TGF-β and WNT signaling pathways in cardiac fibrosis: non-coding RNAs come into focus

Cardiac fibrosis describes the inappropriate proliferation of cardiac fibroblasts (CFs), leading to accumulation of extracellular matrix (ECM) proteins in the cardiac muscle, which is found in many pathophysiological heart conditions. A range of molecular components and cellular pathways, have been implicated in its pathogenesis. In this review, we focus on the TGF-β and WNT signaling pathways, and their mutual interaction, which have emerged as important factors involved in cardiac pathophysiology. The molecular and cellular processes involved in the initiation and progression of cardiac fibrosis are summarized. We focus on TGF-β and WNT signaling in cardiac fibrosis, ECM production, and myofibroblast transformation. Non-coding RNAs (ncRNAs) are one of the main players in the regulation of multiple pathways and cellular processes. MicroRNAs, long non-coding RNAs, and circular long non-coding RNAs can all interact with the TGF-β/WNT signaling axis to affect cardiac fibrosis. A better understanding of these processes may lead to new approaches for diagnosis and treatment of many cardiac conditions. Video Abstract

Finite element modeling of capacitive micromachined ultrasonic transducers

Transducers based on piezoelectric crystals dominate the biomedical ultrasonic imaging field. However, fabrication difficulties for piezoelectric transducers limit their usage for complex imaging modalities such as 2D imaging, high frequency imaging, and forward looking intravascular imaging. Capacitive micromachined ultrasonic transducers (CMUTs) have been proposed to overcome these limitations and they offer competitive advantages in terms of bandwidth and dynamic range. Further, the ease of fabrication enables manufacturing of complex array geometries. A CMUT transducer is composed of many electrostatically actuated membranes. Earlier analysis of these devices concentrated on an equivalent circuit approach, which assumed the motion of the membrane was approximated by a parallel plate capacitor. Finite element analysis is required for more accurate results. In this paper, we present the finite element model developed to evaluate the performance of the CMUTs. The model is composed of a membrane radiating into immersion medium. Electrostatic actuation is added on using electromechanical elements. Symmetry boundary conditions are imposed around the sidewalls of the finite element mesh, so that the model reflects the properties of a cell driven with the same phase as its neighboring membranes in an infinitely large array. Absorbing boundaries are implemented one wavelength away from the membrane to avoid reflections from the end of the finite element mesh. Using the model, we optimized the membrane radius, membrane thickness and gap height. Our optimized designed yielded a center frequency of 13 MHz with hundred percent bandwidth. A maximum output pressure of 20 kPascal per volt was obtained

Analytical calculation of collapse voltage of CMUT membrane

Because the collapse voltage determines the operating point of the capacitive micromachined ultrasonic transducer (CMUT), it is crucial to calculate and control this parameter. One approach uses parallel plate approximation, where a parallel plate motion models the average membrane displacement. This usually yields calculated collapse voltage 25 percent higher than the actual collapse voltage. More accurate calculation involves finite element method (FEM) analysis. However, depending on the required accuracy, the computation time may require many hours

Dynamic analysis of capacitive micromachined ultrasonic transducers

Electrostatic transducers are usually operated under a DC bias below their collapse voltage. The same scheme has been adopted for capacitive micromachined ultrasonic transducers (cMUTs). DC bias deflects the cMUT membranes toward the substrate, so that their centers are free to move during both receive and transmit operations. In this paper, we present time-domain, finite element calculations for cMUTs using LS-DYNA, a commercially available finite element package. In addition to this DC bias mode, other new cMUT operations (collapse and collapse-snapback) have recently been demonstrated. Because cMUT membranes make contact with the substrate in these new operations, modeling of these cMUTs should include contact analysis. Our model was a cMUT transducer consisting of many hexagonal membranes; because it was symmetrical, we modeled only one-sixth of a hexagonal cell loaded with a fluid medium. The finite element results for both conventional and collapse modes were compared to measurements made by an optical interferometer; a good match was observed. Thus, the model is useful for designing cMUTs that operate in regimes where membranes make contact with the substrate

Finite-element analysis of capacitive micromachined ultrasonic transducers

Abstract-Electrostatic transducers are usually operated under a DC bias below their collapse voltage. The same scheme has been adopted for capacitive micromachined ultrasonic transducers (cMUTs). DC bias deflects the cMUT membranes toward the substrate, so that their centers are free to move during both receive and transmit operations. In this paper, we present time-domain, finite element calculations for cMUTs using LS-DYNA, a commercially available finite element package. In addition to this DC bias mode, other new cMUT operations (collapse and collapse-snapback) have recently been demonstrated. Because cMUT membranes make contact with the substrate in these new operations, modeling of these cMUTs should include contact analysis. Our model was a cMUT transducer consisting of many hexagonal membranes; because it was symmetrical, we modeled only one-sixth of a hexagonal cell loaded with a fluid medium. The finite element results for both conventional and collapse modes were compared to measurements made by an optical interferometer; a good match was observed. Thus, the model is useful for designing cMUTs that operate in regimes where membranes make contact with the substrate