Ultrasonography has been widely used for diagnosis since it was first introduced in clinical practice in the 1970's. Since then, new ultrasound modalities have been developed, such as Doppler imaging, which provides new information for diagnosis. Elastography was developed in the 1990's to map tissue stiffness, and reproduces/replaces the palpation performed by clinicians. In this paper, we introduce the principles of elastography and give a technical summary for the main elastography techniques: from quasi-static methods that require a static compression of the tissue to dynamic methods that uses the propagation of mechanical waves in the body. Several dynamic methods are discussed: vibro-acoustography, Acoustic Radiation Force Impulsion (ARFI), transient elastography, shear wave imaging, etc. This paper aims to help the reader at understanding the differences between the different methods of this promising imaging modality that may become a significant tool in medical imaging.

Ultrafast ultrasonic imaging is a rapidly developing field based on the unfocused transmission of plane or diverging ultrasound waves. This recent approach to ultrasound imaging leads to a large increase in raw ultrasound data available per acquisition. Bigger synchronous ultrasound imaging datasets can be exploited in order to strongly improve the discrimination between tissue and blood motion in the field of Doppler imaging. Here we propose a spatiotemporal singular value decomposition clutter rejection of ultrasonic data acquired at ultrafast frame rate. The singular value decomposition (SVD) takes benefits of the different features of tissue and blood motion in terms of spatiotemporal coherence and strongly outperforms conventional clutter rejection filters based on high pass temporal filtering. Whereas classical clutter filters operate on the temporal dimension only, SVD clutter filtering provides up to a four-dimensional approach (3D in space and 1D in time). We demonstrate the performance of SVD clutter filtering with a flow phantom study that showed an increased performance compared to other classical filters (better contrast to noise ratio with tissue motion between 1 and 10mm/s and axial blood flow as low as 2.6 mm/s). SVD clutter filtering revealed previously undetected blood flows such as microvascular networks or blood flows corrupted by significant tissue or probe motion artifacts. We report in vivo applications including small animal fUltrasound brain imaging (blood flow detection limit of 0.5 mm/s) and several clinical imaging cases, such as neonate brain imaging, liver or kidney Doppler imaging.

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SSI provides quantitative elasticity measurements, thus adding complementary information that potentially could help in breast lesion characterization with B-mode US.

Two‐dimensional shear wave elastography (2D‐SWE) has proven to be efficient for the evaluation of liver fibrosis in small to moderate‐sized clinical trials. We aimed at running a larger‐scale meta‐analysis of individual data. Centers which have worked with Aixplorer ultrasound equipment were contacted to share their data. Retrospective statistical analysis used direct and paired receiver operating characteristic and area under the receiver operating characteristic curve (AUROC) analyses, accounting for random effects. Data on both 2D‐SWE and liver biopsy were available for 1,134 patients from 13 sites, as well as on successful transient elastography in 665 patients. Most patients had chronic hepatitis C (n = 379), hepatitis B (n = 400), or nonalcoholic fatty liver disease (n = 156). AUROCs of 2D‐SWE in patients with hepatitis C, hepatitis B, and nonalcoholic fatty liver disease were 86.3%, 90.6%, and 85.5% for diagnosing significant fibrosis and 92.9%, 95.5%, and 91.7% for diagnosing cirrhosis, respectively. The AUROC of 2D‐SWE was 0.022‐0.084 (95% confidence interval) larger than the AUROC of transient elastography for diagnosing significant fibrosis (P = 0.001) and 0.003‐0.034 for diagnosing cirrhosis (P = 0.022) in all patients. This difference was strongest in hepatitis B patients. Conclusion: 2D‐SWE has good to excellent performance for the noninvasive staging of liver fibrosis in patients with hepatitis B; further prospective studies are needed for head‐to‐head comparison between 2D‐SWE and other imaging modalities to establish disease‐specific appropriate cutoff points for assessment of fibrosis stage. (Hepatology 2018;67:260‐272).

In vivo assessment of dispersion affecting the propagation of visco-elastic waves in soft tissues is key to understand the rheology of human tissues. In this paper, the ability of the supersonic shear imaging (SSI) technique to generate planar shear waves propagating in tissues is fully exploited. First, by strongly limiting shear wave diffraction in the imaging plane, this imaging technique enables to discriminate between the usually concomitant influences of both medium rheological properties and diffraction affecting the shear wave dispersion. Second, transient propagation of these plane shear waves in soft tissues can be measured using echographic images acquired at very high frame. In vitro and in vivo experiments demonstrate that dispersion curves, which characterize the rheological behavior of tissues by measuring the frequency dependence of shear wave speed and attenuation, can be recovered in the 75-600 Hz frequency range. Based on a phase difference algorithm, the dispersion curves are computed in 1 cm2 regions of interest from the acquired propagation movie. In vivo measurements in Biceps Brachii muscle and liver of three healthy volunteers show important differences in the rheological behavior of these different tissues. Liver tissue appears to be much more dispersive with a phase velocity ranging from approximately 1.5 m/s at 75 Hz to approximately 3 m/s at 500 Hz whereas muscle tissue shows an important anisotropy, shear waves propagating longitudinally to the muscular fibers are almost nondispersive while those propagating transversally are very dispersive with a shear wave speed ranging from 0.5 to 2 m/s between 75 and 500 Hz. The estimation of dispersion curves is local and can be performed separately in different regions of the organ. This signal processing approach based on the SSI modality introduces the new concept of in vivo shear wave spectroscopy (SWS) that could become an additional tool for tissue characterization. This paper demonstrates the in vivo ability of this SWS to quantify both local shear elasticity and dispersion in real time.

Autoantibody-mediated tissue destruction is among the main features of organ-specific autoimmunity. This report describes ''an antibody enzyme'' (abzyme) contribution to the site-specific degradation of a neural antigen. We detected proteolytic activity toward myelin basic protein (MBP) in the fraction of antibodies purified from the sera of humans with multiple sclerosis (MS) and mice with induced experimental allergic encephalomyelitis. Chromatography and zymography data demonstrated that the proteolytic activity of this preparation was exclusively associated with the antibodies. No activity was found in the IgG fraction of healthy donors. The human and murine abzymes efficiently cleaved MBP but not other protein substrates tested. The sites of MBP cleavage determined by mass spectrometry were localized within immunodominant regions of MBP. The abzymes could also cleave recombinant substrates containing encephalytogenic MBP 85-101 peptide. An established MS therapeutic Copaxone appeared to be a specific abzyme inhibitor. Thus, the discovered epitope-specific antibodymediated degradation of MBP suggests a mechanistic explanation of the slow development of neurodegeneration associated with MS.