Healthy human skin Kelvin-Voigt fractional and spring-pot biomarkers reconstruction using torsional wave elastography.

This paper presents a novel method for reconstructing skin parameters using Probabilistic Inverse Problem (PIP) techniques and Torsional Wave Elastography (TWE) rheological modeling. A comprehensive examination was conducted to compare and analyze the theoretical, time-of-flight (TOF), and full-signal waveform (FSW) approaches. The objective was the identification of the most effective method for the estimation of mechanical parameters. Initially, the most appropriate rheological model for the simulation of skin tissue behavior was determined through the application and comparison of two models, spring pot (SP) and Kevin Voigt fractional derivative (KVFD). A numerical model was developed using the chosen rheological models. The collection of experimental data from 15 volunteers utilizing a TWE sensor was crucial for obtaining significant information for the reconstruction process. The study sample consisted of five male and ten female subjects ranging in age from 25 to 60 years. The procedure was performed on the ventral forearm region of the participants. The process of reconstructing skin tissue parameters was carried out using PIP techniques. The experimental findings were compared with the numerical results. The three methods considered (theoretical, TOF, FSW) have been used. The efficacy of TOF and FSW was then compared with theoretical method. The findings of the study demonstrate that the FSW and TOF techniques successfully reconstructed the parameters of the skin tissue in all of the models. The SP model's the skin tissue [Formula: see text] values ranged from 8 to 12 [Formula: see text], as indicated by the TOF reconstruction parameters. [Formula: see text] values found by the KVFD model ranged from 4.1 to 9.3 [Formula: see text]. The [Formula: see text] values generated by the KVFD model range between 0.61 and 96.86 kPa. However, FSW parameters reveal that skin tissue [Formula: see text] values for the SP model ranged from 7.8 to 12 [Formula: see text]. The KVFD model determined [Formula: see text] values between 6.3 and 9.5 [Formula: see text]. The KVFD model presents [Formula: see text] values ranging between 26.02 and 122.19 kPa. It is shown that the rheological model that best describes the nature of the skin is the SP model and its simplicity as it requires only two parameters, in contrast to the three parameters required by the KVFD model. Therefore, this work provides a valuable addition to the area of dermatology, with possible implications for clinical practice.

Nonlinear fourth-order elastic characterization of the cornea using torsional wave elastography.

Measuring the mechanical nonlinear properties of the cornea remains challenging due to the lack of consensus in the methodology and in the models that effectively predict its behaviour. This study proposed developing a procedure to reconstruct nonlinear fourth-order elastic properties of the cornea based on a mathematical model derived from the theory of Hamilton et al. and using the torsional wave elastography (TWE) technique. In order to validate its diagnostic capability of simulated pathological conditions, two different groups were studied, non-treated cornea samples (n=7), and ammonium hydroxide ([Formula: see text]) treated samples (n=7). All the samples were measured in-plane by a torsional wave device by increasing IOP from 5 to 25 mmHg with 5 mmHg steps. The results show a nonlinear variation of the shear wave speed with the IOP, with higher values for higher IOPs. Moreover, the shear wave speed values of the control group were higher than those of the treated group. The study also revealed significant differences between the control and treated groups for the Lamé parameter [Formula: see text] (25.9-6.52 kPa), third-order elastic constant A (215.09-44.85 kPa), and fourth-order elastic constant D (523.5-129.63 kPa), with p-values of 0.010, 0.024, and 0.032, respectively. These findings demonstrate that the proposed procedure can distinguish between healthy and damaged corneas, making it a promising technique for detecting diseases associated with IOP alteration, such as corneal burns, glaucoma, or ocular hypertension.

Optical micro-elastography with magnetic excitation for high frequency rheological characterization of soft media.

The propagation of shear waves in elastography at high frequency (>3 kHz) in viscoelastic media has not been extensively studied due to the high attenuation and technical limitations of current techniques. An optical micro-elastography (OME) technique using magnetic excitation for generating and tracking high frequency shear waves with enough spatial and temporal resolution was proposed. Ultrasonics shear waves (above 20 kHz) were generated and observed in polyacrylamide samples. A cutoff frequency, from where the waves no longer propagate, was observed to vary depending on the mechanical properties of the samples. The ability of the Kelvin-Voigt (KV) model to explain the high cutoff frequency was investigated. Two alternative measurement techniques, Dynamic Mechanical Analysis (DMA) and Shear Wave Elastography (SWE), were used to complete the whole frequency range of the velocity dispersion curve while avoid capturing guided waves in the low frequency range (<3 kHz). The combination of the three measurement techniques provided rheology information from quasi-static to ultrasonic frequency range. A key observation was that the full frequency range of the dispersion curve was necessary if one wanted to infer accurate physical parameters from the rheological model. By comparing the low frequency range with the high frequency range, the relative errors for the viscosity parameter could reach 60 % and they could be higher with higher dispersive behavior. The high cutoff frequency may be predicted in materials that follow a KV model over their entire measurable frequency range. The mechanical characterization of cell culture media could benefit from the proposed OME technique.

Low P-Selectin Glycoprotein Ligand-1 Expression in Neutrophils Associates with Disease Activity and Deregulated NET Formation in Systemic Lupus Erythematosus.

Systemic Lupus Erythematosus (SLE) is an autoimmune disease characterized by the generation of anti-DNA autoantibodies due to exposure of immune cells to excessive amounts of extracellular DNA. Lack of P-selectin in mice induces the development of a lupus-like syndrome and patients with cutaneous lupus have reduced P-selectin expression in skin vessels. Using flow cytometry we analyzed in healthy donors and patients the expression of P-selectin Glycoprotein Ligand-1 (PSGL-1) in circulating neutrophils and the implication of PSGL-1/P-selectin interaction in neutrophil extracellular traps (NETs) generation. We found a statistical significance that neutrophils from active SLE patients have a reduced expression of PSGL-1 and low levels of PSGL-1 in neutrophils from SLE patients associated with the presence of anti-dsDNA antibodies, clinical lung involvement, Raynaud's phenomenon, and positive lupus anticoagulant. PSGL-1 is present along the DNA in the NET. In healthy donors, neutrophil interaction with immobilized P-selectin triggers Syk activation, increases the NETs percentage and reduces the amount of DNA extruded in the NETs. In active SLE patients, neutrophil interaction with P-selectin does not activate Syk or reduce the amount of DNA extruded in the NETs, that might contribute to increase the extracellular level of DNA and hence, to disease pathogenesis.

Damage Detection Using Ultrasonic Techniques in Concrete-Filled Steel Tubes (CFSTs) Columns.

Concrete-filled steel tubes (CFSTs) are structural elements that, as a consequence of an incorrect elaboration, can exhibit internal defects that cannot be visualized, being usually air voids. In this work, the detection of internal damage in CFST samples elaborated with a percentage of contained air voids in concrete, was carried out by performing a complete ultrasound scan using an immersion tank. The analysis of the ultrasound signals shows the differences presented in the amplitude of the fundamental frequency of the signal, and in the Broadband Ultrasound Attenuation (BUA), in comparison with a sample without defects. The main contribution of this study is the application of the BUA technique in CFST samples for the location of air voids. The results present a linear relationship between BUA averages over the window of the CFSTs and the percentage of air voids contained (Pearson's correlation coefficient r = 0.9873), the higher percentage of air voids, the higher values of BUA. The BUA algorithm could be applied effectively to distinguish areas with defects inside the CFSTs. Similar to the BUA results, the analysis in the frequency domain using the FFT and the STFT was sensitive in the detection of internal damage (Pearson's correlation coefficient r = -0.9799, and r = -0.9672, respectively). The results establish an improvement in the evaluation of CFST elements for the detection of internal defects.

Targeted nanotherapy with everolimus reduces inflammation and fibrosis in scleroderma-related interstitial lung disease developed by PSGL-1 deficient mice.

BACKGROUND AND PURPOSE: Interstitial lung disease (ILD) is the main cause of mortality in systemic sclerosis (SSc), and current therapies available are of low efficacy or high toxicity. Thus, the identification of innovative less toxic and high efficacy therapeutic approaches to ILD treatment is an urgent need. The interaction of P-selectin glycoprotein ligand-1 (PSGL-1) with P-selectin initiates leukocyte extravasation and deletion of the corresponding gene (Selplg) induces a SSc-like syndrome with high incidence of ILD in aged mice. EXPERIMENTAL APPROACH: Aged PSGL-1 KO (Selplg-/- ) mice were used to assess the therapeutic effects of nanotherapy with everolimus, included in liposomes decorated with high MW hyaluronic acid (LipHA+Ev) and administered intratracheally to specifically target CD44-expressing lung cells. KEY RESULTS: PSGL-1 KO mice had increased numbers of CD45+ and CD45- cells, including alveolar and interstitial macrophages, eosinophils, granulocytes and NK cells, and myofibroblasts in bronchoalveolar lavage (BAL). CD45+ and CD45- cells expressing pro-inflammatory and pro-fibrotic cytokines were also increased. Lungs from PSGL-1 KO mice showed increased immune cell infiltration and apoptosis and exacerbated interstitial and peribronchial fibrosis. Targeted nanotherapy with LipHA+Ev decreased the myofibroblasts in BAL, cells producing proinflammatory and profibrotic cytokines, and the degree of lung inflammation at histology. LipHA+Ev treatment also decreased the severity of peribronchial and interstitial lung fibrosis, from moderate to mild levels. CONCLUSIONS AND IMPLICATIONS: In PSGL-1 KO mice, targeted nanotherapy with LipHA+Ev was an effective treatment for SSc-ILD, reducing the number of inflammatory and fibrotic cells in BAL and reducing inflammation and fibrosis in lungs.

Experimental evidence of shear waves in fractional viscoelastic rheological models.

Fractional viscoelastic rheological models, such as the Kelvin Voigt Fractional Derivative model, have been proposed in the literature for modelling shear wave propagation in soft tissue. In this article, our previously developed wave propagation model for transluminal propagation based on a Kelvin Voigt Fractional Derivative wave equation is experimentally validated. The transluminal procedure uses the transmission and detection of shear waves through the luminal wall. The model was compared against high-speed camera observations in translucent elastography phantoms with similar viscoelastic properties to prostate tissue. An ad hoc cross-correlation procedure was used to reconstruct the angular displacement from the high-speed camera observations. Rheometry and shear wave elastography were used for characterising the shear wave velocity dispersion curve for the phantoms. Fractional viscoelastic properties were derived after fitting the dispersion curve to its analytical expression. Propagation features and amplitude spectra from simulations and high-speed camera observations were compared. The obtained results indicate that the model replicates the experimental observations with acceptable accuracy. The model presented here provides a useful tool to model transluminal procedures based on wave propagation and its interaction with the mechanical properties of the tissue outside the lumen.

Torsional wave elastography to assess the mechanical properties of the cornea.

Corneal mechanical changes are believed to occur before any visible structural alterations observed during routine clinical evaluation. This study proposed developing an elastography technique based on torsional waves (TWE) adapted to the specificities of the cornea. By measuring the displacements in the propagation plane perpendicular to the axis of the emitter, the effect of guided waves in plate-like media was proven negligible. Ex vivo experiments were carried out on porcine corneal samples considering a group of control and one group of alkali burn treatment ([Formula: see text]OH) that modified the mechanical properties. Phase speed was recovered as a function of intraocular pressure (IOP), and a Kelvin-Voigt rheological model was fitted to the dispersion curves to estimate viscoelastic parameters. A comparison with uniaxial tensile testing with thin-walled assumptions was also performed. Both shear elasticity and viscosity correlated positively with IOP, being the elasticity lower and the viscosity higher for the treated group. The viscoelastic parameters ranged from 21.33 to 63.17 kPa, and from 2.82 to 5.30 Pa s, for shear elasticity and viscosity, respectively. As far as the authors know, no other investigations have studied this mechanical plane under low strain ratios, typical of dynamic elastography in corneal tissue. TWE reflected mechanical properties changes after treatment, showing a high potential for clinical diagnosis due to its rapid performance time and paving the way for future in vivo studies.

miR-320c Regulates SERPINA1 Expression and Is Induced in Patients With Pulmonary Disease / El miR-320c regula la expresión del gen SERPINA1 y se induce en pacientes con enfermedad pulmonar

Introduction: Alpha-1 antitrypsin deficiency (AATD) is a genetic condition resulting in lung and liver disease with a great clinical variability. MicroRNAs have been identified as disease modifiers; therefore miRNA deregulation could play an important role in disease heterogeneity. Members of miR-320 family are involved in regulating of multiple processes including inflammation, and have potential specific binding sites in the 3′UTR region of SERPINA1 gene. In this study we explore the involvement of miR-320c, a member of this family, in this disease. Methods: Firstly in vitro studies were carried out to demonstrate regulation of SERPINA1 gene by miR-320. Furthermore, the expression of miR-320c was analyzed in the blood of 98 individuals with different AAT serum levels by using quantitative PCR and expression was correlated to clinical parameters of the patients. Finally, HL60 cells were used to analyze induction of miR-320c in inflammatory conditions. Results: Overexpression of miR-320 members in human HepG2 cells led to inhibition of SERPINA1 expression. Analysis of miR-320c expression in patient's samples revealed significantly increased expression of miR-320c in individuals with pulmonary disease. Additionally, HL60 cells treated with the pro-inflammatory factor lipopolysaccharide (LPS) showed increase in miR-320c expression, suggesting that miR-320c responds to inflammation. Conclusion: Our findings demonstrate that miR-320c inhibits SERPINA1 expression in a hepatic cell line and its levels in blood are associated with lung disease in a cohort of patients with different AAT serum levels. These results suggest that miR-320c can play a role in AAT regulation and could be a biomarker of inflammatory processes in pulmonary diseases. (AU)

Introducción: La deficiencia de alfa-1 antitripsina (DAAT) es una condición genética que produce enfermedad pulmonar y hepática con una gran variabilidad clínica. Los microARN se han identificado como modificadores de la gravedad de algunas enfermedades y su desregulación podría desempeñar un papel en la heterogeneidad de esta enfermedad. Los miembros de la familia miR-320 regulan múltiples procesos, incluyendo la inflamación, y tienen lugares de unión en la región 3’UTR del gen SERPINA1. En este estudio exploramos la implicación del miR-320c, un miembro de esta familia, en la DAAT. Métodos: Primero se realizaron estudios in vitro para demostrar la regulación del gen SERPINA1 por parte del miR-320. Además, se analizó la expresión de miR-320c en la sangre de 98 individuos con diferentes niveles de AAT mediante PCR cuantitativa y se correlacionó con los parámetros clínicos. Por último, se utilizaron células HL60 para analizar la inducción de miR-320c en condiciones inflamatorias. Resultados: La sobreexpresión del miR-320 en células HepG2 inhibía la expresión del gen SERPINA1. El análisis de expresión de miR-320c en los pacientes reveló una expresión significativamente aumentada en los casos con enfermedad pulmonar. Por otro lado, las células HL60 tratadas con LPS como factor proinflamatorio mostraron un aumento de expresión de miR-320c, lo que sugiere que este miARN responde a procesos inflamatorios. Conclusión: Nuestros resultados demuestran que el miR-320c inhibe la expresión de SERPINA1 en células hepáticas y que sus niveles en sangre están asociados con la presencia de enfermedad pulmonar en pacientes con diferentes niveles de AAT. Esto sugiere que el miR-320c desempeña un papel en la regulación de los niveles de AAT y podría ser un biomarcador de inflamación en enfermedades pulmonares. (AU)

IGF-1 facilitates extinction of conditioned fear.

Insulin-like growth factor-1 (IGF-1) plays a key role in synaptic plasticity, spatial learning, and anxiety-like behavioral processes. While IGF-1 regulates neuronal firing and synaptic transmission in many areas of the central nervous system, its signaling and consequences on excitability, synaptic plasticity, and animal behavior dependent on the prefrontal cortex remain unexplored. Here, we show that IGF-1 induces a long-lasting depression of the medium and slow post-spike afterhyperpolarization (mAHP and sAHP), increasing the excitability of layer 5 pyramidal neurons of the rat infralimbic cortex. Besides, IGF-1 mediates a presynaptic long-term depression of both inhibitory and excitatory synaptic transmission in these neurons. The net effect of this IGF-1-mediated synaptic plasticity is a long-term potentiation of the postsynaptic potentials. Moreover, we demonstrate that IGF-1 favors the fear extinction memory. These results show novel functional consequences of IGF-1 signaling, revealing IGF-1 as a key element in the control of the fear extinction memory.

Experimental Evidence of Generation and Reception by a Transluminal Axisymmetric Shear Wave Elastography Prototype.

Experimental evidence on testing a non-ultrasonic-based probe for a new approach in transluminal elastography was presented. The proposed modality generated shear waves by inducing oscillatory rotation on the lumen wall. Detection of the propagated waves was achieved at a set of receivers in mechanical contact with the lumen wall. The excitation element of the probe was an electromagnetic rotational actuator whilst the sensing element was comprised by a uniform anglewise arrangement of four piezoelectric receivers. The prototype was tested in two soft-tissue-mimicking phantoms that contained lumenlike conduits and stiffer inclusions. The shear wave speed of the different components of the phantoms was characterized using shear wave elastography. These values were used to estimate the time-of-flight of the expected reflections. Ultrafast ultrasound imaging, based on Loupas' algorithm, was used to estimate the displacement field in transversal planes to the lumenlike conduit and to compare against the readouts from the transluminal transmission-reception tests. Experimental observations between ultrafast imaging and the transluminal probe were in good agreement, and reflections due to the stiffer inclusions were detected by the transluminal probe. The obtained experimental evidence provided proof-of-concept for the transluminal elastography probe and encouraged further exploration of clinical applications.

miR-320c Regulates SERPINA1 Expression and Is Induced in Patients With Pulmonary Disease.

INTRODUCTION: Alpha-1 antitrypsin deficiency (AATD) is a genetic condition resulting in lung and liver disease with a great clinical variability. MicroRNAs have been identified as disease modifiers; therefore miRNA deregulation could play an important role in disease heterogeneity. Members of miR-320 family are involved in regulating of multiple processes including inflammation, and have potential specific binding sites in the 3'UTR region of SERPINA1 gene. In this study we explore the involvement of miR-320c, a member of this family, in this disease. METHODS: Firstly in vitro studies were carried out to demonstrate regulation of SERPINA1 gene by miR-320. Furthermore, the expression of miR-320c was analyzed in the blood of 98 individuals with different AAT serum levels by using quantitative PCR and expression was correlated to clinical parameters of the patients. Finally, HL60 cells were used to analyze induction of miR-320c in inflammatory conditions. RESULTS: Overexpression of miR-320 members in human HepG2 cells led to inhibition of SERPINA1 expression. Analysis of miR-320c expression in patient's samples revealed significantly increased expression of miR-320c in individuals with pulmonary disease. Additionally, HL60 cells treated with the pro-inflammatory factor lipopolysaccharide (LPS) showed increase in miR-320c expression, suggesting that miR-320c responds to inflammation. CONCLUSION: Our findings demonstrate that miR-320c inhibits SERPINA1 expression in a hepatic cell line and its levels in blood are associated with lung disease in a cohort of patients with different AAT serum levels. These results suggest that miR-320c can play a role in AAT regulation and could be a biomarker of inflammatory processes in pulmonary diseases.

Relevance of PSGL-1 Expression in B Cell Development and Activation.

PSGL-1 is expressed in all plasma cells, but only in a small percentage of circulating B cells. Patients with systemic sclerosis (SSc) show reduced expression of PSGL-1 in B cells and increased prevalence of pulmonary arterial hypertension. PSGL-1 deficiency leads to a SSc-like syndrome and SSc-associated pulmonary hypertension in female mice. In this work, the expression of PSGL-1 was assessed during murine B cell development in the bone marrow and in several peripheral and spleen B cell subsets. The impact of PSGL-1 absence on B cell biology was also evaluated. Interestingly, the percentage of PSGL-1 expressing cells and PSGL-1 expression levels decreased in the transition from common lymphoid progenitors to immature B cells. PSGL-1-/- mice showed reduced frequencies of peripheral B cells and reduced B cell lineage-committed precursors in the bone marrow. In the spleen of WT mice, the highest percentages of PSGL-1+ populations were shown by Breg (90%), B1a (34.7%), and B1b (19.1%), while only 2.5-8% of B2 cells expressed PSGL-1; however, within B2 cells, the class-switched subsets showed the highest percentages of PSGL-1+ cells. Interestingly, PSGL-1-/- mice had increased IgG+ and IgD+ subsets and decreased IgA+ population. Of note, the percentage of PSGL-1+ cells was increased in all the B cell subclasses studied in peritoneal fluid. Furthermore, PSGL-1 engagement during in vitro activation with anti-IgM and anti-CD40 antibodies of human peripheral B cells, blocked IL-10 expression by activated human B cells. Remarkably, PSGL-1 expression in circulating plasma cells was reduced in pulmonary arterial hypertension patients. In summary, although the expression of PSGL-1 in mature B cells is low, the lack of PSGL-1 compromises normal B cell development and it may also play a role in the maturation and activation of peripheral naïve B cells.

Hyperelastic Ex Vivo Cervical Tissue Mechanical Characterization.

This paper presents the results of the comparison between a proposed Fourth Order Elastic Constants (FOECs) nonlinear model defined in the sense of Landau's theory, and the two most contrasted hyperelastic models in the literature, Mooney-Rivlin, and Ogden models. A mechanical testing protocol is developed to investigate the large-strain response of ex vivo cervical tissue samples in uniaxial tension in its two principal anatomical locations, the epithelial and connective layers. The final aim of this work is to compare the reconstructed shear modulus of the epithelial and connective layers of cervical tissue. According to the obtained results, the nonlinear parameter A from the proposed FOEC model could be an important biomarker in cervical tissue diagnosis. In addition, the calculated shear modulus depended on the anatomical location of the cervical tissue (µepithelial = 1.29 ± 0.15 MPa, and µconnective = 3.60 ± 0.63 MPa).

miR-320c Regulates SERPINA1 Expression and Is Induced in Patients With Pulmonary Disease.

INTRODUCTION: Alpha-1 antitrypsin deficiency (AATD) is a genetic condition resulting in lung and liver disease with a great clinical variability. MicroRNAs have been identified as disease modifiers; therefore miRNA deregulation could play an important role in disease heterogeneity. Members of miR-320 family are involved in regulating of multiple processes including inflammation, and have potential specific binding sites in the 3'UTR region of SERPINA1 gene. In this study we explore the involvement of miR-320c, a member of this family, in this disease. METHODS: Firstly in vitro studies were carried out to demonstrate regulation of SERPINA1 gene by miR-320. Furthermore, the expression of miR-320c was analyzed in the blood of 98 individuals with different AAT serum levels by using quantitative PCR and expression was correlated to clinical parameters of the patients. Finally, HL60 cells were used to analyze induction of miR-320c in inflammatory conditions. RESULTS: Overexpression of miR-320 members in human HepG2 cells led to inhibition of SERPINA1 expression. Analysis of miR-320c expression in patient's samples revealed significantly increased expression of miR-320c in individuals with pulmonary disease. Additionally, HL60 cells treated with the pro-inflammatory factor lipopolysaccharide (LPS) showed increase in miR-320c expression, suggesting that miR-320c responds to inflammation. CONCLUSION: Our findings demonstrate that miR-320c inhibits SERPINA1 expression in a hepatic cell line and its levels in blood are associated with lung disease in a cohort of patients with different AAT serum levels. These results suggest that miR-320c can play a role in AAT regulation and could be a biomarker of inflammatory processes in pulmonary diseases.

Why Are Viscosity and Nonlinearity Bound to Make an Impact in Clinical Elastographic Diagnosis?

The adoption of multiscale approaches by the biomechanical community has caused a major improvement in quality in the mechanical characterization of soft tissues. The recent developments in elastography techniques are enabling in vivo and non-invasive quantification of tissues' mechanical properties. Elastic changes in a tissue are associated with a broad spectrum of pathologies, which stems from the tissue microstructure, histology and biochemistry. This knowledge is combined with research evidence to provide a powerful diagnostic range of highly prevalent pathologies, from birth and labor disorders (prematurity, induction failures, etc.), to solid tumors (e.g., prostate, cervix, breast, melanoma) and liver fibrosis, just to name a few. This review aims to elucidate the potential of viscous and nonlinear elastic parameters as conceivable diagnostic mechanical biomarkers. First, by providing an insight into the classic role of soft tissue microstructure in linear elasticity; secondly, by understanding how viscosity and nonlinearity could enhance the current diagnosis in elastography; and finally, by compounding preliminary investigations of those elastography parameters within different technologies. In conclusion, evidence of the diagnostic capability of elastic parameters beyond linear stiffness is gaining momentum as a result of the technological and imaging developments in the field of biomechanics.

Viscoelastic Biomarkers of Ex Vivo Liver Samples via Torsional Wave Elastography.

The clinical ultrasound community demands mechanisms to obtain the viscoelastic biomarkers of soft tissue in order to quantify the tissue condition and to be able to track its consistency. Torsional Wave Elastography (TWE) is an emerging technique proposed for interrogating soft tissue mechanical viscoelastic constants. Torsional waves are a particular configuration of shear waves, which propagate asymmetrically in-depth and are radially transmitted by a disc and received by a ring. This configuration is shown to be particularly efficient in minimizing spurious p-waves components and is sensitive to mechanical constants, especially in cylinder-shaped organs. The objective of this work was to validate (TWE) technique against Shear Wave Elasticity Imaging (SWEI) technique through the determination of shear wave velocity, shear moduli, and viscosity of ex vivo chicken liver samples and tissue mimicking hydrogel phantoms. The results of shear moduli for ex vivo liver tissue vary 1.69-4.0kPa using TWE technique and 1.32-4.48kPa using SWEI technique for a range of frequencies from 200 to 800Hz. Kelvin-Voigt viscoelastic parameters reported values of µ = 1.51kPa and η = 0.54Pa·s using TWE and µ = 1.02kPa and η = 0.63Pa·s using SWEI. Preliminary results show that the proposed technique successfully allows reconstructing shear wave velocity, shear moduli, and viscosity mechanical biomarkers from the propagated torsional wave, establishing a proof of principle and warranting further studies.

Spontaneous Pulmonary Hypertension Associated With Systemic Sclerosis in P-Selectin Glycoprotein Ligand 1-Deficient Mice.

OBJECTIVE: Pulmonary arterial hypertension (PAH), one of the major complications of systemic sclerosis (SSc), is a rare disease with unknown etiopathogenesis and noncurative treatments. As mice deficient in P-selectin glycoprotein ligand 1 (PSGL-1) develop a spontaneous SSc-like syndrome, we undertook this study to analyze whether they develop PAH and to examine the molecular mechanisms involved. METHODS: Doppler echocardiography was used to estimate pulmonary pressure, immunohistochemistry was used to assess vascular remodeling, and myography of dissected pulmonary artery rings was used to analyze vascular reactivity. Angiotensin II (Ang II) levels were quantified by enzyme-linked immunosorbent assay, and Western blotting was used to measure Ang II type 1 receptor (AT1 R), AT2 R, endothelial cell nitric oxide synthase (eNOS), and phosphorylated eNOS expression in lung lysates. Flow cytometry allowed us to determine cytokine production by immune cells and NO production by endothelial cells. In all cases, there were 4-8 mice per experimental group. RESULTS: PSGL-1-/- mice showed lung vessel wall remodeling and a reduced mean ± SD expression of pulmonary AT2 R (expression ratio [relative to ß-actin] in female mice age >18 months: wild-type mice 0.799 ± 0.508 versus knockout mice 0.346 ± 0.229). With aging, female PSGL-1-/- mice had impaired up-regulation of estrogen receptor α (ERα) and developed lung vascular endothelial dysfunction coinciding with an increase in mean ± SEM pulmonary Ang II levels (wild-type 48.70 ± 5.13 pg/gm lung tissue versus knockout 78.02 ± 28.09 pg/gm lung tissue) and a decrease in eNOS phosphorylation, leading to reduced endothelial NO production. These events led to a reduction in the pulmonary artery acceleration time:ejection time ratio in 33% of aged female PSGL-1-/- mice, indicating pulmonary hypertension. Importantly, we found expanded populations of interferon-γ-producing PSGL-1-/- T cells and B cells and a reduced presence of regulatory T cells. CONCLUSION: The absence of PSGL-1 induces a reduction in Treg cells, NO production, and ERα expression and causes an increase in Ang II in the lungs of female mice, favoring the development of PAH.

In Vivo Measurement of Cervical Elasticity on Pregnant Women by Torsional Wave Technique: A Preliminary Study.

A torsional wave (TW) sensor prototype was employed to quantify stiffness of the cervix in pregnant women. A cross-sectional study in a total of 18 women between 16 weeks and 35 weeks + 5 days of gestation was performed. The potential of TW technique to assess cervical ripening was evaluated by the measurement of stiffness related to gestational age and cervical length. Statistically significant correlations were found between cervical stiffness and gestational age ( R 2 = 0.370 , p = 0.0074 , using 1 kHz waves and R 2 = 0.445 , p = 0.0250 , using 1.5 kHz waves). A uniform decrease in stiffness of the cervical tissue was confirmed to happen during the complete gestation. There was no significant correlation between stiffness and cervical length. A stronger association between gestational age and cervical stiffness was found compared to gestational age and cervical length correlation. As a conclusion, TW technique is a feasible approach to objectively quantify the decrease of cervical stiffness related to gestational age. Further research is required to evaluate the application of TW technique in obstetric evaluations, such as prediction of preterm delivery and labor induction failure.

Kelvin-Voigt Parameters Reconstruction of Cervical Tissue-Mimicking Phantoms Using Torsional Wave Elastography.

The reconstruction of viscous properties of soft tissues, and more specifically, of cervical tissue is a challenging problem. In this paper, a new method is proposed to reconstruct the viscoelastic parameters of cervical tissue-mimicking phantoms by a Torsional Wave Elastography (TWE) technique. The reconstruction method, based on a Probabilistic Inverse Problem (PIP) approach, is presented and experimentally validated against Shear Wave Elastography (SWE). The anatomy of the cervical tissue has been mimicked by means of a two-layer gelatine phantom that simulates the epithelial and connective layers. Five ad hoc oil-in-gelatine phantoms were fabricated at different proportion to test the new reconstruction technique. The PIP approach was used for reconstructing the Kelvin-Voigt (KV) viscoelastic parameters by comparing the measurements obtained from the TWE technique with the synthetic signals from a Finite Difference Time Domain (FDTD) KV wave propagation model. Additionally, SWE tests were realized in order to characterize the viscoelastic properties of each batch of gelatine. Finally, validation was carried out by comparing the KV parameters inferred from the PIP with those reconstructed from the shear wave dispersion curve obtained from the SWE measurements. In order to test the degree of agreement between both techniques, a Student's T-test and a Pearson's correlation study were performed. The results indicate that the proposed method is able to reconstruct the KV viscoelastic properties of the cervical tissue, for both the epithelial and connective layers, as well as the thickness of the first layer with acceptable accuracy.