Tissue Viscoelastic Properties Research Articles

MR Elastography for Classification of Focal Liver Lesions Using Viscoelastic Parameters: A Pilot Study Based on Intrinsic and Extrinsic Activations.

Intrinsic activation MR elastography (iMRE) uses cardiovascular pulsations to assess tissue viscoelastic properties. Applying it to focal liver lesions extends its capabilities. To assess the viscoelastic parameters of focal liver lesions measured by iMRE and compare its diagnostic performance with extrinsic MRE (eMRE) for differentiating malignant and benign lesions. Prospective. A total of 55 participants underwent MRI with research MRE sequences; 32 participants with 17 malignant and 15 benign lesions underwent both iMRE and eMRE. FIELD STRENGTH/SEQUENCE: iMRE at ~1 Hz heart rate used a 3 T scanner with a modified four-dimensional (4D)-quantitative flow gradient-echo phase contrast and low-velocity encoding cardiac-triggered technique. eMRE employed a gradient-echo sequence at 30, 40, and 60 Hz. Liver displacements were measured using 4D-phase contrast and reconstructed via a nonlinear inversion algorithm to determine shear stiffness (SS) and damping ratio (DR). iMRE parameters were normalized to the corresponding values from the spleen. Lesions were manually segmented, and image quality was reviewed. Kruskal-Wallis, Mann-Whitney, Dunn's test, and areas under receiver operating characteristic curves (AUC) were assessed. SS was significantly higher in malignant than benign lesions with iMRE at 1 Hz (3.69 ± 1.31 vs. 1.63 ± 0.45) and eMRE at 30 Hz (3.76 ± 1.12 vs. 2.60 ± 1.26 kPa), 40 Hz (3.76 ± 1.12 vs. 2.60 ± 1.26 kPa), and 60 Hz (7.32 ± 2.87 vs. 2.48 ± 1.12 kPa). DR was also significantly higher in malignant than benign lesions at 40 Hz (0.36 ± 0.11 vs. 0.21 ± 0.01) and 60 Hz (0.89 ± 0.86 vs. 0.22 ± 0.09). The AUC were 0.86 for iMRE SS, 0.87-0.98 for eMRE SS, 0.47 for iMRE DR, and 0.62-0.86 for eMRE DR. Cardiac-activated iMRE can characterize liver lesions and differentiate malignant from benign lesions through normalized SS maps. 2 TECHNICAL EFFICACY: Stage 2.

Effects of oral contrast agent on the viscoelastic properties of the terminal ileum investigated using magnetic resonance elastography.

While standard clinical magnetic resonance (MR) enterography can detect inflammatory bowel disease, it is of limited value in deciding between medical versus surgical treatment. Alternatively, intestinal MR elastography has the potential to contribute additional information to therapeutic decision-making; however, the influence of bowel distension by oral contrast agent on viscoelastic tissue properties remains elusive. Therefore, we aimed to investigate the influence of oral contrast agent-induced bowel distension on the viscoelastic properties of the terminal ileum in healthy volunteers. In this prospective pilot study, 20 healthy volunteers (33.2±8.2 years; 10 men, 10 women) underwent multifrequency MR elastography using a single-shot spin-echo echo planar imaging sequence at 1.5 Tesla and drive frequencies of 40, 50, 60 and 70 Hz. Maps of shear wave speed (c in ms-1) and loss angle (φ in rad), representing stiffness and viscous properties, respectively, were generated using tomoelastography data processing. The volunteers were scanned before and after ingestion of 1,000 mL of 2% mannitol solution as oral contrast agent. There was no significant difference in terminal ileum biomechanical properties before vs. after ingestion of an oral contrast agent (mean c: 1.47±0.24 vs. 1.40±0.25 ms-1 with P=0.37; mean φ: 0.70±0.12 rad vs. 0.68±0.12 rad with P=0.61). Moreover, there was no statistically significant correlation between MR elastography parameters before and after the ingestion of oral contrast (c: r=0.22, P=0.36; φ: r=0.24, P=0.30). The results of this study suggest that bowel distension for intestinal MR elastography has no systematic effect on the biomechanical tissue properties of the terminal ileum determined by MR elastography. Therefore, future study protocols appear feasible with or without oral contrast agents.

Mechanical rheological model on the assessment of elasticity and viscosity in tissue inflammation: A systematic review.

Understanding the extent of inflammation is crucial for early disease detection, monitoring disease progression, and evaluating treatment responses. Over the past decade, researchers have demonstrated the need to understand the extent of inflammation through qualitative or quantitative characterization of tissue viscoelasticity using different techniques. In this scientific review, an examination of research on the association between elasticity and Viscosity in diseases, particularly as tissue inflammation progresses, is conducted. A review of utilizing mechanical rheological models to characterize quantitative viscoelastic parameters of normal and inflamed tissues is also undertaken. Based on inclusion and exclusion criteria, we identified 14 full-text studies suitable for review out of 290 articles published from January 2000 to January 2024. We used PRISMA guidelines for the systematic review. In the review, three studies demonstrated the criterion used by the researchers in identifying the best rheological model. Eleven studies showed the clinical application of the rheological model in quantifying the viscoelastic properties of normal and pathological tissue. The review quantified viscoelastic parameters for normal and pathological tissue across various soft tissues. It evaluated the effectiveness of each viscoelastic property in distinguishing between normal and pathological tissue stiffness. Furthermore, the review outlined additional viscoelastic-related parameters for researchers to consider in future stiffness classification studies.

The Impact of Contact Force on Signal Quality Indices in Photoplethysmography Measurements

Photoplethysmography (PPG) is widely used to assess cardiovascular health. Yet, its effectiveness is often hindered by external factors like contact force (CF), which significantly affects the accuracy and reliability of measurements. This study investigates how variations in the CF at the index fingertips influence six signal quality indices (SQIs)—including the perfusion index, skewness, kurtosis, entropy, zero-crossing rate, and relative power—using data from 11 healthy participants. Our analysis of normalized CF values reveals that lower CF ranges (0.2 to 0.4) may be optimal for extracting information about perfusion and blood flow. However, they may not be the best range to capture all the physiological details within the PPG pulse. In contrast, higher CF ranges (0.4 to 0.6) enable capturing more complex signals that could be physiologically representative. The findings underscore the necessity of considering viscoelastic tissue properties and individual biomechanical differences, advocating for both the normalization of CF for improved cross-subject comparison and personalized CF calibration to adapt PPG devices to diverse populations. These strategies ensure measurement reliability and consistency, thereby advancing the accuracy of cardiac and vascular assessments. Our study offers guidelines for adjusting the CF levels to balance signal detail and perfusion quality, customized to meet specific analytical requirements, with direct implications for both clinical and research environments.

Effect of rapid cooling, frozen storage, and thawing on the passive viscoelastic properties and structure of the rat aorta

Biological tissues decay over time after harvesting, which alters their biomechanical properties. This poses logistical challenges for studies investigating passive arterial biomechanics as tissues need to be characterized shortly after excision. Freezing and cryopreservation methods can help alleviate the need for biomechanical testing of fresh tissue in human ex vivo studies. However, these methods tend to eliminate or reduce arterial cell functionality and affect passive biomechanics. Furthermore, their impact on dynamic arterial biomechanics remains unknown despite arterial viscoelastic properties being an integral component contributing to arterial stiffness under in vivo loading conditions. The present study aims to investigate the impact of rapid cooling and subsequent storage at −80 °C on the passive viscoelastic properties of arterial tissue and aid in ascertaining whether this is a suitable method to delay tissue analysis for studies investigating passive arterial biomechanics. Control and frozen abdominal rat aorta segments were quasi-statically and dynamically tested using a biaxial testing set-up. The results were modeled using a constituent-based quasi-linear viscoelastic modeling framework, yielding directional stiffness parameters, individual constituent biomechanical contributions, and a quantification of viscoelastic stiffening under dynamic pressurization conditions. Frozen samples displayed significantly decreased wall thickness, viscoelastic dissipation, viscoelastic stiffening, and significantly decreased circumferential deformation with changes in luminal pressure. Furthermore, frozen samples displayed significantly increased circumferential stiffness, pulse wave velocity, and collagen load bearing. Consequently, these changes should be considered when utilizing this tissue preservation method to delay biomechanical characterization of rat aortic tissue.

On the relationship between viscoelasticity and water diffusion in soft biological tissues

Magnetic resonance elastography (MRE) and diffusion-weighted imaging (DWI) are complementary imaging techniques that detect disease based on viscoelasticity and water mobility, respectively. However, the relationship between viscoelasticity and water diffusion is still poorly understood, hindering the clinical translation of combined DWI-MRE markers.We used DWI-MRE to study 129 biomaterial samples including native and cross-linked collagen, glycosaminoglycans (GAGs) with different sulfation levels, and decellularized specimens of pancreas and liver, all with different proportions of solid tissue, or solid fractions. We developed a theoretical framework of the relationship between mechanical loss and tissue-water mobility based on two parameters, solid and fluid viscosity. These parameters revealed distinct DWI-MRE property clusters characterizing weak, moderate, and strong water-network interactions. Sparse networks interacting weakly with water, such as collagen or diluted decellularized tissue, resulted in marginal changes in water diffusion over increasing solid viscosity. In contrast, dense networks with larger solid fractions exhibited both free and hindered water diffusion depending on the polarity of the solid components. For example, polar and highly sulfated GAGs as well as native soft tissues hindered water diffusion despite relatively low solid viscosity.Our results suggest that two fundamental properties of tissue networks, solid fraction and network polarity, critically influence solid and fluid viscosity in biological tissues. Since clinical DWI and MRE are sensitive to these viscosity parameters, the framework we present here can be used to detect tissue remodeling and architectural changes in the setting of diagnostic imaging. Statement of significanceThe viscoelastic properties of biological tissues provide a wealth of information on the vital state of cells and host matrix. Combined measurement of viscoelasticity and water diffusion by medical imaging is sensitive to tissue microarchitecture. However, the relationship between viscoelasticity and water diffusion is still poorly understood, hindering full exploitation of these properties as a combined clinical biomarker. Therefore, we analyzed the parameter space accessible by diffusion-weighted imaging (DWI) and magnetic resonance elastography (MRE) and developed a theoretical framework for the relationship between water mobility and mechanical parameters in biomaterials. Our theory of solid material properties related to particle motion can be translated to clinical radiology using clinically established MRE and DWI.

Free-breathing motion corrected magnetic resonance elastography of the abdomen.

Magnetic resonance elastography (MRE) is a non-invasive method to measure the viscoelastic properties of tissue and has been applied in multiple abdominal organs. However, abdominal MRE suffers from detrimental breathing motion causing misalignment of structures between repeated acquisitions for different MRE dimensions (e.g., motion encoding directions and wave phase offsets). This study investigated motion correction strategies to resolve all breathing motion on sagittal free-breathing MRE acquisitions in a phantom, in healthy volunteers and showed feasibility in patients. First, in silico experiments were performed on a static phantom dataset with simulated motion. Second, eight healthy volunteers underwent two sagittal MRE acquisitions in the pancreas and right kidney. The multi-frequency free-breathing spin-echo echo-planar-imaging (SE-EPI) MRE consisted of four frequencies (30, 40, 50, 60 Hz), eight wave-phase offsets, with 3 mm3 isotropic voxel size. Following data re-sorting in different number of motion states (4 till 12) based on respiratory waveform signal, three intensity-based registration methods (monomodal, multimodal, and phase correlation) and non-rigid local registration were compared. A ranking method was used to determine the best registration method, based on seven signal-to-noise and image quality measures. Repeatability was assessed for no motion correction (Original) and the best performing method (Best) using Bland-Altman analysis. Lastly, the best motion correction method was compared to no motion correction on patient MRE data [pancreatic ductal adenocarcinoma (PDAC, n=5) and metabolic dysfunction-associated steatotic liver disease (MASLD) (n=1)]. In silico experiments showed a deviation of shear wave speed (SWS) with simulated motion to the ground truth, which was (partially) resolved using motion correction. In healthy volunteers ranking resulted in the best motion correction method of monomodal registration using nine motion states, while no motion correction was ranked last. Limits of agreement were (-0.18, 0.14), and (-0.25, 0.18) m/s for Best and Original, respectively. Using motion correction in patients resulted in a significant increase in SWS in the pancreas (Original: 1.39±0.10 and Best: 1.50±0.17 m/s). After motion correction PDAC had a mean SWS of 1.56±0.27 m/s (Original: 1.42±0.25 m/s). The fibrotic liver mean SWS was 2.07±0.20 m/s (Original: 2.12±0.18 m/s). Motion correction in sagittal free-breathing abdominal MRE results in improved data quality, inversion precision, repeatability, and is feasible in patients.

Frequency and time dependent viscoelastic characterization of pediatric porcine brain tissue in compression.

Understanding the viscoelastic behavior of pediatric brain tissue is critical to interpret how external mechanical forces affect head injury in children. However, knowledge of the viscoelastic properties of pediatric brain tissue is limited, and this reduces the biofidelity of developed numeric simulations of the pediatric head in analysis of brain injury. Thus, it is essential to characterize the viscoelastic behavior of pediatric brain tissue in various loading conditions and to identify constitutive models. In this study, the pediatric porcine brain tissue was investigated in compression with determine the viscoelasticity under small and large strain, respectively. A range of frequencies between 0.1 and 40Hz was applied to determine frequency-dependent viscoelastic behavior via dynamic mechanical analysis, while brain samples were divided into three strain rate groups of 0.01/s, 1/s and 10/s for compression up to 0.3 strain level and stress relaxation to obtain time-dependent viscoelastic properties. At frequencies above 20Hz, the storage modulus did not increase, while the loss modulus increased continuously. With strain rate increasing from 0.01/s to 10/s, the mean stress at 0.1, 0.2 and 0.3 strain increased to approximate 6.8, 5.6 and 4.4 times, respectively. The brain compressive response was sensitive to strain rate and frequency. The characterization of brain tissue will be valuable for development of head protection systems and prediction of brain injury.

Reconstructing the source condition for focused shear wave beams in soft elastic media

Shear waves are employed in medical ultrasound imaging because they reveal variations in viscoelastic properties of soft tissue. Focused shear waves produced by a longitudinally vibrating piston at several hundred hertz are investigated here experimentally in soft tissue phantoms and using an analytical model for shear wave beam generation and propagation. Experiments employed a spherically concave piston shaped to focus the shear wave beam at a depth of 4 cm in a soft tissue phantom. Analytical modeling of this data provided a good fit, but required treating the focal length and piston diameter as adjustable parameters. The largest source of error in the modeling is suspected to be that the source condition is assumed to exhibit zero displacement surrounding the piston, whereas the actual condition in the source plane is a traction-free surface surrounding the piston. Here, in order to elucidate the actual source condition, numerical back propagation of field measurements is employed. Simulations show that the shear source condition can be accurately recovered with information related only to the shear wave, i.e., without compressional wave information. Back propagation of measured beams is discussed in the context of more accurately modeling the source condition for future device optimization.

Shear wave propagation in a fiber-laden viscoelastic waveguide under prestress: Inverse modeling challenges

The functional role of skeletal muscle and the hierarchal microstructure and arrangement of fibers within it results in anisotropy and inhomogeneity in both material properties and imposed stresses. Dynamic elastography reconstruction methods for estimating muscle tissue viscoelastic properties that are based on assumptions of homogeneity, isotropy and only bulk wave motion may produce inaccurate estimates. Biases may be introduced in reconstruction by homogenizing muscle with axially aligned fibers and approximating it as transversely isotropic. The significance of these biases, and their interplay with imposed stresses and confounding waveguide effects due to small cross-sectional dimensions, is quantified with a series of numerical finite element and experimental elastography studies on cylindrically-shaped fiber-laden muscle phantoms, with varying fiber dimensions. Specifically, numerical simulations of elastography are conducted on 4-, 60- and 113-fiber models with the aligned fiber cross-sectional area fixed (reduced fiber diameter as fiber count increases) and comprising approximately 40% of the cross-sectional area of the cylindrical phantom that is also undergoing tensile axial pre-loading. Fiber elastic moduli twice that of connective tissue are considered. Experimental studies of the 4-fiber model are used to validate the numerical model. [Funding support: NSF 1852691 and NIH AR071162]

Rayleigh-Lamb wave propagation in a prestressed transversely isotropic viscoelastic waveguide: Inverse modeling challenges

The functional role and structure of skeletal muscle results in anisotropy in both material properties and imposed stresses, as well as waveguide effects. Dynamic elastography reconstruction methods for estimating muscle tissue viscoelastic properties that are rooted in assumptions of isotropy and bulk wave motion may produce inaccurate estimates. The superposition of axially-aligned orthotropy (transverse isotropy) in material properties and axially-aligned prestress conditions due to passive stretch or muscle activation makes it difficult to independently discern how much of the apparent anisotropy is due to the muscle material or the imposed stress field. Furthermore, this stress field may result in large strain conditions that require use of higher order terms in the stress-strain relationship. The significance of this confounding condition and strategies for decoupling material and stress-based anisotropy are investigated with a series of numerical finite element and experimental elastography studies using scanning laser Doppler vibrometry and magnetic resonance elastography. Shear and Rayleigh-Lamb wave motion is studied in a polymeric muscle phantom that is in the shape of a rectangular rod and has either isotropic or transversely isotropic material properties under zero stress conditions. [Funding support: NIH AR071162]

Love waves propagation in layered viscoelastic waveguides characterized by a Zener model

This paper describes a theory of surface Love waves propagating in lossy waveguides consisting of a viscoelastic layer deposited on a semi-infinite elastic substrate. The Zener model to describe the viscoelastic behavior of a medium is used. This simple model captures both the relaxation and retardation. A new form of the unsteady momentum equation for viscoelastic waveguides has been established. By using appropriate boundary conditions, an analytical expression for the complex dispersion equation of Love waves has been deduced. The influence of the loss factor and the ratio of shear moduli of the surface layer on the dispersion curves of Love waves velocity and attenuation is analyzed numerically. The numerical solutions show the dependence of the velocity change and the wave attenuation in terms of the loss factor and the ratio of shear moduli. The obtained results show that the change in the ratio of shear moduli can represent a hardening or softening effect of the surface layer. These effects depend on the loss factor value of the surface layer. In addition, these results are novel, fundamental and can be applied in the characterization of the viscoelastic properties of soft biomaterials and tissues, in nondestructive testing of materials, in geophysics and seismology. Thus, the obtained complex dispersion equation can be very useful to interpret the experimental measurements of Love waves properties in viscoelastic waveguides.

Modeling the effects of hydration on viscoelastic properties of nucleus pulposus tissue in shear using the fractional Zener model

Nucleus pulposus (NP) tissue in the intervertebral disc (IVD) is a viscoelastic material exhibiting both solid- and fluid-like mechanical behaviors. Advances in viscoelastic models incorporating fractional calculus, such as the Fractional Zener (FZ) model, have potential to describe viscoelastic behaviors. The objectives of this study were to determine whether the FZ model can accurately describe the shear viscoelastic properties of NP tissue and determine if the fractional order (α) is related to tissue hydration. 30 caudal IVDs underwent equilibrium dialysis in 5% or 25% polyethylene glycol solutions to alter tissue hydration. Excised NP tissue underwent stress relaxation testing in shear and unconfined compression. Stress relaxation data was fitted to the FZ model to obtain viscoelastic properties. In both loading modes, the initial modulus was greater for the less hydrated 25% equilibrated samples compared to 5% with no change in the equilibrium modulus. Samples with lower water content (25% samples) had shorter relaxation times in shear and longer time constants in compression, highlighting the different interactions between the fluid and solid matrix in loading modes. Samples with lower water content had α values closer to 0, indicating that less hydrated samples behaved more solid-like on the viscoelastic spectrum. Tissue hydration correlated with α values for 25% samples in shear. This study demonstrates that the FZ model may be used to describe IVD tissue behavior under both loading modes; however, the greatest utility of the FZ model is in describing flow-independent shear behaviors, and α may inform tissue hydration in shear.

Photoacoustic viscoelasticity assessment of prefrontal cortex and cerebellum in normal and prenatal valproic acid-exposed rats

Mechanical properties of brain tissues are from principal features from different points of view; diagnosis, the performance of the brain and neurological disorders. Particularly viscoelastic properties of the brain tissues are determinative. In this study based on a proposed accurate and non-invasive method, we have measured the viscoelastic properties of prefrontal cortex and cerebellum, two important brain regions involved in motor learning and pathophysiology of autism spectrum disorder (ASD). In this regard, using photoacoustic systems, viscoelastic properties of tissues from the cerebellum and prefrontal cortex of normal and prenatal VPA (Valproic acid)-exposed (i.e. autistic-like) offspring rats are measured. Results of our study show that the cerebellums of normal tissues are stiffer than the tissue obtained from autistic-like rats, while the viscoelasticity of the prefrontal cortex of normal tissues is higher than that of autistic ones. The proposed method for the measurement of viscoelastic properties of the brain tissue has the potential not only for the fundamental studies but as a diagnosis technique.

Optimization of the Tracking Beam Sequence in Harmonic Motion Imaging.

Harmonic motion imaging (HMI) is an ultrasound elastography technique that estimates the viscoelastic properties of tissues by inducing localized oscillatory motion using focused ultrasound (FUS). The resulting displacement, assumed to be inversely proportional to the tissue local stiffness, is estimated using an imaging array based on RF speckle tracking. In conventional HMI, this is accomplished with plane-wave (PW) imaging, which inherently suffers from low lateral resolution. Coherent PW compounding (PWC) leverages spatial and temporal resolution using synthetic focusing in transmit. In this study, we introduced focused imaging with parallel tracking in HMI and compared parallel tracking of various transmit F-numbers (F/2.6, 3, 4, and 5) qualitatively and quantitatively with PW and PWC imaging at various compounded angle ranges (6°, 12°, and 18°). An in silico model of a 56-kPa spherical inclusion (diameter: 3.6 mm) embedded in a 5.3-kPa background and a 5.3-kPa elastic phantom with cylindrical inclusions (Young's moduli: 22-56 kPa, diameters: 2.0-8.6 mm) were imaged to assess different tracking beam sequences. Speckle biasing in displacement estimation associated with parallel tracking was also investigated and concluded to be negligible in HMI. Parallel tracking in receive (Rx) resulted in 2%-7% and 8%-12% increase compared to PW imaging ( ) in HMI contrast and contrast-to-noise ratio in silico and phantoms. Focused imaging with parallel tracking in Rx was concluded to be most robust among PW and PWC imaging for displacement estimation, and its preclinical feasibility was demonstrated in postsurgical human cancerous breast tissue specimens and in vivo murine models of breast cancer.

Extracellular matrix viscoelasticity regulates TGFβ1-induced epithelial-mesenchymal transition and apoptosis via integrin linked kinase.

Transforming growth factor (TGF)-β1 is a multifunctional cytokine that plays important roles in health and disease. Previous studies have revealed that TGFβ1 activation, signaling, and downstream cell responses including epithelial-mesenchymal transition (EMT) and apoptosis are regulated by the elasticity or stiffness of the extracellular matrix. However, tissues within the body are not purely elastic, rather they are viscoelastic. How matrix viscoelasticity impacts cell fate decisions downstream of TGFβ1 remains unknown. Here, we synthesized polyacrylamide hydrogels that mimic the viscoelastic properties of breast tumor tissue. We found that increasing matrix viscous dissipation reduces TGFβ1-induced cell spreading, F-actin stress fiber formation, and EMT-associated gene expression changes, and promotes TGFβ1-induced apoptosis in mammary epithelial cells. Furthermore, TGFβ1-induced expression of integrin linked kinase (ILK) and colocalization of ILK with vinculin at cell adhesions is attenuated in mammary epithelial cells cultured on viscoelastic substrata in comparison to cells cultured on nearly elastic substrata. Overexpression of ILK promotes TGFβ1-induced EMT and reduces apoptosis in cells cultured on viscoelastic substrata, suggesting that ILK plays an important role in regulating cell fate downstream of TGFβ1 in response to matrix viscoelasticity.

Lung function is related to salivary cytokines and hormones in healthy children. An exploratory cross‐sectional study

AbstractPulmonary mechanics has been traditionally viewed as determined by lung size and physical factors such as frictional forces and tissue viscoelastic properties, but few information exists regarding potential influences of cytokines and hormones on lung function. Concentrations of 28 cytokines and hormones were measured in saliva from clinically healthy scholar children, purposely selected to include a wide range of body mass index (BMI). Lung function was assessed by impulse oscillometry, spirometry, and diffusing capacity for carbon monoxide, and expressed as z‐score or percent predicted. Ninety‐six scholar children (55.2% female) were enrolled. Bivariate analysis showed that almost all lung function variables correlated with one or more cytokine or hormone, mainly in boys, but only some of them remained statistically significant in the multiple regression analyses. Thus, after adjusting by height, age, and BMI, salivary concentrations of granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) in boys were associated with zR5‐R20 and reactance parameters (zX20, zFres, and zAX), while glucagon inversely correlated with resistances (zR5 and zR20). Thus, in physiological conditions, part of the mechanics of breathing might be influenced by some cytokines and hormones, including glucagon and GM‐CSF. This endogenous influence is a novel concept that warrants in‐depth characterization.

Micromechanical characterizations and viscoelastic modeling reveal elastic and viscoelastic heterogeneities in ovarian tissue and the significant viscoelastic contribution to the apparent elastic modulus determined by AFM indentation.

Ovarian follicles develop in a highly regulated mechanical microenvironment and disruptions to the microenvironment may cause infertility. However, the viscoelastic properties of the ovarian tissue are not well studied. Here, we characterize both the elastic and viscoelastic properties of ovarian tissue from both reproductively older and younger domestic cats using atomic force microscopy (AFM) indentation and viscoelastic models of stress relaxation. Importantly, our analyses reveal the apparent elastic modulus obtained from the conventional AFM indentation measurement is significantly higher than the intrinsic elastic modulus and insignificantly different from the equivalent elastic modulus that is the summation of the intrinsic elastic modulus and the viscoelastic contribution to modulus at time 0. Interestingly, the ovarian cortex of both reproductive age groups has a higher apparent/intrinsic modulus than that of the medulla. Furthermore, two different kinetics of stress relaxation are identified with rate constants of ∼1s and ∼20-40s, respectively. Moreover, the rate constant of the slow kinetics is significantly different between the cortex and medulla in the reproductively older ovaries. Finally, these mechanical heterogeneities appear to follow the heterogeneous distribution of hyaluronic acid (HA) in the ovary. These findings may be invaluable to the development of biomimetic follicle culture for treating infertility. STATEMENT OF SIGNIFICANCE: This study investigates not only elastic but also the viscoelastic heterogeneity in both reproductively younger and older ovarian tissues for the first time. Further, by combining AFM indentation measurement and viscoelastic modeling, we show the apparent elastic modulus conventionally reported in the literature for AFM indentation measurement is the summation of the intrinsic elastic modulus and a significant viscoelastic contribution to the modulus at time 0. This is an important consideration for others who use this method to quantify biomaterial properties. In addition, the possible connection between the mechanical and compositional heterogeneities is explored. These findings may be invaluable for designing biomaterials to recapitulate the mechanical environment of the ovary and possibly many other organs for biomimetic tissue engineering.

Characterization of renal fibrosis in rats with chronic kidney disease by in vivo tomoelastography.

Chronic kidney disease (CKD) is characterized by structural changes, such as tubular atrophy, renal fibrosis, and glomerulosclerosis, all of which affect the viscoelastic properties of biological tissues. However, detection of renal viscoelasticity changes because diagnostic markers by in vivo elastography lack histopathological validation through animal models. Therefore, we investigated in vivo multiparametric magnetic resonance imaging (mp-MRI), including multifrequency magnetic resonance elastography-based tomoelastography, in the kidneys of 10 rats with adenine-induced CKD and eight healthy controls. Kidney volume (in mm3 ), water diffusivity (apparent diffusion coefficient [ADC] in mm2 /s), shear wave speed (SWS; in m/s; related to stiffness), and wave penetration rate (PR; in m/s; related to inverse viscosity) were quantified by mp-MRI and correlated with histopathologically determined renal fibrosis (collagen area fraction [CAF]; in %). Kidney volume (40% ± 29%, p = 0.009), SWS (11% ± 12%, p = 0.016), and PR (20% ± 15%, p = 0.004) were significantly increased in CKD, which was accompanied by ADC (-24% ± 27%, p = 0.02). SWS, PR, and ADC were correlated with CAF with R = 0.63, 0.75, and -0.5 (all p < 0.05), respectively. In the CKD rats, histopathology showed tubule dilation due to adenine crystal deposition. Collectively, our results suggest that collagen accumulation during CKD progression transforms soft-compliant renal tissue into a more rigid-solid state with reduced water mobility. We hypothesized that tubule dilation-a specific feature of our model-might lead to higher intraluminal pressure, which could also contribute to elevated renal stiffness. Tomoelastography is a promising tool for noninvasively assessing disease progression, detecting biomechanical properties that are sensitive to different pathologic features of CKD.

Gunshot wounds in parenchymatous organs: the morphology mainly depends on the physical properties of the affected tissues*

In contrast to gunshot wounds in skin and bone, the medico-legal literature pays little attention to the appearance of bullet penetration sites in abdominal organs. It was only in 1983 that Metter and Schulz published an article entitled “Morphological features of gunshot wounds in the liver and spleen.” According to their observations, the organs in question showed stellate tears at the bullet penetration sites resembling skin wounds from contact shots to body regions having a bony support. The study presented simulated the real conditions by means of test shots to composite models consisting of porcine organs embedded in ballistic gelatin. The ammunition used was pistol cartridges 9 mm Luger with full metal jacket round nose bullets. The shots were video-documented with a high-speed camera in order to record the bullet’s travel through the target. In addition, the composite models fired at underwent CT examinations followed by a macroscopic assessment of the organs. The study confirmed the findings of Metter and Schulz with regard to the star-like appearance of gunshot wounds in the liver and spleen. Likewise, the kidney showed radiating tears originating from the bullet path, whereas the wound track in pulmonary tissue was tube-shaped and lacked additional cracks. The varying wound patterns in parenchymatous organs can reasonably be explained as a consequence of the respective viscoelastic tissue properties.