Nine mulard ducks that were being raised for foie gras (steatosis) production went through in vivo shear wave (SW) elastography imaging of their liver during the force-feeding period to investigate ...changes in liver tissue characteristics. A total of 4 imaging sessions at an interval of 3 to 4 d were conducted at the farm on each animal. Three ducks were sacrificed at the second, third, and fourth imaging sessions for histopathology analysis of all animals at these time points. Six SW elastography parameters were evaluated: SW speed, SW attenuation, SW dispersion, Young's modulus, viscosity, and shear modulus. Shear waves of different frequencies propagate with different phase velocities. Thus, SW speed and other dependent parameters such as Young's modulus, viscosity, and shear modulus were computed at 2 frequencies: 75 and 202 Hz. Each parameter depicted a statistically significant trend along the force-feeding process (P-values between 0.001 and 0.0001). The fat fraction of the liver increased over the 12-day period of feeding. All parameters increased monotonically over time at 75 Hz, whereas modal relations were seen at 202 Hz. Shear wave dispersion measured between 75 and 202 Hz depicted a plateau from day 5. Based on this validation, proposed imaging methods are aimed to be used in the future on naturally fed ducks and geese.
Changes in biomechanical properties of biological soft tissues are often associated with physiological dysfunctions. Since biological soft tissues are hydrated, viscoelasticity is likely suitable to ...represent its solid-like behavior using elasticity and fluid-like behavior using viscosity. Shear wave elastography is a non-invasive imaging technology invented for clinical applications that has shown promise to characterize various tissue viscoelasticity. It is based on measuring and analyzing velocities and attenuations of propagated shear waves. In this review, principles and technical developments of shear wave elastography for viscoelasticity characterization from organ to cellular levels are presented, and different imaging modalities used to track shear wave propagation are described. At a macroscopic scale, techniques for inducing shear waves using an external mechanical vibration, an acoustic radiation pressure or a Lorentz force are reviewed along with imaging approaches proposed to track shear wave propagation, namely ultrasound, magnetic resonance, optical, and photoacoustic means. Then, approaches for theoretical modeling and tracking of shear waves are detailed. Following it, some examples of applications to characterize the viscoelasticity of various organs are given. At a microscopic scale, a novel cellular shear wave elastography method using an external vibration and optical microscopy is illustrated. Finally, current limitations and future directions in shear wave elastography are presented.
Ultrasound shear wave (SW) elastography has been widely studied and implemented on clinical systems to assess elasticity of living organs. Imaging of SW attenuation reflecting viscous properties of ...tissues has received less attention. A revisited frequency shift method (R-FS) is proposed to improve robustness of SW attenuation imaging. Performances are compared with the frequency-shift (FS) method that we originally proposed, and to the two-point frequency shift (2P-FS) and attenuation measuring ultrasound SW elastography (AMUSE) methods. In the proposed R-FS method, the shape parameter of the gamma distribution fitting SW spectra is assumed to vary with distance, in contrast to FS. Secondly, an adaptive random sample consensus (A-RANSAC) line fitting method is used to prevent outlier attenuation values in the presence of noise. Validation was made on ten simulated phantoms with two viscosities (0.5 and 2 Pa.s) and different noise levels (15 to -5 dB), two experimental homogeneous gel phantoms, and six in vivo liver acquisitions on awake ducks (including three normal and three fatty duck livers). According to conducted experiments, R-FS revealed mean reductions in coefficients of variation (CV) of 62.6% on simulations, 62.5% with phantoms, and 62.3% in vivo compared with FS. Corresponding reductions compared with 2P-FS were 45.4%, 77.1%, and 62.0%, respectively. Reductions in normalized root-mean-square errors for simulations were 63.9% and 48.7% with respect to FS and 2P-FS, respectively.
Attenuation map or measurements based on local attenuation coefficient slope (ACS) in quantitative ultrasound (QUS) has shown potential for diagnosis of liver steatosis. In liver cancers, tissue ...abnormalities and tumors detected using ACS are also of interest to provide new image contrast to clinicians. Current phantom-based approaches have the limitation of assuming comparable speed of sound between the reference phantom and insonified tissues. Moreover, these methods present the inconvenience for operators to acquire data on phantoms as well as on patients. The main goal was to alleviate these drawbacks by proposing a methodology for constructing phantom-free regularized (PF-R) local ACS maps and investigate the performance in both homogeneous and heterogeneous media. The proposed method was tested on two tissue mimicking media with different ACS constructed as homogeneous phantoms, side-by-side and top-to-bottom phantoms, and inclusion phantoms with different attenuations. Moreover, an in-vivo proof-of-concept was performed on healthy, steatotic and cancerous human liver datasets. Modifications brought to previous works include: a) a linear interpolation of the power spectrum in log-scale; b) the relaxation of the underlying hypothesis on the diffraction factor; c) a generalization to nonhomogeneous local ACS; and d) an adaptive restriction of frequencies to a more reliable range than the usable frequency range. Regularization was formulated as a generalized LASSO, and a variant of the Bayesian Information Criterion (BIC) was applied to estimate the Lagrangian multiplier on the LASSO constraint. In addition, we evaluated the proposed algorithm when applying median filtering before and after regularization. Tests conducted showed that the PF-R yielded robust results in all tested conditions, suggesting potential for additional validation as a diagnosis method.
Objective
Improve the characterization of mechanical properties of blood clots. Parameters derived from shear wave (SW) velocity and SW amplitude spectra were determined for gel phantoms and in vitro ...blood clots.
Methods
Homogeneous phantoms and phantoms with gel or blood clot inclusions of different diameters and mechanical properties were analyzed. SW amplitude spectra were used to observe resonant peaks. Parameters derived from those resonant peaks were related to mimicked blood clot properties. Three regions of interest were tested to analyze where resonances occurred the most. For blood experiments, 20 samples from different pigs were analyzed over time during a 110‐minute coagulation period using the Young modulus, SW frequency dispersion, and SW attenuation.
Results
The mechanical resonance was manifested by an increase in the number of SW spectral peaks as the inclusion diameter was reduced (P < .001). In blood clot inclusions, the Young modulus increased over time during coagulation (P < .001). Descriptive spectral parameters (frequency peak, bandwidth, and distance between resonant peaks) were linearly correlated with clot elasticity values (P < .001) with R2 = .77 for the frequency peak, .60 for the bandwidth, and .48 for the distance between peaks. The SW dispersion and SW attenuation reflecting the viscous behavior of blood clots decreased over time (P < .001), mainly in the early stage of coagulation (first minutes).
Conclusion
The confined soft inclusion configuration favored SW mechanical resonances potentially challenging the computation of spectral‐based parameters, such as the SW attenuation. The impact of resonances can be reduced by properly selecting the region of interest for data analysis.
Ultrasound shear wave elastography and assessment of attenuation can increase the diagnostic accuracy of numerous diseases. The main objective of this work was to propose two improvements to the ...frequency shift (FS) method for shear wave attenuation assessment. First, the shape parameter of the gamma distribution employed to fit the spectrum amplitude of shear waves now varies spatially. Second, a random sample consensus (RANSAC) line fitting method is utilized for calculating the attenuation due to its superiority in the presence of noise and outliers. The shear wave propagation in a tissue-mimicking numerical phantom was modeled as a Kelvin-Voigt (KV) viscoelastic material with finite element (FE) simulations in COMSOL. The shear wave amplitude spectrum was fit using a gamma distribution function, and the slope of the rate parameter of this function obtained by the RANSAC method provided the attenuation coefficient. This method was applied to two numerical phantoms (viscosity of 0.5 and 2 Pa.s), two experimental tissue-mimicking viscoelastic phantoms, and two ex vivo blood clot samples embedded in phantoms. Numerical phantoms were also investigated in the presence of Gaussian random noise at SNR levels of 20 dB to 0 dB. Results were compared with FS, two-point frequency shift (2P-FS) method, and attenuation measuring ultrasound shear wave elastography (AMUSE) method. Mean values of the attenuation coefficient, averaged over a region of interest, were compared between implemented methods. For simulations at different SNRs, the proposed, 2P-FS and AMUSE methods gave mean values close to the KV model. At a SNR of 0 dB, biases of the proposed method were 0.0025 and 0.0258 Np/m/Hz, and variances were 0.0024 and 0.0158 (Np/m/Hz) 2 , for viscosities of 0.5 and 2 Pa.s, respectively. For homogeneous gel phantoms, mean values of the proposed method were: #1) 0.4351; #2) 0.4621. For blood clot phantoms, mean values were: #1) 0.2573; #2) 0.9875. Biases of the proposed method compared to KV or AMUSE were smaller for numerical phantoms, whereas its variance was less than 2P-FS for all datasets.
Pour le diagnostic et la stratification de la fibrose hépatique, la rigidité du foie est un biomarqueur quantitatif estimé par des méthodes d'élastographie. L'élastographie par ondes de cisaillement ...(« shear wave », SW) utilise des ultrasons médicaux non invasifs pour évaluer les propriétés mécaniques du foie sur la base des propriétés de propagation des ondes de cisaillement. La vitesse des ondes de cisaillement (« shear wave speed », SWS) et l'atténuation des ondes de cisaillement (« shear wave attenuation », SWA) peuvent fournir une estimation de la viscoélasticité des tissus. Les tissus biologiques sont intrinsèquement viscoélastiques et un modèle mathématique complexe est généralement nécessaire pour calculer la viscoélasticité en imagerie SW. Le calcul précis de l'atténuation est essentiel, en particulier pour une estimation précise du module de perte et de la viscosité. Des études récentes ont tenté d'augmenter la précision de l'estimation du SWA, mais elles présentent encore certaines limites.;
Comme premier objectif de cette thèse, une méthode de décalage de fréquence revisitée a été développée pour améliorer les estimations fournies par la méthode originale de décalage en fréquence Bernard et al 2017. Dans la nouvelle méthode, l'hypothèse d'un paramètre de forme décrivant les caractéristiques spectrales des ondes de cisaillement, et assumé initialement constant pour tous les emplacements latéraux, a été abandonnée permettant un meilleur ajustement de la fonction gamma du spectre d'amplitude. En second lieu, un algorithme de consensus d'échantillons aléatoires adaptatifs (« adaptive random sample consensus », A-RANSAC) a été mis en œuvre pour estimer la pente du paramètre de taux variable de la distribution gamma afin d’améliorer la précision de la méthode. Pour valider ces changements algorithmiques, la méthode proposée a été comparée à trois méthodes récentes permettant d’estimer également l’atténuation des ondes de cisaillements (méthodes de décalage en fréquence, de décalage en fréquence en deux points et une méthode ayant comme acronyme anglophone AMUSE) à l'aide de données de simulations ou fantômes numériques. Également, des fantômes de gels homogènes in vitro et des données in vivo acquises sur le foie de canards ont été traités.;
Comme deuxième objectif, cette thèse porte également sur le diagnostic précoce de la stéatose hépatique non alcoolique (NAFLD) qui est nécessaire pour prévenir sa progression et réduire la mortalité globale. À cet effet, la méthode de décalage en fréquence revisitée a été testée sur des foies humains in vivo. La performance diagnostique de la nouvelle méthode a été étudiée sur des foies humains sains et atteints de la maladie du foie gras non alcoolique. Pour minimiser les sources de variabilité, une méthode d'analyse automatisée faisant la moyenne des mesures prises sous plusieurs angles a été mise au point. Les résultats de cette méthode ont été comparés à la fraction de graisse à densité de protons obtenue de l'imagerie par résonance magnétique (« magnetic resonance imaging proton density fat fraction », MRI-PDFF) et à la biopsie du foie. En outre, l’imagerie SWA a été utilisée pour classer la stéatose et des seuils de décision ont été établis pour la dichotomisation des différents grades de stéatose.;
Finalement, le dernier objectif de la thèse consiste en une étude de reproductibilité de six paramètres basés sur la technologie SW (vitesse, atténuation, dispersion, module de Young, viscosité et module de cisaillement). Cette étude a été réalisée chez des volontaires sains et des patients atteints de NAFLD à partir de données acquises lors de deux visites distinctes. En conclusion, une méthode robuste de calcul du SWA du foie a été développée et validée pour fournir une méthode de diagnostic de la NAFLD.
For diagnosis and staging of liver fibrosis, liver stiffness is a quantitative biomarker estimated by elastography methods. Ultrasound shear wave (SW) elastography utilizes noninvasive medical ultrasound to assess the mechanical properties of the liver based on the monitoring of the SW propagation. SW speed (SWS) and SW attenuation (SWA) can provide an estimation of tissue viscoelasticity. Biological tissues are inherently viscoelastic in nature and a complex mathematical model is usually required to compute viscoelasticity in SW imaging. Accurate computation of attenuation is critical, especially for accurate loss modulus and viscosity estimation. Recent studies have made attempts to increase the precision of SWA estimation, but they still face some limitations.;
As a first objective of this thesis, a revisited frequency-shift method was developed to improve the estimates provided by the original implementation of the frequency-shift method Bernard et al 2017. In the new method, the assumption of a constant shape parameter of the gamma function describing the SW magnitude spectrum has been dropped for all lateral locations, allowing a better gamma fitting. Secondly, an adaptive random sample consensus algorithm (A-RANSAC) was implemented to estimate the slope of the varying rate parameter of the gamma distribution to improve the accuracy of the method. For the validation of these algorithmic changes, the proposed method was compared with three recent methods proposed to estimate SWA (frequency-shift, two-point frequency-shift and AMUSE methods) using simulation data or numerical phantoms. In addition, in vitro homogenous gel phantoms and in vivo animal (duck) liver data were processed.;
As a second objective, this thesis also aimed at improving the early diagnosis of nonalcoholic fatty liver disease (NAFLD), which is necessary to prevent its progression and decrease the overall mortality. For this purpose, the revisited frequency-shift method was tested on in vivo human livers. The new method's diagnosis performance was investigated with healthy and NAFLD human livers. To minimize sources of variability, an automated analysis method averaging measurements from several angles has been developed. The results of this method were compared to the magnetic resonance imaging proton density fat fraction (MRI-PDFF) and to liver biopsy. SWA imaging was used for grading steatosis and cut-off decision thresholds were established for dichotomization of different steatosis grades.;
As a third objective, this thesis is proposing a reproducibility study of six SW-based parameters (speed, attenuation, dispersion, Young’s modulus, viscosity and shear modulus). The assessment was performed in healthy volunteers and NAFLD patients using data acquired at two separate visits. In conclusion, a robust method for computing the liver’s SWA was developed and validated to provide a diagnostic method for NAFLD.
Vitiligo is a skin disorder with melanocyte destruction and an autoimmune basis. Given the importance of cytokines in autoimmunity, we aimed to find the cytokine profile of innate and adaptive ...immunity in vitiligo patients, and correlate them with clinical parameters. The serum levels of innate immunity interleukin(IL)-1α, IL-1β, IL-6, IL-8, IL-12, IL-15 and tumor necrosis factor (TNF)-α and T helper(Th)1 IL-2, interferon (IFN)-γ, TNF-β, Th2 (IL-4, IL-5, IL-10, IL-13) and Th17 (IL-17, IL-23) cytokines in 44 vitiligo patients were measured by multiplex cytokine assay and compared with 44 healthy subjects. All innate immunity (
p
< 0.04), Th1 (
p
< 0.01), Th2 (
p
< 0.05) and Th17 (
p
< 0.001) cytokines were higher in patients than controls. Total summation levels of innate immunity and adaptive immunity cytokines showed a remarkable up-regulation in the patients (
p
< 0.0001). The ratio of innate immunity to Th1 (
p
= 0.03), Th2 (
p
= 0.01) and Th17 (
p
= 0.03) cytokines was significantly higher in patients vs. controls. We found significant higher ratio of Th1 to Th2 cytokines and TNF-β elevated levels in patients with a family history of autoimmunity (
p
< 0.05). IL-4 and IL-13 (
p
< 0.04) levels were lower in patients with amelanotic hair. Increased IL-10 level was observed in patients with stable disease (
p
= 0.02).
In conclusion, the profile of cytokines in patients showed a dominant role of innate immunity pro-inflammatory cytokines in vitiligo, which suggests the potential of targeting these cytokines for vitiligo treatment. While a higher ratio of Th1/Th2 cytokines was observed in the patients, association of decreased Th2 cytokines with disease complications suggests a protective role for Th2 pathway.
Context
Understanding self‐regulated learning (SRL) is complicated due to the different measures used to identify the key SRL processes. There is a growing trend in applying event measures of SRL ...(microanalysis and trace) but aptitude measures (questionnaires) continue to be widely used in medical education. A major concern is whether aptitude measures are a valid approach to capture the dimensions of SRL processes. This study examined correlations between SRL microanalysis, SRL trace and the Motivated Strategies for Learning Questionnaire (MSLQ) and how these measures were associated with biomedical science performance.
Methods
An SRL microanalysis assessment interview was administered to 76 first‐year medical students individually when performing a biomedical science learning task. All written materials by students were collected for further trace analysis. Students completed an MSLQ 2 weeks before completing their biomedical science course. Correlation analyses were used to determine the correlations between the three SRL assessment measures. Bivariate and multiple analyses were conducted to compare students on different course or task performance using the three SRL assessment measures.
Results
Microanalytic metacognitive monitoring (κ = 0.30, P < .001) and causal attributions (κ = 0.17, P = .009) had statistically significant correlations with use of the SRL trace strategy. MSLQ self‐efficacy correlated with microanalytic self‐efficacy (r = .39, P = .001). Bivariate tests showed that microanalytic metacognitive monitoring, causal attributions and adaptive inferences, and SRL trace strategy use had significant associations with task performance (P < .05). Microanalytic self‐efficacy, metacognitive monitoring and causal attributions, SRL trace strategy use and MSLQ self‐efficacy had significant associations with course performance (P < .05). Measures of use of the SRL trace strategy and MSLQ subscales did not show significant associations with task and course outcomes in multiple analyses (P > .05).
Conclusions
Event measures, specifically SRL microanalysis, had greater associations with both task and course outcomes compared with the MSLQ measure. The SRL microanalysis is recommended for the assessment of SRL in biomedical science learning. However, to fully understand medical students’ SRL a multidimensional assessment approach that combines event and aptitude measures should be used.
Trying to measure engagement in self‐regulated learning? This paper stresses the value of prioritizing microanalysis given relationships with biomedical science learning outcomes.
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