Elasticity Imaging Research Articles

Two-dimensional elastic distribution imaging of the sclera using acoustic radiation force optical coherence elastography.

The scleral elasticity is closely related with many ocular diseases, but the relevant research is still insufficient. Here, we utilized optical coherence elastography to carefully study biomechanical properties of the sclera at different positions and under different intraocular pressures. Meanwhile, elastic wave velocity and Young's modulus of each position were obtained using a phase velocity algorithm. Accordingly, the two-dimensional elasticity distribution image was achieved by mapping the Young's modulus values to the corresponding structure based on the relationship between the position and its Young's modulus. Therefore, elastic information in regions-of-interest can be read and compared directly from the scleral structure, indicating that our method may be a very useful tool to evaluate the elasticity of sclera and provide intuitive and reliable proof for diagnosis and research.

Converted-wave reflection traveltime inversion with free-surface multiples for ocean-bottom-node data

Advancements in ocean-bottom-node (OBN) technologies have enabled the recording of high-quality multicomponent seismic data, which can provide crucial information about subsurface properties through elastic seismic imaging. However, imaging multicomponent data is challenging due to the requirement for P- and S-wave velocity models. Conventional processing relies on estimating the S-wave velocity model using a primary converted wave (C wave) because the pure S-wave primaries are not available if using standard air-gun sources. When a free surface is present, the C waves recorded with geophones can be contaminated by source-side P-wave multiples, especially water-layer reverberations, which are difficult to remove even using state-of-the-art wavefield decomposition methods. These C-wave multiples can cause significant mismatches between synthetic and observed data during reflection traveltime or waveform inversion if only primary P-to-S (PS) conversions are simulated. To address these issues and reliably build an S-wave velocity model for PS imaging, we develop a C-wave reflection traveltime inversion method that takes source-side free-surface multiples into account. The traveltime misfit of C-wave data is extracted using dynamic image warping to ensure a better match between the synthetic and observed data. The functional gradient of the objective function is derived using the adjoint state method. Based on sensitivity kernel analyses, a convenient gradient preconditioning strategy is developed to robustly separate the contribution of primary and multiple C waves during backpropagation. This strategy can effectively mitigate the high-wavenumber crosstalk associated with nonphysical wavepaths in the gradient and thus allow more accurate updating for the S-wave velocity model. The synthetic data and shallow-water OBN data from the East China Sea indicate that this approach can reliably recover the S-wave macrovelocity structures for PS imaging.

Characterization of anisotropy of elastic modulus with three-dimensional freehand scan shear wave elasticity imaging

Characterization of anisotropy of elastic modulus with three-dimensional freehand scan shear wave elasticity imaging

Physics-informed UNets for discovering hidden elasticity in heterogeneous materials

Soft biological tissues often have complex mechanical properties due to variation in structural components. In this paper, we develop a novel UNet-based neural network model for inversion in elasticity (El-UNet) to infer the spatial distributions of mechanical parameters from strain maps as input images, normal stress boundary conditions, and domain physics information. We show superior performance – both in terms of accuracy and computational cost – by El-UNet compared to fully-connected physics-informed neural networks in estimating unknown parameters and stress distributions for isotropic linear elasticity. We characterize different variations of El-UNet and propose a self-adaptive spatial loss weighting approach. To validate our inversion models, we performed various finite-element simulations of isotropic domains with heterogenous distributions of material parameters to generate synthetic data. El-UNet is faster and more accurate than the fully-connected physics-informed implementation in resolving the distribution of unknown fields. Among the tested models, the self-adaptive spatially weighted models had the most accurate reconstructions in equal computation times. The learned spatial weighting distribution visibly corresponded to regions that the unweighted models were resolving inaccurately. Our work demonstrates a computationally efficient inversion algorithm for elasticity imaging using convolutional neural networks and presents a potential fast framework for three-dimensional inverse elasticity problems that have proven unachievable through previously proposed methods.

Acoustic diffraction–resistant adaptive profile technology (ADAPT) for elasticity imaging

Acoustic beam shaping with high degrees of freedom is critical for applications such as ultrasound imaging, acoustic manipulation, and stimulation. However, the ability to fully control the acoustic pressure profile over its propagation path has not yet been achieved. Here, we demonstrate an acoustic diffraction–resistant adaptive profile technology (ADAPT) that can generate a propagation-invariant beam with an arbitrarily desired profile. By leveraging wave number modulation and beam multiplexing, we develop a general framework for creating a highly flexible acoustic beam with a linear array ultrasonic transducer. The designed acoustic beam can also maintain the beam profile in lossy material by compensating for attenuation. We show that shear wave elasticity imaging is an important modality that can benefit from ADAPT for evaluating tissue mechanical properties. Together, ADAPT overcomes the existing limitation of acoustic beam shaping and can be applied to various fields, such as medicine, biology, and material science.

Predicting stress and interstitial fluid pressure in tumors based on biphasic theory

The uncontrolled proliferation of cancer cells causes the growth of the tumor mass. Consequently, the normal surrounding tissue exerts a compressive force on the tumor mass to oppose its expansion. These stresses directly promote tumor metastasis and invasion and affect drug delivery.In the past, the mechanical behavior of solid tumors has been extensively studied using linear elastic and nonlinear hyperelastic constitutive models. In this study, we develop a two-dimensional biomechanical model based on the biphasic assumption of the solid matrix and fluid phase of the tissues. Heterogeneous vasculature and nonuniform blood perfusion are also investigated by incorporating in the model a necrotic core and a well-vascularized zone. The findings of our study demonstrate a significant difference between the linear and nonlinear tissue responses to stress, while the interstitial fluid pressure (IFP) distribution is found to be independent of the constitutive model. The proposed biphasic model may be useful for elasticity imaging techniques aiming at predicting stress and IFP in tumors.

On the Role of Coherent Plane Wave Compounding in Shear Wave Elasticity Imaging: The Convolution Effect and Its Implications

Objective: The clinical applicability of shear wave elasticity imaging (SWEI) has been confounded by its appreciable inter-system variability and unsatisfactory sensitivity. While SWEI relies on plane wave imaging (PWI) to achieve real-time rendering, it has been rarely noticed that PWI can affect SWEI’s performance. This work is aimed at demonstrating that the use of coherent plane wave compounding (CPWC) can be a factor causing SWEI’s underperformance. Methods: We presented a model to formally describe the slow-time behavior of CPWC in motion tracking. This model reveals that CPWC introduces temporal convolution on the observed motion, making the motion sampling process a low-pass filter (LPF). For validation, shear waves were produced in a phantom in the same way but sampled via PWI using different compounding numbers (CN) and pulse repetition frequencies (PRF), with the obtained signals compared with the inferences drawn from our model. Similar experiments were performed to reconstruct two small targets in the phantom in order to appraise the impact of CPWC on SWEI’s sensitivity. Discussion: The validation experiment shows that the measurements match well with the model inferences, which verifies the LPF nature of CPWC. The phantom study also shows that either increasing CN or decreasing PRF can cause the loss of high-frequency motion information, leading to blurred target delineation by SWEI. Conclusion: The convolution effect can help understand the variability of SWEI. Researchers should beware this effect when working on SWEI standardization. Clinicians using SWEI should also be cautious because this effect makes it harder to identify small lesions.

Harmonic Motion Imaging-Guided Focused Ultrasound Ablation: Comparison of Three Focused Ultrasound Interference Filtering Methods

Harmonic motion imaging (HMI) is an acoustic radiation force-based elasticity imaging technique, which can be used to monitor changes in tissue mechanical properties caused by focused ultrasound (FUS)-induced thermal ablation. In conventional HMI, the amplitude-modulated FUS sequence and imaging pulse are transmitted simultaneously. With this method, the high-amplitude FUS signal must be separated from the imaging data for tissue displacement estimation. Frequency domain notch filtering and bandpass filtering were previously used to filter FUS interference from imaging data. However, FUS interference becomes more pronounced at the increased intensities and durations necessary for thermal ablation, rendering frequency domain filtering challenging. In this study, three methods for FUS interference filtering during HMI-guided FUS ablation (HMIgFUS) were compared. The methods were notch filtering; interleaved HMIgFUS, with interleaved FUS and imaging pulses; and FUS-net, a convolutional neural network-based U-Net autoencoder developed by our group for FUS interference filtering in radiofrequency data. FUS-net was applied here for the first time for the purpose of ablation displacement monitoring. The three filtering methods were tested during 20 HMIgFUS acquisitions in an ex vivo canine liver using a range of peak positive pressures from 11 to 18 MPa and durations ranging from 60 to 180 seconds. The B-mode mean squared errors (MSEs) and displacement amplitude contrast-to-noise ratios (CNRs) of the three methods were calculated and compared. The interleaved method for HMIgFUS was found to be significantly robust in avoiding FUS interference in all tested cases for FUS ablation monitoring, especially cases with high FUS pressure and long durations, as opposed to traditional notch filtering and FUS-net filtering. CNRs obtained from displacement amplitude maps in the interleaved data set were significantly higher in all cases than those obtained from the notch filtered and FUS-net data sets. There was not a significant trend in displacement CNR between the FUS-net and notch filtered data sets. However, B-mode MSE was found to be significantly higher when comparing the FUS-net and interleaved data sets as opposed to the notch filtered and interleaved data sets, suggesting further potential of FUS-net as an FUS interference filtering method. These findings indicate the robustness of interleaved HMIgFUS in avoiding FUS interference during HMIgFUS monitoring and the advantages, limitations and future potential of FUS-net and notch filtering.

Microwave-induced thermoacoustic elastic imaging: A simulation study

Microwave-induced thermoacoustic imaging (MTI) has the advantages of high resolution, high contrast, non-ionization, and non-invasive. Recently, MTI was used in the field of breast cancer screening. In this paper, based on the finite element method (FEM) and COMSOL Multiphysics software, a three-dimensional breast cancer model suitable for exploring the MTI process is proposed to investigate the influence of Young’s modulus (YM) of breast cancer tissue on MTI. It is found that the process of electromagnetic heating and initial pressure generation of the entire breast tissue is earlier in time than the thermal expansion process. Besides, compared with normal breast tissue, tumor tissue has a greater temperature rise, displacement, and pressure rise. In particular, YM of the tumor is related to the speed of thermal expansion. In particular, the larger the YM of the tumor is, the higher the heating and contraction frequency is, and the greater the maximum pressure is. Different Young’s moduli correspond to different thermoacoustic signal spectra. In MTI, this study can be used to judge different degrees of breast cancer based on elastic imaging. In addition, this study is helpful in exploring the possibility of microwave-induced thermoacoustic elastic imaging (MTAE).

The value of shear wave elasticity and shear wave dispersion imaging to evaluate the viscoelasticity of renal parenchyma in children with glomerular diseases

BackgroundTo study the value of shear wave elasticity and shear wave dispersion imaging to evaluate the viscoelasticity of renal parenchyma in children with glomerular diseases.MethodsForty-three children with glomerular diseases were prospectively evaluated by shear wave elasticity (SWE) and shear wave dispersion imaging (SWD); 43 healthy volunteers served as the control group. The shear wave velocities (SWV) and the dispersion slopes were measured at the upper, middle, and lower poles of both kidneys. The analysis of mean SWV and mean dispersion slope in control and patient groups was used to further evaluate the value of SWE and SWD in the viscoelasticity of renal parenchyma in children with glomerular disease.ResultsThe mean SWV in children with glomerular disease was higher than that in the healthy control group (1.61 ± 0.09 m/s vs. 1.43 ± 0.07 m/s, p < 0.001). Compared with healthy group, the mean dispersion slope in children with glomerular disease was significantly increased (13.5 ± 1.39 (m/s)/kHz vs. 12.4 ± 1.40 (m/s)/kHz, p < 0.001). Correlation analysis showed absence of correlation between the SWV and dispersion slope of occult blood, serum creatinine, 24-h urine protein, blood albumin, BMI and ROI box depth of children with glomerular disease.ConclusionsThe present study shows that it is feasible to use SWE and SWD to evaluate the difference of viscoelasticity of the renal parenchyma between healthy children and those with glomerular disease.

Magneto-acoustic protein nanostructures for non-invasive imaging of tissue mechanics in vivo

Measuring cellular and tissue mechanics inside intact living organisms is essential for interrogating the roles of force in physiological and disease processes. Current agents for studying the mechanobiology of intact, living organisms are limited by poor light penetration and material stability. Magnetomotive ultrasound is an emerging modality for real-time in vivo imaging of tissue mechanics. Nonetheless, it has poor sensitivity and spatiotemporal resolution. Here we describe magneto-gas vesicles (MGVs), protein nanostructures based on gas vesicles and magnetic nanoparticles that produce differential ultrasound signals in response to varying mechanical properties of surrounding tissues. These hybrid nanomaterials significantly improve signal strength and detection sensitivity. Furthermore, MGVs enable non-invasive, long-term and quantitative measurements of mechanical properties within three-dimensional tissues and in vivo fibrosis models. Using MGVs as novel contrast agents, we demonstrate their potential for non-invasive imaging of tissue elasticity, offering insights into mechanobiology and its application to disease diagnosis and treatment.

Assessing vaginal wall indexes in premenopausal versus postmenopausal women by transrectal linear array high-frequency probe

ObjectiveThis study aimed to verify the feasibility of 2D measurement of full-layer thickness of vaginal wall and evaluation of its elasticity by shear wave elastic imaging using transrectal linear array high-frequency ultrasound and to investigate the differences of vaginal wall indexes in premenopausal versus postmenopausal women.MethodFrom September to November 2022, a total of 87 women in the Department of Gynecology, Nanjing First Hospital were examined by a sonographer using transrectal linear array high-frequency ultrasound, including 34 women of reproductive age and 53 postmenopausal women. The vagina was divided into upper, middle, and lower segments, and the full-layer thickness of each part was measured. Then shear wave elastography (SWE) was used, and the average value of Young's modulus was used to evaluate the degree of vaginal elasticity.ResultsTransrectal linear array high-frequency ultrasound can clearly display structures of vaginal wall; measurement of the full thickness of the vaginal wall and evaluation of the degree of vaginal elasticity were feasible. There was a statistically significant difference in the thickness of each part of the vaginal wall between pre- and postmenopausal women (P < 0.001); there was no significant difference in the vaginal Young's modulus of pre- and postmenopausal women (P = 0.073). ConclusionTransrectal linear array high-frequency ultrasonography is a non-invasive and feasible method to measure vaginal wall thickness (VWT) and elasticity. There are significant differences in VWT between pre- and postmenopausal women.

Application of real time shear wave elastography to the differential diagnosis of secondary parathyroid hyperplasia and adenoma.

We aimed to explore the value of ultrasonic elastic imaging in the diagnosis of parathyroid hyperplasia and adenoma in patients with secondary hyperparathyroidism and provide more evidence for clinical treatment. Forty patients who were on dialysis and underwent parathyroid surgery were selected All patients underwent routine ultrasound, ultrasound elasticity examination and blood biochemical examination before surgery, including calcium, phosphorus, parathyroid hormone (PTH), etc. According to postoperative results, adenoma group and hyperplasia group were divided into 2 groups. Receiver operating characteristic curve was drawn to evaluate the diagnostic efficacy and combined diagnostic efficacy of each index. The PTH levels significantly differed between the adenoma and hyperplasia groups (P < .001). The volume and blood flow grades significantly differed between the adenoma and hyperplasia groups (P < .001) The minimum of the adenoma group was 14.62 ± 6.79 kPa, mean was 19.42 ± 6.29 kPa, and maximum was 24.25 ± 6.35 kPa which were significantly different from those in the hyperplasia group (P < .05). The combinations of more than 6 indicators in the diagnosis of parathyroid adenoma resulted in an area under the curve of 0.892 (P < .001), and the sensitivity and specificity were 78.9% and 97.4%, respectively. Shear wave elastography can be used as an effective tool to distinguish secondary parathyroid hyperplasia from adenoma. When combined with PTH, conventional ultrasound blood flow grading and volume measurement, it has higher diagnostic efficacy.

Clinical Application of Ultrasound Elastic Imaging in Assessing Poststroke Complex Regional Pain Syndrome (CRPS).

This study aimed to explore the characteristics and clinical application of ultrasonic elastography in peripheral soft tissue in patients with poststroke complex regional pain syndrome (CRPS). Complex regional pain syndrome (CRPS) type I is also known as shoulder hand syndrome (SHS). Its main symptoms include shoulder pain, limited activity, upper arm, wrist, and knuckle joint pain. Ultrasonic elastic imaging technology is gradually being applied to musculoskeletal system evaluation, primarily for the elastic examination of superficial tissue, as a result of the continual advancements in ultrasound technology. To make up for the absence of conventional imaging, functional state evaluation of the motor system can offer conventional ultrasonic tissue elasticity and hardness data. The purpose of this study was to objectively quantify the soft tissue surrounding the shoulder joint of stroke patients with CRPS using ultrasonic elastic imaging and to determine the diagnostic usefulness of ultrasonic elastic imaging for CRPS in stroke in order to promote its usage in clinical practice. Patients diagnosed with CRPS following a stroke and admitted to the rehabilitation unit at Shanxi Bethune Hospital between January, 2021 to June, 2021 were included in the analysis. The control group consisted of people without pain in their shoulder joints. Each group consisted of 30 patients. A high-frequency wire array probe (frequency = 8-16 Hz) was employed in conjunction with an ultrasonic diagnostic apparatus. A quantitative analytic system determined Young's modulus of the tissue, while the tracking of the shear wave provided an elastin map in real-time. An excitation pulse of acoustic radiation force was used to cause shear waves in the tissue. The Young's modulus of supraspinatus muscle in the study and control groups was 289.16±22.07 Kpa and 231.99±23.61 Kpa, respectively (P <0.01). Young's modulus values of the study group's subscapular biceps were compared to those of the control group (P > 0.05). The supraspinatus shear wave elastographic (SWE) imaging value was 10.01±0.49 m/s in the study group and 7.92±0.50 in the control group (P <0.05). The study and control groups had subscapular muscle SWE values of 15.99±1.95 and 8.64±0.56 m/s, respectively (P <0.05). The average biceps tendon SWE value in the study and control groups was 6.39±0.42 and 4.69±0.36 m/s, respectively (P <0.05). In conclusion, the SWE assessed by ultrasound elastography is useful for early diagnosis and evaluation of the superior shoulder tendon, subscapular tendon, and biceps tendon of CRPS following stroke.

In vivo shear wave elasticity imaging for assessment of diaphragm function in muscular dystrophy.

Duchenne muscular dystrophy (DMD) causes patients to suffer from ambulatory disability and cardiorespiratory failure, the latter of which leads to premature death. Due to its role in respiration, the diaphragm is an important muscle for study. A common method for evaluating diaphragm function is ex vivo force testing, which only allows for an end point measurement. In contrast, ultrasound shear wave elastography imaging (US-SWEI) can assess diaphragm function over time; however, US-SWEI studies in dystrophic patients to date have focused on the limbs without preclinical studies. In this work, we used US-SWEI to estimate the shear wave speed (SWS) in diaphragm muscles of healthy (WT) mice, mdx mice, and mdx mice haploinsufficient for utrophin (mdx-utr) at 6 and 12 months of age. Diaphragms were then subjected to ex vivo force testing and histological analysis at 12 months of age. Between 6 and 12 months, a 23.8% increase in SWS was observed in WT mice and a 27.8% increase in mdx mice, although no significant difference was found in mdx-utr mice. Specific force generated by mdx-utr diaphragms was lower than that of WT diaphragms following twitch stimulus. A strong correlation between SWS and collagen deposition was observed, as well as between SWS and muscle fiber size. Together, these data demonstrate the ability of US-SWEI to evaluate dystrophic diaphragm functionality over time and predict the biochemical and morphological make-up of the diaphragm. Additionally, our results highlight the advantage of US-SWEI over ex vivo testing by obtaining longitudinal measurements in the same subject. STATEMENT OF SIGNIFICANCE: In DMD patients, muscles experience cycles of regeneration and degeneration that contribute to chronic inflammation and muscle weakness. This pathology only worsens with time and leads to muscle wasting, including in respiratory and cardiac muscles. Because respiratory failure is a major contributor to premature death in DMD patients, the diaphragm muscle is an important muscle to evaluate and treat over time. Currently, diaphragm function is assessed using ex vivo force testing, a technique that only allows measurement at sacrifice. In contrast, ultrasonography, particularly shear wave elasticity imaging (USSWEI), is a promising tool for longitudinal assessment; however, most US-SWEI in DMD patients aimed for limb muscles only with the absence of preclinical studies. This work broadens the applications of US-SWE imaging by demonstrating its ability to track properties and function of dystrophic diaphragm muscles longitudinally in multiple dystrophic mouse models.

Toward peripheral nerve mechanical characterization using Brillouin imaging spectroscopy.

Peripheral nerves are viscoelastic tissues with unique elastic characteristics. Imaging of peripheral nerve elasticity is important in medicine, particularly in the context of nerve injury and repair. Elasticity imaging techniques provide information about the mechanical properties of peripheral nerves, which can be useful in identifying areas of nerve damage or compression, as well as assessing the success of nerve repair procedures. We aim to assess the feasibility of Brillouin microspectroscopy for peripheral nerve imaging of elasticity, with the ultimate goal of developing a new diagnostic tool for peripheral nerve injury in vivo. Viscoelastic properties of the peripheral nerve were evaluated with Brillouin imaging spectroscopy. An external stress exerted on the fixed nerve resulted in a Brillouin shift. Quantification of the shift enabled correlation of the Brillouin parameters with nerve elastic properties. Brillouin microscopy provides sufficient sensitivity to assess viscoelastic properties of peripheral nerves.

The impact of amplitude modulation frequency in harmonic motion imaging on inclusion characterization.

Ultrasound elasticity imaging techniques aim to provide a non-invasive characterization of tissue mechanical properties to detect pathological changes and monitor disease progression. Harmonic motion imaging (HMI) is an ultrasound-based elasticity imaging technique that utilizes an oscillatory acoustic radiation force to induce localized displacements and estimate relative tissue stiffness. Previous studies have applied a low amplitude modulation (AM) frequency of 25 or 50 Hz in HMI to assess the mechanical properties of different tissue types. In this study, we investigate the dependence of AM frequency in HMI and whether the frequency can be adjusted based on the size and mechanical properties of the underlying medium for enhanced image contrast and inclusion detection. A tissue-mimicking phantom with embedded inclusions at different sizes and stiffnesses was imaged within a range of AM frequencies from 25 to 250 Hz at 25-Hz step size. The AM frequency at which the maximum contrast and CNR are achieved depends on the size and stiffness of the inclusions. A general trend shows that contrast and CNR peak at higher frequencies for smaller inclusions. In addition, for some inclusions with the same size but different stiffnesses, the optimized AM frequency increases with the stiffness of the inclusion. Nevertheless, there is a shift between the frequencies at which the contrast peaks and those with maximum CNR. Finally, in agreement with the phantom findings, imaging an ex-vivo human specimen with a 2.7-cm breast tumor at a range of AM frequencies showed that the highest contrast and CNR are achieved at the AM frequency of 50 Hz. These findings indicate that the AM frequency can be optimized in different applications of HMI, especially in the clinic, for improved detection and characterization of tumors with different geometries and mechanical properties.

Unsupervised deep learning-based displacement estimation for vascular elasticity imaging applications

Objective. Arterial wall stiffness can provide valuable information on the proper function of the cardiovascular system. Ultrasound elasticity imaging techniques have shown great promise as a low-cost and non-invasive tool to enable localized maps of arterial wall stiffness. Such techniques rely upon motion detection algorithms that provide arterial wall displacement estimation. Approach. In this study, we propose an unsupervised deep learning-based approach, originally proposed for image registration, in order to enable improved quality arterial wall displacement estimation at high temporal and spatial resolutions. The performance of the proposed network was assessed through phantom experiments, where various models were trained by using ultrasound RF signals, or B-mode images, as well as different loss functions. Main results. Using the mean square error (MSE) for the training process provided the highest signal-to-noise ratio when training on the B-modes images (30.36 ± 1.14 dB) and highest contrast-to-noise ratio when training on the RF signals (32.84 ± 1.89 dB). In addition, training the model on RF signals demonstrated the capability of providing accurate localized pulse wave velocity (PWV) maps, with a mean relative error (MREPWV) of 3.32 ± 1.80% and an R2 of 0.97 ± 0.03. Finally, the developed model was tested in human common carotid arteries in vivo, providing accurate tracking of the distension pulse wave propagation, with an MREPWV = 3.86 ± 2.69% and R2 = 0.95 ± 0.03. Significance. In conclusion, a novel displacement estimation approach was presented, showing promise in improving vascular elasticity imaging techniques.

Radiation force of compressional plane waves on a sphere embedded in an elastic medium

The aim of this work is to derive exact partial-wave series expressions for the radiation force of plane compressional progressive waves propagating inside an elastic medium and incident upon an embedded elastic sphere. The analytical modeling is needed to provide fundamental physical understanding of the underlying phenomenon of mode conversion and its contribution to the acousto-elastic radiation force, and in experimental design. In the context of linear elasticity theory, a rigorous derivation for the acousto-elastic radiation force, based on the integration of the time-averaged radial component of the elastodynamic Poynting vector (or power flow density), is presented and discussed. Initially, the elastic scattering problem is determined and subsequently used to derive the mathematical expression for the acousto-elastic radiation force of progressive compressional waves. The method is also verified using the extended optical theorem for elastic compressional plane waves. Extension to the case of elastic plane standing wave is also provided. Particular importance is made on the contributions of elastic mode preservation (P → P) and mode conversion (P → S) to the acousto-elastic radiation force. Numerical computations for the dimensionless radiation force efficiency and its components demonstrate the importance of compressional-to-shear mode conversion in the scattering by the sphere encased in a linearly-elastic medium. The analytical formalism presented here can be used to validate numerical methods, and the results of the simulations can be utilized as a priori knowledge in optimizing and designing acousto-elastic radiation force experiments involving elastic compressional progressive waves on a sphere in acoustically-engineered materials applications, elasticity imaging methods, activation of implantable devices, characterization of biological tissue, and non-destructive evaluation to name some examples.

Extracellular matrix remodelling and stiffening contributes to tumorigenesis of salivary carcinoma ex pleomorphic adenoma——A study based on patient-derived organoids

BackgroundSalivary carcinoma ex pleomorphic adenoma (CXPA) is defined as a carcinoma that develops from benign pleomorphic adenoma (PA). Abnormally activated Androgen signaling pathway and amplification of HER-2/neu(ERBB-2) gene are known to be involved in CXPA tumorigenesis. Recent progress in tumour microenvironment research has led to identification that extracellular matrix (ECM) remodelling and increased stiffness act as critical contributing role in tumour carcinogenesis. This study examined ECM modifications to elucidate the mechanism underlying CXPA tumorigenesis.ResultsPA and CXPA organoids were successfully established. Histological observation, immunohistochemistry (IHC), and whole-exome sequencing demonstrated that organoids recapitulated phenotypic and molecular characteristics of their parental tumours. RNA-sequencing and bioinformatic analysis of organoids showed that differentially expressed genes are highly enriched in ECM-associated terms, implying that ECM alternations may be involved in carcinogenesis. Microscopical examination for surgical samples revealed that excessive hyalinized tissues were deposited in tumour during CXPA tumorigenesis. Transmission electron microscopy confirmed that these hyalinized tissues were tumour ECM in nature. Subsequently, examination by picrosirius red staining, liquid chromatography with tandem mass spectrometry, and cross-linking analysis indicated that tumour ECM was predominantly composed of type I collagen fibers, with dense collagen alignment and an increased level of collagen cross-linking. IHC revealed the overexpression of COL1A1 protein and collagen-synthesis-related genes, DCN and IGFBP5 (p < 0.05). Higher stiffness of CXPA than PA was demonstrated by atomic force microscopy and elastic imaging analysis. We utilized hydrogels to mimic ECM with varying stiffness degrees in vitro. Compared with softer matrices (5Kpa), CXPA cell line and PA primary cells exhibited more proliferative and invasive phenotypes in stiffer matrices (50Kpa, p < 0.01). Protein-protein interaction (PPI) analysis of RNA-sequencing data revealed that AR and ERBB-2 expression was associated with TWIST1. Moreover, surgical specimens demonstrated a higher TWIST1 expression in CXPA over PA. After knocking down TWIST1 in CXPA cells, cell proliferation, migration, and invasiveness were significantly inhibited (p < 0.01).ConclusionDeveloping CXPA organoids provides a useful model for cancer biology research and drug screening. ECM remodelling, attributed to overproduction of collagen, alternation of collagen alignment, and increased cross-linking, leads to increased ECM stiffness. ECM modification is an important contributor in CXPA tumorigenesis.