An integrated vertex model of the mesoderm invagination during the embryonic development of Drosophila.

The mesoderm invagination of the Drosophila embryo is known as an archetypal morphogenic process. To explore the roles of the active cellular forces and the regulation of these forces, we developed an integrated vertex model that combines the regulation of morphogen expression with cell movements and tissue mechanics. Our results suggest that a successful furrow formation requires an apical tension gradient, decreased basal tension, and increased lateral tension, which corresponds to apical constriction, basal expansion, and apicobasal shortening respectively. Our model also considers the mechanical feedback which leads to an ectopic twist expression with external compression as observed in experiments. Our model predicts that ectopic invagination could happen if an external compressive gradient is applied.

[Study on the difference of high frequency dielectric properties of biological tissues measured by air and packed coaxial probe].

In this paper, the differences between air probe and filled probe for measuring high-frequency dielectric properties of biological tissues are investigated based on the equivalent circuit model to provide a reference for the methodology of high-frequency measurement of biological tissue dielectric properties. Two types of probes were used to measure different concentrations of NaCl solution in the frequency band of 100 MHz-2 GHz. The results showed that the accuracy and reliability of the calculated results of the air probe were lower than that of the filled probe, especially the dielectric coefficient of the measured material, and the higher the concentration of NaCl solution, the higher the error. By laminating the probe terminal, liquid intrusion could be prevented, to a certain extent, to improve the accuracy of measurement. However, as the frequency decreased, the influence of the film on the measurement increased and the measurement accuracy decreased. The results of the study show that the air probe, despite its simple dimensional design and easy calibration, differs from the conventional equivalent circuit model in actual measurements, and the model needs to be re-corrected for actual use. The filled probe matches the equivalent circuit model better, and therefore has better measurement accuracy and reliability.

High-efficiency mechanically assisted alkaline extraction of nanoparticles from biological tissues for spICP-MS analysis.

The widespread use and increased exposure of nanoparticles call for technology to quantify their concentration and size distribution in biological matrices. As ex situ evaluation, facile extraction with high fidelity and efficiency is critical. In this work, single particle inductively coupled plasma mass spectrometry (spICP-MS) was used for nanoparticle number and distribution analysis, where a facile and highly efficient mechanically assisted alkaline digestion has been developed to extract nanoparticles at low alkali concentration. The optimization was performed using chicken tissues in vitro mixed with 30 nm gold nanoparticles, mixture of 30 nm and 60 nm gold nanoparticles, and 45 nm silver nanoparticles, respectively, which is, then, mechanically ground to form tissue homogenate and 2% TMAH is added. The nanoparticles are extracted with a recovery of more than 94% for all the spiked nanoparticle tissue samples. The extraction method has also been attempted to be applied to extract single-sized gold nanoparticles from various organs of mice mixed in vivo with the nanoparticles through intravenous injection, and led to consistent results with acid digestion. Mice injected intravenously with double-sized gold nanoparticle mixture were also studied, further showing that gold nanoparticles of 30 nm and 60 nm have no significant difference in their biodistribution in the same organ. To the best of our knowledge, this is the first attempt for multiple nanoparticles being extracted simultaneously and measured quantitatively from various organs, such as the heart, liver, spleen, lungs, and kidneys. We believe this method is beneficial to the safety assessment and toxicokinetics studies for nanoparticles in tissues.

Thermophysical and mechanical properties of biological tissues as a function of temperature: a systematic literature review.

BACKGROUND: Detailed information on the temperature dependence of tissue thermophysical and mechanical properties is pivotal for the optimal implementation of mathematical models and simulation-based tools for the pre-planning of thermal ablation therapies. These models require in-depth knowledge of the temperature sensitivity of these properties and other influential terms (e.g., blood perfusion and metabolic heat) to maximize the treatment prediction outcome. METHODOLOGY: A systematic literature review of experimental trials investigating thermophysical and mechanical properties of biological media, as well as blood perfusion and metabolic heat, as a function of temperature in hyperthermic and ablative thermal range, was conducted up to June 2021. RESULTS: A total of 61 articles was selected, thus enabling a comprehensive overview of the temperature dependence of thermophysical properties (i.e. thermal conductivity, specific heat, volumetric heat capacity, density, thermal diffusivity), and mechanical properties (shear, elastic, storage, loss and complex moduli, loss factor, stiffness) along with the principal measurement techniques. The reviewed studies considered different tissues, e.g., liver, fat, cartilage, brain, myocardium, muscle, bone, skin, pancreas tissues, and also some tumorous tissues. CONCLUSIONS: The thermophysical properties of soft tissues appear rather constant until 90 °C, with slight differences ascribable to tissues characteristics and measurement methods. Conversely, the information on mechanical properties is heterogeneous because most of the articles investigated different types of properties in different biological tissues. Furthermore, most of the experiments were conducted ex vivo; only a small percentage concerned in vivo studies. Limited recent information about the temperature dependence of metabolic heat and blood perfusion was observed.

Young's moduli of subcutaneous tissues and muscles under different loads at the gluteal region calculated using ultrasonography.

[Purpose] Young's modulus distributions for subcutaneous and muscle tissues in a large sample of healthy individuals, based on ultrasonography and compression testing, remains uninvestigated till date. This study aimed to separately estimate the hardness of subcutaneous tissues and muscles in the human gluteal region under a range of loads in terms of mean Young's moduli and associated distributions. [Participants and Methods] Data of 21 males aged 20-22 years were acquired using synchronous compression testing and ultrasonography. Stress-strain curves comprised the loads applied (stress) were plotted against ultrasonographic changes in subcutaneous/muscle tissue thickness (strain). Young's moduli were calculated as slopes of approximation curves fitted to highly linear regions of the stress-strain curves. [Results] Young's moduli (mean ± standard deviation) for gluteal subcutaneous and muscle tissues were estimated as: 26.1 ± 19.0 kPa, 1-N load; 2,199.1 ± 1,354.8 kPa, 30-N load; and 62.2 ± 10.3 kPa, 5-N load; 440.4 ± 80.0 kPa, 30-N load, respectively. No correlation between any pair of these measures reached statistical significance. [Conclusion] Young's moduli were successfully measured for subcutaneous and muscle tissues in a large participant sample using ultrasonography and compression testing. Our results may serve as reference data when assessing tissue hardness by palpation.

Thermoelastic behavior of skin tissue induced by laser irradiation based on the generalized dual-phase lag model.

This paper analyzes the thermoelastic responses of skin tissue during laser irradiation based on a generalized dual-phase-lag (DPL) model. The method of separation of variables is utilized to obtain the analytical solutions for thermal and mechanical responses. The influences of some crucial parameters on temperature, displacement and stress evolutions are discussed, including the phase lag of heat flux, the phase lag of temperature gradient and the phase lag of laser pulse, the coupling factor between tissue and blood, the porosity of tissue, the equivalent diameter of tissue and the diameter of blood vessels. The generalized DPL bio-heat transfer model predicts different results from those by the classical DPL model and Pennes model. The equivalent diameter of tissue affects the coupling factor between tissue and blood, while the diameter of blood vessels mainly affects the porosity of tissue.

The Ring-Pull Assay for Mechanical Properties of Fibrous Soft Tissues - An Analysis of the Uniaxial Approximation and a Correction for Nonlinear Thick-Walled Tissues.

BACKGROUND: The ring-pull test, where a ring of tissue is hooked via two pins and stretched, is a popular biomechanical test, especially for small arteries. Although convenient and reliable, the ring test produces inhomogeneous strain, making determination of material parameters non-trivial. OBJECTIVE: To determine correction factors between ring-pull-estimated and true tissue properties. METHODS: A finite-element model of ring pulling was constructed for a sample with nonlinear, anisotropic mechanical behavior typical of arteries. The pin force and sample cross-section were used to compute an apparent modulus at small and large strain, which were compared to the specified properties. The resulting corrections were validated with experiments on porcine and ovine arteries. The correction was further applied to experiments on mouse aortic rings to determine material and failure properties. RESULTS: Calculating strain based on centerline stretch rather than inner-wall or outer-wall stretch afforded better estimation of tissue properties. Additional correction factors were developed based on ring wall thickness H, centerline ring radius R c , and pin radius a. The corrected estimates for tissue properties were in good agreement with uniaxial stretch experiments. CONCLUSIONS: The computed corrections improved estimation of tissue material properties for both the small-strain (toe) modulus and the large-strain (lockout) modulus. When measuring tensile strength, one should minimize H/a to ensure that peak stress occurs at the sample midplane rather than near the pin. In this scenario, tensile strength can be estimated accurately by using inner-wall stretch at the midplane and the corrected properties.

[Experimental study on temperature dependence of dielectric properties of biological tissues at 2 450 MHz].

The temperature dependence of relative permittivity and conductivity of ex-vivo pig liver, lung and heart at 2 450 MHz was studied. The relative permittivity and conductivity of three kinds of biological tissues were measured by the open-end coaxial line method. The dielectric model was fitted according to the principle of least square method. The results showed that the relative permittivity and conductivity of pig liver, pig lung and pig heart decreased with the increase of tissue temperature from 20 to 80 ℃. The relative permittivity and conductivity models of pig liver, pig lung and pig heart were established to reflect the law of dielectric properties of biological tissue changing with temperature and provide a reference for the parameters setting of thermal ablation temperature field.

Validation of conductivity tensor imaging using giant vesicle suspensions with different ion mobilities.

BACKGROUND: Electrical conductivity of a biological tissue at low frequencies can be approximately expressed as a tensor. Noting that cross-sectional imaging of a low-frequency conductivity tensor distribution inside the human body has wide clinical applications of many bioelectromagnetic phenomena, a new conductivity tensor imaging (CTI) technique has been lately developed using an MRI scanner. Since the technique is based on a few assumptions between mobility and diffusivity of ions and water molecules, experimental validations are needed before applying it to clinical studies. METHODS: We designed two conductivity phantoms each with three compartments. The compartments were filled with electrolytes and/or giant vesicle suspensions. The giant vesicles were cell-like materials with thin insulating membranes. We controlled viscosity of the electrolytes and the giant vesicle suspensions to change ion mobility and therefore conductivity values. The conductivity values of the electrolytes and giant vesicle suspensions were measured using an impedance analyzer before CTI experiments. A 9.4-T research MRI scanner was used to reconstruct conductivity tensor images of the phantoms. RESULTS: The CTI technique successfully reconstructed conductivity tensor images of the phantoms with a voxel size of [Formula: see text]. The relative [Formula: see text] errors between the conductivity values measured by the impedance analyzer and those reconstructed by the MRI scanner was between 1.1 and 11.5. CONCLUSIONS: The accuracy of the new CTI technique was estimated to be high enough for most clinical applications. Future studies of animal models and human subjects should be pursued to show the clinical efficacy of the CTI technique.

Exploiting Tissue Dielectric Properties to Shape Microwave Thermal Ablation Zones.

The dielectric characterization of tissue targets of microwave thermal ablation (MTA) have improved the efficacy and pre-procedural planning of treatment. In some clinical scenarios, the tissue target lies at the interface with an external layer of fat. The aim of this work is to investigate the influence of the dielectric contrast between fat and target tissue on the shape and size of the ablation zone. A 2.45 GHz monopole antenna is placed parallel to an interface modelled by fat and a tissue characterized by higher dielectric properties and powered at 30 and 60 W for 60 s. The performances of MTA are numerically investigated considering different interface scenarios (i.e., different widths of fat layer, shifts in the antenna alignment) and a homogeneous reference scenario. Experiments (N = 10) are conducted on ex vivo porcine tissue to validate the numerical results. Asymmetric heating patterns are obtained in the interface scenario, the ablation zone in the target tissue is two-fold to ten-fold the size of the zone in the adipose tissue, and up to four times larger than the homogenous scenario. The adipose tissue reflects the electromagnetic energy into the adjacent tissue target, reducing the heating in the opposite direction.

Development of an Anthropomorphic Phantom of the Axillary Region for Microwave Imaging Assessment.

We produced an anatomically and dielectrically realistic phantom of the axillary region to enable the experimental assessment of Axillary Lymph Node (ALN) imaging using microwave imaging technology. We segmented a thoracic Computed Tomography (CT) scan and created a computer-aided designed file containing the anatomical configuration of the axillary region. The phantom comprises five 3D-printed parts representing the main tissues of interest of the axillary region for the purpose of microwave imaging: fat, muscle, bone, ALNs, and lung. The phantom allows the experimental assessment of multiple anatomical configurations, by including ALNs of different size, shape, and number in several locations. Except for the bone mimicking organ, which is made of solid conductive polymer, we 3D-printed cavities to represent the fat, muscle, ALN, and lung and filled them with appropriate tissue-mimicking liquids. Existing studies about complex permittivity of ALNs have reported limitations. To address these, we measured the complex permittivity of both human and animal lymph nodes using the standard open-ended coaxial-probe technique, over the 0.5 GHz-8.5 GHz frequency band, thus extending current knowledge on dielectric properties of ALNs. Lastly, we numerically evaluated the effect of the polymer which constitutes the cavities of the phantom and compared it to the realistic axillary region. The results showed a maximum difference of 7 dB at 4 GHz in the electric field magnitude coupled to the tissues and a maximum of 10 dB difference in the ALN response. Our results showed that the phantom is a good representation of the axillary region and a viable tool for pre-clinical assessment of microwave imaging technology.

Recent Advances on the Model, Measurement Technique, and Application of Single Cell Mechanics.

Since the cell was discovered by humans, it has been an important research subject for researchers. The mechanical response of cells to external stimuli and the biomechanical response inside cells are of great significance for maintaining the life activities of cells. These biomechanical behaviors have wide applications in the fields of disease research and micromanipulation. In order to study the mechanical behavior of single cells, various cell mechanics models have been proposed. In addition, the measurement technologies of single cells have been greatly developed. These models, combined with experimental techniques, can effectively explain the biomechanical behavior and reaction mechanism of cells. In this review, we first introduce the basic concept and biomechanical background of cells, then summarize the research progress of internal force models and experimental techniques in the field of cell mechanics and discuss the latest mechanical models and experimental methods. We summarize the application directions of cell mechanics and put forward the future perspectives of a cell mechanics model.

Recent trends in analysis of nanoparticles in biological matrices.

The need to assess the human and environmental risks of nanoparticles (NPs) has prompted an adaptation of existing techniques and the development of new ones. Nanoparticle analysis poses a great challenge as the analytical information has to consider both physical (e.g. size and shape) and chemical (e.g. elemental composition) state of the analyte. Furthermore, one has to contemplate the transformation of NPs during the sample preparation and provide sufficient information about the new species derived from such alteration. Traditional techniques commonly used for NP analysis such as microscopy and light scattering are still frequently used for NPs in simple matrices; however, they have limitations in the analysis of complex environmental and biological samples. On the other hand, recent improvements in data acquisition frequencies and reduction of settling time of ICP-MS brought inorganic mass spectrometry into the forefront of NPs analysis. However, with the increasing demand of analytical information related to NPs, emerging techniques such as enhanced darkfield hyperspectral imaging, nano-SIMS and mass cytometry are in their way to fill the gaps. This trend review presents and discusses the state-of-the-art analytical techniques and sample preparation methods for NP analysis in biological matrices. Graphical abstract ᅟ.

Clinical significance of HDAC9 in hepatocellular carcinoma.

In recent years, most related studies have found that chronic hepatitis B virus infection is the main cause of hepatocellular carcinoma (HCC), but the specific pathogenesis is still unclear. To investigate the function of HDAC in hepatocellular carcinoma (HCC), this study used qRT-PCR to determine the expression levels of miR-376a and HDAC9 mNRA in HCC and para-cancerous tissues. The clinical significance of HDAC9 in HCC was assessed in a study cohort containing 37 patients with HCC using immunohistochemistry. The expression level of miR-376a in liver cancer tissues was significantly lower than that in para-cancerous tissues, while the expression level of HDAC9 mRNA in liver cancer tissue was significantly higher than that in para-cancerous tissues. The expression of HDAC9 occurred mainly in the nucleus. There was a significant correlation between tumor differentiation and HDAC9. Survival analysis showed that HCC patients with higher HDAC9 expression had poorer prognosis, and subsequent multivariate analysis showed that HDAC9 expression level was an independent predictor. There was a definite correlation between HDAC9 and the expressions of AFP and Ki67. These results suggest that the expression level of HDAC9 in HCC is abnormally high while the expression level of miR-376a is significantly decreased, indicating that HDAC9 may be a potential prognostic indicator of HCC.

Movement of steel-jacketed projectiles in biological tissue in the magnetic field of a 3-T magnetic resonance unit.

PURPOSE: The fact that ferromagnetic bullets can move in air or gelatine when subjected to magnetic resonance (MR) units is well known. A previous study showed that the movement of 7.5-mm GP 11 Suisse bullets also depends on their orientation toward the gantry. In order to compare the movement in gelatine to that in real tissue, we decided to measure the movement of these bullets, as well as 9-mm Luger bullets, in the brain and liver. METHODS: The GP 11 and 9-mm Luger bullets were inserted into the fresh calf brain or pig liver either vertically or horizontally in the x- or z-axis to the gantry. Before and after exposure to a 3-T MR unit, their position was documented by CT. RESULTS: GP 11 bullets rotated more readily and in general proved to be more mobile than the 9-mm Luger. All GP 11 bullets and a large amount of the 9-mm Luger bullets exited the brain. Sliding toward the gantry was easier for 9-mm Luger bullets in the brain than in the liver. CONCLUSIONS: The orientation of a ferromagnetic object influences its mobility in a strong magnetic field. Tipping is easier than sliding for longish ferromagnetic projectiles, probably due to the lesser tissue resistance. The bullets moved more readily in biological tissue, especially brain tissue, compared to gelatine, thus implying that gelatine is not a suitable substitute for soft tissues when examining the movement of ferromagnetic objects in MR units.

Closed-form equation to estimate the dielectric properties of biological tissues as a function of age.

Developing microwave systems for biomedical applications requires accurate dielectric properties of biological tissues for reliable modeling before prototyping and subject testing. Dielectric properties of tissues decrease with age due to the change in their water content, but there are no detailed age-dependent data, especially for young tissue-like newborns, in the literature. In this article, an age-dependent formula to predict the dielectric properties of biological tissues was derived. In the proposed method, the variation of water concentration in each type of tissue as a function of age was used to calculate its relative permittivity and conductivity. The derived formula shows that the concentration of water in each tissue type can be modeled as a negative exponential function of age. The dielectric properties of each tissue type can then be calculated as a function of the dielectric properties of water and dielectric properties of the organ forming the tissue and its water concentration. The derived formula was used to generate the dielectric properties of several types of human tissues at different ages using the dielectric properties of a human adult. Moreover, the formula was validated on pig tissues of different ages. A close agreement was achieved between the calculated and measured data with a maximum difference of only 2%. Bioelectromagnetics. 38:474-481, 2017. © 2017 Wiley Periodicals, Inc.

A composite smeared finite element for mass transport in capillary systems and biological tissue.

One of the key processes in living organisms is mass transport occurring from blood vessels to tissues for supplying tissues with oxygen, nutrients, drugs, immune cells, and - in the reverse direction - transport of waste products of cell metabolism to blood vessels. The mass exchange from blood vessels to tissue and vice versa occurs through blood vessel walls. This vital process has been investigated experimentally over centuries, and also in the last decades by the use of computational methods. Due to geometrical and functional complexity and heterogeneity of capillary systems, it is however not feasible to model in silico individual capillaries (including transport through the walls and coupling to tissue) within whole organ models. Hence, there is a need for simplified and robust computational models that address mass transport in capillary-tissue systems. We here introduce a smeared modeling concept for gradient-driven mass transport and formulate a new composite smeared finite element (CSFE). The transport from capillary system is first smeared to continuous mass sources within tissue, under the assumption of uniform concentration within capillaries. Here, the fundamental relation between capillary surface area and volumetric fraction is derived as the basis for modeling transport through capillary walls. Further, we formulate the CSFE which relies on the transformation of the one-dimensional (1D) constitutive relations (for transport within capillaries) into the continuum form expressed by Darcy's and diffusion tensors. The introduced CSFE is composed of two volumetric parts - capillary and tissue domains, and has four nodal degrees of freedom (DOF): pressure and concentration for each of the two domains. The domains are coupled by connectivity elements at each node. The fictitious connectivity elements take into account the surface area of capillary walls which belongs to each node, as well as the wall material properties (permeability and partitioning). The overall FE model contains geometrical and material characteristics of the entire capillary-tissue system, with physiologically measurable parameters assigned to each FE node within the model. The smeared concept is implemented into our implicit-iterative FE scheme and into FE package PAK. The first three examples illustrate accuracy of the CSFE element, while the liver and pancreas models demonstrate robustness of the introduced methodology and its applicability to real physiological conditions.

Frequency-domain optical tomographic image reconstruction algorithm with the simplified spherical harmonics (SP3) light propagation model.

We introduce here the finite volume formulation of the frequency-domain simplified spherical harmonics model with n-th order absorption coefficients (FD-SPN) that approximates the frequency-domain equation of radiative transfer (FD-ERT). We then present the FD-SPN based reconstruction algorithm that recovers absorption and scattering coefficients in biological tissue. The FD-SPN model with 3rd order absorption coefficient (i.e., FD-SP3) is used as a forward model to solve the inverse problem. The FD-SP3 is discretized with a node-centered finite volume scheme and solved with a restarted generalized minimum residual (GMRES) algorithm. The absorption and scattering coefficients are retrieved using a limited-memory Broyden-Fletcher-Goldfarb-Shanno (L-BFGS) algorithm. Finally, the forward and inverse algorithms are evaluated using numerical phantoms with optical properties and size that mimic small-volume tissue such as finger joints and small animals. The forward results show that the FD-SP3 model approximates the FD-ERT (S12) solution within relatively high accuracy; the average error in the phase (<3.7%) and the amplitude (<7.1%) of the partial current at the boundary are reported. From the inverse results we find that the absorption and scattering coefficient maps are more accurately reconstructed with the SP3 model than those with the SP1 model. Therefore, this work shows that the FD-SP3 is an efficient model for optical tomographic imaging of small-volume media with non-diffuse properties both in terms of computational time and accuracy as it requires significantly lower CPU time than the FD-ERT (S12) and also it is more accurate than the FD-SP1.

[Non-contacting photoacoustic tomography in biological samples].

In photoacoustic imaging the ultrasonic signals are usually detected by contacting transducers. For some applications, contact with the tissue should be avoided, e.g. in those of brain functional imaging. As alternatives to contacting transducers interferometric techniques can be used to acquire photoacoustic signals remotely. Here, a system for non-contact photoacoustic tomography imaging (NCPAT) has been established. This approach enables NCPAT not to exceed laser exposure safety limits. The stimulated source of NCPAT utilized a laser with center wavelength of 532 nm and output intensity of 17.5 mJ/cm 2, and a laser heterodyne interferometry was used to receive the photoacoustic signals. The NCPAT was used to implement on a rotational imaging geometry for photoacoustic tomography with a real-tissue phantom. The photoacoustic imaging was obtained by applying a reconstruction algorithm to the data acquired for NCPAT. Experiments results showed that the NCPAT system with detection 15 dB bandwidth of 2.25 MHz could resolve spherical optical inclusions with dimension of 500 µm and multi-layered structure with optical contrast in strongly scattering medium. The method could expand the scope of photoacoustic and ultrasonic technology to in-vivo biomedical applications where contact is impractical.

Dielectric properties of dog brain tissue measured in vitro across the 0.3-3 GHz band.

Dielectric properties of dead Greyhound female dogs' brain tissues at different ages were measured at room temperature across the frequency range of 0.3-3 GHz. Measurements were made on excised tissues, in vitro in the laboratory, to carry out dielectric tests on sample tissues. Each dataset for a brain tissue was parametrized using the Cole-Cole expression, and the relevant Cole-Cole parameters for four tissue types are provided. A comparison was made with the database available in literature for other animals and human brain tissue. Results of two types of tissues (white matter and skull) showed systematic variation in dielectric properties as a function of animal age, whereas no significant change related to age was noticed for other tissues. Results provide critical information regarding dielectric properties of animal tissues for a realistic animal head model that can be used to verify the validity and reliability of a microwave head scanner for animals prior to testing on live animals. Bioelectromagnetics. 37:549-556, 2016. © 2016 Wiley Periodicals, Inc.