EASL Clinical Practice Guidelines on non-invasive tests for evaluation of liver disease severity and prognosis - 2021 update.

Non-invasive tests are increasingly being used to improve the diagnosis and prognostication of chronic liver diseases across aetiologies. Herein, we provide the latest update to the EASL Clinical Practice Guidelines on the use of non-invasive tests for the evaluation of liver disease severity and prognosis, focusing on the topics for which relevant evidence has been published in the last 5 years.

Historical trends for the standards in scrotal ultrasonography: What was, what is and what will be normal.

BACKGROUND: Ultrasonography is the gold standard imaging method for scrotal investigation. Colour Doppler ultrasonography, contrast-enhanced ultrasonography and sonoelastography allow sonographers to assess size, echotexture, vascular features and stiffness of the scrotal organs and abnormalities. Scrotal ultrasonography has been used to investigate male reproductive health, scrotal pain, masses and trauma. However, ultrasonography thresholds/classifications used to distinguish normal and pathologic features of the scrotal organs have changed over time, and have not yet been fully standardized. OBJECTIVES: To evaluate historical trends for the standards in scrotal ultrasonography: what was, what is and what will be normal. METHODS: An extensive Medline search was performed identifying the most relevant studies in the English language from inception to date. RESULTS: We provide here (i) a brief overview of the history of ultrasonography, (ii) current indications for scrotal ultrasonography and (iii) previous and current normal values, cut-offs and classifications of the main colour-Doppler ultrasonography parameters/characteristics of the scrotal organs, as derived from recent guidelines and evidence-based studies. In addition, we report recommendations and the clinical utility of contrast-enhanced ultrasonography and sonoelastography. Finally, we discuss critical issues needing further evidence and future directions to fill in the current gaps. DISCUSSION: Several studies on scrotal ultrasonography are available. However, guidelines/recommendations dealing with specific ultrasonography applications have been published only in recent years. More recently, the European Academy of Andrology published evidence-based scrotal colour-Doppler ultrasonography reference ranges/normative parameters derived from a cohort of healthy, fertile men. In addition, a standardization of the methodology to evaluate qualitative and quantitative colour-Doppler ultrasonography parameters was reported. Other international societies reported indications, methodological standards, clinical utility and limitations of contrast-enhanced ultrasonography and sonoelastography. CONCLUSIONS: To date, colour-Doppler ultrasonography normative values for the scrotal organs are available. However, a wide international consensus on assessment and classification of several ultrasonography parameters is still lacking. An alignment of the world societies on these issues is advocated.

Shear Wave Elastography: A Review on the Confounding Factors and Their Potential Mitigation in Detecting Chronic Kidney Disease.

Early detection of chronic kidney disease is important to prevent progression of irreversible kidney damage, reducing the need for renal transplantation. Shear wave elastography is ideal as a quantitative imaging modality to detect chronic kidney disease because of its non-invasive nature, low cost and portability, making it highly accessible. However, the complexity of the kidney architecture and its tissue properties give rise to various confounding factors that affect the reliability of shear wave elastography in detecting chronic kidney disease, thus limiting its application to clinical trials. The objective of this review is to highlight the confounding factors presented by the complex properties of the kidney, in addition to outlining potential mitigation strategies, along with the prospect of increasing the versatility and reliability of shear wave elastography in detecting chronic kidney disease.

Advancements in the Application of Ultrasound Elastography in the Cervix.

Ultrasound elastography is a modern imaging technique that has developed rapidly in recent years. It enables objective measurement of tissue stiffness, a physical property intuitive to the human sense of touch. This novel technology has become a hotspot and plays a major role in scientific research and academic practice. Presently, ultrasound elastography has been used in the identification of benign and malignant tumors in superficial organs, such as breast and thyroid, providing clinically accurate diagnosis and treatment. The method has also been widely used for the liver, kidney, prostate, lymph nodes, blood vessels, skin and muscle system. In the application of cervical lesions, ultrasound elastography can distinguish normal cervix from abnormal cervix and differentiate benign from malignant lesions. It can significantly improve the diagnostic specificity for cervical cancer and is also useful for assessing infiltration depth and stage of cervical cancer, as well as predicting chemoradiotherapy treatment response. For cervical evaluation during pregnancy, ultrasound elastography is useful for assessing cervical softening and predicting premature delivery and outcome of induced labor. This article reviews the principles of ultrasound elastography as well as the current status and limitations in its application for cervical lesions and the cervix during pregnancy.

Aging brain mechanics: Progress and promise of magnetic resonance elastography.

Neuroimaging techniques that can sensitivity characterize healthy brain aging and detect subtle neuropathologies have enormous potential to assist in the early detection of neurodegenerative conditions such as Alzheimer's disease. Magnetic resonance elastography (MRE) has recently emerged as a reliable, high-resolution, and especially sensitive technique that can noninvasively characterize tissue biomechanical properties (i.e., viscoelasticity) in vivo in the living human brain. Brain tissue viscoelasticity provides a unique biophysical signature of neuroanatomy that are representative of the composition and organization of the complex tissue microstructure. In this article, we detail how progress in brain MRE technology has provided unique insights into healthy brain aging, neurodegeneration, and structure-function relationships. We further discuss additional promising technical innovations that will enhance the specificity and sensitivity for brain MRE to reveal considerably more about brain aging as well as its potentially valuable role as an imaging biomarker of neurodegeneration. MRE sensitivity may be particularly useful for assessing the efficacy of rehabilitation strategies, assisting in differentiating between dementia subtypes, and in understanding the causal mechanisms of disease which may lead to eventual pharmacotherapeutic development.

MR Elastography of the Breast: Evolution of Technique, Case Examples, and Future Directions.

Recognizing that breast cancers present as firm, stiff lesions, the foundation of breast magnetic resonance elastography (MRE) is to combine tissue stiffness parameters with sensitive breast MR contrast-enhanced imaging. Breast MRE is a non-ionizing, cross-sectional MR imaging technique that provides for quantitative viscoelastic properties, including tissue stiffness, elasticity, and viscosity, of breast tissues. Currently, the technique continues to evolve as research surrounding the use of MRE in breast tissue is still developing. In the setting of a newly diagnosed cancer, associated desmoplasia, stiffening of the surrounding stroma, and necrosis are known to be prognostic factors that can add diagnostic information to patient treatment algorithms. In fact, mechanical properties of the tissue might also influence breast cancer risk. For these reasons, exploration of breast MRE has great clinical value. In this review, we will: (1) address the evolution of the various MRE techniques; (2) provide a brief overview of the current clinical studies in breast MRE with interspersed case examples; and (3) suggest directions for future research.

Usability and Pitfalls of Shear-Wave Elastography for Evaluation of Muscle Quality and Its Potential in Assessing Sarcopenia: A Review.

Sarcopenia is age-related progressive and generalized loss of skeletal muscle mass and strength. Its prevalence is rising, which poses a burden for society because it increases disability and dependency and therefore raises health care costs. Muscle mass quality, however-an essential part of sarcopenia-is not easily diagnosable yet. Recent interest has risen for ultrasonographic evaluation of muscle. This review introduces muscle elastography as a possible, easy and cheap tool to evaluate qualitative muscle parameters. Basic principles of muscle elastography are described, as well as different elastography techniques and some technical considerations. Furthermore, a proposal for practical guidelines is offered and factors influencing muscle stiffness are highlighted.

Ultrasound Elastography in Musculoskeletal Radiology: Past, Present, and Future.

Ultrasound elastography (USE) is becoming an important adjunct tool in the evaluation of various musculoskeletal (MSK) traumatic conditions and diseases, with an increasing number of applications and publications in recent years. This rapidly evolving technique enhances the conventional ultrasound (US) examination by providing information on the elastic properties of tissue alongside the morphological and vascular information obtained from B-mode US and Doppler imaging. Those performing USE must have basic knowledge of its proper imaging techniques and limitations. In this review article, we place the USE in historical perspective and discuss basic techniques and current applications of USE in the evaluation of various traumatic and pathologic conditions of fasciae, nerves, muscles, tendons, ligaments, and MSK soft tissue masses.

Real-time shear wave ultrasound elastography: a new tool for the evaluation of diaphragm and limb muscle stiffness in critically ill patients.

BACKGROUND: Muscle weakness following critical illness is the consequence of loss of muscle mass and alteration of muscle quality. It is associated with long-term disability. Ultrasonography is a reliable tool to quantify muscle mass, but studies that evaluate muscle quality at the critically ill bedside are lacking. Shear wave ultrasound elastography (SWE) provides spatial representation of soft tissue stiffness and measures of muscle quality. The reliability and reproducibility of SWE in critically ill patients has never been evaluated. METHODS: Two operators tested in healthy controls and in critically ill patients the intra- and inter-operator reliability of the SWE using transversal and longitudinal views of the diaphragm and limb muscles. Reliability was calculated using the intra-class correlation coefficient and a bootstrap sampling method assessed their consistency. RESULTS: We collected 560 images. Longitudinal views of the diaphragm (ICC 0.83 [0.50-0.94]), the biceps brachii (ICC 0.88 [0.67-0.96]) and the rectus femoris (ICC 0.76 [0.34-0.91]) were the most reliable views in a training set of healthy controls. Intra-class correlation coefficient for inter-operator reproducibility and intra-operator reliability was above 0.9 for all muscles in a validation set of healthy controls. In critically ill patients, inter-operator reproducibility and intra-operator 1 and 2 reliability ICCs were respectively 0.92 [0.71-0.98], 0.93 [0.82-0.98] and 0.92 [0.81-0.98] for the diaphragm; 0.96 [0.86-0.99], 0.98 [0.94-0.99] and 0.99 [0.96-1] for the biceps brachii and 0.91 [0.51-0.98], 0.97 [0.93-0.99] and 0.99 [0.97-1] for the rectus femoris. The probability to reach intra-class correlation coefficient greater than 0.8 in a 10,000 bootstrap sampling for inter-operator reproducibility was respectively 81%, 84% and 78% for the diaphragm, the biceps brachii and the rectus femoris respectively. CONCLUSIONS: SWE is a reliable technique to evaluate limb muscles and the diaphragm in both healthy controls and in critically ill patients. TRIAL REGISTRATION: The study was registered (ClinicalTrial NCT03550222).

Emerging technologies in neuromuscular ultrasound.

Neuromuscular ultrasound is an accepted and valuable element in the evaluation of peripheral nerve and muscle disease. However, ultrasound has several limitations to consider, including operator dependency and lack of a viable contrast agent. Fortunately, new technological advances show promise in resolving these issues. Ultra-high resolution ultrasound enables imaging of the nerve at the fascicular level. Shear wave elastography imaging can provide measures of tissue stiffness that can act as a surrogate measure of nerve and muscle health. Photoacoustic imaging may overcome neuromuscular ultrasound's current lack of contrast agents to detect inflammation and other functional changes within nerve and muscle, while artificial intelligence stands to address operator dependency and improve diagnostic imaging. The basic principles of each of these technologies are discussed along with current research and potential future applications in neuromuscular imaging.

Aplicación ecográfica con cuantificación de la estructura acústica (ASQ) en las enfermedades pulmonares intersticiales / Ultrasound Application with Acoustic Structure Quantification (ASQ) in Interstitial Lung Diseases

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Advanced Ultrasound Techniques for Pediatric Imaging.

Ultrasound has become a useful tool in the workup of pediatric patients because of the highly convenient, cost-effective, and safe nature of the examination. With rapid advancements in anatomic and functional ultrasound techniques over the recent years, the diagnostic and interventional utility of ultrasound has risen tremendously. Advanced ultrasound techniques constitute a suite of new technologies that employ microbubbles to provide contrast and enhance flow visualization, elastography to measure tissue stiffness, ultrafast Doppler to deliver high spatiotemporal resolution of flow, three- and four-dimensional technique to generate accurate spatiotemporal representation of anatomy, and high-frequency imaging to delineate anatomic structures at a resolution down to 30 µm. Application of these techniques can enhance the diagnosis of organ injury, viable tumor, and vascular pathologies at bedside. This has significant clinical implications in pediatric patients who are not easy candidates for lengthy MRI or radiation-requiring examination, and are also in need of a highly sensitive bedside technique for therapeutic guidance. To best use the currently available, advanced ultrasound techniques for pediatric patients, it is necessary to understand the diagnostic utility of each technique. In this review, we will educate the readers of emerging ultrasound techniques and their respective clinical applications.

Advances and Future Direction of Magnetic Resonance Elastography.

The mechanical properties of soft tissues are closely associated with a variety of diseases. This motivates the development of elastography techniques in which tissue mechanical properties are quantitatively estimated through imaging. Magnetic resonance elastography (MRE) is a noninvasive phase-contrast MR technique wherein shear modulus of soft tissue can be spatially and temporally estimated. MRE has recently received significant attention due to its capability in noninvasively estimating tissue mechanical properties, which can offer considerable diagnostic potential. In this work, recent technology advances of MRE, its future clinical applications, and the related limitations will be discussed.

Clinical elastography.

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Elastografía hepática y otras secuencias avanzadas de RM (RM multiparamétrica) / Hepatic Elastography and Other Advanced MRI Sequences (Multiparametric MRI)

La fibrosis es un destino donde convergen variados trastornos hepáticos. Al tratarse de un proceso dinámico y reversible, su detección temprana y una intervención terapéutica oportuna, pueden frenar su progresión. La elastografía por resonancia magnética (ERM), es un método no invasivo con notable eficacia para la valoración del grado de fibrosis hepática. La tendencia actual es combinar esa técnica con secuencias de cuantificación de lípidos y hierro, lo cual permite un abordaje multiparamétrico de los trastornos difusos del hígado.

Fibrosis is a common destination where multiple liver disorders converge. Due to its dynamic and reversible process, an early detection and timely therapeutic intervention can interrupt its progression. Magnetic Resonance Elastography (MRE) is a non-invasive method with remarkable efficacy for assessing the degree of liver fibrosis. The current trend is to combine this technique with lipid and iron quantification sequences, which allows a multiparametric approach to diffuse liver disorders.

Temporal changes in liver stiffness after Fontan operation: Results of serial magnetic resonance elastography.

BACKGROUND: The relationship between temporal progression of magnetic resonance elastography derived liver stiffness (MRE-LS) and progression of Fontan associated liver disease (FALD) is unknown. To assess this relationship, we hypothesized that progression of MRE-LS correlated with progression FALD severity and clinical outcomes. METHODS: Retrospective review of Fontan patients who had >1 liver MRE, 2010-2016. Annual change in MRE-LS was the quotient of the difference between baseline and subsequent MRE-LS, and the interval between scans. RESULTS: 22 patients were enrolled; median age 29(19-38) years, 14 (64%) males and 10 (46%) with atriopulmonary Fontan. Baseline and subsequent MRE-LS values were 5.4 ±â€¯1.1 kPa and 5.8 ±â€¯0.9 kPa" for clarity, interval between scans was 25 ±â€¯5 months, and annual change in MRE-LS was 0.3 ±â€¯0.2 kPa. Temporal change in MRE-LS correlated with temporal changes in model for end-stage liver disease (MELD) score (r = 0.84, p < 0.001) and model for end-stage liver disease excluding international normalized ratio (MELD-XI) score (r = 0.75, p = 0.001). The study cohort was divided into 2 groups using the mean annual change in MRE-LS as the cut point. Groups A and B comprised of patients with annual increase in MRE-LS ≥0.3 kPa (n = 6) and <0.3 kPa (n = 16) respectively. Composite adverse event endpoint (death, heart-liver transplant listing, palliative care, hospitalization, paracentesis) was more common in Group A (4 of 6, 67%) compared to Group B (3 of 16, 19%), p = 0.13 although this did not reach statistical significance due to small sample size. CONCLUSIONS: Progression of MRE-LS correlated with clinical deterioration as measured by worsening liver disease severity scores and the occurrence of adverse events.

Quantitative Elastography Methods in Liver Disease: Current Evidence and Future Directions.

Chronic liver diseases often result in the development of liver fibrosis and ultimately, cirrhosis. Treatment strategies and prognosis differ greatly depending on the severity of liver fibrosis, thus liver fibrosis staging is clinically relevant. Traditionally, liver biopsy has been the method of choice for fibrosis evaluation. Because of liver biopsy limitations, noninvasive methods have become a key research interest in the field. Elastography enables the noninvasive measurement of tissue mechanical properties through observation of shear-wave propagation in the tissue of interest. Increasing fibrosis stage is associated with increased liver stiffness, providing a discriminatory feature that can be exploited by elastographic methods. Ultrasonographic (US) and magnetic resonance (MR) imaging elastographic methods are commercially available, each with their respective strengths and limitations. Here, the authors review the technical basis, acquisition techniques, and results and limitations of US- and MR-based elastography techniques. Diagnostic performance in the most common etiologies of chronic liver disease will be presented. Reliability, reproducibility, failure rate, and emerging advances will be discussed. © RSNA, 2018 Online supplemental material is available for this article.

Novel ultrasound-based methods to assess liver disease: The game has just begun.

In the last 10 years the availability of ultrasound elastography allowed to diagnose and stage liver fibrosis in a non-invasive way and changed the clinical practice of hepatology. Newer ultrasound-based techniques to evaluate properties of the liver tissue other than fibrosis are emerging and will lead to a more complete characterization of the full spectrum of diffuse and focal liver disease. Since these methods are currently undergoing validation and go beyond elastography for liver tissue evaluation, they were not included in the recent guidelines regarding elastography issued by the European Federation of Societies in Ultrasound in Medicine and Biology. In this review paper, we outline the major advances in the field of ultrasound for liver applications, with special emphasis on techniques that could soon be part of the future armamentarium of ultrasound specialists devoted to the assessment of liver disease. Specifically, we discuss current and future ultrasound assessment of steatosis, spleen stiffness for portal hypertension, and elastography for the evaluation of focal liver lesions; we also provide a short glimpse into the next generation of ultrasound diagnostic methods.

Recent technological advancements in cardiac ultrasound imaging.

About 92.1 million Americans suffer from at least one type of cardiovascular disease. Worldwide, cardiovascular diseases are the number one cause of death (about 31% of all global deaths). Recent technological advancements in cardiac ultrasound imaging are expected to aid in the clinical diagnosis of many cardiovascular diseases. This article provides an overview of such recent technological advancements, specifically focusing on tissue Doppler imaging, strain imaging, contrast echocardiography, 3D echocardiography, point-of-care echocardiography, 3D volumetric flow assessments, and elastography. With these advancements ultrasound imaging is rapidly changing the domain of cardiac imaging. The advantages offered by ultrasound imaging include real-time imaging, imaging at patient bed-side, cost-effectiveness and ionizing-radiation-free imaging. Along with these advantages, the steps taken towards standardization of ultrasound based quantitative markers, reviewed here, will play a major role in addressing the healthcare burden associated with cardiovascular diseases.