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Purpose: To evaluate the reliability of quantitative ultrasonic measurement of renal allograft elasticity using supersonic shear imaging (SSI) and its relationship with parenchymal pathological changes.Materials and Methods: Forty-three kidney transplant recipients (22 women, 21 men) (mean age, 51 years; age range, 18-70 years) underwent SSI elastography, followed by biopsy. The quantitative measurements of cortical elasticity were performed by two radiologists and expressed in terms of Young's modulus (kPa). Intra- and inter-observer reproducibility was assessed (Kruskal-Wallis test and Bland-Altman analysis), as well as the correlation between elasticity values and clinical, biological and pathological data (semi-quantitative Banff scoring). Interstitial fibrosis was evaluated semi-quantitatively by the Banff score and measured by quantitative image analysis.Results: Intra- and inter-observer variation coefficients of cortical elasticity were 20 % and 12 %, respectively. Renal cortical stiffness did not correlate with any clinical parameters, any single semi-quantitative Banff score or the level of interstitial fibrosis; however, a significant correlation was observed between cortical stiffness and the total Banff scores of chronic lesions and of all elementary lesions (R = 0.34, P = 0.05 and R = 0.41, P = 0.03,respectively).Conclusion: Quantitative measurement of renal cortical stiffness using SSI is a promising non-invasive tool to evaluate global histological deterioration.Key Points: • Supersonic shear imaging elastography can measure cortical stiffness in renal transplants • The level of cortical stiffness is correlated with the global degree of tissue lesions • The global histological deterioration of transplanted kidneys can be quantified using elastography. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate, in a rat model of glomerulosclerosis, whether ultrasonic shear wave elastography detects kidney cortex stiffness changes and predicts histopathological development of fibrosis.Materials and Methods: Three groups were studied transversally: a control group (n = 8), a group after 4 weeks of L-NAME administration (H4, n = 8), and a group after 6 weeks (H6, n = 15). A fourth group was studied longitudinally (n = 8) before, after 4 weeks and after 7 weeks of L-NAME administration. Shear modulus of renal cortex was quantified using supersonic shear imaging technique. Urine was analysed for dosage of protein/creatinine ratio. Kidneys were removed for histological quantification of fibrosis.Results: Diseased rats showed an increased urinary protein/creatinine ratio. Cortical stiffness expressed as median (interquartile range) was 4.0 kPa (3.3-4.5) in control kidneys. It increased in all but one pathological groups: H4: 7.7 kPa (5.5-8.6) (p < 0.01); H6: 4.8 kPa (3.9-5.9) (not significant); in the longitudinal cohort, from 4.5 kPa (3.1-5.9) to 7.7 kPa (5.9-8.3) at week 4 (p < 0.05) and to 6.9 kPa (6.1-7.8) at week 7 (p < 0.05). Stiffness values were correlated with the proteinuria/creatininuria ratio (r = 0.639, p < 0.001).Conclusions: Increased cortical stiffness is correlated with the degree of renal dysfunction. More experience in other models is necessary to understand its relationship with microstructural changes. [ABSTRACT FROM AUTHOR]

Ultrasound shear wave elastography (SWE) has emerged as a promising non-invasive method for muscle evaluation by assessing the propagation velocity of an induced shear wavefront. In skeletal muscles, the propagation of shear waves is complex, depending not only on the mechanical and acoustic properties of the tissue but also upon its geometry. This study aimed to comprehensively investigate the influence of muscle pennation angle on the shear wave propagation, which is directly related to the shear modulus. A novel elastography method based on steered pushing beams (SPB) was used to assess the shear modulus along the fibers of the gastrocnemius medialis (pennate) muscle in twenty healthy volunteers. Ultrasound scans were performed during passive muscle lengthening (n = 10) and submaximal isometric contractions (n = 10). The shear modulus along the fibers was compared to the apparent shear modulus, as commonly assessed along the muscle shortening direction using conventional SWE sequences. The shear modulus along the muscle fibers was significantly greater than the apparent shear modulus for passive dorsiflexion angles, while not significantly different throughout the range of plantar flexion angles (i.e., under any or very low tensile loads). The concomitant decrease in pennation angle along with the gradual increase in the shear modulus difference between the two methods as the muscle lengthens, strongly indicates that non-linear elasticity exerts a greater influence on wave propagation than muscle geometry. In addition, significant differences between methods were found across all submaximal contractions, with both shear modulus along the fibers and the pennation angle increasing with the contraction intensity. Specifically, incremental contraction intensity led to a greater bias than passive lengthening, which could be partly explained by distinct changes in pennation angle. Overall, the new SPB sequence provides a rapid and integrated geometrical correction of shear modulus quantification in pennate muscles, thereby eliminating the necessity for specialized systems to align the ultrasound transducer array with the fiber's orientation. We believe that this will contribute for improving the accuracy of SWE in biomechanical and clinical settings., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective. Cavitation dose monitoring plays a key role in ultrasound drug delivery to the brain. The use of capacitive micromachined ultrasonic transducer (CMUT) technology has a great potential for passive cavitation detection (PCD). Approach. Here, a circular (diameter 7 mm) CMUT centered at 5 MHz was designed to be inserted into a therapeutic transducer (1.5 MHz) used for ultrasound-induced blood-brain barrier (BBB) disruption on mice. CMUT-based real-time cavitation detection was performed during the ultrasound procedure (50 μ l intravenous injection of SonoVue microbubbles, frequency 1.5 MHz, PNP 480 kPa, duty Cycle 10%, PRF 10 Hz, duration 60 s). BBB disruption were confirmed by contrast-enhanced 7T-MRI. Main results. The CMUT device has a fractional bandwidth of 140%, almost twice a conventional piezocomposite PCD transducer. As expected, the CMUT device was able to detect the occurrence of harmonic, subharmonic and ultraharmonic frequencies as well as the increase of broadband signal indicating inertial cavitation in a wide frequency range (from 0.75 to 6 MHz). Signal-to-noise ratio was high enough (>40 dB) to perform ultrafast monitoring and follow the subtle intrapulse variations of frequency components at a rate of 10 kHz. Significance . This first in vivo proof of concept demonstrates the interest of CMUT for PCD and encourages us to develop devices for PCD in larger animals by integrating an amplifier directly to the CMUT front-end to considerably increase the signal-to-noise ratio., (© 2024 Institute of Physics and Engineering in Medicine. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Objective. To optimize and ensure the safety of ultrasound brain therapy, personalized transcranial ultrasound simulations are very useful. They allow to predict the pressure field, depending on the patient skull and probe position. Most transcranial ultrasound simulations are based on numerical methods which have a long computation time and a high memory usage. The goal of this study is to develop a new semi-analytical field computation method that combines realism and computation speed. Approach. Instead of the classic ray tracing, the ultrasonic paths are computed by time of flight minimization. Then the pressure field is computed using the pencil method. This method requires a smooth and homogeneous skull model. The simulation algorithm, so-called SplineBeam, was numerically validated, by comparison with existing solvers, and experimentally validated by comparison with hydrophone measured pressure fields through an ex vivo human skull. Main results. SplineBeam simulated pressure fields were close to the experimentally measured ones, with a focus position difference of the order of the positioning error and a maximum pressure difference lower than 6.02%. In addition, for those configurations, SplineBeam computation time was lower than another simulation software, k-Wave's, by two orders of magnitude, thanks to its capacity to compute the field only at the focal spot. Significance. These results show the potential of this new method to compute fast and realistic transcranial pressure fields. The combination of this two assets makes it a promising tool for real time transcranial pressure field prediction during ultrasound brain therapy interventions., (© 2024 Institute of Physics and Engineering in Medicine.)

Objective. Skeletal muscles are organized into distinct layers and exhibit anisotropic characteristics across various scales. Assessing the arrangement of skeletal muscles may provide valuable biomarkers for diagnosing muscle-related pathologies and evaluating the efficacy of clinical interventions. Approach . In this study, we propose a novel ultrafast ultrasound sequence constituted of steered pushing beams was proposed for ultrasound elastography applications in transverse isotropic muscle. Based on the propagation of the shear wave vertical mode, it is possible to fit the experimental results to retrieve in the same imaging plane, the shear modulus parallel to fibers as well as the elastic anisotropy factor (ratio of Young's moduli times the shear modulus perpendicular to fibers). Main results . The technique was demonstrated in vitro in phantoms and ex vivo in fusiform beef muscles. At last, the technique was applied in vivo on fusiform muscles ( biceps brachii ) and mono-pennate muscles ( gastrocnemius medialis ) during stretching and contraction. Significance . This novel sequence provides access to new structural and mechanical biomarkers of muscle tissue, including the elastic anisotropy factor, within the same imaging plane. Additionally, it enables the investigation of multiples parameters during muscle active and passive length changes., (© 2024 Institute of Physics and Engineering in Medicine.)

Acoustoelasticity theory describes propagation of shear waves in uniaxially stressed medium and allows the retrieval of nonlinear elastic coefficients of tissues. In transverse isotropic medium such as muscles the theory leads to 9 different configurations of propagating shear waves (stress axis vs. fibers axis vs. shear wave polarization axis vs. shear wave propagation axis). In this work we propose to use 4 configurations to quantify these nonlinear parameters ex vivo and in vivo. Ex vivo experiments combining ultrasound shear wave elastography and mechanical testing were conducted on iliopsoas pig muscles to quantify three third-order nonlinear coefficients A, H and K that are possibly linked to the architectural structure of muscles. In vivo experiments were performed with human volunteers on biceps brachii during a stretching exercise on an ergometer. A combination of the third order nonlinear elastic parameters was assessed. The knowledge of this nonlinear elastic parameters paves the way to quantify in vivo the local forces produced by muscle during exercise, contraction or movements., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The authors declare no competing interest: Jean-Luc Gennisson reports a relationship with Supersonic Imagine that includes: consulting or advisory., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective . The aim of this study is to validate the estimation of the nonlinear shear modulus (A) from the acoustoelasticity theory with two experimental methods, ultrasound (US) elastography and magnetic resonance elastography (MRE), and a finite element method. Approach . Experiments were performed on agar (2%)-gelatin (8%) phantom considered as homogeneous, elastic and isotropic. Two specific setups were built to ensure a uniaxial stress step by step on the phantom, one for US and a nonmagnetic version for MRE. The stress was controlled identically in both imaging techniques, with a water tank placed on the top of the phantom and filled with increasing masses of water during the experiment. In US, the supersonic shear wave elastography was implemented on an ultrafast US device, driving a 6 MHz linear array to measure shear wave speed. In MRE, a gradient-echo sequence was used in which the three spatial directions of a 40 Hz continuous wave displacement generated with an external driver were encoded successively. Numerically, a finite element method was developed to simulate the propagation of the shear wave in a uniaxially stressed soft medium. Main results . Similar shear moduli were estimated at zero stress using experimental methods,μ0US= 12.3 ± 0.3 kPa andμ0MRE= 11.5 ± 0.7 kPa. Numerical simulations were set with a shear modulus of 12 kPa and the resulting nonlinear shear modulus was found to be -58.1 ± 0.7 kPa. A very good agreement between the finite element model and the experimental models (AUS= -58.9 ± 9.9 kPa andAMRE= -52.8 ± 6.5 kPa) was obtained. Significance . These results show the validity of such nonlinear shear modulus measurement quantification in shear wave elastography. This work paves the way to develop nonlinear elastography technique to get a new biomarker for medical diagnosis., (© 2023 Institute of Physics and Engineering in Medicine.)

Quantification of vascularization volume can provide valuable information for diagnosis and prognosis in vascular pathologies. It can be adapted to inform the surgical management of gliomas, aggressive brain tumors characterized by exuberant sprouting of new blood vessels (neoangiogenesis). Filtered ultrafast Doppler data can provide two main parameters: vascularization index (VI) and fractional moving blood volume (FMBV) that clinically reflect tumor micro vascularization. Current protocols lack robust, automatic, and repeatable filtering methods. We present a filtrating method called Multi-layered Adaptive Neoangiogenesis Intra-Operative Quantification (MANIOQ). First, an adaptive clutter filtering is implemented, based on singular value decomposition (SVD) and hierarchical clustering. Second a method for noise equalization is applied, based on the subtraction of a weighted noise profile. Finally, an in vivo analysis of the periphery of the B-mode hyper signal area allows to measure the vascular infiltration extent of the brain tumors. Ninety ultrasound acquisitions were processed from 23 patients. Compared to reference methods in the literature, MANIOQ provides a more robust tissue filtering, and noise equalization allows for the first time to keep axial and lateral gain compensation (TGC and LGC). MANIOQ opens the way to an intra-operative clinical analysis of gliomas micro vascularization.

Purpose: Heat acclimation (HA) is recommended before competing in hot and humid conditions. HA has also been recently suggested to increase muscle strength, but its effects on human's muscle and tendon mechanical properties are not yet fully understood. This study investigated the effect of active HA on gastrocnemius medialis (GM) muscle-tendon properties., Methods: Thirty recreationally active participants performed 13 low-intensity cycling sessions, distributed over a 17-d period in hot (HA = ~38°C, ~58% relative humidity; n = 15) or in temperate environment (CON = ~23°C, ~35% relative humidity; n = 15). Mechanical data and high-frame rate ultrasound images were collected during electrically evoked and voluntary contractions pre- and postintervention. Shear modulus was measured at rest in GM, and vertical jump performance was assessed., Results: Core temperature decreased from the first to the last session in HA (-0.4°C ± 0.3°C; P = 0.015), while sweat rate increased (+0.4 ± 0.3 L·h -1 ; P = 0.010), suggesting effective HA, whereas no changes were observed in CON (both P ≥ 0.877). Heart rate was higher in HA versus CON and decreased throughout intervention in groups (both P ≤ 0.008), without an interaction effect ( P = 0.733). Muscle-tendon unit properties (i.e., maximal and explosive isometric torque production, contractile properties, voluntary activation, joint and fascicular force-velocity relationship, passive muscle, and active tendon stiffness) and vertical jump performance did not show training ( P ≥ 0.067) or group-training interaction ( P ≥ 0.232) effects., Conclusions: Effective active HA does not alter muscle-tendon properties. Preparing hot and humid conditions with active HA can be envisaged in all sporting disciplines without the risk of impairing muscle performance., (Copyright © 2023 by the American College of Sports Medicine.)

Purpose: The aim of the present study was to investigate whether the electrically evoked muscle responses are differently affected over time by the knee joint angle after an exercise-induced muscle damage (EIMD). We hypothesized that low-frequency-evoked responses would be less affected at long than short muscle length, and that mechanisms located within the muscle and tendinous tissues would be involved., Methods: Fifteen males performed 45 min loaded downhill walking (DW) exercise. Maximal voluntary contraction torque (MVC), optimal angle for torque production, voluntary activation level (VAL), twitch, doublet at 10 and 100 Hz (Db10 and Db100, respectively), rate of torque development (RTD), post-activation potentiation (PAP), muscle shear elastic modulus (µ) and aponeurosis stiffness were assessed before, after, and 4, 24, 48, 72 and 168 h after the exercise at a knee angle of 40°, 90° and 120° (0°: full extension)., Results: MVC, VAL and Db100 were similarly decreased across joint angles after the DW and optimal angle was not affected. Twitch, Db10, Db10/Db100, PAP and RTD were less affected and muscle µ more increased at long than short muscle lengths (p < 0.05), especially during the first 24 h after the DW exercise., Conclusion: Low-frequency-evoked responses were more preserved at long than short muscle length the first 24 h after the DW exercise, suggesting that joint angle should be taken into account to assess muscular alterations after EIMD. This length-dependence could be associated to the higher sensitivity to Ca 2+ and the higher increase in muscle stiffness at long than short muscle length., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Transcranial ultrasound is more and more used for therapy and imaging of the brain. However, the skull is a highly attenuating and aberrating medium, with different structures and acoustic properties among samples and even within a sample. Thus, case-specific simulations are needed to perform transcranial focused ultrasound interventions safely. In this article, we provide a review of the different methods used to model the skull and to simulate ultrasound propagation through it., (© 2022 The Authors. Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

In recent years, ultrasensitive Pulsed-Wave Doppler (uPWD) ultrasound (US) has emerged as an alternative imaging approach for microcirculation imaging and as a complementary tool to other imaging modalities, such as positron emission tomography (PET). uPWD is based on the acquisition of a large set of highly spatiotemporally coherent frames, which allows high-quality images of a wide field of view to be obtained. In addition, these acquired frames allow calculation of the resistivity index (RI) of the pulsatile flow detected over the entire field of view, which is of great interest to clinicians, for example, in monitoring the transplanted kidney course. This work aims to develop and evaluate a method to automatically obtain an RI map of the kidney based on the uPWD approach. The effect of time gain compensation (TGC) on the visualization of vascularization and aliasing on the blood flow frequency response, was also assessed. A pilot study conducted in patients referred for renal transplant Doppler examination showed that the proposed method provided relative errors of about 15% for RI measurements with respect to conventional pulsed-wave (PW) Doppler.

Mechanical properties of biological tissues are of key importance for proper function and in situ methods for mechanical characterization are sought after in the context of both medical diagnosis as well as understanding of pathophysiological processes. Shear wave elastography (SWE) and accompanying physical modelling methods provide valid estimates of stiffness in quasi-linear viscoelastic, isotropic tissue but suffer from limitations in assessing non-linear viscoelastic or anisotropic material, such as tendon. Indeed, mathematical modelling predicts the longitudinal shear wave velocity to be unaffected by the tensile but rather the shear viscoelasticity. Here, we employ a heuristic experimental testing approach to the problem to assess the most important potential confounders, namely tendon mass density and diameter, and to investigate associations between tendon tensile viscoelasticity with shear wave descriptors. Small oscillatory testing of animal flexor tendons at two baseline stress levels over a large frequency range comprehensively characterized tensile viscoelastic behavior. A broad set of shear wave descriptors was retrieved on the unloaded tendon based on high frame-rate plane wave ultrasound after applying an acoustic deformation impulse. Tensile modulus and strain energy dissipation increased logarithmically and linearly, respectively, with the frequency of the applied strain. Shear wave descriptors were mostly unaffected by tendon diameter but were highly sensitive to tendon mass density. Shear wave group and phase velocity showed no association with tensile elasticity or strain rate-stiffening but did show an association with tensile strain energy dissipation. The longitudinal shear wave velocity may not characterize tensile elasticity but rather tensile viscous properties of transversely isotropic collagenous tissues., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The evolutionary emergence of the primitive gut in Metazoa is one of the decisive events that conditioned the major evolutionary transition, leading to the origin of animal development. It is thought to have been induced by the specification of the endomesoderm (EM) into the multicellular tissue and its invagination (i.e., gastrulation). However, the biochemical signals underlying the evolutionary emergence of EM specification and gastrulation remain unknown. Herein, we find that hydrodynamic mechanical strains, reminiscent of soft marine flow, trigger active tissue invagination/gastrulation or curvature reversal via a Myo-II-dependent mechanotransductive process in both the metazoan Nematostella vectensis ( cnidaria ) and the multicellular choanoflagellate Choanoeca flexa. In the latter, our data suggest that the curvature reversal is associated with a sensory-behavioral feeding response. Additionally, like in bilaterian animals, gastrulation in the cnidarian Nematostella vectensis is shown to participate in the biochemical specification of the EM through mechanical activation of the β-catenin pathway via the phosphorylation of Y654-βcatenin. Choanoflagellates are considered the closest living relative to metazoans, and the common ancestor of choanoflagellates and metazoans dates back at least 700 million years. Therefore, the present findings using these evolutionarily distant species suggest that the primitive emergence of the gut in Metazoa may have been initiated in response to marine mechanical stress already in multicellular pre-Metazoa. Then, the evolutionary transition may have been achieved by specifying the EM via a mechanosensitive Y654-βcatenin dependent mechanism, which appeared during early Metazoa evolution and is specifically conserved in all animals., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Nguyen, Merle, Broders-Bondon, Brunet, Battistella, Land, Sarron, Jha, Gennisson, Röttinger, Fernández-Sánchez and Farge.)

Ultrasound shear wave elastography was developed the past decade, bringing new stiffness biomarker in clinical practice. This biomarker reveals to be of primarily importance for the diagnosis of breast cancer or liver fibrosis. In muscle this biomarker become much more complex due to the nature of the muscle itself: an anisotropic medium. In this manuscript we depict the underlying theory of propagating waves in such anisotropic medium. Then we present the available methods that can consider and quantify this parameter. Advantages and drawbacks are discussed to open the way to imagine new methods that can free this biomarker in a daily clinical practice., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ngo, Poulard, Brum and Gennisson.)

Background: The relationship between the diaphragm thickening fraction and the transdiaphragmatic pressure, the reference method to evaluate the diaphragm function, has not been clearly established. This study investigated the global and intraindividual relationship between the thickening fraction of the diaphragm and the transdiaphragmatic pressure. The authors hypothesized that the diaphragm thickening fraction would be positively and significantly correlated to the transdiaphragmatic pressure, in both healthy participants and ventilated patients., Methods: Fourteen healthy individuals and 25 mechanically ventilated patients (enrolled in two previous physiologic investigations) participated in the current study. The zone of apposition of the right hemidiaphragm was imaged simultaneously to transdiaphragmatic pressure recording within different breathing conditions, i.e., external inspiratory threshold loading in healthy individuals and various pressure support settings in patients. A blinded offline breath-by-breath analysis synchronously computed the changes in transdiaphragmatic pressure, the diaphragm pressure-time product, and diaphragm thickening fraction. Global and intraindividual relationships between variables were assessed., Results: In healthy subjects, both changes in transdiaphragmatic pressure and diaphragm pressure-time product were moderately correlated to diaphragm thickening fraction (repeated measures correlation = 0.40, P < 0.0001; and repeated measures correlation = 0.38, P < 0.0001, respectively). In mechanically ventilated patients, changes in transdiaphragmatic pressure and thickening fraction were weakly correlated (repeated measures correlation = 0.11, P = 0.008), while diaphragm pressure-time product and thickening fraction were not (repeated measures correlation = 0.04, P = 0.396). Individually, changes in transdiaphragmatic pressure and thickening fraction were significantly correlated in 8 of 14 healthy subjects (ρ = 0.30 to 0.85, all P < 0.05) and in 2 of 25 mechanically ventilated patients (ρ = 0.47 to 0.64, all P < 0.05). Diaphragm pressure-time product and thickening fraction correlated in 8 of 14 healthy subjects (ρ = 0.41 to 0.82, all P < 0.02) and in 2 of 25 mechanically ventilated patients (ρ = 0.63 to 0.66, all P < 0.01)., Conclusions: Overall, diaphragm function as assessed with transdiaphragmatic pressure was weakly related to diaphragm thickening fraction. The diaphragm thickening fraction should not be used in healthy subjects or ventilated patients when changes in diaphragm function are evaluated., (Copyright © 2021, the American Society of Anesthesiologists. All Rights Reserved.)

Recent developments in the field of elastography aim at developing the quantification of new mechanical properties of tissues, that are complementary to the shear modulus, which is characteristic of the linear elastic properties of a quasi-incompressible medium. In this context, measurement of the elastic nonlinearity of tissues was recently proposed based on acoustoelasticity. Up to now, most of the experimental applications of acoustoelasticity theory using Landau formalism in human tissues have assumed isotropy. However, this strong hypothesis does not hold in all human tissues, such as muscles that are generally considered as transversely isotropic (TI). In this work, after reviewing the constraints imposed by TI symmetry on the linear and nonlinear elastic properties of TI media, the acoustoelasticity theory in TI incompressible media is developed and implemented experimentally on a TI polyvinyl alcohol phantom and on ex vivo muscular tissues. Based on this theory and on the evolutions of the shear wave speed, with respect to uniaxial static stress, the nonlinear elastic parameter A is experimentally quantified. The estimations of A in ex vivo bovine and porcine muscles are on the order of hundreds of kPa. This work paves the way for more thorough muscle mechanical properties characterization as well as for the development of a potential new biomarker.

Hybridization of positron emission tomography (PET) with other functional neuroimaging techniques such as functional magnetic resonance imaging (fMRI) or functional ultrasound (fUS) still raises technical and methodological challenges. Beyond the co-registration of anatomical images with functional data, development of hybrid imaging systems has paved the way for a large field of research based on the concept of bimodal functional neuroimaging such as PET/fMRI. In this framework, comparison of respective performances of brain PET and fUS suggests complementarity and great potential of hybrid PET/fUS for preclinical neuroimaging. Hybridization of functional neuroimaging techniques first offers opportunities to validate or improve measurement made by each modality. Future research may propose and validate hybrid parameters that quantitatively connect the brain molecular environment and the neuro-vascular coupling, which may improve our understanding of brain function in health and disease, with perspectives in neuroscience and neuropharmacology. In the coming years, cross-fertilization of neuroimaging communities and training of young researchers on multiple imaging modalities may foster the development of hybrid neuroimaging protocols that will take the full potential and the limitations of each modality into account., (Copyright © 2020. Published by Elsevier Ltd.)

Using shear wave elastography, we measure the changes in the wave speed with the stress produced by a striated muscle during isometric voluntary contraction. To isolate the behaviour of an individual muscle from complementary or antagonistic actions of adjacent muscles, we select the flexor digiti minimi muscle, whose sole function is to extend the little finger. To link the wave speed to the stiffness, we develop an acousto-elastic theory for shear waves in homogeneous, transversely isotropic, incompressible solids subject to an uniaxial stress. We then provide measurements of the apparent shear elastic modulus along, and transversely to, the fibre axis for six healthy human volunteers of different age and sex. The results display a great variety across the six subjects. We find that the slope of the apparent shear elastic modulus along the fibre direction changes inversely to the maximum voluntary contraction (MVC) produced by the volunteer. We propose an interpretation of our results by introducing the S (slow) or F (fast) nature of the fibres, which harden the muscle differently and accordingly, produce different MVCs. A natural follow-up on this study is to apply the method to patients with musculoskeletal disorders or neurodegenerative diseases., (© 2021 Institute of Physics and Engineering in Medicine.)

Malignant tumors have abnormal biomechanical characteristics, including high viscoelasticity, solid stress, and interstitial fluid pressure. Magnetic resonance (MR) elastography is increasingly used to non-invasively assess tissue viscoelasticity. However, solid stress and interstitial fluid pressure measurements are performed with invasive methods. We studied the feasibility and potential role of MR elastography at basal state and under controlled compression in assessing altered biomechanical features of malignant liver tumors. MR elastography was performed in mice with patient-derived, subcutaneously xenografted hepatocellular carcinomas or cholangiocarcinomas to measure the basal viscoelasticity and the compression stiffening rate, which corresponds to the slope of elasticity versus applied compression. MR elastography measurements were correlated with invasive pressure measurements and digital histological readings. Significant differences in MR elastography parameters, pressure, and histological measurements were observed between tumor models. In multivariate analysis, collagen content and interstitial fluid pressure were determinants of basal viscoelasticity, whereas solid stress, in addition to collagen content, cellularity, and tumor type, was an independent determinant of compression stiffening rate. Compression stiffening rate had high AUC (0.87 ± 0.08) for determining elevated solid stress, whereas basal elasticity had high AUC for tumor collagen content (AUC: 0.86 ± 0.08). Our results suggest that MR elastography compression stiffening rate, in contrast to basal viscoelasticity, is a potential marker of solid stress in malignant liver tumors.

Purpose: To investigate the diagnostic accuracy of applying four levels of manual pressure in Shear Wave Elastography (SWE) of the breast and to assess inter-rater reliability., Materials and Methods: Single-center prospective preliminary study including patients receiving ultrasound examination of breast lesions as part of routine clinical practice. SWE was performed on 60 breast masses (26 benign and 34 malignant) in 54 patients by a breast fellowship trained radiologist. Stiffness values were compared between benign and malignant masses at four levels of manual compression: none, mild, moderate, and marked. Accuracy of SWE was assessed using receiving operating characteristics analysis at each level. In 18 patients, a second radiologist repeated the SWE acquisitions to evaluate reproducibility. Reproducibility was assessed using intraclass correlation coefficient., Results: Without compression, we observed no significant difference in stiffness (p > 0.99) between benign and malignant lesions, and SWE demonstrated low accuracy (area under the curve = 0.64). Stiffness was higher in malignant lesions at all levels of compression (p < 0.001). SWE demonstrated good accuracy at all three levels of compression (from area under the curve = 0.71 to 0.84 across Emax and Emean), with high interobserver agreement., Conclusion: This preliminary study suggests that not using compression during SWE for breast lesion characterization offers suboptimal results. On the contrary, application of compression yields high diagnostic performance with good interobserver agreement and, as such, should be included in routine clinical practice., Competing Interests: Declaration of Competing Interest FC is a speaker for SupersonicImagine; JLG is a consultant for Supersonic Imagine., (Copyright © 2020 The Association of University Radiologists. All rights reserved.)

Key Points: Twitch transdiaphragmatic pressure elicited by cervical magnetic stimulation of the phrenic nerves is a fully non-volitional method for assessing diaphragm contractility in humans, yet it requires invasive procedures such as oesophageal and gastric catheter balloons.  Ultrafast ultrasound enables a very high frame rate allowing the capture of transient events, such as muscle contraction elicited by nerve stimulation (twitch). Whether indices derived from ultrafast ultrasound can be used as an alternative to the invasive measurement of twitch transdiaphragmatic pressure is unknown.  Our findings demonstrate that maximal diaphragm tissue velocity assessed using ultrafast ultrasound following cervical magnetic stimulation is reliable, sensitive to change in cervical magnetic stimulation intensity, and correlates to twitch transdiaphragmatic pressure.  This approach provides a novel fully non-invasive and non-volitional tool for the assessment of diaphragm contractility in humans., Abstract: Measuring twitch transdiaphragmatic pressure (P di,tw ) elicited by cervical magnetic stimulation (CMS) is considered as a reference method for the standardized evaluation of diaphragm function. Yet, the measurement of P di requires invasive oesophageal and gastric catheter-balloons. Ultrafast ultrasound is a non-invasive imaging technique enabling frame rates high enough to capture transient events such as evoked muscle contractions. This study investigated relationships between indices derived from ultrafast ultrasound and P di,tw , and how these indices might be used to estimate P di,tw . CMS was performed in 13 healthy volunteers from 30% to 100% of maximal stimulator intensity in units of 10% in a randomized order. P di,tw was measured and the right hemidiaphragm was imaged using a custom ultrafast ultrasound sequence with 1 kHz framerate. Maximal diaphragm axial velocity (V di , max ) and diaphragm thickening fraction (TF di,tw ) were computed. Intra-session reliability was assessed. Repeated-measures correlation (R) and Spearman correlation coefficients (ρ) were used to assess relationships between variables. Intra-session reliability was strong for P di,tw and V di,max and moderate for TF di,tw . V di,max correlated with P di,tw in all subjects (0.64 < ρ < 1.00, R = 0.75; all P < 0.05). TF di,tw correlated with P di,tw in eight subjects only (0.85 < ρ < 0.93, R = 0.69; all P < 0.05). Coupling ultrafast ultrasound and CMS shows promise for the non-invasive and fully non-volitional assessment of diaphragm contractility. This approach opens up the prospect of both diagnosis and follow-up of diaphragm contractility in clinical populations., (© 2020 The Authors. The Journal of Physiology © 2020 The Physiological Society.)

Background: Diaphragm dysfunction is highly prevalent in mechanically ventilated patients. Recent work showed that changes in diaphragm shear modulus (ΔSMdi) assessed using ultrasound shear wave elastography (SWE) are strongly related to changes in Pdi (ΔPdi) in healthy subjects. The aims of this study were to investigate the relationship between ΔSMdi and ΔPdi in mechanically ventilated patients, and whether ΔSMdi is responsive to change in respiratory load when varying the ventilator settings., Methods: A prospective, monocentric study was conducted in a 15-bed ICU. Patients were included if they met the readiness-to-wean criteria. Pdi was continuously monitored using a double-balloon feeding catheter orally introduced. The zone of apposition of the right hemidiaphragm was imaged using a linear transducer (SL10-2, Aixplorer, Supersonic Imagine, France). Ultrasound recordings were performed under various pressure support settings and during a spontaneous breathing trial (SBT). A breath-by-breath analysis was performed, allowing the direct comparison between ΔPdi and ΔSMdi. Pearson's correlation coefficients (r) were used to investigate within-individual relationships between variables, and repeated measure correlations (R) were used for determining overall relationships between variables. Linear mixed models were used to compare breathing indices across the conditions of ventilation., Results: Thirty patients were included and 930 respiratory cycles were analyzed. Twenty-five were considered for the analysis. A significant correlation was found between ΔPdi and ΔSMdi (R = 0.45, 95% CIs [0.35 0.54], p < 0.001). Individual correlation displays a significant correlation in 8 patients out of 25 (r = 0.55-0.86, all p < 0.05, versus r = - 0.43-0.52, all p > 0.06). Changing the condition of ventilation similarly affected ΔPdi and ΔSMdi. Patients in which ΔPdi-ΔSMdi correlation was non-significant had a faster respiratory rate as compared to that of patient with a significant ΔPdi-ΔSMdi relationship (median (Q1-Q3), 25 (18-33) vs. 21 (15-26) breaths.min -1 , respectively)., Conclusions: We demonstrate that ultrasound SWE may be a promising surrogate to Pdi in mechanically ventilated patients. Respiratory rate appears to negatively impact SMdi measurement. Technological developments are needed to generalize this method in tachypneic patients., Trial Registration: NCT03832231 .

Passive cavitation detection can be performed to monitor microbubble activity during brain therapy. Microbubbles under ultrasound exposure generate a response characterized by multiple nonlinear emissions. Here, the wide bandwidth of capacitive micromachined ultrasonic transducers (CMUTs) was exploited to monitor the microbubble signature through a rat skull and a macaque skull. The intrinsic nonlinearity of the CMUTs was characterized in receive mode. Indeed, undesirable nonlinear components generated by the CMUTs must be minimized as they can mask the microbubble harmonic response. The microbubble signature at harmonic and ultra-harmonic components (0.5-6 MHz) was successfully extracted through a rat skull using moderate bias voltage.

We present a new, to the best of our knowledge, method to perform acousto-optic imaging based on a spatiotemporal structuration of long-duration acoustic plane waves. This approach is particularly relevant when using detectors with long integration times. We show how it is possible to reconstruct an image by measuring its two-dimensional Fourier components. A proof of concept is presented using a photorefractive detection scheme, demonstrating equal performances to direct imaging. The overall acquisition time is compatible with medical monitoring applications.

2 D shear wave elastography (2D-SWE) is the latest evolution of elastography techniques and allows real-time quantitative assessment of the medium stiffness. The aim of this review is to identify, describe, explain and illustrate some technical restrictions and artifacts in 2D-SWE. Encountered artifacts and technical restrictions may be categorized according to acquisition technique, medium, or operator: · Acquisition technique: B-mode & SWE entanglement, transducer frequency, posterior elastographic shadowing artifact, mirrored elastogram artifact, "vertical striped" artifact, resolution limits in SWE, non-equivalence of elastographic devices. · Medium: SWE in liquid medium, "black hole phenomenon", pseudo-liquid lesions, musculotendinous anisotropy, intrinsic stiffness variations of tendons and muscles, depth of analysis, movement artifacts. · Operator: Region of interest compression, acquisition and measurement parameters (ROI size, ROI location, elastogram acquisition time). Clear knowledge of the underlying physical basis is necessary in 2D-SWE because radiologists have to deal with technical restrictions and a wide range of artifacts. Proper use of 2D-SWE ensures the reliability and reproducibility of the technique., Competing Interests: Two authors involved in this work declare potential conflicts of interest : J. L. Gennisson has patents with and is a scientific consultant for SuperSonic Imagine® (Aix-en-provence, France), and S. Aubry presented Supersonic Imagine® (Aix-en-provence, France) at symposiums. The other authors have no potential conflicts of interest to disclose., (© Georg Thieme Verlag KG Stuttgart · New York.)

The multidrug resistance-associated protein 2 (MRP2) mediates the biliary excretion of drugs and metabolites. [ 99m Tc]mebrofenin may be employed as a probe for hepatic MRP2 activity because its biliary excretion is predominantly mediated by this transporter. As the liver uptake of [ 99m Tc]mebrofenin depends on organic anion-transporting polypeptide (OATP) activity, a safe protocol for targeted inhibition of hepatic MRP2 is needed to study the intrinsic role of each transporter system. Diltiazem (DTZ) and cyclosporin A (CsA) were first confirmed to be potent MRP2 inhibitors in vitro. Dynamic acquisitions were performed in rats ( n = 5-6 per group) to assess the kinetics of [ 99m Tc]mebrofenin in the liver, intestine and heart-blood pool after increasing doses of inhibitors. Their impact on hepatic blood flow was assessed using Doppler ultrasound ( n = 4). DTZ (s.c., 10 mg/kg) and low-dose CsA (i.v., 0.01 mg/kg) selectively decreased the transfer of [ 99m Tc]mebrofenin from the liver to the bile ( k 3 ). Higher doses of DTZ and CsA did not further decrease k 3 but dose-dependently decreased the uptake ( k 1 ) and backflux ( k 2 ) rate constants between blood and liver. High dose of DTZ (i.v., 3 mg/kg) but not CsA (i.v., 5 mg/kg) significantly decreased the blood flow in the portal vein and hepatic artery. Targeted pharmacological inhibition of hepatic MRP2 activity can be achieved in vivo without impacting OATP activity and liver blood flow. Clinical studies are warranted to validate [ 99m Tc]mebrofenin in combination with low-dose CsA as a novel substrate/inhibitor pair to untangle the role of OATP and MRP2 activity in liver diseases.

We investigated the in vivo effects of voluntary fatiguing isometric contractions of the knee extensor muscles on the viscoelastic properties of the vastus lateralis (VL). Twelve young males (29.0 ± 4.5 years) performed an intermittent voluntary fatigue protocol consisting of 6 sets × 10 repetitions of 5-s voluntary maximal isometric contractions with 5-s passive recovery periods between repetitions. Voluntary and evoked torque were assessed before, immediately after, and 20 min after exercise. The shear modulus (μ) of the VL muscle was estimated at rest and during a ramped isometric contraction using a conventional elastography technique. An index of active muscle stiffness was then calculated (slope from the relationship between shear modulus and absolute torque). Resting muscle viscosity (η) was quantified using a shear-wave spectroscopy sequence to measure the shear-wave dispersion. Voluntary and evoked torque decreased by ∼37% ( P < 0.01) immediately after exercise. The resting VL μ was lower at the end of the fatigue protocol (-57.9 ± 5.4%, P < 0.001), whereas the resting VL η increased (179.0 ± 123%, P < 0.01). The active muscle stiffness index also decreased with fatigue ( P < 0.05). By 20 min post-fatigue, there were no significant differences from the pre-exercise values for VL η and the active muscle stiffness index, contrary to the resting VL μ. We show that the VL μ is greatly reduced and η greatly enhanced by fatigue, reflecting a more compliant and viscous muscle. The quantification of both shear μ and η moduli in vivo may contribute to a better understanding of the mechanical behavior of muscles during fatigue in sports medicine, as well as in clinical situations., (Copyright © 2020 Chalchat, Gennisson, Peñailillo, Oger, Malgoyre, Charlot, Bourrilhon, Siracusa and Garcia-Vicencio.)

Purpose:  To evaluate the ability of a new ultrasound (US) method based on sound speed estimation (SSE) with respect to the detection, quantification, and grading of hepatic steatosis using magnetic resonance (MR) proton density fat fraction (PDFF) as the reference standard and to calculate one US fat index based on the patient's SSE., Materials and Methods:  This study received local IRB approval. Written informed consent was obtained from patients. We consecutively included N = 50 patients as the training cohort and a further N = 50 as the validation cohort who underwent both SSE and abdominal MR. Hepatic steatosis was classified according to MR-PDFF cutoffs as: S0 ≤ 6.5 %, S1 6.5 to 16.5 %, S2 16.5 to 22 %, S3 ≥ 22 %. Receiver operating curve analysis was performed to evaluate the diagnostic performance of SSE in the diagnosis of steatosis (S1-S3). Based on the optimal data fit derived from our study, we proposed a correspondence between the MR-PDFF and a US fat index. Coefficient of determination R2 was used to evaluate fit quality and was considered robust when R2 > 0.6., Results:  The training and validation cohorts presented mean SSE values of 1.570 ± 0.026 and 1.568 ± 0.023 mm/µs for S0 and 1.521 ± 0.031 and 1.514 ± 0.019 mm/µs for S1-S3 (p < 0.01) patients, respectively. An SSE threshold of ≤ 1.537 mm/µs had a sensitivity of 80 % and a specificity of 85.7 % in the diagnosis of steatosis (S1-S3) in the training cohort. Robust correspondence between MR-PDFF and the US fat index was found both for the training (R2 = 0.73) and the validation cohort (R2 = 0.76)., Conclusion:  SSE can be used to detect, quantify and grade liver steatosis and to calculate a US fat index., Competing Interests: The authors declare that they have no conflict of interest., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background and Objective: Different biological models have shown how mechanical stimulation may induce physiological responses from solicited cells, tissues, or organs. In models of cultured skin cells, the frequency of the mechanical stress appears to be a paramount parameter, generating a biological response in some cells, particularly from dermal fibroblasts. Our objective was to explore in ex vivo human skin explants the effects of mechanical stimulation., Materials and Methods: Mechanical stimulations were provided by a torque test device, with different end effectors, able to generate cyclic strains at different frequencies (from 40 to 120 Hz). Skin explant samples were stimulated twice daily by the device for one minute, over 10 days., Results: At days 0, 5, and 10, samples were processed by immunohistological procedures, allowing some structural dermal proteins to be quantified (fluorescence). As compared to untreated skin explant samples, the stimulation procedure clearly led some proteins of the dermal-epidermal and some dermal proteins to be overexpressed. This stimulation was found to be frequency-dependent, with the greatest overall increases occurring at 60 and 90 Hz., Conclusion: For the first time, ultrafast ultrasound imaging in vitro (phantom mimicking skin mechanical properties) was used to analyze mechanical waves transmitted to the skin layers as a function of end effector shape., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The paraspinal compartment acts as a bone-muscle composite beam of the spine. The elastic properties of the paraspinal muscles play a critical role in spine stabilization. These properties depend on the subjects' posture, and they may be drastically altered by low back pain. Supersonic shear wave elastography can be used to provide quantitative stiffness maps (elastograms), which characterize the elastic properties of the probed tissue. The aim of this study was to challenge shear wave elastography sensitivity to postural stiffness changes in healthy paraspinal muscles. The stiffness of the main paraspinal muscles (longissimus, iliocostalis, multifidus) was measured by shear wave elastography at the lumbosacral level (L3 and S1) for six static postures performed by volunteers. Passive postures (rest, passive flexion, passive extension) were performed in a first shear wave elastography session, and active postures (upright, bending forward, bending backward) with rest posture for reference were performed in a second session. Measurements were repeated three times for each posture. Sixteen healthy young adults were enrolled in the study. Non-parametric paired tests, multiple analyses of covariance, and intra-class correlations were implemented for analysis. Shear wave elastography showed good to excellent reliability, except in the multifidus at S1, during bending forward, and in the multifidus at L3, during bending backward. Yet, during bending forward, only poor quality was recorded for nine volunteers in the longissimus. Significant intra- and inter-muscular changes were observed with posture. Stiffness significantly increased for the upright position and bending forward with respect to the reference values recorded in passive postures. In conclusion, shear wave elastography allows reliable assessment of the stiffness of the paraspinal muscles except in the multifidus at S1 and longissimus, during bending forward, and in the multifidus at L3, during bending backward. It reveals a different biomechanical behaviour for the multifidus, the longissimus, and the iliocostalis., (© 2019 Anatomical Society.)

Angiogenesis, the formation of new vessels, is one of the key mechanisms in tumor development and an appealing target for therapy. Non-invasive, high-resolution, high-sensitivity, quantitative 3-D imaging techniques are required to correctly depict tumor heterogeneous vasculature over time. Ultrafast Doppler was recently introduced and provides an unprecedented combination of resolution, penetration depth and sensitivity without requiring any contrast agents. The technique was further extended to three dimensions with ultrafast Doppler tomography (UFD-T). In this work, UFD-T was applied to the monitoring of tumor angiogenesis in vivo, providing structural and functional information at different stages of development. UFD-T volume renderings revealed that our murine model's vasculature stems from pre-existing vessels and sprouts to perfuse the whole volume as the tumor grows until a critical size is reached. Then, as the network becomes insufficient, the tumor core is no longer irrigated because the vasculature is concentrated mainly in the periphery. In addition to spatial distribution and growth patterns, UFD-T allowed a quantitative analysis of vessel size and length, revealing that the diameter distribution of vessels remained relatively constant throughout tumor growth. The network is dominated by small vessels at all stages of tumor development, with more than 74% of the vessels less than 200 µm in diameter. This study also found that cumulative vessel length is more closely related to tumor radius than volume, indicating that the vascularization becomes insufficient when a critical mass is reached. UFD-T was also compared with dynamic contrast-enhanced ultrasound and found to provide complementary information regarding the link between structure and perfusion. In conclusion, UFD-T is capable of in vivo quantitative assessment of the development of tumor vasculature (vessels with blood speed >1 mm/s [sensitivity limit] assessed with a resolution limit of 80 µm) in 3 dimensions. The technique has very interesting potential as a tool for treatment monitoring, response assessment and treatment planning for optimal drug efficiency., (Copyright © 2019. Published by Elsevier Inc.)

We present an experimental investigation of Rayleigh-like wave propagation along the surface of a dense granular suspension. Using an ultrafast ultrasound scanner, we monitor the softening of the shear modulus via the Rayleigh-like wave velocity slowdown in the optically opaque medium as the driving amplitude increases. For such nonlinear behavior two regimes are found when increasingthe driving amplitude progressively: First, we observe a significant shear modulus weakening due to the microslip on the contact level without macroscopic rearrangements of grains. Second, there is a clear macroscopic plastic rearrangement accompanied by a modulus decrease up to 88%. A friction model is proposed to describe the interplay between nonlinear elasticity and plasticity, which highlights the crucial effect of contact slipping before contact breaking or loss. Investigation of this nonlinear Rayleigh-like wave may bridge the gap between two disjoint approaches for describing the dynamics near unjamming: linear elastic soft modes and nonlinear collisional shock.

Ultrasound-modulated optical tomography (UOT) is an imaging technique that couples light and ultrasound in order to perform in-depth imaging of highly scattering media. In previous work, we introduced plane wave UOT, an imaging method analogous to x-ray tomography based on the filtered backprojection for image reconstruction. Angle-limited measurements, however, led to drastic loss of lateral spatial resolution. Here, we present a new structured ultrasonic plane wave UOT method that allows partial recovery of the resolution. For image reconstruction, we present a generalization of the Fourier slice theorem along with a generalized filtered backprojection formalism. The method is successfully tested on simulated and experimental data.

We prospectively evaluated the performance of combined shear wave elastography (SWE) and conventional ultrasound (US) for the characterization of 89 testicular focal masses. Testes were evaluated with B-mode, color Doppler and SWE measurements, locating a region of interest on the normal and pathologic parenchyma. Thirty-seven malignant tumors (MTs), 12 burned out tumors (BOTs), 28 Leydig cell tumors (LCTs), 2 dermoid cysts and other benign lesions were included. MTs + BOTs exhibited more microliths and macrocalcifications compared with benign lesions (p < 10 -4 ). LCTs manifested mostly a dominant peripheral vascularization pattern compared with other lesions. MTs + BOTs were stiffer compared with benign lesions (p < 2 × 10 -4 ) but with a moderate area under the receiver operating characteristic curve (AUROC) of 80%. By focusing on LCTs versus MTs + BOTs, diagnostic performance led to an AUROC of 89% for the best stiffness parameter. For combined conventional US and SWE, the diagnostic performance to differentiate all benign lesions versus MTs + BOTs and LCTs versus MTs + BOTs increased to AUROCs of 93% and 98%, respectively., (Copyright © 2018 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

The reference method for the assessment of diaphragm function relies on the measurement of transdiaphragmatic pressure (Pdi). Local muscle stiffness measured using ultrafast shear wave elastography (SWE) provides reliable estimates of muscle force in locomotor muscles. This study aimed at investigating whether SWE could be used as a surrogate of Pdi to evaluate diaphragm function. Fifteen healthy volunteers underwent a randomized stepwise inspiratory loading protocol of 0-60% of maximal isovolumetric inspiratory pressure during closed-airways maneuvers and 0-50% during ventilation against an external inspiratory threshold load. During all tasks, Pdi was measured and SWE was used to assess shear modulus of the right hemidiaphragm (SMdi) at the zone of apposition. Pearson correlation coefficients ( r) and repeated-measures correlation coefficients ( R) were computed to determine within-individual and overall relationships between Pdi and SMdi, respectively. During closed-airways maneuvers, mean Pdi correlated to mean SMdi in all participants [ r ranged from 0.77 to 0.96, all P < 0.01; R = 0.82, 95% confidence intervals (0.76, 0.86), P < 0.01]. During ventilation against inspiratory threshold loading, Pdi swing correlated to maximal SMdi in all participants [ r ranged from 0.40 to 0.90, all P < 0.01; R = 0.70, 95% confidence intervals (0.66, 0.73), P < 0.001]. Changes in diaphragm stiffness as assessed by SWE reflect changes in transdiaphragmatic pressure. SWE provides a new opportunity for direct and noninvasive assessment of diaphragm function. NEW & NOTEWORTHY Accurate and specific estimation of diaphragm effort is critical for evaluating and monitoring diaphragm dysfunction. The measurement of transdiaphragmatic pressure requires the use of invasive gastric and esophageal probes. In the present work, we demonstrate that changes in diaphragm stiffness assessed with ultrasound shear wave elastography reflect changes in transdiaphragmatic pressure, therefore offering a new noninvasive method for gauging diaphragm effort.

The non-invasive quantification of human tissue fat fraction using easily scalable and accessible imaging technologies is crucial for the diagnosis of many diseases including liver steatosis. Here, we propose a non-invasive quantification of fat content using a highly accessible ultrasonic imaging technology. Ultrasonic echoes backscattered from human liver tissues are recombined to synthetize echoes of a virtual point-like reflector within the organs. This virtual point-like reflector is an ultrasonic analogue of artificial stars generated by laser beams in the field of astronomy, which are used to estimate the aberrations induced in the propagation medium. Here, the ultrasonic echoes from the point-like reflector provide an estimate of the Green's function relating the ultrasonic array and the reflector location and consequently represent a measurement of the aberrations induced along the ultrasonic beam travel path. Maximizing the spatial coherence of echoes backscattered from this targeted region provides an estimate of the acoustic sound speed while iteratively making the reflector more echogenic. The acoustic sound speed is dependent of the organ fat content, and we derive and cross-validate a theoretical equation relating acoustic sound speed and fat content both in phantom experiments and humans. An ultrasound-based fat fraction was found to be highly correlated with the oil paraffin concentration (R 2   =  0.985) in phantoms and well correlated with the gold standard magnetic resonance imaging proton density fat fraction measurements (R 2   =  0.73) in patients.

Background Ultrasensitive Doppler is a novel non-invasive ultrasound (US) Doppler technique that improves sensitivity and resolution for the detection of slow flow. Purpose To investigate the feasibility of ultrasensitive Doppler (USD) for testicular disease diagnosis, using both qualitative and quantitative results. Material and Methods This prospective study was conducted in 160 successive men referred for scrotal US including B-mode and conventional Color-Doppler. A new USD sequence and algorithm dedicated to academic research were implemented into the US system. The quality criterion for a successful examination was the detection of well delineated intratesticular vessels. Qualitative USD results were described in terms of tumor vascular architecture and flow intensity for different pathologies for 41 patients. The testicular vascularization (TV), defined as a vessel's surface ratio, was quantified using customized MATLAB® software and compared in azoospermic and normal patients. Results USD was acquired successfully in 153/160 patients (95.6%). The tumor vascular architecture differed depending on the nature of the tumors. Leydig cell tumors exhibited mostly circumferential vascularization, while germ cell tumors exhibited straight vessels through the tumors, or anarchic vascular maps. USD improved the diagnostic performance of testicular Doppler US in a case of incomplete spermatic cord torsion and acute epididymitis. The reproducibility of TV measurements established an interclass correlation of 0.801. Non-Klinefelter syndrome non-obstructive azoospermia patients exhibited a lower TV compared to normal patients, to Klinefelter syndrome, and to obstructive azoospermia patients ( P < 0.002, P < 0.005, and P < 0.05, respectively). Conclusion Testicular USD can become a promising technique for improving US diagnosis of tumors, acute scrotum, and for determining infertility status.

Diffuse optical tomography (DOT) is a reliable and widespread technique for monitoring qualitative changes in absorption inside highly scattering media. It has been shown, however, that acousto-optic (AO) imaging can provide significantly more qualitative information without the need for inversion algorithms due to the spatial resolution afforded by ultrasound probing. In this Letter, we show how, by using multiple-wavelength AO imaging, it is also possible to perform quantitative measurements of absorber concentration inside scattering media.

A recent ultrasound imaging technique-shear wave elastography-showed its ability to image and quantify the mechanical properties of biological tissues, such as prostate or liver tissues. In the present study this technique was used to evaluate the relationship among tumor growth, stiffness and reduction of treatment with combretastatin (CA4 P) in allografted colon tumor CT26 in mice. During 12 d, CT26 tumor growth (n = 52) was imaged by ultrasound, and shear modulus was quantified, showing a good correlation between tumor volume and stiffness (r = 0.59). The treatment was initiated at d 12 and monitored every d during 4 d. Following the treatment, the tumor volume had decreased, while the elasticity of the tumor volume remained steady throughout the treatment. After segmentation using the shear modulus map, a detailed analysis showed a decrease in the stiffness after treatment. This reduction in the mechanical properties was shown to correlate with tissue reorganization, particularly, fibrosis and necrosis, assessed by histology., (Copyright © 2017 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Longitudinal imaging techniques are needed that can meaningfully probe the tumor microenvironment and its spatial heterogeneity. Contrast-enhanced ultrasound, shear wave elastography and quantitative ultrasound are ultrasound-based techniques that provide information on the vascular function and micro-/macroscopic tissue structure. Modifications of the tumor microenvironment induced by cytotoxic and anti-angiogenic molecules in ectopic murine Lewis lung carcinoma tumors were monitored. The most heterogenous structures were found in tumors treated with anti-angiogenic drug that simultaneously accumulated the highest levels of necrosis and fibrosis. The anti-angiogenic group presented the highest number of correlations between parameters related to vascular function and those related to the micro-/macrostructure of the tumor microenvironment. Results suggest how patterns of multiparametric ultrasound modifications can be related to provide a more insightful marker of changes occurring within tumors during therapy., (Copyright © 2017. Published by Elsevier Inc.)

The functional mapping of brain activity is essential to perform optimal glioma surgery and to minimize the risk of postoperative deficits. We introduce a new, portable neuroimaging modality of the human brain based on functional ultrasound (fUS) for deep functional cortical mapping. Using plane-wave transmissions at an ultrafast frame rate (1 kHz), fUS is performed during surgery to measure transient changes in cerebral blood volume with a high spatiotemporal resolution (250 µm, 1 ms). fUS identifies, maps and differentiates regions of brain activation during task-evoked cortical responses within the depth of a sulcus in both awake and anaesthetized patients.

Functional ultrasound (fUS) imaging by ultrasensitive Doppler detection of blood volume was previously reported to measure adult rat brain activation and functional connectivity with unmatched spatiotemporal sampling (100 μm, 1 ms), but skull-induced attenuation of ultrasonic waves imposed skull surgery or contrast agent use. Also, fUS feasibility remains to be validated in mice, a major pre-clinical model organism. In the study described here, we performed full-depth ultrasensitive Doppler imaging and 3-D Doppler tomography of the entire mouse brain under anesthesia, non-invasively through the intact skull and skin, without contrast agents. Similar results were obtained in anesthetized young rats up to postnatal day 35, thus enabling longitudinal studies on postnatal brain development. Using a newly developed ultralight ultrasonic probe and an optimized ultrasonic sequence, we also performed minimally invasive full-transcranial fUS imaging of brain vasculature and whisker stimulation-induced barrel cortex activation in awake and freely moving mice, validating transcranial fUS for brain imaging, without anesthesia-induced bias, for behavioral studies., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Hepatic steatosis is a common condition, the prevalence of which is increasing along with non-alcoholic fatty liver disease (NAFLD). Currently, the most accurate noninvasive imaging method for diagnosing and quantifying hepatic steatosis is MRI, which estimates the proton-density fat fraction (PDFF) as a measure of fractional fat content. However, MRI suffers several limitations including cost, contra-indications and poor availability. Although conventional ultrasound is widely used by radiologists for hepatic steatosis assessment, it remains qualitative and operator dependent. Interestingly, the speed of sound within soft tissues is known to vary slightly from muscle (1.575 mm · µs -1 ) to fat (1.450 mm · µs -1 ). Building upon this fact, steatosis could affect liver sound speed when the fat content increases. The main objectives of this study are to propose a robust method for sound speed estimation (SSE) locally in the liver and to assess its accuracy for steatosis detection and staging. This technique was first validated on two phantoms and SSE was assessed with a precision of 0.006 and 0.003 mm · µs -1 respectively for the two phantoms. Then a preliminary clinical trial (N  =  17 patients) was performed. SSE results was found to be highly correlated with MRI proton density fat fraction (R 2   =  0.69) and biopsy (AUROC  =  0.952) results. This new method based on the assessment of spatio-temporal properties of the local speckle noise for SSE provides an efficient way to diagnose and stage hepatic steatosis.

The assessment of myocardial fiber disarray is of major interest for the study of the progression of myocardial disease. However, time-resolved imaging of the myocardial structure remains unavailable in clinical practice. In this study, we introduce 3D Backscatter Tensor Imaging (3D-BTI), an entirely novel ultrasound-based imaging technique that can map the myocardial fibers orientation and its dynamics with a temporal resolution of 10 ms during a single cardiac cycle, non-invasively and in vivo in entire volumes. 3D-BTI is based on ultrafast volumetric ultrasound acquisitions, which are used to quantify the spatial coherence of backscattered echoes at each point of the volume. The capability of 3D-BTI to map the fibers orientation was evaluated in vitro in 5 myocardial samples. The helicoidal transmural variation of fiber angles was in good agreement with the one obtained by histological analysis. 3D-BTI was then performed to map the fiber orientation dynamics in vivo in the beating heart of an open-chest sheep at a volume rate of 90 volumes/s. Finally, the clinical feasibility of 3D-BTI was shown on a healthy volunteer. These initial results indicate that 3D-BTI could become a fully non-invasive technique to assess myocardial disarray at the bedside of patients.

3D functional imaging of the whole brain activity during visual task is a challenging task in rodents due to the complex tri-dimensional shape of involved brain regions and the fine spatial and temporal resolutions required to reveal the visual tract. By coupling functional ultrasound (fUS) imaging with a translational motorized stage and an episodic visual stimulation device, we managed to accurately map and to recover the activity of the visual cortices, the Superior Colliculus (SC) and the Lateral Geniculate Nuclei (LGN) in 3D. Cerebral Blood Volume (CBV) responses during visual stimuli were found to be highly correlated with the visual stimulus time profile in visual cortices (r=0.6), SC (r=0.7) and LGN (r=0.7). These responses were found dependent on flickering frequency and contrast, and optimal stimulus parameters for largest CBV increases were obtained. In particular, increasing the flickering frequency higher than 7Hz revealed a decrease of visual cortices response while the SC response was preserved. Finally, cross-correlation between CBV signals exhibited significant delays (d=0.35s +/-0.1s) between blood volume response in SC and visual cortices in response to our visual stimulus. These results emphasize the interest of fUS imaging as a whole brain neuroimaging modality for brain vision studies in rodent models., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Our aim in the study described here was to prospectively establish the feasibility of using and reproducibility of testicular shear-wave elastography in the assessment of testicular stiffness in 62 normal patients and 539 infertile men with obstructive azoospermia (OA), non-Klinefelter syndrome non-obstructive azoospermia (non-KS NOA), Klinefelter syndrome NOA (KS NOA), oligoasthenoteratozoospermia (OAT) or a left varicocele. The feasibility rate was 96.9%, with an intra-class correlation coefficient of 0.85 (95% confidence interval: 0.83-0.88). Median stiffness (interquartile range) values were 2.4 kPa (2.0, 2.9), 2.1 kPa (1.8, 2.5), 2.4 kPa (2.0, 2.7), 2.0 kPa (1.7, 2.4), 2.6 kPa (2, 3.2) and 2.2 kPa (1.8, 2.6) for men with a normal testis (n = 108), OAT (n = 689), OA (n = 119), non-KS NOA (n = 183), KS NOA (n = 70) and varicocele (n = 132), respectively. Testicular shear wave elastography is a feasible and reproducible technique. A significant positive association was found between stiffness and testis volume (p = 0.001). Testicular stiffness was higher in OA than in non-KS NOA populations (p = 1.e-10) and in KS NOA than in NOA populations (p = 2.0e-8), but the substantial number of overlapping values limited the clinical impact., (Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)