present algorithms allow either the exclusion or the exact definition of advanced fibrosis stages in ca. 95% of patients. The correct interpretation of liver stiffness requires a timely abdominal ultrasound and actual transaminase levels. Other non-invasive methods such as controlled attenuation parameter, serum levels of M30 or M65, susceptometry or breath tests are under current evaluation to assess the degree of steatosis, apoptosis and iron overload in these patients. Liver biopsy still remains an important option to rule out comorbidities and to confirm the prognosis namely for patients with AH.
Magnetic resonance elastography (MRE) is a non-invasive tool for staging liver fibrosis. We conducted a meta-analysis of individual participant data collected from published studies to assess the diagnostic accuracy of MRE and for staging liver fibrosis in patients with chronic liver diseases (CLD).
Chronic hepatitis B describes a spectrum of disease resulting from chronic hepatitis B virus (HBV) infection. About a third of the world’s population has serological evidence of past or present HBV infection, and 350-400 million people have chronic HBV infection.1 In the UK about 326 000 people are thought to have chronic hepatitis B.2 In some people, chronic hepatitis B may cause liver fibrosis, cirrhosis, and hepatocellular carcinoma; in others it is inactive and does not lead to important health problems.3 Antiviral therapy suppresses HBV replication and decreases the risk of progressive liver disease.4 This article summarises the most recent recommendations from the National Institute for Health and Care Excellence (NICE) on the diagnosis and management of chronic hepatitis B in children, young people, and adults.5
NICE recommendations are based on systematic reviews of the best available evidence and explicit consideration of cost effectiveness. When minimal evidence is available, recommendations are based on the Guideline Development Group’s experience and opinion of what constitutes good practice. Evidence levels for the recommendations are given in italic in square brackets.
### Assessment and referral in primary care
#### Children, young people, and adults who are seropositive for HBV surface antigen (HBsAg)
To estimate the validity of the point shear-wave elastography method by evaluating its reproducibility and accuracy for assessing liver stiffness.
This was a single-center, cross-sectional study. Consecutive patients with chronic viral hepatitis scheduled for liver biopsy (LB) (Group 1) and healthy volunteers (Group 2) were studied. In each subject 10 consecutive point shear-wave elastography (PSWE) measurements were performed using the iU22 ultrasound system (Philips Medical Systems, Bothell, WA, United States). Patients in Group 1 underwent PSWE, transient elastography (TE) using FibroScan (Echosens, Paris, France) and ultrasound-assisted LB. For the assessment of PSWE reproducibility two expert raters (rater 1 and rater 2) independently performed the examinations. The performance of PSWE was compared to that of TE using LB as a reference standard. Fibrosis was staged according to the METAVIR scoring system. Receiver operating characteristic curve analyses were performed to calculate the area under the receiver operating characteristic curve (AUC) for F ≥ 2, F ≥ 3 and F = 4. The intraobserver and interobserver reproducibility of PSWE were assessed by calculating Lin's concordance correlation coefficient.
To assess the performance of PSWE, 134 consecutive patients in Group 1 were studied. The median values of PSWE and TE (in kilopascals) were 4.7 (IQR = 3.8-5.4) and 5.5 (IQR = 4.7-6.5), respectively, in patients at the F0-F1 stage and 3.5 (IQR = 3.2-4.0) and 4.4 (IQR = 3.5-4.9), respectively, in the healthy volunteers in Group 2 (P < 10(-5)). In the univariate analysis, the PSWE and TE values showed a high correlation with the fibrosis stage; low correlations with the degree of necroinflammation, aspartate aminotransferase and gamma-glutamyl transferase (GGT); and a moderate negative correlation with the platelet count. A multiple regression analysis confirmed the correlations of both PSWE and TE with fibrosis stage and GGT but not with any other variables. The following AUC values were found: 0.80 (0.71-0.87) for PSWE and 0.82 (0.73-0.89) for TE (P = 0.42); 0.88 (0.80-0.94) for PSWE and 0.95 (0.88-0.98) for TE (P = 0.06); and 0.95 (0.89-0.99) for PSWE and 0.92 (0.85-0.97) for TE (P = 0.30) for F ≥ 2, F ≥ 3 and F = 4, respectively. To assess PSWE reproducibility, 116 subjects were studied, including 47 consecutive patients scheduled for LB (Group 1) and 69 consecutive healthy volunteers (Group 2). The intraobserver agreement ranged from 0.83 (95%CI: 0.79-0.88) to 0.96 (95%CI: 0.95-0.97) for rater 1 and from 0.84 (95%CI: 0.79-0.88) to 0.96 (95%CI: 0.95-0.97) for rater 2. The interobserver agreement yielded values from 0.83 (95%CI: 0.78-0.88) to 0.93 (95%CI: 0.91-0.95).
PSWE is a reproducible method for assessing liver stiffness, and it compares with TE. Compared with patients with nonsignificant fibrosis, healthy volunteers showed significantly lower values.
To evaluate reproducibility of measurements of spleen stiffness (SS) and liver stiffness (LS) at several sites by using point shear wave elastography (pSWE) and to investigate any training effect.
Healthy volunteers were consecutively enrolled. Measurements of SS and LS were performed by an expert (observer 1) and a novice (observer 2) at three different sites of liver and spleen. To assess the effect of training the study was conducted in two periods (period 1 and period 2). Concordance correlation coefficient was used to assess intra-observer and inter-observer reproducibility.
A total of 92 subjects (67 men and 25 women) were enrolled in the study. Both intra-observer and inter-observer agreement were higher for the liver than for the spleen. Overall, the highest intra-observer and inter-observer agreement were obtained for the assessment of LS through intercostal space, and for measurements at this site there was a significantly better performance of observer 2 after the training period. For both observers, training improved the repeatability of SS measurements at all sites. A good intra-observer agreement was obtained only for measurements at the spleen lower pole.
The results of this study show that a learning curve in pSWE acquisition should be taken into account both for SS and LS measurements.
• Reproducibility of SS measurements depends on the expertise of the operator. • To achieve good reproducibility between measurements a training period is required. • A learning curve in pSWE acquisition should be taken into account. • SS measurements are less reproducible than LS measurements.
This review considers three general classes of physical as opposed to phenomenological models of the shear elasticity of tissues. The first is simple viscoelasticity. This model has a special role in elastography because it is the language in which experimental and clinical data are communicated. The second class of models involves acoustic relaxation, in which the medium contains inner time-dependent systems that are driven through the external bulk medium. Hysteresis, the phenomenon characterizing the third class of models, involves losses that are related to strain rather than time rate of change of strain. In contrast to the vast efforts given to tissue characterization through their bulk moduli over the last half-century, similar research using low-frequency shear data is in its infancy. Rather than a neat summary of existing facts, this essay is a framework for hypothesis generation—guessing what physical mechanisms give tissues their shear properties.
An interlaboratory study of shear wave speed estimation was performed. Commercial shear wave elastography systems from Fibroscan, Philips, Siemens and Supersonic Imagine, as well as several custom laboratory systems, were involved. Fifteen sites were included in the study. CIRS manufactured and donated 11 pairs of custom phantoms designed for the purposes of this investigation. Dynamic mechanical tests of equivalent phantom materials was also performed. The results of this study demonstrate that there is very good agreement among SWS estimation systems, but there are several sources of bias and variance that can be addressed to improve consistency of measurement results
The clinical part of these Guidelines and Recommendations produced under the auspices of the European Federation of Societies for Ultrasound in Medicine and Biology EFSUMB assesses the clinically used applications of all forms of elastography, stressing the evidence from meta-analyses and giving practical advice for their uses and interpretation. Diffuse liver disease forms the largest section, reflecting the wide experience with transient and shear wave elastography . Then follow the breast, thyroid, gastro-intestinal tract, endoscopic elastography, the prostate and the musculo-skeletal system using strain and shear wave elastography as appropriate. The document is intended to form a reference and to guide clinical users in a practical way.
The development of ultrasound-based elasticity imaging methods has been the focus of intense research activity since the mid-1990s. In characterizing the mechanical properties of soft tissues, these techniques image an entirely new subset of tissue properties that cannot be derived with conventional ultrasound techniques. Clinically, tissue elasticity is known to be associated with pathological condition and with the ability to image these features in vivo; elasticity imaging methods may prove to be invaluable tools for the diagnosis and/or monitoring of disease. This review focuses on ultrasound-based elasticity imaging methods that generate an acoustic radiation force to induce tissue displacements. These methods can be performed noninvasively during routine exams to provide either qualitative or quantitative metrics of tissue elasticity. A brief overview of soft tissue mechanics relevant to elasticity imaging is provided, including a derivation of acoustic radiation force, and an overview of the various acoustic radiation force elasticity imaging methods.
Non-alcoholic fatty liver disease (NAFLD) affects one in every three subjects in the occidental world. The vast majority will not progress, but a relevant minority will develop liver cirrhosis and its complications. The classical gold-standard for diagnosing and staging NAFLD and assessing fibrosis is liver biopsy (LB). However, it has important sample error issues and subjectivity in the interpretation, apart from a small but real risk of complications. The decision to perform a LB is even harder in a condition so prevalent such as NAFLD in which the probability of finding severe liver injury is low. In an attempt to overcome a LB and to subcategorize patients with NAFLD in different prognosis allowing better management decisions, several non-invasive methods have been studied in the last decade. The literature is vast and confusing. This review will summarize what methods have been tested and how they perform, which tests are adequate for clinical practice and how can they change the management of these patients.
Liver stiffness (LS) measurement by means of transient elastography (TE) is accurate to predict fibrosis stage. The effect of antiviral treatment and virologic response on LS was assessed and compared with untreated patients with chronic hepatitis C (CHC).
TE was performed at baseline, and at weeks 24, 48, and 72 in 515 patients with CHC.
323 treated (62.7%) and 192 untreated patients (37.3%) were assessed. LS experienced a significant decline in treated patients and remained stable in untreated patients at the end of study (P<0.0001). The decline was significant for patients with baseline LS ≥ 7.1 kPa (P<0.0001 and P 0.03, for LS ≥9.5 and ≥7.1 kPa vs lower values, respectively). Sustained virological responders and relapsers had a significant LS improvement whereas a trend was observed in nonresponders (mean percent change -16%, -10% and -2%, for SVR, RR and NR, respectively, P 0.03 for SVR vs NR). In multivariate analysis, high baseline LS (P<0.0001) and ALT levels, antiviral therapy and non-1 genotype were independent predictors of LS improvement.
LS decreases during and after antiviral treatment in patients with CHC. The decrease is significant in sustained responders and relapsers (particularly in those with high baseline LS) and suggests an improvement in liver damage.
Chronic hepatitis C remains a significant medical and economic burden in Canada, affecting nearly 1% of the population. Since the last consensus conference on the management of chronic hepatitis C, major advances have warranted a review of recommended management approaches for these patients. Specifically, direct-acting antiviral agents with dramatically improved rates of virological clearance compared with standard therapy have been developed, and several single nucleotide polymorphisms associated with an increased probability of spontaneous and treatment-induced viral clearance have been identified. In light of this new evidence, a consensus development conference was held in November 2011; the present document highlights the results of the presentations and discussions surrounding these issues. It reviews the epidemiology of hepatitis C in Canada, preferred diagnostic testing approaches and recommendations for the treatment of chronically infected patients with the newly approved protease inhibitors (boceprevir and telaprevir), including those who have previously failed pegylated interferon and ribavirin therapy. In addition, recommendations are made regarding approaches to reducing the burden of hepatitis C in Canada.
We reconstruct the in vivo spatial distribution of linear and nonlinear elastic parameters in ten patients with benign (five) and malignant (five) tumors. The mechanical behavior of breast tissue is represented by a modified Veronda-Westmann model with one linear and one nonlinear elastic parameter. The spatial distribution of these elastic parameters is determined by solving an inverse problem within the region of interest (ROI). This inverse problem solution requires the knowledge of the displacement fields at small and large strains. The displacement fields are measured using a free-hand ultrasound strain imaging technique wherein, a linear array ultrasound transducer is positioned on the breast and radio frequency echo signals are recorded within the ROI while the tissue is slowly deformed with the transducer. Incremental displacement fields are determined from successive radio-frequency frames by employing cross-correlation techniques. The rectangular regions of interest were subjectively selected to obtain low noise displacement estimates and therefore were variables that ranged from 346 to 849.6 mm2 . It is observed that malignant tumors stiffen at a faster rate than benign tumors and based on this criterion nine out of ten tumors were correctly classified as being either benign or malignant.
From times immemorial manual palpation served as a source of information on the state of soft tissues and allowed detection of various diseases accompanied by changes in tissue elasticity. During the last two decades, the ancient art of palpation gained new life due to numerous emerging elasticity imaging (EI) methods. Areas of applications of EI in medical diagnostics and treatment monitoring are steadily expanding. Elasticity imaging methods are emerging as commercial applications, a true testament to the progress and importance of the field.In this paper we present a brief history and theoretical basis of EI, describe various techniques of EI and, analyze their advantages and limitations, and overview main clinical applications. We present a classification of elasticity measurement and imaging techniques based on the methods used for generating a stress in the tissue (external mechanical force, internal ultrasound radiation force, or an internal endogenous force), and measurement of the tissue response. The measurement method can be performed using differing physical principles including magnetic resonance imaging (MRI), ultrasound imaging, X-ray imaging, optical and acoustic signals.Until recently, EI was largely a research method used by a few select institutions having the special equipment needed to perform the studies. Since 2005 however, increasing numbers of mainstream manufacturers have added EI to their ultrasound systems so that today the majority of manufacturers offer some sort of Elastography or tissue stiffness imaging on their clinical systems. Now it is safe to say that some sort of elasticity imaging may be performed on virtually all types of focal and diffuse disease. Most of the new applications are still in the early stages of research, but a few are becoming common applications in clinical practice.
To find out if by combining 2 ultrasound based elastographic methods: acoustic radiation force impulse (ARFI) elastography and transient elastography (TE), we can improve the prediction of fibrosis in patients with chronic hepatitis C.
Our study included 197 patients with chronic hepatitis C. In each patient, we performed, in the same session, liver stiffness (LS) measurements by means of TE and ARFI, respectively, and liver biopsy (LB), assessed according to the Metavir score. 10 LS measurements were performed both by TE and ARFI; median values were calculated and expressed in kilopascals (kPa) and meters/second (m/s), respectively. Only TE and ARFI measurements with IQR < 30% and SR ≥ 60% were considered reliable.
On LB 13 (6.6%) patients had F0, 32 (16.2%) had F1, 52 (26.4%) had F2, 47 (23.9%) had F3, and 53 (26.9%) had F4. A direct, strong correlation was found between TE measurements and fibrosis (r = 0.741), between ARFI and fibrosis (r = 0.730) and also between TE and ARFI (r = 0.675). For predicting significant fibrosis (F ≥ 2), for a cut-off of 6.7 kPa, TE had 77.5% sensitivity (Se) and 86.5% specificity (Sp) [area under the receiver operating characteristic curve (AUROC) 0.87] and for a cut-off of 1.2 m/s, ARFI had 76.9% Se and 86.7% Sp (AUROC 0.84). For predicting cirrhosis (F = 4), for a cut-off of 12.2 kPa, TE had 96.2% Se and 89.6% Sp (AUROC 0.97) and for a cut-off of 1.8 m/s, ARFI had 90.4% Se and 85.6% Sp (AUROC 0.91). When both elastographic methods were taken into consideration, for predicting significant fibrosis (F ≥ 2), (TE ≥ 6.7 kPa and ARFI ≥ 1.2 m/s) we obtained 60.5% Se, 93.3% Sp, 96.8% positive predictive value (PPV), 41.4% negative predictive value (NPV) and 68% accuracy, while for predicting cirrhosis (TE ≥ 12.2 kPa and ARFI ≥ 1.8 m/s) we obtained 84.9% Se, 94.4% Sp, 84.9% PPV, 94.4% NPV and 91.8% accuracy.
TE used in combination with ARFI is highly specific for predicting significant fibrosis; therefore when the two methods are concordant, liver biopsy can be avoided.
Transient elastography (TE) is adequate for a diagnosis of cirrhosis, but its accuracy for milder stages of fibrosis is much less satisfactory. The objective of this study was to compare the performance and the discordance rate of acoustic radiation force impulse (ARFI) and TE with liver biopsy in a cohort of chronic hepatitis C (CHC) patients.
One hundred thirty-nine consecutive patients with CHC were enrolled in two tertiary centers, and evaluated for histological (Metavir score) and biochemical features. All patients underwent TE and ARFI.
TE was unreliable in nine patients (6.5%), while in no cases (0%) were ARFI invalid measurements recorded (P=0.029). By area under receiver operating characteristic curve (AUROC), the best cutoff values for TE and ARFI for significant fibrosis (≥F2) were ≥6.5 kPa (AUROC: 0.78) and ≥1.3 m/s (AUROC: 0.86), respectively. For severe fibrosis (F3-F4), these cutoff values were 8.8 kPa (AUROC: 0.83) for TE and 1.7 m/s (AUROC: 0.94) for ARFI. For cirrhosis, TE had its best cutoff at ≥11 kPa (AUROC: 0.80) and ARFI at ≥2.0 m/s (AUROC: 0.89). By pairwise comparison of AUROC, ARFI was significantly more accurate than TE for a diagnosis of significant and severe fibrosis (P=0.024 and P=0.002, respectively), while this difference was only marginal for cirrhosis (P=0.09). By partial AUROC analysis, ARFI performance results significantly higher for all three stages of fibrosis. The average concordance rates of TE and ARFI vs. liver biopsy were 45.4 and 54.7%, respectively. By multivariate analysis, ARFI was not associated with alanine aminotransferase (ALT), body mass index, Metavir grade, and liver steatosis, while TE was significantly correlated with the ALT value (P=0.027).
In a cohort of patients with CHC, ARFI imaging was more accurate than TE for the non-invasive staging of both significant and severe classes of liver fibrosis.
Real-time shear wave elastography (RT-SWE) might be useful to assess the severity of portal hypertension; reliability criteria for measurement are needed.
We prospectively included 88 consecutive patients undergoing hepatic venous pressure gradient measurement (HVPG, reference standard) for portal hypertension. Liver stiffness (LS) was measured by RT-SWE and by transient elastography (TE). Spleen stiffness (SS) was measured by RT-SWE. Reliability criteria for RT-SWE were searched, and the accuracy of these techniques to identify HVPG⩾10 mmHg (clinically significant portal hypertension, CSPH) was tested and internally validated by bootstrapping analysis.
LS and SS by RT-SWE were feasible respectively in 87 (99%) and 58 (66%) patients. Both correlated with HVPG (LS: R=0.611, p<0.0001 and SS: R=0.514,p<0.0001). LS performed well for diagnosing CSPH (optimism corrected AUROC 0.858). Reliability of measurements was influenced by standard deviation (SD)/median ratio and depth. SD/median ⩽0.10 and depth of measurement <5.6 cm were associated to 96.3% well classified for CSPH, while when one or none of the criteria were fulfilled the rated was, respectively, 76.4% and 44.4%. Measurements fulfilling at least one criterion were considered acceptable; in these patients RT-SWE performance to detect CSPH was excellent (AUROC 0.939; 95%CI: 0.865-1.000;p<0.0001; best cut-off: 15.4 kPa). LS by RT-SWE and by TE were strongly correlated (R=0.795,p<0.0001) and performed similarly both in "per protocol" and in "intention-to-diagnose" analysis after applying reliability criteria. Data CONCLUSIONS: LS by RT-SWE is an accurate method to diagnose CSPH if reliability criteria (SD/median ⩽0.10 and/or depth <5.6 cm) are fulfilled.
Copyright © 2014. Published by Elsevier B.V.
To evaluate and validate the reproducibility of MR Elastography (MRE)-derived liver stiffness values on two different MR vendor platforms performed on the same subject on the same day.
This investigation was approved by the hospital IRB. MRE exams were performed twice in identical fashion in eight volunteers and in five clinical patients on two different 1.5 T MR scanners-once on a Philips MR scanner and immediately afterward in back-to-back fashion on a General Electric MR scanner, or vice versa. All scan parameters were kept identical on the two platforms to the best extent possible. After the MRE magnitude and phase images were obtained, the data were converted into quantitative images displaying the stiffness of the liver parenchyma. Mean liver stiffness values between the two platforms were compared using interclass correlation with a p value <0.05 considered statistically significant.
Interclass correlation coefficient (ICC) value of 0.994 was obtained for 13 subjects with p value <0.001 indicating a significantly positive correlation.
As MRE gains in acceptance and as its availability becomes more widespread, it is important to ascertain and confirm that liver stiffness values obtained on different MRE vendor platforms are consistent and reproducible. In this small pilot investigation, we demonstrate that liver stiffness measurement with MRE is reproducible and has very good consistency across two vendor platforms.
Magnetic resonance elastography (MRE) assesses tissue stiffness in vivo by imaging propagating shear waves through the tissues and processing the wave information. MRE is a robust technology with excellent technical success; is applicable in almost all patients and body habitus; and has excellent reproducibility, repeatability, and interobserver agreement for assessing liver stiffness. It is currently the most accurate noninvasive technique for detection and staging of liver fibrosis and has the potential to replace liver biopsy. This article describes the principles and technique of MRE, current clinical applications, and emerging clinical indications.
With widespread screening and increasingly effective treatments for patients with viral hepatitis as well as the increasing prevalence of nonalcoholic fatty liver disease, the population presenting to the care of gastroenterologists and hepatologists is certain to rise. Assessment of advanced liver disease is traditionally invasive and expensive. Vibration controlled transient elastography (VCTE) commonly delivered by the FibroScan device (Echosens; Paris, France) is a recently FDA approved option for the noninvasive assessment of liver disease at the point of care. Herein we review the promise and pitfalls of VCTE with the aim of providing clinicians with a framework to interpret its results and apply this technology to the changing needs of our patients.
Noninvasive assessment of liver fibrosis by elastography is a rapidly developing field with frequent technological innovations. The aim of this study was to assess the diagnostic performances of Supersonic Shear Imaging (SSI) for the diagnosis of liver fibrosis in chronic liver disease.
A total of 349 consecutive patients with chronic liver diseases who underwent liver biopsy from November 2011 to October 2013 were prospectively enrolled. For each patient, liver stiffness was assessed by SSI, ARFI, Fibroscan (M probe for patients with BMI<30kg/m(2), and XL probe for patients with BMI⩾30kg/m(2)), performed within two weeks of liver biopsy. Areas under the receiver operating curves (AUROCs) were performed and compared for each degree of liver fibrosis.
SSI, Fibroscan, and ARFI correlated significantly with histological fibrosis score (r=0.79, p<.00001; r=0.70, p<.00001; r=0.64, p<.00001, respectively). AUROCs of SSI, Fibroscan, and ARFI were 0.89, 0.86 and 0.84 for the diagnosis of mild fibrosis; 0.88, 0.84, and 0.81 for the diagnosis of significant fibrosis; 0.93, 0.87, and 0.89, for the diagnosis of severe fibrosis; 0.93, 0.90, and 0.90 for the diagnosis of cirrhosis, respectively. SSI had a higher accuracy than Fibroscan for the diagnosis of severe fibrosis (⩾F3) (p=0.0016), and a higher accuracy than ARFI for the diagnosis of significant fibrosis (⩾F2) (p=0.0003). No significant difference was observed for the diagnosis of mild fibrosis and cirrhosis.
SSI is an efficient method for the assessment of liver fibrosis in chronic liver diseases, comparing favorably to Fibroscan and ARFI.
The accumulation of fat droplets within the liver is an important marker of liver disease. This study assesses gradations of steatosis in mouse livers using crawling waves, which are interfering patterns of shear waves introduced into the liver by external sources. The crawling waves are detected by Doppler ultrasound imaging techniques, and these are analyzed to estimate the shear wave speed as a function of frequency between 200 and 360 Hz. In a study of 70 mice with progressive increases in steatosis from 0% to >60%, increases in steatosis are found to increase the dispersion, or frequency dependence, of shear wave speed. This finding confirms an earlier, smaller study and points to the potential of a scoring system for steatosis based on shear wave dispersion.
Although the use of ultrasonic plane-wave transmissions rather than line-per-line focused beam transmissions has been long studied in research, clinical application of this technology was only recently made possible through developments in graphical processing unit (GPU)-based platforms. Far beyond a technological breakthrough, the use of plane or diverging wave transmissions enables attainment of ultrafast frame rates (typically faster than 1000 frames per second) over a large field of view. This concept has also inspired the emergence of completely novel imaging modes which are valuable for ultrasound-based screening, diagnosis, and therapeutic monitoring. In this review article, we present the basic principles and implementation of ultrafast imaging. In particular, present and future applications of ultrafast imaging in biomedical ultrasound are illustrated and discussed.
This meta-analysis aims to compare the diagnostic performance of acoustic radiation force impulse (ARFI) elastography and transient elastography (TE) in the assessment of liver fibrosis using liver biopsy (LB) as 'gold-standard'.
PubMed, Medline, Lilacs, Scopus, Ovid, EMBASE, Cochrane and Medscape databases were searched for all studies published until 31 May 2012 that evaluated the liver stiffness by means of ARFI, TE and LB. Information abstracted from each study according to a fixed protocol included study design and methodological characteristics, patient characteristics, interventions, outcomes and missing outcome data.
Thirteen studies (11 full-length articles and 2 abstracts) including 1163 patients with chronic hepatopathies were included in the analysis. Inability to obtain reliable measurements was more than thrice as high for TE as that of ARFI (6.6% vs. 2.1%, P < 0.001). For detection of significant fibrosis, (F ≥ 2) the summary sensitivity (Se) was 0.74 (95% CI: 0.66-0.80) and specificity (Sp) was 0.83 (95% CI: 0.75-0.89) for ARFI, while for TE the Se was 0.78 (95% CI: 0.72-0.83) and Sp was 0.84 (95% CI: 0.75-0.90). For the diagnosis of cirrhosis, the summary Se was 0.87 (95% CI: 0.79-0.92) and Sp was 0.87 (95% CI: 0.81-0.91) for ARFI elastography, and, respectively, 0.89 (95% CI: 0.80-0.94) and 0.87 (95% CI: 0.82-0.91) for TE. The diagnostic odds ratio of ARFI and TE did not differ significantly in the detection of significant fibrosis [mean difference in rDOR = 0.27 (95% CI: 0.69-0.14)] and cirrhosis [mean difference in rDOR = 0.12 (95% CI: 0.29-0.52)].
Acoustic radiation force impulse elastography seems to be a good method for assessing liver fibrosis, and shows higher rate of reliable measurements and similar predictive value to TE for significant fibrosis and cirrhosis.
Many pathological processes cause marked changes in the mechanical properties of tissue. MR elastography (MRE) is a noninvasive MRI based technique for quantitatively assessing the mechanical properties of tissues in vivo. MRE is performed by using a vibration source to generate low frequency mechanical waves in tissue, imaging the propagating waves using a phase contrast MRI technique, and then processing the wave information to generate quantitative images showing mechanical properties such as tissue stiffness. Since its first description in 1995, published studies have explored many potential clinical applications including brain, thyroid, lung, heart, breast, and skeletal muscle imaging. However, the best-documented application to emerge has been the use of MRE to assess liver disease. Multiple studies have demonstrated that there is a strong correlation between MRE-measured hepatic stiffness and the stage of fibrosis at histology. The emerging literature indicates that MRE can serve as a safer, less expensive, and potentially more accurate alternative to invasive liver biopsy which is currently the gold standard for diagnosis and staging of liver fibrosis. This review describes the basic principles, technique of performing a liver MRE, analysis and calculation of stiffness, clinical applications, limitations, and potential future applications. J. Magn. Reson. Imaging 2013;37:544-555. © 2012 Wiley Periodicals, Inc.
Background:
Whether long-term suppression of replication of hepatitis B virus (HBV) has any beneficial effect on regression of advanced liver fibrosis associated with chronic HBV infection remains unclear. We aimed to assess the effects on fibrosis and cirrhosis of at least 5 years' treatment with tenofovir disoproxil fumarate (DF) in chronic HBV infection.
Methods:
After 48 weeks of randomised double-blind comparison (trials NCT00117676 and NCT00116805) of tenofovir DF with adefovir dipivoxil, participants (positive or negative for HBeAg) were eligible to enter a 7-year study of open-label tenofovir DF treatment, with a pre-specified repeat liver biopsy at week 240. We assessed histological improvement (≥2 point reduction in Knodell necroinflammatory score with no worsening of fibrosis) and regression of fibrosis (≥1 unit decrease by Ishak scoring system).
Findings:
Of 641 patients who received randomised treatment, 585 (91%) entered the open-label phase, and 489 (76%) completed 240 weeks. 348 patients (54%) had biopsy results at both baseline and week 240. 304 (87%) of the 348 had histological improvement, and 176 (51%) had regression of fibrosis at week 240 (p<0·0001). Of the 96 (28%) patients with cirrhosis (Ishak score 5 or 6) at baseline, 71 (74%) no longer had cirrhosis (≥1 unit decrease in score), whereas three of 252 patients without cirrhosis at baseline progressed to cirrhosis at year 5 (p<0·0001). Virological breakthrough occurred infrequently and was not due to resistance to tenofovir DF. The safety profile was favourable: 91 (16%) patients had adverse events but only nine patients had serious events related to the study drug.
Interpretation:
In patients with chronic HBV infection, up to 5 years of treatment with tenofovir DF was safe and effective. Long-term suppression of HBV can lead to regression of fibrosis and cirrhosis.
Funding:
Gilead Sciences.
Background & aims:
We evaluated whether spleen stiffness (SS), measured by acoustic radiation force impulse imaging, can identify patients who have esophageal varices (EVs); those without EVs would not require endoscopic examination.
Methods:
In a prospective study, we measured SS and liver stiffness (LS) in 340 patients with cirrhosis undergoing endoscopic screening for EVs and 16 healthy volunteers (controls) at the Kurashiki Central Hospital in Okayama, Japan. The diagnostic accuracy of SS for the presence of EVs was compared with that of other noninvasive parameters (LS, spleen diameter, and platelet count). Optimal cutoff values of SS were chosen to confidently rule out the presence of varices.
Results:
Patients with cirrhosis had significantly higher SS and LS values than controls (P < .0001 and P < .0001, respectively). Levels of SS were higher among patients with EVs (n = 132) than controls, and values were highest among patients with high-risk EVs (n = 87). SS had the greatest diagnostic accuracy for the identification of patients with EVs or high-risk EVs compared with other noninvasive parameters, independent of the etiology of cirrhosis. An SS cutoff value of 3.18 m/s identified patients with EVs with a 98.4% negative predictive value, 98.5% sensitivity, 75.0% accuracy, and 0.025 negative likelihood ratio. An SS cutoff value of 3.30 m/s identified patients with high-risk EVs with a 99.4% negative predictive value, 98.9% sensitivity, 72.1% accuracy, and 0.018 negative likelihood ratio. SS values less than 3.3 m/s ruled out the presence of high-risk varices in patients with compensated or decompensated cirrhosis. SS could not be measured in 16 patients (4.5%).
Conclusions:
Measurements of SS can be used to identify patients with cirrhosis with EVs or high-risk EVs. A cutoff SS was identified that could rule out the presence of varices and could be used as an initial noninvasive screening test; UMIN Clinical Trials Registry number, UMIN000004363.
Unlabelled:
Liver stiffness evaluation (LSE) is usually considered as reliable when it fulfills all the following criteria: ≥10 valid measurements, ≥60% success rate, and interquartile range / median ratio (IQR/M) ≤0.30. However, such reliable LSE have never been shown to be more accurate than unreliable LSE. Thus, we aimed to evaluate the relevance of the usual definition for LSE reliability, and to improve reliability by using diagnostic accuracy as a primary outcome in a large population. 1,165 patients with chronic liver disease from 19 French centers were included. All patients had liver biopsy and LSE. 75.7% of LSE were reliable according to the usual definition. However, these reliable LSE were not significantly more accurate than unreliable LSE with, respectively: 85.8% versus 81.5% well-classified patients for the diagnosis of cirrhosis (P = 0.082). In multivariate analyses with different diagnostic targets, LSE median and IQR/M were independent predictors of fibrosis staging, with no significant influence of ≥10 valid measurements or LSE success rate. These two reliability criteria determined three LSE groups: "very reliable" (IQR/M ≤0.10), "reliable" (0.10< IQR/M ≤0.30, or IQR/M >0.30 with LSE median <7.1 kPa), and "poorly reliable" (IQR/M >0.30 with LSE median ≥7.1 kPa). The rates of well-classified patients for the diagnosis of cirrhosis were, respectively: 90.4%, 85.8%, and 69.5% (P < 10(-3) ). According to these new reliability criteria, 9.1% of LSE were poorly reliable (versus 24.3% unreliable LSE with the usual definition, P < 10(-3) ), 74.3% were reliable, and 16.6% were very reliable.
Conclusion:
The usual definition for LSE reliability is not relevant. LSE reliability depends on IQR/M according to liver stiffness median level, defining thus three reliability categories: very reliable, reliable, and poorly reliable LSE. (HEPATOLOGY 2013).
Time-of-flight methods allow quantitative measurement of shear wave speed (SWS) from ultrasonically tracked displacements following impulsive acoustic radiation force excitation in tissue. In heterogeneous materials, reflections at boundaries can distort the wave shape and confound determination of the wave arrival time. The magnitude of these effects depends on the shear wavelength of the excitation, the kernel size used to calculate the SWS, and the method used to determine the wave arrival time. In this study, we perform a parametric analysis of these factors using finite element modeling of the tissue response and simulated ultrasonic tracking. Two geometries are used, a stiff vertical layer and a stiff spherical inclusion, each in a uniform background. Wave arrival times are estimated using the peak displacement, peak slope of the leading edge, and cross-correlation methods. Results are evaluated in terms of reconstruction accuracy, resolution, contrast, and contrast-to-noise ratio of reconstructed SWS images. Superior results are obtained using narrower excitation widths and arrival time estimators which identify the leading edge of the propagating wave. The optimal kernel size is determined by a tradeoff between improved accuracy for larger kernels at the expense of spatial resolution.
Unlabelled:
Real-time shear wave elastography (SWE) is a novel, noninvasive method to assess liver fibrosis by measuring liver stiffness. This single-center study was conducted to assess the accuracy of SWE in patients with chronic hepatitis C (CHC), in comparison with transient elastography (TE), by using liver biopsy (LB) as the reference standard. Consecutive patients with CHC scheduled for LB by referring physicians were studied. One hundred and twenty-one patients met inclusion criteria. On the same day, real-time SWE using the ultrasound (US) system, Aixplorer (SuperSonic Imagine S.A., Aix-en-Provence, France), TE using FibroScan (Echosens, Paris, France), and US-assisted LB were consecutively performed. Fibrosis was staged according to the METAVIR scoring system. Analyses of receiver operating characteristic (ROC) curve were performed to calculate optimal area under the ROC curve (AUROC) for F0-F1 versus F2-F4, F0- F2 versus F3-F4, and F0-F3 versus F4 for both real-time SWE and TE. Liver stiffness values increased in parallel with degree of liver fibrosis, both with SWE and TE. AUROCs were 0.92 (95% confidence interval [CI]: 0.85-0.96) for SWE and 0.84 (95% CI: 0.76-0.90) for TE (P = 0.002), 0.98 (95% CI: 0.94-1.00) for SWE and 0.96 (95% CI: 0.90-0.99) for TE (P = 0.14), and 0.98 (95% CI: 0.93-1.00) for SWE and 0.96 (95% CI: 0.91-0.99) for TE (P = 0.48), when comparing F0-F1 versus F2- F4, F0- F2 versus F3-F4, and F0 -F3 versus F4, respectively.
Conclusion:
The results of this study show that real-time SWE is more accurate than TE in assessing significant fibrosis (≥ F2). With respect to TE, SWE has the advantage of imaging liver stiffness in real time while guided by a B-mode image. Thus, the region of measurement can be guided with both anatomical and tissue stiffness information.
Our aim was to compare liver stiffness (LS) measurements by means of acoustic radiation force impulse (ARFI) elastography and transient elastography (TE) in patients with chronic hepatitis B and C, according to the severity of fibrosis. We also compared the correlation strength of ARFI and TE measurements with liver fibrosis. We included 53 patients with hepatitis B and 107 with hepatitis C in which liver biopsy, ARFI and TE measurements were performed in the same session. The mean LS values measured with ARFI were similar in patients with chronic hepatitis B and C and depended on the stage of fibrosis. The correlation strength of LS measurements by ARFI and by TE with fibrosis was similar in chronic hepatitis B and C patients. In conclusion, for the same stage of fibrosis, the mean LS values by ARFI were similar in patients with chronic hepatitis B and C. ARFI had similar predictive value with TE in both chronic viral hepatitis.
Our study assessed acoustic radiation force impulse (ARFI) reproducibility and the factors influencing it. The intra- and interoperator reproducibility were studied in 33 and 58 patients, respectively. Intraclass correlation coefficient (ICC) was used to assess ARFI reproducibility. The overall intraoperator agreement was better than the interoperator one: ICC 0.90 vs. ICC 0.81. The correlation of repeated ARFI measurements was higher, but not significantly so, in cases in which intraoperator reproducibility was assessed compared with the ones in which interoperator reproducibility was studied: r = 0.848 vs. r = 0.694 (p = 0.08). For both intra- and interoperator reproducibility, the ICCs were smaller in women vs. men (0.88 vs. 0.91 and 0.67 vs. 0.86, respectively), in patients with high body mass index (BMI) ≥25 kg/m² vs. <25 kg/m² (0.88 vs. 0.91 and 0.79 vs. 0.82, respectively), in patients with ascites vs. no ascites (0.80 vs. 0.93 and 0.78 vs. 0.84, respectively) and in noncirrhotic vs. cirrhotic patients (0.77 vs. 0.82 and 0.70 vs. 0.83, respectively).
Acoustic radiation force based elasticity imaging methods are under investigation by many groups. These methods differ from traditional ultrasonic elasticity imaging methods in that they do not require compression of the transducer, and are thus expected to be less operator dependent. Methods have been developed that utilize impulsive (i.e. < 1 ms), harmonic (pulsed), and steady state radiation force excitations. The work discussed herein utilizes impulsive methods, for which two imaging approaches have been pursued: 1) monitoring the tissue response within the radiation force region of excitation (ROE) and generating images of relative differences in tissue stiffness (Acoustic Radiation Force Impulse (ARFI) imaging); and 2) monitoring the speed of shear wave propagation away from the ROE to quantify tissue stiffness (Shear Wave Elasticity Imaging (SWEI)). For these methods, a single ultrasound transducer on a commercial ultrasound system can be used to both generate acoustic radiation force in tissue, and to monitor the tissue displacement response. The response of tissue to this transient excitation is complicated and depends upon tissue geometry, radiation force field geometry, and tissue mechanical and acoustic properties. Higher shear wave speeds and smaller displacements are associated with stiffer tissues, and slower shear wave speeds and larger displacements occur with more compliant tissues. ARFI images have spatial resolution comparable to that of B-mode, often with greater contrast, providing matched, adjunctive information. SWEI images provide quantitative information about the tissue stiffness, typically with lower spatial resolution. A review these methods and examples of clinical applications are presented herein.
Unlabelled:
A meta-analysis was performed to assess and compare the accuracies of magnetic resonance elastography (MRE) and diffusion-weighted imaging (DWI) for the staging of hepatic fibrosis. Online journal databases and a manual search from January 2000 to May 2011 were used. We identified 41 studies, but only 14 met the criteria to perform a meta-analysis assessing MRE (five trials) or DWI (10 trials). Fibrosis was categorized by redistribution into five stages according to histopathological description. A bivariate binomial model was used to combine the sensitivity and specificity and their 95% confidence intervals (CIs), from which diagnostic odds ratio (DOR), positive likelihood ratio (PLR), negative likelihood ratio (NLR), and summary receiver operating characteristic (sROC) were derived to indicate the diagnostic accuracy of imaging modalities. With MRE, the sensitivity, specificity, DOR, PLR, NLR, and area under sROC curve (with 95% CIs) for staging F0 ∼ F1 versus F2 ∼ F4 and F0 ∼ F2 versus F3 ∼ F4 were 0.94 (0.81-0.98), 0.95 (0.87-0.98), 20 (7-57), 0.06 (0.02-0.22), 317 (55-1,796), 0.98 (0.97-0.99) and 0.92 (0.85-0.96), 0.96 (0.91-0.98), 21 (10-45), 0.08 (0.04-0.16), 251 (103-609), and 0.98 (0.96-0.99), respectively; and with DWI, these values were 0.77 (0.71-0.82), 0.78 (0.69-0.85), 3 (2-5), 0.30 (0.22-0.40), 12 (6-21), 0.83 (0.79-0.86) and 0.72 (0.60-0.81), 0.84 (0.77-0.89), 5 (3-7), 0.34 (0.23-0.50), 13 (6-29), and 0.86 (0.83-0.89), respectively. A z test demonstrated that MRE had a significantly higher accuracy than DWI in those indicators (P < 0.05).
Conclusion:
MRE is more reliable for staging hepatic fibrosis, compared with DWI, with a high combination of sensitivity, specificity, likelihood ratios, DOR, and area under sROC curve.
Unlabelled:
The development of liver fibrosis markers in primary biliary cirrhosis (PBC) is needed to facilitate the assessment of its progression and the effectiveness of new therapies. Here, we investigated the potential usefulness of transient elastography (TE) in the noninvasive evaluation of liver fibrosis stage and disease progression in PBC. We performed, first, a prospective performance analysis of TE for the diagnosis of METAVIR fibrosis stages in a diagnostic cohort of 103 patients and, second, a retrospective longitudinal analysis of repeated examinations in a monitoring cohort of 150 patients followed-up for up to 5 years. All patients were treated with ursodeoxycholic acid. Diagnostic thresholds of liver stiffness in discriminating fibrosis stages ≥ F1, ≥ F2, ≥ F3, and =F4 were 7.1, 8.8, 10.7, and 16.9 kPa, respectively. TE showed high performance and was significantly superior to biochemical markers (e.g., aspartate aminotransferase [AST]/platelet ratio, FIB-4, hyaluronic acid, AST/alanine aminotransferase ratio, and Mayo score) in diagnosing significant fibrosis, severe fibrosis, or cirrhosis. Analysis of the monitoring cohort data set using generalized linear models showed the following: (1) an overall progression rate of 0.48 ± 0.21 kPa/year (P = 0.02) and (2) no significant progression in patients with F0-F1, F2, or F3 stages, but a significant increase (4.06 ± 0.72 kPa/year; P < 0.0001) in cirrhotic patients. A cut-off value of 2.1 kPa/year was associated with an 8.4-fold increased risk of liver decompensations, liver transplantations, or deaths (P < 0.0001, Cox regression analysis).
Conclusion:
TE is one of the best current surrogate markers of liver fibrosis in PBC. Over a 5-year period, on-treatment liver stiffness appears stable in most noncirrhotic PBC patients, whereas it significantly increases in patients with cirrhosis. Progression of liver stiffness in PBC is predictive of poor outcome.
Strain developed under quasi-static deformation has been mostly used in ultrasound elasticity imaging (UEI) to determine the stiffness change of tissues. However, the strain measure in UEI is often less sensitive to a subtle change of stiffness. This is particularly true for Crohn's disease where we have applied strain imaging to the differentiation of acutely inflamed bowel from chronically fibrotic bowel. In this study, a new nonlinear elastic parameter of the soft tissues is proposed to overcome this limit. The purpose of this study is to evaluate the newly proposed method and demonstrate its feasibility in the UEI. A nonlinear characteristic of soft tissues over a relatively large dynamic range of strain was investigated. A simplified tissue model based on a finite element (FE) analysis was integrated with a laboratory developed ultrasound radio-frequency (RF) signal synthesis program. Two-dimensional speckle tracking was applied to this model to simulate the nonlinear behavior of the strain developed in a target inclusion over the applied average strain to the surrounding tissues. A nonlinear empirical equation was formulated and optimized to best match the developed strain-to-applied strain relation obtained from the FE simulation. The proposed nonlinear equation was applied to in vivo measurements and nonlinear parameters were further empirically optimized. For an animal model, acute and chronic inflammatory bowel disease was induced in Lewis rats with trinitrobenzene sulfonic acid (TNBS)-ethanol treatments. After UEI, histopathology and direct mechanical measurements were performed on the excised tissues. The extracted nonlinear parameter from the developed strain-to-applied strain relation differentiated the three different tissue types with 1.96 ± 0.12 for normal, 1.50 ± 0.09 for the acutely inflamed and 1.03 ± 0.08 for the chronically fibrotic tissue. T-tests determined that the nonlinear parameters between normal, acutely inflamed and fibrotic tissue types were statistically significantly different (normal/ fibrotic [p = 0.0000185], normal/acutely inflamed [p = 0.0013] and fibrotic/acutely inflamed [p = 0.0029]). This technique may provide a sensitive and robust tool to assess subtle stiffness changes in tissues such as in acutely inflamed bowel wall.
Acoustic Radiation Force Impulse (ARFI) imaging is a novel ultrasound-based elastography method that is integrated in a conventional ultrasound machine enabling the exact localization of measurement site. It might present an alternative method to transient elastography for the noninvasive assessment of liver fibrosis. At present, studies with small patient population have shown promising results. A systematic review and meta-analysis of pooled patient data were performed to evaluate the overall performance of ARFI for the staging of liver fibrosis. Literature databases were searched up to 10/2010. The authors of the original publication were contacted, and the original patient data were requested. A meta-analysis was performed using a random effect meta-analytic method for diagnostic tests. In addition, available data comparing ARFI with FibroScan with the DeLong test were evaluated. Literature search yielded nine full-paper publications evaluating ARFI while using liver biopsy as reference method. Original patient data were available from eight studies including 518 patients. The mean diagnostic accuracy of ARFI expressed as areas under ROC curves (AUROC) was 0.87 for the diagnosis of significant fibrosis (F ≥ 2), 0.91 for the diagnosis of severe fibrosis (F ≥ 3), and 0.93 for the diagnosis of cirrhosis. ARFI can be performed with good diagnostic accuracy for the noninvasive staging of liver fibrosis.
Crawling waves, which are interfering shear wave patterns, can be generated in liver tissue over a range of frequencies. Some important biomechanical properties of the liver can be determined by imaging the crawling waves using Doppler techniques and analyzing the patterns. We report that the dispersion of shear wave velocity and attenuation, that is, the frequency dependence of these parameters, are strongly correlated with the degree of steatosis in a mouse liver model, ex vivo. The results demonstrate the possibility of assessing liver steatosis using noninvasive imaging methods that are compatible with color Doppler scanners and, furthermore, suggest that liver steatosis can be separated from fibrosis by assessing the dispersion or frequency dependence of shear wave propagations.
Transient elastography (TE) and acoustic radiation force impulse (ARFI)-imaging have shown promising results for the staging of liver fibrosis.
The aim of the present study was to compare ARFI of the left and right liver lobe with TE using the standard and obese probes for the diagnosis of liver fibrosis in NAFL/NASH. In addition, liver steatosis is evaluated using the novel controlled attenuation parameter (CAP).
Sixty-one patients with NAFLD/NASH were included in the study. All patients received TE with both probes, ARFI of both liver lobes and CAP. The results were compared with liver histology.
57 patients were included in the final analysis. The diagnostic accuracy for TE measurements with the M-and XL-probe and for ARFI of the right and left liver lobe was 0.73, 0.84, 0.71 and 0.60 for the diagnosis of severe fibrosis, and 0.93, 0.93, 0.74 and 0.90 for the diagnosis of cirrhosis, respectively. No significant difference of results was observed between TE and ARFI in the subgroup of patients with reliable TE-measurement when taking into account the best results of both methods. However, while a significant correlation could be found for TE with histological liver fibrosis, the correlation of ARFI with liver fibrosis was not statistically significant. A significant correlation was found for CAP with histological steatosis (r=0.49, p<0.001).
No significant difference in diagnostic accuracy for the non-invasive assessment of liver fibrosis was found for transient elastography and ARFI. Nevertheless TE significantly correlated with liver fibrosis while ARFI did not. CAP enables the non-invasive assessment of steatosis.
Measurement of shear wave propagation speed has important clinical applications because it is related to tissue stiffness and health state. Shear waves can be generated in tissues by the radiation force of a focused ultrasound beam (push beam). Shear wave speed can be measured by tracking its propagation laterally from the push beam focus using the time-of-flight principle. This study shows that shear wave speed measurements with such methods can be transducer, depth and lateral tracking range dependent. Three homogeneous phantoms with different stiffness were studied using curvilinear and linear array transducer. Shear wave speed measurements were made at different depths, using different aperture sizes for push and at different lateral distance ranges from the push beam. The curvilinear transducer shows a relatively large measurement bias that is depth dependent. The possible causes of the bias and options for correction are discussed. These bias errors must be taken into account to provide accurate and precise time-of-flight shear wave speed measurements for clinical use.