Ultrasound shear wave elastography for liver disease. A critical appraisal of the many actors on the stage

In the last 12\u200a-\u200a18 months nearly all ultrasound manufacturers have arrived to implement ultrasound shear wave elastography modality in their equipment for the assessment of chronic liver disease; the few remaining players are expected to follow in 2016.When all manufacturers rush to a new technology at the same time, it is evident that the clinical demand for this information is of utmost value. Around 1990, there was similar demand for color Doppler ultrasound; high demand for contrast-enhanced ultrasonography was evident at the beginning of this century, and around 2010 demand increased for strain elastography. However, some issues regarding the new shear wave ultrasound technologies must be noted to avoid misuse of the resulting information for clinical decisions. As new articles are expected to appear in 2016 reporting the findings of the new technologies from various companies, we felt that the beginning of this year was the right time to present an appraisal of these issues. We likewise expect that in the meantime EFSUMB will release a new update of the existing guidelines 1 2.The first ultrasound elastography method became available 13 years ago in the form of transient elastography with Fibroscan(\uae) 3. It was the first technique providing non-invasive quantitive information about the stiffness of the liver and hence regarding the amount of fibrosis in chronic liver disease 3. The innovation was enormous, since a non-invasive modality was finally available to provide findings otherwise achievable only by liver biopsy. In fact, prior to ultrasound elastography, a combination of conventional and Doppler ultrasound parameters were utilized to inform the physician about the presence of cirrhosis and portal hypertension 4. However, skilled operators were required, reproducibility and diagnostic accuracy were suboptimal, and it was not possible to differentiate the pre-cirrhotic stages of fibrosis. All these limitations were substantially improved by transient elastography, performed with Fibroscan(\uae), a technology dedicated exclusively to liver elastography. Since then, more than 1300 articles dealing with transient elastography have been listed in PubMed, some describing results with more than 10,000 patients 5. The technique has been tested in nearly all liver disease etiologies, with histology as the reference standard. Meta-analysis of data, available in many etiologies 6, showed good performance and reproducibility as well as some situations limiting reliability 5. Thresholds for the different fibrosis stages (F0 to F4) have been provided by many large-scale studies utilizing histology as the reference standard 7. Transient elastography tracks the velocity of shear waves generated by the gentle hit of a piston on the skin, with the resulting compression wave traveling in the liver along its longitudinal axis. The measurement is made in a 4\u200acm long section of the liver, thus able to average slightly inhomogeneous fibrotic deposition.In 2008 a new modality became available, Acoustic Radiation Force Impulse (ARFI) quantification, and classified by EFSUMB 1 as point shear wave elastography (pSWE), since the speed of the shear wave (perpendicular to the longitudinal axis) is measured in a small region (a "point", few millimeters) at a freely-choosen depth within 8\u200acm from the skin. This technology was the first to be implemented in a conventional ultrasound scanner by Siemens(\uae) 8. Several articles have been published regarding this technology, most with the best reference standards 9, some including findings on more than 1000 hepatitis C patients 10 or reporting meta-analysis of data 11. Although the correlation between Siemens pSWE and transient elastography appeared high 12 13, the calculated thresholds for the different fibrosis stages and the stiffness ranges between the two techniques are not superimposable.Interestingly, pSWE appears to provide greater applicability than transient elastography for measuring both liver 13 and spleen stiffness, which is a new application of elastography 14, of interest for the prediction of the degree of portal hypertension 15 16.Nowadays other companies have started producing equipment with pSWE technology, but only very few articles have been published so far, for instance describing the use of Philips(\uae) equipment, which was the second to provide pSWE. These articles show preliminary good results also in comparison with TE 17 18. Not enough evidence is currently available in the literature about the elastographic performance of the products most recently introduced to the market. Furthermore, with some products the shear wave velocities generated by a single ultrasound acoustic push pulse can be measured in a bidimensional area (a box in the range of 2\u200a-\u200a3\u200acm per side) rather than in a single small point, producing a so-called bidimensional 2D-SWE 1. The stiffness is depicted in color within the area and refreshing of the measurement occurs every 1\u200a-\u200a2 seconds. Once the best image is acquired, the operator chooses a Region Of Interest (ROI) within the color box, where the mean stiffness is then calculated. 2D-SWE can be performed as a "one shot" technique or as a semi-"real-time" technique for a few seconds (at about 1 frame per second) in order to obtain a stable elastogram. With either technique, there should be no motion/breathing during image acquisition. A bidimensional averaged area should overcome the limitation of pSWE to inadvertently investigate small regions of greater or lesser stiffness than average. A shear wave quality indicator could be useful to provide real-time feedback and optimize placement of the sampling ROIs, a technology recently presented by Toshiba(\uae), but which is still awaiting validation in the literature.Supersonic Imagine by Aixplorer(\uae) which works with a different modality of insonation and video analysis compared to the the previously-mentioned three techniques (i.\u200ae., transient elastography, pSWE and 2D-SWE), leading to a bidimensional assessment of liver stiffness in real time up to 5\u200aHz and in larger regions; thus this technique is also termed real-time 2\u200aD SWE. It has been available on the market for a few years 19 20, and many articles have been published showing stiffness values quite similar to those of Fibroscan(\uae) 21; likewise, defined thresholds based on histological findings have appeared in several articles 19 20 21.After this brief summary of the technological state of the art we would like to mention the following critical issues that we believe every user should note prior to providing liver stiffness reports. \ub7 The thresholds obtained from the "oldest" techniques for the various fibrosis stages based on hundreds of patients with histology as reference standard cannot be straightforwardly applied to the new ultrasound elastography techniques, even if based on the same principle (e.\u200ag. pSWE). In fact, the different manufacturers apply proprietary patented calculation modes, which might result in slightly to moderately different values. It should be kept in mind that the range for intermediate fibrosis stages (F1 to F3) is quite narrow, in the order of 2\u200a-\u200a3 kilopascal (over a total range spanning 2 to 75 kPa with Fibroscan), so that slightly different differences in outputs could shift the assessment of patients from one stage to another. Comparative studies using phantoms and healthy volunteers, as well as patients, are eagerly awaited. In fact, the equipment might not produce linear correlations of measurements at different degrees of severity of fibrosis. As a theoretical example, some equipment might well correlate in their values with an older technique, such as transient elastography, at low levels of liver fibrosis, but not as well in cases of more advanced fibrosis or vice versa. Consequentely, when elastography data are included in a report, the equipment utilized for the measurement should be clearly specified, and conclusions about the fibrosis stage should be withheld if an insufficient number of comparative studies with solid reference standards are available for that specific equipment.. \ub7 Future studies using histology as a reference might be biased in comparison to previous studies, since nowadays fewer patients with chronic hepatitis C or hepatitis B undergo biopsy. In fact, due to wide availability of effective drugs as well as the use of established elastography methods for patients with viral hepatitis, most cases submitted to biopsy today have uncertain etiology or inconsistent and inconclusive clinical data. Therefore, extrapolated thresholds from such inhomogeneous populations applied to more ordinary patients with viral hepatitis might become problematic in the future, although no better solution is currently anticipated. This situation might lead to the adoption of a standard validated elastographic method as reference, but this has to be agreed-upon at an international level.. \ub7 Ultrasound elastography embedded in conventional scanners usually allows the choice of where to place the ROI within the color stiffness box and whether to confirm or exclude each single measurement when determining the final value. Thus, the operator has a greater potential to influence the final findings than with Fibroscan\uae, where these choices are not available. This has to be kept in mind to avoid the possibility that an operator could, even inadvertently, tend to confirm an assumption about that specific patient or to confirm the patient's expectations.. \ub7 Quality criteria for the new technologies following transient elastography are absent (depending on the manufacturer) or have not been satisfactorily defined, so that the information potentially inserted in a report cannot currently be judged for its reliability by the clinician.. (ABSTRACT TRUNCATED

Evaluation of the clinical impact of CEUS in the abdominal aneurysm treatment

Dirigente Medico I Livello Radiologo, Dip. Scienze Radiologiche, oncologiche e anatomo-patologiche, University Sapienza, RomeEndovascular aneurysm repair (EVAR) is an effective alternative treatment to open repair of abdominal aortic aneurysm and the number of EVAR procedures carried out worldwide is continuously growing. Incomplete exclusion of the aneurysm sac from the circulation, defined as endoleak, is the most frequent complication after EVAR occurring in 10% to 45% of cases, and it can be associated with aneurysm enlargement and possible rupture. Despite its notable advantages, ultrasonography has not yet achieved reference standard status in the EVAR follow-up because of low diagnostic specificity and sensitivity. Recent studies on ultrasound examinations performed without echo-contrast agents reported sensitivity rates ranging from 43% to 97%, such wide differences suggesting that it does not guarantee the necessary reliability. Therefore, to date computed tomography angiography (CTA) is the preferred imaging modality to follow-up patients after EVAR. However, CTA surveillance carries the risks associated with radiation and contrast media exposure. Magnetic resonance angiography (MRA) and contrast-enhanced ultrasonography (CEUS) have been shown in some studies a better accuracy than CTA. However, there is no consensus with regard of optimal work-up with diagnostic imaging modalities in surveillance after EVAR. The accuracy of current imaging modalities in the detection and characterization of endoleaks in aortic endografts, focusing especially on the accuracy of CEUS with the use of second generation contrast agent have been presented. The advantages, the limitations of CEUS in comparison with CTA and MRA, will be discussed. In conclusion, CDUS is inadequate for the surveillance of patients after EVAR. The results of the present study showed that CEUS is an effective tool for surveillance after EVAR because it is fast, cheaper but equally accurate compared to CTA or MRA, can be repeated frequently even at bedside, also in the immediate postoperative period. The limitations of CEUS are mainly due to its operator dependence and patients’ habitus. Based on these findings, we do believe that CEUS is a valuable adjunctive imaging modality to CTA and MRA in detecting endoleaks after EVAR

Living kidney donation: practical considerations on setting up a program

Living kidney donation represents the best treatment for end stage renal disease patients, with the potentiality to pre-emptively address kidney failure and significantly expand the organ pool. Unfortunately, there is still limited knowledge about this underutilized resource. The present review aims to describe the general principles for the establishment, organization, and oversight of a successful living kidney transplantation program, highlighting recommendation for good practice and the work up of donor selection, in view of potential short- and long-terms risks, as well as the additional value of kidney paired exchange programs. The need for donor registries is also discussed, as well as the importance of lifelong follow up

Interobserver agreement of various thyroid imaging reporting and data systems

Ultrasonography is the best available tool for the initial work-up of thyroid nodules. Substantial interobserver variability has been documented in the recognition and reporting of some of the lesion characteristics. A number of classification systems have been developed to estimate the likelihood of malignancy: several of them have been endorsed by scientific societies, but their reproducibility has yet to be assessed. We evaluated the interobserver variability of the AACE/ACE/AME, ACR, ATA, EU-TIRADS, and K-TIRADS classification systems and the interobserver concordance in the indication to FNA biopsy. Two raters independently evaluated 1055 ultrasound images of thyroid nodules identified in 265 patients at multiple time points, in two separate sets (501 and 554 images). After the first set of nodules, a joint reading was performed to reach a consensus in the feature definitions. The interobserver agreement (Krippendorff alpha) in the first set of nodules was 0.47, 0.49, 0.49, 0.61, and 0.53, for AACE/ACE/AME, ACR, ATA, EU-TIRADS, and K-TIRADS systems, respectively. The agreement for the indication to biopsy was substantial to near-perfect, being 0.73, 0.61, 0.75, 0.68, and 0.82, respectively (Cohen's kappa). For all systems, agreement on the nodules of the second set increased. Despite the wide variability in the description of single ultrasonographic features, the classification systems may improve the interobserver agreement, that further ameliorates after a specific training. When selecting nodules to be submitted to FNA biopsy, that is main purpose of these classifications, the interobserver agreement is substantial to almost perfect

Ultrasound of the Kidneys and Adrenal gland

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The effects of a common stainless steel orthodontic bracket on the diagnostic quality of cranial and cervical 3T-MR images: a prospective, case-control study

Abstract OBJECTIVES: To evaluate the effect of orthodontic stainless steel brackets and two different types of archwires (stainless steel and nickel-titanium) on the diagnostic quality of 3T-MR images. METHODS: This prospective, case-control study was conducted following STROBE guidelines. The imaging protocol consisted of the axial Fluid Attenuated Inversion Recovery (FLAIR) and axial oblique double echo proton density (PD) and weighted/turbo spin echo (TSE) T2-weighted sequences for brain, paranasal sinuses and cervical region evaluation; sagittal TSE T2w, sagittal TSE T1w and axial T2* Gradient echo sequences (GRE) sequences for the cervical vertebrae; axial and coronal TSE T2w images for the head and neck structures; and sagittal, axial and coronal PD and TSE T2-weighted sequences for the temporo-mandibular joint. Two experts in neuroradiology evaluated the images. The statistical analysis was performed at the level of anatomical districts. The following statistical methods were used: descriptive statistics, Cohen's kappa coefficient (k), Kruskal-Wallis test, pairwise comparisons using the Dunn-Bonferroni approach. Significance was set at p≤0.05. RESULTS: 80 patients were included, providing 80 MRI. The presence of stainless steel brackets with or without archwires negatively influenced the MR images of the cervical region, paranasal sinuses, head and neck region and cervical vertebrae but did not influence the MR images of brain and temporomandibular joint regions. CONCLUSIONS: Patients with a stainless steel multi-bracket orthodontic appliance should remove it before cervical vertebrae, cervical region, paranasal sinuses and head and neck MRI scans. The brain and temporomandibular joint regions MRI should not require the removal of such appliances

New patents on topical anesthetics.

Anesthesia is defined as a total or partial loss of sensation and it may be general, local or topical, depending on the method of drug administration and area of the body affected. General anesthesia is a reversible state of unconsciousness produced by anesthetic agents, characterized by amnesia, muscle relaxation and loss of sensitivity to pain of the whole body. General anesthetic drugs can be classified into two main groups according to their predominant molecular pharmacological effects: volatile and intravenous agents. Local anesthesia produce a reversible loss of sensation in a portion of the body and it reversibly block impulse conduction along nerve axons and other excitable membrane. All local anesthetics (LA) are membrane stabilizing drugs; they reversibly decrease the rate of depolarization and repolarization of excitable membranes. They act mainly by inhibiting sodium influx through sodium-specific ion channels in the neuronal cell membrane, in particular the voltage-gated sodium channels. When the influx of sodium is interrupted, an action potential cannot arise and signal conduction is inhibited. The main local anesthetic (LA) agents for skin anesthesia are benzocaine (aminoester), prilocaine and lidocaine (aminoamides) which are commercially available as gels, ointments and creams (benzocaine and eutectic mixture of lidocaine and prilocaine) or as a bioadhesive (lidocaine) with different compositions (vehicles and excipients) for adults or pediatric use. Topical anesthetics decrease anxiety, pain and discomfort during cutaneous procedures and provide effective analgesia with rapid onset, prolonged duration and minimal side effects. This article outlines the different classes of topical anesthetics available and gives an overview of the mechanism of action, metabolism of each different class, of the possible complications that can occur because of their use and their possible treatment options and new patents. © 2014 Bentham Science Publishers

Performance of contrast-enhanced ultrasound in thyroid nodules : Review of current state and future perspectives

Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.Ultrasound has been established as a baseline imaging technique for thyroid nodules. The main advantage of adding CEUS is the ability to assess the sequence and intensity of vascular perfusion and hemodynamics in the thyroid nodule, thus providing real-time characterization of nodule features, considered a valuable new approach in the determination of benign vs. malignant nod-ules. Original studies, reviews and six meta-analyses were included in this article. A total of 624 studies were retrieved, and 107 were included in the study. As recognized for thyroid nodule malignancy risk stratification by US, for acceptable accuracy in malignancy a combination of several CEUS parameters should be applied: hypo-enhancement, heterogeneous, peripheral irregular enhancement in combination with internal enhancement patterns, and slow wash-in and wash-out curve lower than in normal thyroid tissue. In contrast, homogeneous, intense enhancement with smooth rim enhancement and “fast-in and slow-out” are indicative of the benignity of the thyroid nodule. Even though overlapping features require standardization, with further research, CEUS may achieve reliable performance in detecting or excluding thyroid cancer. It can also play an op-erative role in guiding ablation procedures of benign and malignant thyroid nodules and metastatic lymph nodes, and providing accurate follow-up imaging to assess treatment efficacy.publishersversionPeer reviewe

Is contrast-enhanced US alternative to spiral CT in the assessment of treatment outcome of radiofrequency ablation in hepatocellular carcinoma?

Purpose: The present study was conducted to assess the efficacy of contrast-enhanced ultrasound with low mechanical index in evaluating the response of percutaneous radiofrequency ablation treatment of hepatocellular carcinoma by comparing it with 4-row spiral computed tomography. Materials and Methods: 100 consecutive patients (65 men and 35 women; age range: 62 – 76 years) with solitary hepatocellular carcinomas (mean lesion diameter: 3.7cm± 1.1cm SD) underwent internally cooled radiofrequency ablation. Therapeutic response was evaluated at one month after the treatment with triple-phasic contrast-enhanced spiral CT and low-mechanical index contrast-enhanced ultrasound following bolus injection of 2.4 ml of Sonovue (Bracco, Milan). 60 out of 100 patients were followed up for another 3 months. Contrast-enhanced sonographic studies were reviewed by two blinded radiologists in consensus. Sensitivity, specificity, NPV and PPV of contrast-enhanced ultrasound examination were determined. Results: After treatment, contrast-enhanced ultrasound identified persistent signal enhancement in 24 patients (24%), whereas no intratumoral enhancement was detected in the remaining 76 patients (76%). Using CT imaging as gold standard, the sensitivity, specificity, NPV, and PPV of contrast enhanced ultrasound were 92.3% (95% CI = 75.9 – 97.9%), 100% (95% CI = 95.2 – 100%), 97.4% (95% CI = 91.1 – 99.3%), and 100% (95% CI = 86.2 – 100%). Conclusion: Contrast-enhanced ultrasound with low mechanical index using Sonovue is a feasible tool in evaluating the response of hepatocellular carcinoma to radiofrequency ablation. Accuracy is comparable to 4-row spiral CT