Admittance measurement is a promising tool for evaluating the status of the middle ear in newborns. However, the newborn ear is anatomically very different from the adult one, and the acoustic input admittance is different than in adults. To aid in understanding the differences, a finite-element model of the newborn ear canal and middle ear was developed and its behaviour was studied for frequencies up to 2000 Hz. Material properties were taken from previous measurements and estimates. The simulation results were within the range of clinical admittance measurements made in newborns. Sensitivity analyses of the material properties show that in the canal model, the maximum admittance and the frequency at which that maximum admittance occurs are affected mainly by the stiffness parameter; in the middle-ear model, the damping is as important as the stiffness in influencing the maximum admittance magnitude but its effect on the corresponding frequency is negligible. Scaling up the geometries increases the admittance magnitude and shifts the resonances to lower frequencies. The results suggest that admittance measurements can provide more information about the condition of the middle ear when made at multiple frequencies around its resonance.
Recent studies have suggested that platelets have a crucial role in enhancing the survival of circulating tumor cells in the bloodstream and aggravating cancer metastasis. The main function of platelets is to bind to the sites of the damaged vessels to stop bleeding. However, in cancer patients, activated platelets adhere to circulating tumor cells and exacerbate metastatic spreading. Several hypotheses have been proposed about the platelet–cancer cell interactions, but the underlying mechanisms of these interactions are not completely understood yet. In this work, we quantitatively investigated the interactions between circulating tumor cells, red blood cells, platelets, plasma flow and microvessel walls via computational modelling at the cellular scale. Our highly detailed computational model allowed us to understand and quantitatively explain the role of platelets in deformation, adhesion and survival of tumor cells in their active arrest to the endothelium.
We present a finite-element model of the gerbil middle ear that, using a set of baseline parameters based primarily on a priori estimates from the literature, generates responses that are comparable with responses we measured in vivo using multi-point vibrometry and with those measured by other groups. We investigated the similarity of numerous features (umbo, pars-flaccida and pars-tensa displacement magnitudes, the resonance frequency and break-up frequency, etc.) in the experimental responses with corresponding ones in the model responses, as opposed to simply computing frequency-by-frequency differences between experimental and model responses. The umbo response of the model is within the range of variability seen in the experimental data in terms of the low-frequency (i.e., well below the middle-ear resonance) magnitude and phase, the main resonance frequency and magnitude, and the roll-off slope and irregularities in the response above the resonance frequency, but is somewhat high for frequencies above the resonance frequency. At low frequencies, the ossicular axis of rotation of the model appears to correspond to the anatomical axis but the behaviour is more complex at high frequencies (i.e., above the pars-tensa break-up). The behaviour of the pars tensa in the model is similar to what is observed experimentally in terms of magnitudes, phases, the break-up frequency of the spatial vibration pattern, and the bandwidths of the high-frequency response features. A sensitivity analysis showed that the parameters that have the strongest effects on the model results are the Young's modulus, thickness and density of the pars tensa; the Young's modulus of the stapedial annular ligament; and the Young's modulus and density of the malleus. Displacements of the tympanic membrane and manubrium and the lowfrequency displacement of the stapes did not show large changes when the material properties of the incus, stapes, incudomallear joint, incudostapedial joint, and posterior incudal ligament were changed by ±10 % from their values in the baseline parameter set.
The purpose of the present work is to investigate the spatial vibration pattern of the gerbil tympanic membrane (TM) as a function of frequency. In vivo vibration measurements were done at several locations on the pars flaccida and pars tensa, and along the manubrium, on surgically exposed gerbil TMs with closed middle ear cavities. A laser Doppler vibrometer was used to measure motions in response to audio frequency sine sweeps in the ear canal. Data are presented for two different pars flaccida conditions: naturally flat and retracted into the middle ear cavity. Resonance of the flat pars flaccida causes a minimum and a shallow maximum in the displacement magnitude of the manubrium and pars tensa at low frequencies. Compared with a flat pars flaccida, a retracted pars flaccida has much lower displacement magnitudes at low frequencies and does not affect the responses of the other points. All manubrial and pars tensa points show a broad resonance in the range of 1.6 to 2 kHz. Above this resonance, the displacement magnitudes of manubrial points, including the umbo, roll off with substantial irregularities. The manubrial points show an increasing displacement magnitude from the lateral process toward the umbo. Above 5 kHz, phase differences between points along the manubrium start to become more evident, which may indicate flexing of the tip of the manubrium or a change in the vibration mode of the malleus. At low frequencies, points on the posterior side of the pars tensa tend to show larger displacements than those on the anterior side. The simple low-frequency vibration pattern of the pars tensa becomes more complex at higher frequencies, with the breakup occurring at between 1.8 and 2.8 kHz. These observations will be important for the development and validation of middle ear finite-element models for the gerbil.
Cancer is a major cause of death worldwide and becomes particularly threatening once it begins to metastasize. During metastasis, the blood vessels serve as pathways for cancerous cell transportation and hence are crucial for understanding cancer growth. Existing medical imaging modalities can provide 3-D contrast images of the vascular tissues but with limited quality and detailedness. A much-needed tool for cancer research is thus one that can reconstruct vascular networks from low-quality clinical images. To this end, we developed a computational framework that takes 3-D medical images as input and reconstructs complete, patient-specific vascular network models using a mathematical optimization procedure. Our framework extracts major vessels from the images and uses the organ geometry to select vessel termination points. Then, it generates the remainder network based on physiological optimality principles. Using the framework, we obtained a set of network models with over 3000 terminal segments from a brain MRA scan. We analyzed the Strahler order, vessel radius, and branch length distributions of the models, which match with actual human data. We also performed fluid dynamics simulation inside the reconstructed vessels and showed that the pressure and shear stress distributions agree with existing in vivo measurements. The qualitative and quantitative agreements in vessel morphometry and hemodynamics demonstrate the effectiveness of the framework. Our method bridges the gap between image-based vessel models, accuracy of which is limited by the resolution of clinical images, and hypothetical models.
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